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1.
Article in Chinese | WPRIM | ID: wpr-936286

ABSTRACT

OBJECTIVE@#To identify the target genes mediating anti-tumor effect of sesquiterpenoids from Cryptoporus volvatus and explore the possible mechanism using molecular docking and molecular dynamics simulation.@*METHODS@#Based on the chemical structure of sesquiterpenes from C. volvatus, we explored the online reverse target finding websites PharmMapper, SEA, Target Hunter and related literature for preliminary prediction of possible anti-tumor targets. Discovery Studio 4.0 (Libdock function) and Maestro 12.3 were used to connect sesquiterpenes with the possible targets, and the potential targets were selected according to the scores. The interaction between the sesquiterpenes and the targets were analyzed using 2D interaction diagram, and the influence of different sesquiterpene skeletons on their activity was inferred based on their activity measurements in experiment. Kinetic simulation was performed for front-end protein sequence (1UNQ) of the Akt (protein kinase B) and for the complex formed by 1UNQ and compound 4 (which had the best cytotoxic activity in vitro) in its optimal conformation, and the root mean square deviation (RMSD) value and root mean square float (RMSF) value of the complex and 1UNQ were measured to evaluate the stability of the binding of compound 4 to the target.@*RESULTS@#The sesquiterpenes showed optimal binding with 1UNQ. Analysis of 2D interaction diagram suggested that the hydrogen bonding and electrostatic force were the most important forces mediating the interaction between the sesquiterpenes and 1UNQ. Analysis of the optimal 3D conformation showed that for different sesquiterpenes, a slight change of the molecular framework produced a steric hindrance effect and caused changes in their bioactivity. Kinetic simulation showed that the complex formed by compound 4 and1UNQ had a lower RMSD than the target pure protein sequence, indicating that compound 4 could stably bind to 1UNQ. The anti-tumor effect of the sesquiterpenoids from C. volvatus was associated with their ability to cause Lys-144 acetylation, which blocks Akt binding to the downstream PIP3 and thus affects the proliferation of tumor cells.@*CONCLUSION@#1UNQ is the target of sesquiterpenoids from C. volvatus, which affects the proliferation of tumor cells by acetylating Lys-14.


Subject(s)
Humans , Molecular Docking Simulation , Neoplasms , Polyporaceae , Sesquiterpenes/pharmacology
2.
Article in Chinese | WPRIM | ID: wpr-940566

ABSTRACT

ObjectiveTo explore medication regularity of traditional Chinese medicine (TCM) in the treatment of non-small cell lung cancer (NSCLC) and thereby to lay a theoretical basis for clinical medication and drug development. MethodArticles on clinical treatment of intermediate and advanced NSCLC with TCM in the past 40 years were retrieved from CNKI, which were taken the data source. Then the articles were screened to establish a formula database, followed by frequency statistics, association rule analysis, cluster analysis, factor analysis, and complex network construction. ResultA total of 307 eligible articles were screened out, involving 483 formulas. The common syndrome of intermediate and advanced NSCLC was the deficiency of both Qi and Yin, with the common syndrome elements of Qi deficiency, Yin deficiency, phlegm, blood stasis, pathogenic heat (fire), toxin, and pathogenic dampness. The frequently used medicinals mainly had the functions of tonifying deficiency, clearing heat, resolving phlegm and relieving cough and dyspnea, promoting urination and draining dampness, and activating blood and resolving stasis. The high-frequency medicinals were Astragali Radix, Glycyrrhizae Radix et Rhizome, Ophiopogonis Radix, Fritillariae Thunbergii Bulbus, and Poria, which were mainly cold, bitter, sweet, and pungent, with tropism at lung, spleen, and stomach. The association rule analysis yielded 17 rules with strong association. Ten common factors were extracted from the factor analysis, and cluster analysis classified the medicinals into 5 groups. Complex network analysis suggested that the core formula was modified Liujunzi Tang and Yiqi Yangyin Jiedu prescription. ConclusionThe treatment principle for intermediate and advanced NSCLC is replenishing Qi and nourishing Yin, invigorating spleen and resolving phlegm, clearing heat and detoxifying, promoting blood circulation and removing blood stasis. The core combinations new prescription discovered by data mining are of important guiding significance, but they should be further verified in clinical practice and by experiments based on the theory of TCM.

3.
Acta Pharmaceutica Sinica ; (12): 1679-1688, 2022.
Article in Chinese | WPRIM | ID: wpr-929422

ABSTRACT

Although current synthetic anti-gout drugs have significant therapeutic effects in reducing serum uric acid levels, they have serious side effects such as allergic reactions and liver and kidney damage. Natural products with a wide range of uric acid-lowering and high safety have played a critical role in anti-gout drug discovery and development. This paper reviews the natural products with uric acid-lowering or anti-gout pharmacological effects and the investigation on their mechanisms of action, to provide information for drug discovery and development.

