Chrysophanol accelerates astrocytic mitochondria transfer to neurons and attenuates the cerebral ischemia-reperfusion injury in rats.

Astrocytes transfer extracellular functional mitochondria into neurons to rescue injured neurons after a stroke. However, there are no reports on drugs that interfere with intercellular mitochondrial transfer. Chrysophanol (CHR) was an effective drug for the treatment of cerebral ischemia-reperfusion injury (CIRI) and was selected as the test drug. The oxygen-glucose deprivation/reoxygenation (OGD/R) cell model and the middle cerebral artery occlusion animal model were established to investigate the effect of CHR on CIRI. The result showed that astrocytes could act as mitochondrial donors to ameliorate neuronal injury. Additionally, the neuroprotective effect of astrocytes was enhanced by CHR, the CHR improved the neuronal mitochondrial function, decreased the neurological deficit score and infarction volume, recovered cell morphology in ischemic penumbra. The mitochondrial fluorescence probe labeling technique has shown that the protective effect of CHR is associated with accelerated astrocytic mitochondrial transfer to neurons. The intercellular mitochondrial transfer may be an important way to ameliorate ischemic brain injury and be used as a key target for drug treatment.

Involvement of glyphosate in disruption of biotransformation P450 enzymes and hepatic lipid metabolism in chicken.

The current study investigated the potentially harmful consequences of pure glyphosate or Roundup® on CYP family members and lipid metabolism in newly hatched chicks. On the sixth day, 225 fertilized eggs were randomly divided into three treatments: (1) the control group injected with deionized water, (2) the glyphosate group injected with 10 mg pure glyphosate/Kg egg mass and (3) the Roundup group injected 10 mg the active ingredient glyphosate in Roundup®/Kg egg. The results of the study revealed a reduction in hatchability in chicks treated with Roundup®. Moreover, change of Lipid concentration in serum and the liver-treated groups. Additionally, increased liver function enzymes and increased oxidative stress in the glyphosate and Roundup® groups. Furthermore, liver tissues showed histological changes and several lipid deposits in glyphosate-treated groups. Hepatic CYP1A2 and CYP1A4 expressions were significantly increased (p < .05) after glyphosate exposure, and suppression of CYP1C1 mRNA expression was significant (p < .05) after Roundup® exposure. The pro-inflammatory cytokines genes IFN-γ and IL-1ß expression were significantly increased (p < .05) after Roundup® exposure. In addition, there were significant differences in the levels of expression genes which are related to lipid synthesis or catabolism in the liver. In conclusion, in ovo glyphosate exposure caused disruption of biotransformation, pro-inflammatory and lipid metabolism in chicks.

An Insight into Antihyperlipidemic Effects of Polysaccharides from Natural Resources.

Hyperlipidemia is a chronic metabolic disease caused by the abnormal metabolism of lipoproteins in the human body. Its main hazard is to accelerate systemic atherosclerosis, which causes cerebrovascular diseases such as coronary heart disease and thrombosis. At the same time, although the current hypolipidemic drugs have a certain therapeutic effect, they have side effects such as liver damage and digestive tract discomfort. Many kinds of polysaccharides from natural resources possess therapeutic effects on hyperlipidemia but still lack a comprehensive understanding. In this paper, the research progress of natural polysaccharides on reducing blood lipids in recent years is reviewed. The pharmacological mechanisms and targets of natural polysaccharides are mainly introduced. The relationship between structure and hypolipidemic activity is also discussed in detail. This review will help to understand the value of polysaccharides in lowering blood lipids and provide guidance for the development and clinical application of new hypolipidemic drugs.

Effects of bed cleanliness on tucked and extended sleep-related lying postures of Japanese Black fattening cattle.

OBJECTIVE: Resting comfort may influence sleep-related lying postures in cattle. This study aimed to investigate the effects of bed cleanliness on tucked (TSP) and extended (ESP) head positions in sleep-related lying postures. METHODS: The study was conducted over two experimental periods. In each period, four Japanese Black fattening cattle were assigned to the cleaning treatment (CL), in which bedding material was replaced once during each experimental period. Four cattle were assigned to the control treatment (CON) with no bed cleaning. Daily duration, bout frequency, and bout length of sleep-related lying postures were measured, and bed moisture, ammonia concentration in the air, plasma cortisol, and serotonin concentration were also measured within one week before and after cleaning treatment in each period. RESULTS: The bed moisture and ammonia concentrations decreased in CL after bed cleaning. Following bed cleaning, the duration and bout frequency of TSP in CL decreased compared to that observed in CON, whereas ESP in CL increased after bed cleaning. Total duration of sleep-related lying postures and cortisol and serotonin levels did not differ between CL and CON. CONCLUSION: These results suggest that cattle in sleep-related lying postures shifted from tucked head positions to extended head positions in response to improved bed cleanliness.

[Optimization of processing technology for semen cuscuta by uniform and regression analysis].

OBJECTIVE: To optimize the best preparation technology for the contains of total flavornoids, polysaccharides, the percentage of water and alcohol-soluble components in Semen Cuscuta herb processing. METHODS: UV-spectrophotometry was applied to determine the contains of total flavornoids and polysaccharides, which were extracted from Semen Cuscuta. And the processing was optimized by the way of uniform design and contour map. RESULTS: The best preparation technology was satisfied with some conditions as follows: baking temperature 150 degrees C, baking time 140 seconds. CONCLUSION: The regression models are notable and reasonable, which can forecast results precisely.

Differential gene expression profiles of DNA repair genes in esophageal cancer cells after X-ray irradiation.

