The role of Keap1/Nrf2/HO-1 signal pathway in liver injury induced by rare earth neodymium oxide in mice / 中华劳动卫生职业病杂志

Objective: To investigate the role of Keap1/Nrf2/HO-1 signaling pathway in liver injury induced by neodymium oxide (Nd(2)O(3)) in mice. Methods: In March 2021, forty-eight SPF grade healthy male C57BL/6J mice were randomly divided into control group (0.9% NaCl), low dose group (62.5 mg/ml Nd(2)O(3)), medium dose group (125.0 mg/ml Nd(2)O(3)), and high dose group (250.0 mg/ml Nd(2)O(3)), each group consisted of 12 animals. The infected groups were treated with Nd(2)O(3) suspension by non-exposed tracheal drip and were killed 35 days after dust exposure. The liver weight of each group was weighed and the organ coefficient was calculated. The content of Nd(3+) in liver tissue was detected by inductively coupled plasma mass spectrometry (ICP-MS). HE staining and immunofluorescence was used to observe the changes of inflammation and nuclear entry. The mRNA expression levels of Keap1, Nrf2 and HO-1 in mice liver tissue were detected by qRT-PCR. Western blotting was used to detect the protein expression levels of Keap1 and HO-1. The contents of catalase (CAT), glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) were detected by colorimetric method. The contents of interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) were determined by ELISA. The data was expressed in Mean±SD. Two-independent sample t-test was used for inter-group comparison, and one-way analysis of variance was used for multi-group comparison. Results: Compared with the control group, the liver organ coefficient of mice in medium and high dose groups were increased, and the Nd(3+) accumulation in liver of mice in all dose groups were significantly increased (P<0.05). Pathology showed that the structure of liver lobules in the high dose group was slightly disordered, the liver cells showed balloon-like lesions, the arrangement of liver cell cords was disordered, and the inflammatory exudation was obvious. Compared with the control group, the levels of IL-1β and IL-6 in liver tissue of mice in all dose groups were increased, and the levels of TNF-α in liver tissue of mice in high dose group were increased (P<0.05). Compared with the control group, the mRNA and protein expression levels of Keap1 in high dose group were significantly decreased, while the mRNA expression level of Nrf2, the mRNA and protein expression levels of HO-1 were significantly increased (P<0.05), and Nrf2 was successfully activated into the nucleus. Compared with the control group, the activities of CAT, GSH-Px and T-SOD in high dose group were significantly decreased (P<0.05) . Conclusion: A large amount of Nd(2)O(3) accumulates in the liver of male mice, which may lead to oxidative stress and inflammatory response through activation of Keap1/Nrf2/HO-1 signal pathway. It is suggested that Keap1/Nrf2/HO-1 signal pathway may be one of the mechanisms of Nd(2)O(3) expose-induced liver injury in mice.

Pharmacokinetic effects of metformin hydrochloride, food and alcohol on Ramulus Mori (Sangzhi) alkaloids / 药学学报

Ramulus Mori (Sangzhi) alkaloids (SZ-A) are a group of polyhydroxy alkaloids extracted and isolated from the traditional Chinese medicine mulberry twig, which is mainly used for the treatment of type 2 diabetes mellitus (T2DM). In addition to acting as a glycosidase inhibitor in the small intestine after oral administration, SZ-A can also be absorbed into blood and widely distributed to target organs related to diabetes, exerting multiple pharmacological effects. It is important to elucidate the possible pharmacokinetic influences of SZ-A for its clinical rational applications, such as drug interactions, the effects of food and alcohol on the absorption of SZ-A. However, studies in this area are limited. Therefore, the pharmacokinetic interactions between orally administrated SZ-A (50 mg·kg-1) and metformin hydrochloride (Met, 200 mg·kg-1) in Sprague-Dawley (SD) rats were examined. Then, the effect of food (standard feed) on the pharmacokinetics of SZ-A was investigated using fasting administration of SZ-A (50 mg·kg-1) in rats as a control. Finally, we investigated the pharmacokinetic characteristics of SZ-A (50 mg·kg-1) in different concentrations alcohol solutions using aqueous solution of SZ-A administered to rats as a control to evaluate the effect of alcohol on the bioabsorption of SZ-A. The results showed no significant pharmacokinetic interactions between SZ-A and Met after combination treatment. The standard feed had little effect on the pharmacokinetic profile of SZ-A. Alcohol retarded the absorption of SZ-A, resulting in a significant decrease in the Cmax of SZ-A. The decrease was greater at higher alcohol concentrations; however, no significant difference was observed in the AUC0-t. These results support the clinical rational applications of SZ-A. All animal protocols were approved by the Ethics Committee of Kangtai Medical Laboratory Service Hebei Co., Ltd. (Hebei, China) (No. MDL2022-01-17-1).