4.
Acta Pharmaceutica Sinica B ; (6): 581-599, 2022.
Article in English | WPRIM | ID: wpr-929274

ABSTRACT

Novel therapies are urgently needed to improve global treatment of SARS-CoV-2 infection. Herein, we briefly provide a concise report on the medicinal chemistry strategies towards the development of effective SARS-CoV-2 inhibitors with representative examples in different strategies from the medicinal chemistry perspective.

5.
Article in Chinese | WPRIM | ID: wpr-927328

ABSTRACT

OBJECTIVE@#To compare the clinical effect of SUN 's abdominal acupuncture and conventional acupuncture in the treatment of depression after methamphetamine withdrawal.@*METHODS@#A total of 80 female patients with depression after methamphetamine withdrawal were randomly divided into an observation group (40 cases, 1 case dropped off) and a control group (40 cases, 2 cases dropped off). The control group was treated with conventional acupuncture at Baihui (GV 20), Yintang (GV 29), Taichong (LR 3), Shenmen (HT 7), Neiguan (PC 6), Danzhong (GV 17), and the observation group was treated with SUN 's abdominal acupuncture at area 1 of the abdomen and area 8 of the abdomen. Both groups were treated once a day, 30 min each time, 6 days as a course of treatment, 1 day rest between treatment courses, a total of 4 courses of treatment. The scores of withdrawal symptoms, Hamilton depression scale (HAMD), Pittsburgh sleep quality index (PSQI) scale and serum serotonin (5-HT) level were compared between the two groups before and after treatment.@*RESULTS@#After treatment, the scores of withdrawal symptoms, HAMD and the various scores and total score of PSQI scale in the two groups were all lower than before treatment (P<0.01), and the scores of withdrawal symptoms, HAMD and the sleep quality, time to fall asleep, sleep time scores and total score of PSQI in the observation group were lower than the control group (P<0.05, P<0.01). After treatment, the serum 5-HT level of the two groups was increased (P<0.01), and that in the observation group was higher than the control group (P<0.05).@*CONCLUSION@#SUN 's abdominal acupuncture can improve withdrawal symptom, depression and sleep quality, increase serum 5-HT content in treatment of depression after methamphetamine withdrawal, and has better effect than conventional acupuncture.


Subject(s)
Abdomen , Acupuncture Points , Acupuncture Therapy , Depression/therapy , Female , Humans , Methamphetamine/adverse effects , Sleep Quality , Substance Withdrawal Syndrome/therapy , Treatment Outcome
6.
Acta Pharmaceutica Sinica ; (12): 1612-1620, 2021.
Article in Chinese | WPRIM | ID: wpr-881562

ABSTRACT

Hyperglycemic kidney injury (HKI) is a common complication of diabetic patients. We examined the relationship between HKI and the abnormal expression of 5-hydroxytryptamine (5-HT) system induced by hyperglycemia in type 2 diabetes mellitus (T2DM). In animal experiments, a T2DM model was established in mice by feeding a high-fat diet with intraperitoneal injection of streptozotocin. The mice were treated with the 5-HT2A receptor (5-HT2AR) antagonist sarpogrelate hydrochloride (SH) and 5-HT synthesis inhibitor carbidopa (CDP) (respectively or in combination). In cell culture experiments, human glomerular mesangial cells (HMC) were stimulated with D-glucose (D-Glu), and 5-HT2AR, 5-HT synthesis, and 5-HT degradation were inhibited by SH, CDP, or monoamine oxidase A (MAO-A) inhibitor clorgyline. Periodic acid-Schiff (PAS) staining and Masson staining, immunohistochemistry and Western blot, fluorescent probe, and enzyme linked immunosorbent assay (ELISA) and enzyme reagent were respectively used to detect histopathology, protein expression, intracellular reactive oxygen species (ROS), and biochemical indexes. The animal experiments were in accordance with the regulations of the Animal Ethics Committee of China Pharmaceutical University. The results showed that 5-HT2AR, 5-HT synthases, and MAO-A were expressed in glomerular basement membrane and kidney tubular epithelial cells of mouse kidney and HMC. The expression of these proteins was significantly up-regulated in T2DM mice or when HMC cells were exposed to high concentration of D-Glu. HKI, characterized by abnormal renal function, glomerular swelling, and glomerular basement membrane thickening and fibrosis, is closely associated with an increase in kidney 5-HT2AR, 5-HT synthesis, and 5-HT degradation. Among them, 5-HT2AR can mediate the expression of 5-HT synthases and MAO-A; MAO-A can catalyze the degradation of 5-HT to increase the production of mitochondrial ROS, leading to the phosphorylation of nuclear factor kappa B (NF-κB) with the production of inflammatory cytokines, and the up-regulation of matrix metalloproteinase-2 (MMP-2) and α-smooth muscle actin (α-SMA) with the production of collagens. SH and CDP can effectively treat HKI, and the combination of SH and CDP has a clear synergistic effect.