BACKGROUND AND OBJECTIVE: Various factors affect the radioresistance of tumor cells, with unknown molecular mechanism(s). Many genes have been found to associate with the radioresistance of tumor cells, however, the precise mechanism of these genes have not been elucidated. This paper was to analyze the differential expressions of DNA repair genes in esophageal carcinoma cells at different time after X-ray irradiation, and to investigate the role of these DNA repair genes in radiation resistance. METHODS: Esophageal cancer parental cells Seg-1 were treated with continuous 2 Gy of fractionated irradiation until the total dose reached 60 Gy to establish the radioresistant cell line Seg-1R. Total RNA was extracted from each cell line at 0, 8, and 24 h after irradiation. Illumine Human-6 V3 microarray was used to identify differentially expressed genes between parental and radioresistant cells. Ten genes involved in DNA repair were obtained and their expressions at different time points after irradiation were analyzed by Gene Ontology analysis. RESULTS: Ten DNA repair associated genes were found to be differentially expressed. Three of these genes, SLK, HMGB1, and PMS1, were not only differentially expressed between parental and radioresistant cell lines, but also expressed differently at different time points after irradiation in the same cell line. CONCLUSIONS: PMS1 may be an important factor involved in the mechanism of radioresistance of esophageal carcinoma cells.

[Study on the optimal extraction process of chaihushugan powder].

OBJECTIVE: To study the optimal extraction process of chaihushugan powder by orthogonal design. METHODS: RP-HPLC method was developed for the determination of saikosaponin a, ferulic acid, hesperidin and paeoniflorin in chaihushugan powder. The contents of the components and the extraction yield were selected as assessment indices. Four factors were study by L9 (3(4)), including the alcohol concentration, amount of alcohol, duration of extraction and times of extraction. RESULTS: The optimal extracting condition was 80% alcohol consumed as 10 times of crude herb amount, and extracting two times for 90 min each time. CONCLUSION: This study supplies theoretical base for the development of chaihushugan powder formulation.

[High throughput screening for glutathione S-transferase inhibitors].

To identify the inhibitor of glutathione S-transferase (GST), a high-throughput screening method was established in a 384-well microplate with total 35 microL volume, and the absorbance at 340 nm is detected. The concentrations of substrates, CDNB and GST were determined by chromatometry. The optimal enzyme kinetics reaction time and temperature are 2 h and 30 degrees C , respectively. The established model was evaluated by NaOCl, a known GST inhibitor, and the parameter Z' was 0.77, which showed a high feasibility and stability of the assay. A total of 31,098 compounds were screened, of which 4 compounds were shown to inhibit GST activity, high inhibiting activity for their IC50 of GST inhibition was 3.94, 4.05, 74.85, and 77.41 mg x L(-1), separately. The results indicated that the colorimetric method by using CDNB and GSH as substrate is stable, sensitive, reproducible and also suitable for high throughput screening.

Indocyanine green staining technique combined with laparoscopic hepatectomy with a Glisson pedicle approach for the treatment of liver cancer in 68 patients / 中国基层医药

Objective:To investigate the clinical value of indocyanine green (ICG) staining technique combined with laparoscopic hepatectomy with a Glisson pedicle approach in the treament of liver cancer.Methods:The clinical data of 150 patients with primary liver cancer, who received treatment in Yuyao People's Hospital from January 2019 to December 2020, were retrospectively analyzed. Group A ( n = 82) and group B ( n = 68) were designated according to the surgery methods used. The group A was subject to laparoscopic hepatectomy with a Glisson pedicle approach. The group B received ICG staining technique combined with laparoscopic hepatectomy with a Glisson pedicle approach. Operation-related conditions, postoperative complications, and the change in liver function indexes after surgery relative to before surgery were compared between the two groups. Results:There were no significant differences in the time taken to first anal exhaust, extubation time, and length of hospital stay between group A and group B (all P > 0.05). Operative time and intraoperative bleeding in the group B were (205.04 ± 35.01) minutes and (230.05 ± 17.53) mL, respectively, which were significantly lower than those in the group A [(228.07 ± 28.05) minutes, (255.07 ± 19.00) mL, t = 4.47, 8.31, both P < 0.05]. R0 resection rate was significantly lower in group B than in group A [85.29% (58/68) vs. 70.73% (58/82), χ2 = 4.50, P < 0.05]. There were no significant differences in postoperative complications between the two groups ( P > 0.05). Before treatment, there were no significant differences in serum levels of alanine aminotransferase (ALT), aspartate transaminase (AST), and total bilirubin between the two groups (all P > 0.05). At 1 day after surgery, serum ALT, AST, and TBil levels in each group were significantly increased compared with before surgery (all P < 0.05). Furthermore, serum levels of ALT, AST and TBil in the group A were (108.51 ± 30.23) U/L, (107.66 ± 26.93) U/L, and (32.16 ± 4.73) μmol/L, respectively, which were significantly higher than those in the group B [(88.38 ± 24.76) U/L, (86.85 ± 19.74) U/L, (27.95 ± 4.31) μmol/L, t = 4.40, 5.30, 5.65, all P < 0.05]. At 3 days after surgery, serum levels of ALT, AST, and TBil in each group were significantly lower than those at 1 day after surgery, but they were still higher than those before surgery. At 3 days after surgery, serum levels of ALT, AST and TBil in group A were (74.20 ± 13.83) U/L, (65.22 ± 9.68) U/L, and (28.18 ± 4.14) μmol/L, respectively, which were significantly higher than those in group B [(54.72 ± 10.31) U/L, (55.41 ± 7.63) U/L, (24.25 ± 3.98) μmol/L, t = 9.61, 6.79, 5.89, all P < 0.05]. Conclusion:Although the ICG staining technique has certain limitations, it can improve the accuracy of hepatectomy to a certain extent. ICG staining technique combined with laparoscopic hepatectomy with the Glisson pedicle approach is a safe and accurate treatment for liver cancer. The combined therapy is worthy of clinical application.