Effect of auricular acupoint acupuncture and acupressure on bladder function of the patients with urinary retention after operation / 国际中医中药杂志

Objective To evaluate the effect of auricular acupoint acupressure combined with acupuncture and moxibustion on urinary retention after operation. Methods Ninety patients with urinary retention after operation were retrospectively analyzed. They were divided into two groups according to different treatment methods, 45 cases in each group. The control group was treated with acupuncture and moxibustion, while the observation group was treated with auricular acupoint sticking on the basis of the control group. Both groups were treated for 7 days. The urination volume of the two groups was observed 3-5 h, 5-8 h after treatment, and the residual urine volume, maximum urinary flow rate, average urinary flow rate, urination time, bladder compliance (BC), maximum detrusor pressure (MDP) before and 48 h after treatment, and the clinical efficacy were evaluated. Results The urinary outputs of the observation group were significantly higher than this of the control group at 3-5 h and 5-8 h after treatment (t values were 3.189 and 4.325, respectively, P<0.01). After 48 hours of treatment, the maximum urinary flow rate, average urinary flow rate, BC and MDP in the observation group were significantly higher than those in the control group (t values were 5.292, 3.655, 3.364, 5.042 respectively, all Ps<0.01), and the residual urine volume and urination time in the observation group were significantly lower than this in the control group (t values were -5.261, -4.174 respectively, P<0.01). The total effective rate was 95.6% (42/45) in the observation group and 88.9% (40/45) in the control group. There were significant differences in clinical efficacy between the two groups (Z=-2.157, P=0.031). Conclusions The Auricular acupoint pressure with acupuncture can improve the urinary function of patients with urinary retention after operation and improve the clinical efficacy.

Clinical effect of Weitan-Waifu powder combined with acupuncture on postoperative gastroparesis in patients with digestive tract cancer / 国际中医中药杂志

Objective To explore the clinical effect of Weitan-Waifu powder combined with acupuncture on postoperative gastroparesis in patients with digestive tract tumors. Methods Patients with gastric fistula after 97 cases of gastric surgery admitted to our hospital from March 2014 to March 2017 were randomly divided into treatment group (48 cases) and control group (49 case) by random number table method. The control group received routine basic treatment. The treatment group was treated with Weitan-Waifu powder and acupuncture on the basis of the control group. The serum gastrin and gastric juice were compared before and after treatment. The gastrointestinal motility recovery time, gastric tube extraction time, and time of first feeding after surgery were recorded. Results After treatment, the gastric emptying time (38.6 ± 2.9 min vs. 43.1 ± 3.7 min, t=-6.658), gastric tube extraction time (6.6 ± 1.5 d vs. 8.2 ± 1.9 d, t=-4.597), and first feeding time (8.5 ± 2.0 d vs. 12.0 ± 2.9 d, t=-6.906) were significantly lower in the treatment group than those in the control group (P<0.05). After treatment, the serum gastrin levels of the treatment group (115.3 ± 8.1 ng/L vs. 107.6 ± 9.5 ng/L, t=4.292) were significantly higher than the control group (P<0.05). After treatment, the gastric juice volume (252.8 ± 51.9 ml/d vs. 375.1 ± 88.6 ml/d, t=-8.273) of the treatment group was significantly lower than that of the control group (P<0.05). After treatment, the clinical treatment effect of the treatment group was of the treatment group better than that of the control group (Z=-2.003, P=0.045). Conclusions The Weitan-Waifu powder combined with acupuncture and moxibustion for postoperative gastroparesis in patients with digestive tract tumors can effectively shorten the treatment time, improve serum gastrin levels, and improve the therapeutic effect.

Study on antidepressant effect and mechanism of self-made prescription of strengthening spleen and replenishing Qi / 中国药理学通报

Aim To explore the antidepressant effect and the mechanism of self-made prescription of strengthening spleen and replenishing Qi ( SMP-SS-RQ) . Methods The depression model of chronic un-predictable mild stress ( CUMS ) was established in mice. The animals were randomly divided into control group, model group, SMP-SSRQ low, middle and high dose groups (8, 16, 32 mg·kg-1), with 12 mice for each group. The control group and the model group were given the same volume of saline, and other groups were given corresponding dose of SMP-SSRQ. Animals of each group were administered by gavage twice a day for two weeks. Behavioral indexes of mice were deter-mined by open field experiment, sugar consumption test, forced swimming test and tail suspension test. Quantitative real-time PCR (qPCR) and Western blot were respectively performed to detect mRNA and pro-tein expression levels of Igsf11 , Pdia2 and Sec14 l2 inprefrontal cortex and hippocampus. Results Com-pared with model group, depressed mice' s horizontal mobile score, upright number and the sugar water pref-erence index increased and FST as well as TST de-creased in all SMP-SSRQ groups(P<0.05). The de-pression symptoms in mice were obviously improved by SMP-SSRQ therapy. Low and high doses of SMP-SSRQ significantly reduced mRNA and protein expression lev-el of Igsf11 , Pdia2 and Sec14 l2 in the prefrontal cortex and hippocampus of the depressed mice, presenting significant statistical difference compared with model group ( P<0.05 ) . Conclusions SMP-SSRQ can ef-fectively improve mouse depressive behavior, and its mechanism may be related to the down-regulation of Igsf11 , Pdia2 and Sec14 l2 in mouse prefrontal cortex and hippocampus.