A study on the relationship between serum transferrin and prognosis of elderly patients with sepsis / 中华老年医学杂志

Objective:To investigate the relationship between serum transferrin(TRF)and the characteristics and prognosis of elderly patients with sepsis.Methods:A retrospective analysis was conducted on 49 elderly patients with sepsis treated at the Department of Critical Medicine and the Department of Respiratory and Critical Medicine of the First Affiliated Hospital of Suzhou University between October 2020 and March 2022 who had met the inclusion criteria.These patients were divided into a shock group(n=18)and a non-shock group(n=31); Based on outcomes, they were also divided into a death group(n=16)and a survival group(n=33).Through the random number table method, 30 healthy elderly people from the physical examination center of our hospital were selected as the control group.TRF and ferritin(SF)were measured on the 1st, 3rd and 7th day after admission, and the correlation between TRF and the sequential organ failure assessment score(SOFA)was analyzed.The predictive value of TRF on prognosis was evaluated via the receiver operating characteristic curve.Finally, the influence of multiple factors on prognosis was analyzed using the binary logistic regression model.Results:Compared with the control group at admission, SF levels of elderly patients with sepsis increased[709.20(402.40, 2000.00)μg/L vs.102.05(79.55, 199.75)μg/L, Z=-5.482, P<0.01], but TRF levels decreased[1.43(1.12, 1.72)g/L vs.2.23(1.80, 3.12)g/L, Z=5.395, all P<0.01], with statistical significance.On the 3rd and 7th day, TRF levels in the shock group were lower than in the non-shock group[(1.25±0.35)g/L vs.(1.55 ±0.51)g/L, 1.15(9.68, 1.34)g/L vs.1.56(1.19, 2.03)g/L]( t=-2.186, Z=3.258, P<0.05).There was a linear correlation between TRF and SOFA score on the 1st, 3rd and 7th day( R2=0.177, 0.176, 0.275, all P<0.01).TRF levels in the death group were lower than in the survival group on the 3rd and 7th day( Z=2.208, 3.423, P<0.05 for both).TRF levels on the 3rd and 7th day in elderly patients with sepsis had predictive value in evaluating the prognosis[area under receiver operating characteristic curve( AUC)values=0.696, 0.804, P<0.05, P<0.01].The survival curves based upon the best cutoff values(TRF=1.085 g/L on the 3rd day, TRF=1.330 g/L on the 7th day)between the two groups were statistically significantly( χ2=10.903, 13.318, P<0.01 for both).With TRF<1.085 g/L on the 3rd day, the risk of death in elderly patients with sepsis on the 28th day was 9.388 times the usual risk( OR=9.388, P<0.01), and with TRF<1.330 g/L on the 7th day, the risk of death was 14.625 times the usual risk on the 28th day( OR=14.625, P<0.01). Conclusions:Increased SF in elderly patients with sepsis is not related to disease severity, but the level of TRF is related to disease severity, and the level of TRF on the 3rd and 7th day is related to the prognosis and is an independent risk factor for all-cause death on the 28th day.

Detection of peripheral blood T lymphocyte subpopulations among patients positive for both hepatitis B virus surface antigen and surface antibody / 中国热带医学

@#Abstract: Objective　To investigate the frequency of peripheral blood T cells among patients positive for both hepatitis B virus surface antigen (HBsAg) and surface antibody (HBsAb). Methods　 Thirty six patients with co-existence of HBsAg and HBsAb diagnosed were enrolled as the experimental group, who were admitted by Shanghai tenth people's hospital and Wuxi 9th people's hospital from 2014 to 2020. while 40 patients tested positive for HBsAg and negative for HBsAb served as controls, who were admitted by Wuxi 9th people's hospital. Flow cytometry was used to detect and compare the proportions of peripheral blood CD3+, CD4+ and CD8+ T cells between the experimental and control groups. In addition, the associations of serum HBsAb level with peripheral blood T cell proportions, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were examined among chronic hepatitis B patients with co-existence of HBsAg and HBsAb using Pearson correlation analysis. Results　The median age, gender distribution, mean ALT and AST concentrations, proportion of HBV DNA viral load>103 copies/mL, seroprevalence of HBV E antigen (HBeAg), seroprevalence of HBV E antibody (HBeAb), seroprevalence of HBV core antibody (HBcAb) were comparable between the experimental and control groups, and there were no significant difference in them (P>0.05). There were no significant difference between the experimental and control groups in terms of CD3+ T cell proportion [(71.83±1.50)% vs (72.75±1.47)%; t=0.66, P>0.05], CD4+ T cell proportion [(36.81±1.53)% vs (39.88±1.57)%; t=1.43, P>0.05] and CD8+ T cell proportion [(33.17±2.04)% vs (32.40±1.75)%; t=0.77, P>0.05]. Pearson correlation analysis revealed that the serum HBsAb level did not significantly correlate with peripheral blood CD3+ (r=0.026, P=0.65), CD4+ (r=‒0.08, P=0.16) and CD8+ T cell proportions (r=0.09, P=0.24), CD4+/CD8+ T proportion (r=‒0.005, P=0.35), serum ALT (r=0.04, P=0.56) and AST levels (r=0.002, P=0.69) among chronic hepatitis B patients with co-existence of HBsAg and HBsAb. Conclusions　There are no significant differences between HBsAg+/HBsAb+ and HBsAg+/HBsAb- CHB patients in terms of peripheral blood CD3+, CD4+ and CD8+ T cell proportions.

Clinical factors of positive surgical margin after robot-assisted laparoscopic radical prostatectomy in patients with high-risk prostate cancer / 中华泌尿外科杂志

Objective:To investigate the relationship between the positive surgical margin and clinical factors such as neoadjuvant hormonal therapy after robot-assisted laparoscopic radical prostatectomy (RARP) in high-risk patients with prostate cancer.Methods:The clinical data of 164 patients with high-risk prostate cancer being performed RARP by one surgeon were analyzed retrospectively in our hospital from January 2016 to January 2022. The mean patient’s age was (65.3±6.2) years old, mean body mass index (BMI) was (25.6±3.0) kg/m 2, the median value of total prostate specific antigen (tPSA) before operation was 18.6(11.3, 31.3)ng/ml, the median value of Gleason score before operation was 7 (7, 8), the median value of prostate volume was 29.3 (22.4, 40.2) ml, and the clinical stage was T 2aN 0M 0-T 4N 0M 0. 80 patients with prostate cancer were treated with neoadjuvant endocrine therapy. All of them were treated with complete androgen blockade with a median course of 3 months. Univariate analysis was used to analyze the correlation between age, BMI, prostate volume, neoadjuvant hormonal therapy, preoperative tPSA, clinical stage, Gleason score before operation and positive surgical margin. Then multivariate logistic regression was used to further analyze the independent risk factor of positive surgical margin after RARP. Results:The postoperative pathological diagnosis included pT 2 stage in 111 cases (67.7%), pT 3a stage in 15 cases (9.1%), pT 3b stage in 25 cases (15.2%), pT 4 stage in 13 cases (7.9%). No lymph node metastasis was noticed in all patients. The Gleason scores included 6 in 11 cases (6.7%), 3+ 4 in 26 cases (15.9%), 4+ 3 in 36 cases (22.0%), 8 in 17 cases (10.4%), 9-10 in 24 cases (14.6%), un-evaluation due to endocrine therapy in 50 (30.5%). The positive surgical margin of high-risk patients with prostate cancer was 44.5% (73/164). Univariate analysis showed that the neoadjuvant hormonal therapy, tPSA and clinical stage were correlated with positive surgical margin ( P<0.05). Multivariate logistic regression analysis showed that non-neoadjuvant hormonal therapy, preoperative tPSA>20ng/ml and clinical stage>T 2b were independent risk factors for positive surgical margin of high-risk patients with prostate cancer. Stratified analysis showed that when the preoperative tPSA was 10-20 ng/ml(21.1% vs.55.9%, P=0.014), the clinical stage was T 2c(29.6% vs.49.1%, P=0.040), the Gleason score before operation was 7(19.4% vs.54.1%, P=0.003), the positive surgical margin of high-risk patients in the neoadjuvant hormonal therapy group was significantly lower than that in the non-neoadjuvant hormonal therapy group ( P<0.05). Conclusions:Non-neoadjuvant hormonal therapy, preoperative tPSA>20 ng/ml and clinical stage>T 2b were independent risk factors for positive surgical margin of RARP in the high-risk patients with prostate cancer. For high-risk patients with preoperative tPSA of 10-20 ng/ml, clinical stage of T 2c and Gleason score before operation of 7, neoadjuvant hormonal therapy has important clinical significance in reducing the positive surgical margin of RARP.

Ginsenoside Rg1-induced antidepressant effects involve the protection of astrocyte gap junctions within the prefrontal cortex.

Ginsenoside Rg1 (Rg1) exhibits antidepressant-like activity by increasing neurogenesis and dendritic spine density without discernible side effects. However, the molecular mechanisms underlying Rg1 antidepressant activity remain poorly understood. As the dysfunction of gap junctions between astrocytes in the prefrontal cortex (PFC) is implicated in major depression disorder, the aim of this study was to investigate the effects of Rg1 on astrocyte gap junctions in the PFC. Rats exposed to chronic unpredictable stress (CUS) were administered Rg1 (5, 10, and 20mg/kg) for 28days and analyzed for depressive symptoms using the sucrose preference and forced swimming tests. Functional and morphological changes of gap junction channels in the PFC were evaluated using dye transfer and electron microscopy, respectively. The expression of connexin 43 (Cx43) was analyzed by western blotting. Rg1 markedly alleviated depression-like behavior in rats. Long-term Rg1 treatment of CUS-exposed rats also significantly prevented the decrease in dye diffusion and improved the ultrastructure of astrocyte gap junctions in the PFC, indicating beneficial effects on the functional activity of gap junction channels in the brain. In addition, Rg1 upregulated Cx43 expression in the PFC reduced by CUS exposure, which significantly correlated with its antidepressant-like effects. The results demonstrate that Rg1-induced antidepressant effects are might be mediated, in part, by protecting astrocyte gap junctions within the prefrontal cortex.

Application value of extrathecal Glisson blood flow occlusion in the resection of primary liver cancer / 中国基层医药