Chinmedomics strategy to discover effective constituents and elucidate action mechanism of Nanshi capsule against kidney-yang deficiency syndrome / 中国中药杂志

The chinmedomics method was used to explore the effect of Nanshi capsule on endogenous metabolites of rats with kidney-yang deficiency syndrome, investigate the metabolites and metabolic pathways closely related to kidney-yang deficiency syndrome (KYDS)and identify the therapeutic basis of Nanshi capsule(NPC)as well as its action mechanism for KYDS. The routine biochemical indexes of serum were detected and histomorphology was observed. Based on the chinmedomics technology platform, discriminatory analysis in multivariate modes was conducted for rat blood and urine, thus to investigate the biomarkers of KYDS and the therapeutic effect of NPC against KYDS. Meanwhile, the main constituents of NPC in rat serum were also detected to analyze its correlation between the constituents in vivo and the biomarkers of KYDS, and determine the potential effective compounds for therapeutic effect. Eleven biomarkers of KYDS were identified in the rat models, involving steroid hormone biosynthesis, tryptophan metabolism and tyrosine metabolism. It was found that NPC could regulate steroid hormone biosynthesis, tryptophan metabolism and tyrosine metabolism; PCMS analysis showed that caffeic acid, 2-hydroxy-1-methoxy-anthraquinone, 1-hydroxy-2-methoxyanthraquinone, ferulic acid glucuronide conjugation, deacetylasperulosidic acid, cynaroside, betaine and umbelliferone were the main effective compounds of NPC for KYDS. In this study, cynaroside, betaine, umbelliferone and other compounds in NPC could integrally regulate the disturbance of metabolic profile in KYDS by improving the hormone synthesis, hormone synthesis pathway, hormone synthesis and release pathway in tyrosine metabolism and linoleic acid synthesis pathway in linoleic acid metabolism. These results indicated that the NPC had the characteristics of multi-pathway, multi-target and overall regulation in the treatment of KYDS. Chinmedomics approach can provide methodology support to discover innovative drug from traditional Chinese medicine.

Evaluating Pharmacological Effects of Two Major Components of Shuangdan Oral Liquid: Role of Danshensu and Paeonol in Diabetic Nephropathy Rat

Shuangdan oral liquid (SDO) containing radix Salviae miltiorrhizae (Chinese name Danshen) and cortex moutan (Chinese name Mudanpi) is a traditional Chinese medicine using for treating vascular diseases. Danshensu (DSS) is a main effective monomer composition derived from radix Salviae miltiorrhizae and paeonol (Pae) from cortex moutan. Although the two herbs are widely used in traditional Chinese medicine, the pharmacological functions of their active compositions were not reported. Therefore, the research of DSS and Pae in mechanisms and pharmacodynamics interaction can provide scientific evidence to support clinical application. The diabetic nephropathy (DN) rats which were induced by streptozotocin (STZ) were treated with SDO, DSS, Pae, and DSS+Pae for eight weeks. The positive effects on DN animal models were investigated by detection of physiological and biochemical indexes and oxidative stress markers, within five treatments: SDO, DSS, Pae, DSS+Pae and insulin group. Compared with the model group, the DSS+Pae group improved the renal function, blood lipid metabolism and blood viscosity, increased the vitality of T-SOD or T-AOC and decreased the level of MDA or NO after the treatment. The study was successfully showed that the DSS+Pae group could delay the process of DN, especially in the renal injury part of histopathology changes. Our results suggest that the co-administration of DSS and Pae significantly may play a protective role in DN rats through decreasing the oxidative stress and improving the blood lipid metabolism mechanisms.

Stimulation by Lycium bararum polysaccharides of the maturation of dendritic cells in murine bone marrow / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To study the effect of Lycium bararum polysaccharides (LBPs) stimulation on the maturation of murine bone marrow derived dendritic cells (BMDCs).</p><p><b>METHODS</b>Murine bone marrow cells were cultured in GM-CSF and IL-4 for 5 days, then were purified with a MACS column. Respectively, BMDCs were stimulated with LBPs, LPS and RPMI1640 for 2 days. Cell phenotypes and antigens uptake by BMDCs were analyzed by flow cytometry. Cytokines released by BMDCs were detected. The antigen presenting by BMDCs was evaluated by mixed lymphocyte responses.</p><p><b>RESULT</b>Compared with to the BMDCs that only subjected to RPMI 1640, the expression of I-A/I-E, CD11c and secretion of IL-12 by BMDCs stimulated with LBPs were increased, the phagocytosis of FITC-dextran by BMDCs stimulated with LBPs was impaired but the activation of proliferation of allogenic lymphocytes by BMDCs was strengthened.</p><p><b>CONCLUSION</b>LBPs promote not only the maturation of cultured murine BMDCs in vitro, but also the immune response initiation induced by BMDCs.</p>