Objective:To investigate the application value of extrathecal Glisson blood flow occlusion in the resection of primary liver cancer.Methods:74 patients with primary liver cancer who received treatment in Yuyao People's Hospital from January 2019 to January 2020 were included in this study. They were randomly assigned to undergo resection of the primary liver cancer with either extracorporeal Pringle maneuver (control group, n = 37) or extrathecal Glisson maneuver (observation group, n = 37). Surgery-related indexes, postoperative liver function and gastrointestinal function recovery, and complications were monitored in each group. Results:Blood flow occlusion time and hospital length of stay in the observation group were (25.10 ± 5.19) minutes and (12.45 ± 1.10) days, which were significantly shorter than those in the control group [(30.65 ± 8.54) minutes, (14.85 ± 1.28) days, t = 3.378, 8.650, both P < 0.05]. Volume of blood loss in the observation group was significantly less than that in the control group [(490.36 ± 120.19) mL vs. (655.58 ± 152.24) mL, t = 5.181, P < 0.05]. Intraoperative blood transfusion rate in the observation group was significantly lower than that in the control group [21.62% (8/37) vs. 45.95% (17/37), χ2 = 4.893, P < 0.05]. At 1, 3 and 7 days after surgery, aspartate aminotransferase level in the observation group was (240.36 ± 60.52) U/L, (145.69 ± 42.18) U/L and (60.13 ± 12.58) U/L, respectively, which was significantly lower than that in the control group [(350.21 ± 60.16) U/L, (212.53 ± 40.21) U/L, (103.65 ± 20.54) U/L, t = 7.930, 6.977 and 10.991, all P < 0.05]. At 1 and 7 days after surgery, alanine aminotransferase level in the observation group was (228.52 ± 65.28) U/L and (44.26 ± 12.85) U/L, respectively, which was significantly lower than that in the control group [(350.16 ± 68.58) U/L, (466.36 ± 40.29) U/L, t = 7.815 and 3.179, both P < 0.05]. At 1 and 7 days after surgery, total bilirubin level in the observation group was (28.58 ± 5.24) μmol/L and (20.30 ± 5.10) μmol/L, which was significantly lower than that in the control group [(43.32 ± 10.26) μmol/L, (26.08 ± 5.68) μmol/L, t = 7.783, 4.606, both P < 0.05]. At 1 day after surgery, albumin level in the observation group was significantly lower than that in the control group [(34.65 ± 2.42) g/L vs. (31.12 ± 2.23) g/L, t = 6.525, P < 0.05). The time to recovery of bowel sounds, the time to the first exhaust, and the time to defecation in the observation group were (14.28 ± 2.10) hours, (29.21 ± 5.10) hours, and (54.20 ± 5.69) hours, which were significantly shorter than those in the control group [(16.65 ± 2.16) hours, (33.25 ± 5.47) hours, (59.85 ± 5.87) hours, t = 4.783, 3.286 and 4.204, all P < 0.05]. The total incidence of postoperative complications in the observation group was significantly lower than that in the control group [13.51% (5/37) vs. 35.14% (13/37), χ2 = 4.698, P < 0.05]. Conclusion:Extrathecal Glisson maneuver for the resection of primary liver cancer exhibits better performance in the control of bleeding, reduction of postoperative complications, and acceleration of rehabilitation than extracorporeal Pringle maneuver.

Research progress in mechanism of curcumin in treatment of Parkinson disease / 中国药理学与毒理学杂志

Curcumin (Cur) is an important bioactive component of polyphenols in the rhizomes of Curcuma longa L., Tulipa gesneriana L. and other Curcuma plants. It has a wide range of pharmacological effects such as anti-tumor, anti-atherosclerosis, anti-inflammatory, and neuroprotection. Parkinson disease (PD) is a neurodegenerative disease that often occurs in the elderly. Its main pathological characteristics are the characteristic loss of substantia nigra dopaminer?gic neurons, the decrease of dopamine content in the striatum, and the formation of Lewy bodies. At present, the main methods of clinical treatment of PD include drug therapy and surgical operation, but due to its complicated pathogene?sis, they can only play a role in relieving, but cannot be completely cured. Modern pharmacological studies have shown that Cur has certain effects in the treatment of PD. ① Anti-oxidative stress: oxidative stress is closely related to the degeneration of dopaminergic neurons. Studies have found that Cur can increase the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), reduce malondialdehyde (MDA) content, thereby reducing oxidative stress damage and protecting dopaminergic neuron.②Reduce inflammation in brain tissue:neuroinflammation plays an impor?tant role in the development of PD. Reducing the level of inflammatory factors can have a certain therapeutic effect on PD. Studies have shown that high-dose Cur can reduce the levels of interleukin-6 (IL-6), IL-1β, and tumor necrosis fac?tor-α (TNF-α) in brain tissue, reduce inflammation, inhibit further neuronal damage, improve learning and memory, and exert neuroprotective effects. ③ Activation of autophagy: the abnormal accumulation of α-Synuclein (α-Syn) in Lewy bodies is closely related to PD, and autophagy dysfunction leads to α-Syn clearance obstacles and an important factor of abnormal aggregation. Cur can increase the expression of microtubule-associated protein 1 light chain 3 (LC3-Ⅱ) and lysosome-associated membrane protein 2A (LAMP2A), and reduce the protein and mRNA expression of α-Syn. It can be seen that Cur promotes the elimination ofα-Syn and protects neurons from damage by activating autophagy.④Inhi?bition of mitochondrial dysfunction:mitochondria plays a central regulatory role in the process of cell apoptosis, and mito?chondrial dysfunction is related to reactive oxygen species, energy and mitochondrial membrane potential, which may cause substantia nigra striatal neuropathy. Experiments have shown that Cur can reduce the active oxygen content in PC12 cells induced by MPP+, maintain the normal membrane potential of mitochondria, thereby stabilizing mitochondrial function and inhibiting PC12 cell apoptosis. This study summarized the action mechanism of Cur in the treatment of PD, and clarified the basis of its pharmacodynamics, providing a reference for the clinical research and new drug develop?ment research of Cur in the treatment of PD.

Study on pharmacological effect of Chuanxiong Rhizoma on vascular neuropathic headache / 中国药理学与毒理学杂志

Chuanxiong Rhizoma is the dry rhizome of Ligusticum chuanxiong in the umbelliferae family. Chuanxiong Rhizoma pungent, warm, go to liver, gallbladder and pericardium. Effective in promoting blood circulation, promoting Qi, dispelling wind and relieving pain, it could treat chest pain, tingling pain in chest and flank, lump, irregular menstruation, amenorrhea, symptomatic abdominal pain, headache and rheumatic pain. Neurovascular headache is a primary disease caused by dysregulation of intracranial vascular movement and nerve function. It has the characteristics of long course, intermittent recurrent attacks, lingering and difficult to heal. Attacks are often accompanied by many plant nervous sys?tem symptoms, such as rapid breathing, accelerated heart rate, vomiting, and gastrointestinal dysfunction. Vascular nerve headache is a common clinical disease, frequently bidity. Studies have shown that Chuanxiong Rhizoma has good pharmacological effects in the treatment of vascular neuropathic headache.① The action of Qi and blood circula?tion: vascular and neurovascular headache is caused by the evil of external wind and cold and damp heat, which leads to the disconnection of the veins, the disorder of Qi and blood, the obstruction of Qi and blood channels, the loss of brain collateral, and finally causes migraine. Modern Chinese medicine points out that"wind, blood stasis, deficiency, phlegm"are the key factors of the disease. Chuanxiong Rhizoma is the medicine of Qi in the blood. It is pungent and warm. It is good at activating blood and promoting Qi, dispelling wind, relieving pain and dispelling cold, so as to achieve the effect of treating vascular headaches. ② Improve brain circulation: angioneurotic headache is caused by dysfunction of the central nervous system related to the regulation of vascular movement, which causes vasospasm or extreme vasodi?lation, and the decrease of intracranial blood flow causes cerebral ischemia and hypoxia. Sodium ferulate is a chemical component in Chuanxiong Rhizoma. It has a relatively good inhibitory effect on platelet aggregation and the release of 5-HT from platelets. It can ensure the normal contraction of intracranial and extracranial blood vessels, improve the patient's brain circulation and nerve function, so as to achieve the effect of treating angioneurotic headaches.③Sedative and analgesic effect:the volatile oil and water decoction of Chuanxiong Rhizoma have sedative and analgesic effects, and the water decoction can counteract the excitatory effect of caffeine. Studies have shown that the ATP activa?tion current of rat dorsal root ganglion neurons can be inhibited by ligustrazine in a non-competitive way, which also indi?cates that Chuanxiong Rhizoma has a good analgesic effect. In this study, the effects of Chuanxiong Rhizoma on angoneeurotic headache were reviewed, and the pharmacological effects of Chuanxiong Rhizoma were further elucidated, providing basis for clinical application and new drug development of Chuanxiong Rhizoma in the treatment of angoneeu?rotic headache.

Pharmacological effects of Schisandra Chinensis Fructus polysaccharide on intestinal protection / 中国药理学与毒理学杂志

Schisandra Chinensis Fructus (SCF) is the fruit of Schisandra chinensis (Turcz.) Baill., a perennial vine. It was first recorded in Shen Nong's herbal classic and has a long application history. Studies have shown that SCF has anti-inflammatory, protective liver, antioxidant, antibacterial and other pharmacological effects. Ancient prescriptions are commonly used in the treatment of chronic diarrhea and other intestinal diseases and diabetes. Modern clinical phar?macology features of SCF polysaccharide (SCFP) in diabetes, liver diseases, enteritis and other aspects have achieved excellent results. Gut is an important digestive organ of human body, but intestinal diseases are varied, including Crohn's disease, ulcerative colitis, intestinal flora imbalance, etc.. It is a chronic and non-specific inflammatory disease. The disease is persisted for a long time and the incidence rate is expected to rise. Most of the symptoms are recurrent diarrhea, bloody stool and abdominal pain. It is considered by the World Health Organization as a refractory disease. At present, there is little possibility of complete cure, which is closely related to complex environmental factors, eating hab?its and heredity. In recent years, clinical studies have found that SCFP has a variety of pharmacological effects on intes?tinal protection.①Reduce inflammatory factors:intestinal mucositis is a common adverse reaction in patients with chemo?therapy. The development of mucositis is related to pro-inflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, Interferon-γ(IFN-γ). SCFP can significantly reduce IL-6 TNF-α, IL-1β, and IL-8, as well as the accumulation of T cells in the process of resisting apoptosis, reduce the inflammatory reaction and protect the dam?age to villi and crypts, improve the symptoms of small intestinal mucositis caused by weight loss and diarrhea. ② Pro?mote immunoglobulin A secretion: intestinal mucosal immunity is the first line of defense of the body's immune system. Its main antibody is secretory immunoglobulin A, which can destroy and phagocytize microorganisms, bacteria and viruses. SCFP can improve intestinal immunity by increasing the number and activity of T lymphocytes, promoting the secre?tion of secretory immunoglobulin A, and affecting the activity of a variety of cytokines. ③ Regulation of intestinal flora:the flora in the intestine has the functions of auxiliary nutrient absorption, biological antagonism and immune regulation, and can form a natural barrier for the host's intestine. When the human intestinal flora is disordered, probiotics will be greatly reduced, harmful bacteria will proliferate and destroy the intestinal environment. Under these conditions, the intake of SCFP significantly increased the number of beneficial bacteria such as bifidobacteria and lactobacillus, and sig?nificantly decreased the number of conditional pathogens such as enterococcus and escherichia coli, indicating that SCFP can indeed regulate the intestinal disorder caused by lincomycin hydrochloride to a certain extent. This may be because beneficial bacteria in the intestine metabolize polysaccharides produce short chain fatty acids such as lactic acid and acetic acid, which reduces the pH value in the intestine and inhibits the growth of enterococcus and Escherichia coli. In conclusion, SCFP can treat and protect intestinal diseases to a certain extent, which provides a favorable basis for the treatment of intestinal diseases.

Progress in protective effect and mechanism of 6-gingerol on myocardial ischemia/reperfusion injury / 中国药理学与毒理学杂志

The morbidity and mortality of cardiovascular diseases are very high, which has attracted more and more attention all over the world. Common treatment methods for clinical treatment of acute myocardial infarction include direct percutaneous coronary intervention and coronary artery bypass grafting, which can quickly restore blocked coronary blood flow and reduce the infarct size. However, the inevitable ischemia/reperfusion injury will occur during the recovery of coronary blood flow, its pathological mechanism is complicated, and the Western medicine countermeasures are very limited. Among the current drugs for the treatment of cardiovascular diseases, traditional Chinese medicine has become a research hotspot due to its multiple targets, safety, and low side effects. Ginger is the fresh rhizome of Zingiber offici?nale Rosc., a perennial herbaceous plant in the ginger family. It is a dual-purpose resource of medicine and food. Ginger has the functions of relieving the appearance and dispelling cold, warming up and relieving vomiting, resolving phlegm and relieving cough, and relieving fish and crab poison. The chemical components of ginger mainly include volatile oil, gingerol, diphenylheptane, etc.. Among them, 6-gingerol, as the main active component of gingerols, has obvious phar?macological effects in myocardial protection, anti-oxidation, anti-inflammatory, etc.. Studies have shown that 6-gingerol protects myocardium mainly through anti-oxidative stress, anti-inflammatory, inhibiting cell apoptosis, and preventing cal?cium influx. ① Anti-oxidative stress: oxidative stress is a state where oxidation and anti-oxidation in the body are out of balance, and it is also an important factor leading to myocardial damage. Many studies have confirmed that 6-gingerol has an antioxidant effect, and it is considered a natural antioxidant. 6-gingerol can significantly reduce the degree of oxi?dative stress and the level of reactive oxygen species caused by cardiomyocyte damage, and has a significant cardiopro?tective effect. ② Anti-inflammatory: inflammation can cause substantial cell damage and organ dysfunction, which is another important cause of myocardial damage. 6-gingerol can reduce the levels of inflammatory factors such as inter?leukin-6, interleukin-1β, and tumor necrosis factor-αin cardiomyocytes, and at the same time inhibit the TLR4/NF-κB sig?naling pathway, an important regulatory pathway of inflammation, showing that it may improve myocardial damage through anti-inflammatory effects. ③ Inhibition of apoptosis: apoptosis is a complex and orderly process in the autono?mous biochemical process of cells, and one of the main mechanisms of myocardial injury. This process can be roughly divided into three pathways: mitochondria, endoplasmic reticulum, and death receptors. Among them, the mitochondrial pathway plays an important role, and Bcl-2 and Bax located upstream of this pathway can regulate the entire process of cell apoptosis by regulating the permeability of the mitochondrial membrane. Studies have found that the preventive application of 6-gingerol can reduce cell damage, reduce the number of apoptotic cells, reduce the activity of Bax and caspase-3, and increase the expression of Bcl-2. Therefore, 6-gingerol pretreatment can reduce the damage of cardio?myocytes, and its mechanism may be related to the inhibition of apoptosis.④Prevent calcium influx:calcium overload is involved in the pathogenesis of myocardial ischemic injury, which may be related to excessive contracture, arrhythmia, and mitochondrial Ca2+accumulation that impairs myocardial function. 6-gingerol inhibits the increase of intracellular Ca2+concentration by inhibiting L-type calcium current, thereby reducing extracellular Ca2+ influx, thereby avoiding calcium overload and playing a cardioprotective effect. In summary, 6-gingerol can effectively treat and improve myocardial isch?emia/reperfusion injury, and it has great development potential in the fields of medicine and health products.

Research progress in immune regulation mechanism of Polygonati Rhizoma polysaccharide / 中国药理学与毒理学杂志

Polygonati Rhizoma is the dry rhizome of Liliaceae plants Polygonatum kingianum coil ethemsl, Polygona?tum sibiricum Redoute and Polygonatum cyrtonem Hua. It tastes sweet and has a flat nature. It belongs to the spleen, lung and kidney channels. Polygonati Rhizoma contains a variety of chemical components, including polysaccharides, alkaloids, steroidal saponins, lignans, phytosterols, and so on. Polygonati Rhizoma polysaccharide (PSP) is one of the main bioactive components of Polygonati Rhizoma. It is widely used. It has the effects of enhancing immunity, anti-inflammatory, anti-virus and regulating blood lipid. In recent years, the immunomodulatory function of PSP has been paid more and more attention by researchers. PSP can play an immunomodulatory role through a variety of mecha?nisms. (1) Effects of PSP on innate immunity. ① Macrophages have a strong ability to phagocytize and clear foreign bodies. When polysaccharides bind to macrophage specific membrane receptors, the immune response will be officially activated. RAW264.7 cells can be activated by PSP MR and TLR4 mediated signal pathway to improve the pinocytosis and phagocytosis of RAW264.7 cells. ② Natural killer cell (NK cell) is a very important immune cell in the body. It is a non-specific immune killer cell naturally existing in the body. It has the dual functions of immune regulation and cytotoxic?ity. It was found that the signal pathway mediated by PSP CR3 and TRL2 may play a major role in the stimulation of NK cells. (2) Effects of PSP on adaptive immune response. ① Lymphocytes can be divided into two forms: T cells and B cells due to different differentiation and maturation sites. T lymphocytes are the general name of thymus dependent lym?phocytes. B lymphocytes differentiate and mature from animal bone marrow cells and exert their humoral immune func?tion by secreting different antibodies. It was found that PSP could activate T/B lymphocytes and increase the ratio of CD4+/CD8+in lymph cells to promote the regulation of immune system.②Thymus and spleen index refers to the level of body immunity through the development of immune organs and the functional status of immune cells. The higher the index of thymus and spleen, the higher the immune activity. A large number of studies have found that PSP can improve immune activity by promoting the proliferation of spleen lymphocytes and regulating organ index, so as to increase the weight and index of thymus and spleen induced by CY. ③ Antibody is a glycoprotein secreted by B cells after antigen stimulation and a series of proliferation and differentiation into plasma cells. Antibody production level is one of the main indicators of nonspecific immune function. PSP can not only improve the serum antibody level of mice by regulating the phagocytosis of mouse macrophages and the level of serum hemolysin, but also enhance the concentration of IL-2 secreted by spleen lymphocytes in vitro to increase the level of antibody response, and then improve the humoral immune function of the body. (3) Effect of PSP on cytokines. ① A large number of experiments have proved that PSP has a significant effect on promoting the production of interleukin (IL). PSP can combine with specific receptors on the surface of immune cells to activate various intracellular signal transduction pathways, enhance the secretion of cytokines such as IL-2, IL-4, IL-6 and IL-10 by spleen lymphocytes in vitro, make them directly kill target cells and regulate the immune function of the body at the molecular level. ② Interferon (IFN) is a special protein or glycoprotein produced by human or animal cells in response to various stimuli. It plays an important role in anti-virus, immune regulation and cell proliferation control. It was found that PSP could increase IFN-γsecreted by T cells and NK cells, activate macrophages to regulate immune function. ③ Tumor necrosis factor (TNF) is mainly produced by activated macrophages, NK cells and activated T cells. It is a cytokine with important biological activity in antitumor immune response.④ Tumor necrosis factor (TNF) is mainly produced by activated macrophages, NK cells and activated T cells. It is a cytokine with important biological activity in antitumor immune response. PSP can promote the proliferation and phagocytic activity of macro?phage RAW264.7 to reduce its apoptosis rate. By increasing the secretion of TNF-α, PSP can promote the dissociation between NF-κВprotein and IκВp65 protein after phosphorylation, so as to start the expression and transcription of related immune genes. In conclusion, PSP can improve immunity and has a good application prospect in the development of immunomodulatory drugs.

Research progress in mulberry leaf polysaccharide in treating diabetic nephropathy / 中国药理学与毒理学杂志

Diabetic nephropathy (DN) is one of the most common complications of diabetes. It is an important cause of diabetes disability and death. DN is a systemic metabolic syndrome. In its pathogenesis, the interaction of various cell activities and a large number of cytokine biological activities, the activation of signal pathways and so on are involved in the development of DN. At present, the clinical treatment of DN is mainly Western medicine, but it has limitations such as strong toxicity, high side effects and poor compliance. Therefore, the discovery of natural anti-DN substances has also become an important means to treat DN. Mulberry leaves are the dry leaves of Morus alba L. It is not only a tradi?tional Chinese medicine, but also a dual-purpose medicinal material for medicine and food. It has the effects of dispelling wind and clearing heat, cooling blood and brightening eyes, tonifying and so on. Mulberry leaf polysaccharide (MLP) is a kind of high molecular compound in mulberry leaves. It has many pharmacological effects, such as hypoglycemic, antiox?idant, anti-stress, anti-virus and so on. Therefore, the pharmacological effects of mulberry leaf polysaccharides on dia?betic nephropathy are reviewed in this paper, so as to provide references for further research and application. The patho?genesis of DN is complex, and the mechanism of renal injury has not been completely clarified. The current studies believe that DN is closely related to heredity, abnormal glucose metabolism, abnormal lipid metabolism, microcirculation disorder, cytokine action, oxidative stress and so on. Relevant studies show that the pharmacological effects of mulberry leaf polysaccharide in the prevention and treatment of DN mainly include: ① Effect on transforming factor-β1 (TGF-β1):TGF-β1 has become an important cytokine involved in the formation of renal fibrosis by regulating cell proliferation and differentiation and the production of extracellular matrix (ECM). MLP can significantly inhibit TGF-β1 protein, and then inhibit the synthesis of extracellular matrix by renal interstitial fibroblasts and inhibit the realization of fibrosis.②Effect on insulin receptor substrate (IRS-1): IRS-1 is an important signal molecule at the beginning of IR signal transduction. The decrease of IRS-1 gene expression or the decrease of expression can affect the effective transmission of IR signal and lead to the development and deterioration of diabetes. MPL can significantly increase the expression of IRS-1 mRNA in liver tissue of DN rats, so as to prevent and treat DN. ③ Effect on the expression of resistin protein in adipose tis?sue. Resistin is a secretory polypeptide derived from adipose tissue and is specifically expressed in white adipose tissue and is closely related to type 2 diabetes mellitus (T2DM). Experimental studies show that MLP can effectively reduce the expression of resistin protein in white adipose tissue of T2DM rats, indicating that MLP may reduce the level of IR by inhibiting the expression of resistin in adipose tissue, thereby reducing the insulin resistance state of T2DM rats, so as to achieve the goal of treating diabetes.④Effect on adiponectin receptor 1 (AdipoR1):adiponectin can improve insulin resistance, reduce blood glucose and lipid. AdipoR1 is mainly expressed in skeletal muscle and kidney. Studies have shown that AdipoR1 is closely related to the occurrence and development of DN. The results showed that MLP could reduce the blood glucose and blood lipid level and up regulate the expression of AdipoR1 mRNA in DN rats, suggesting that MLP may delay the occurrence and development of DN. This article reviewed the pharmacological effects of mulberry leaf polysaccharides on diabetic nephropathy, and provided a useful basis for further development and utilization of mul?berry leaf polysaccharides in the treatment of DN.