7.
Journal of Integrative Medicine ; (12): 418-427, 2021.
Article in English | WPRIM | ID: wpr-888773

ABSTRACT

OBJECTIVE@#Exercise, as a common non-drug intervention, is one of several lifestyle choices known to reduce the risk of cancer. Mitochondrial division has been reported to play a key role in the occurrence and transformation of hepatocellular carcinoma (HCC). This study investigated whether exercise could regulate the occurrence and development of HCC through mitosis.@*METHODS@#Bioinformatics technology was used to analyze the expression level of dynamin-related protein 1 (DRP1), a key protein of mitochondrial division. The effects of DRP1 and DRP1 inhibitor (mdivi-1) on the proliferation and migration of liver cancer cells BEL-7402 were observed using cell counting kit-8, plate colony formation, transwell cell migration, and scratch experiments. Enzyme-linked immunosorbent assay, Western blot and real-time polymerase chain reaction were used to detect the expression of DRP1 and its downstream phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. A treadmill exercise intervention was tested in a nude mouse human liver cancer subcutaneous tumor model expressing different levels of DRP1. The size and weight of subcutaneous tumors in mice were detected before and after exercise.@*RESULTS@#The expression of DRP1 in liver cancer tissues was significantly upregulated compared with normal liver tissues (P < 0.001). The proliferation rate and the migration of BEL-7402 cells in the DRP1 over-expression group were higher than that in the control group. The mdivi-1 group showed an inhibitory effect on the proliferation and migration of BEL-7402 cells at 50 μmol/L. Aerobic exercise was able to inhibit the expression of DRP1 and decrease the size and weight of subcutaneous tumors. Moreover, the expression of phosphorylated PI3K (p-PI3K) and phosphorylated AKT (p-AKT) decreased in the exercise group. However, exercise could not change p-PI3K and p-AKT levels after knocking down DRP1 or using mdivi-1 on subcutaneous tumor.@*CONCLUSION@#Aerobic exercise can suppress the development of tumors partially by regulating DRP1 through PI3K/AKT pathway.


Subject(s)
Animals , Apoptosis , Carcinoma, Hepatocellular/therapy , Cell Line, Tumor , Cell Proliferation , Down-Regulation , Dynamins , Liver Neoplasms/therapy , Mice , Phosphatidylinositol 3-Kinase/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction
8.
Article in English | WPRIM | ID: wpr-922253

ABSTRACT

: To investigate the protective effect of 7-hydroxyethyl chrysin (7-HEC) on rats with exercise-induced fatigue in hypobaric hypoxic condition.Forty healthy male Wistar rats were randomly divided into four groups with 10 rats in each group: control group, model group, chrysin group and 7-HEC group. The rats in control group were raised at local altitude but other three groups were raised in a simulating altitude of for hypobaric hypoxia treatment. The chrysin group and 7-HEC group were given chrysin or 7-HEC by gavage for respectively; while the control group and model group were given the same amount of sterilized water. The weight-bearing swimming tests were performed 3 d later, and the weight-bearing swimming time was documented. After rats were sacrificed, the liver and skeletal muscle tissue samples were taken for pathological examination and determination of lactate, malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glycogen levels. Blood urea nitrogen was also determined. Compared with the model group, weight-bearing swimming times were significantly prolonged in 7-HEC group [ vs. (4.04±1.30) min, <0.01]; pathological changes in liver and skeletal muscle tissue were attenuated; generation rate of blood urea nitrogen vs. 0.60) mmol·L·min, <0.05], lactate [liver: (0.14±0.05) vs. (0.10±0.03) mg·g·min, skeletal muscle: vs. (0.18±] and MDA [liver: (0.48) vs. (0.78±0.28) nmol·mg·min, skeletal muscle: (0.87±0.19) vs. (0.63±0.11) nmol·mg·min] were significantly reduced (all < 0.05); glycogen content [liver: (15.16±2.69) vs. skeletal muscle: (1.46±0.49) vs.0.48) mg/g] and T-SOD [liver: (1.87±0.01) vs. (2.68±0.12) U/mL, skeletal muscle: 0.42) vs. 0.96) U/mL] were significantly improved (all <0.05). 7-HEC has significant protective effect on the rats with exercise-induced fatigue in hypobaric hypoxia condition.


Subject(s)
Altitude , Animals , Fatigue/prevention & control , Flavonoids , Hypoxia , Male , Rats , Rats, Wistar
9.
Article in Chinese | WPRIM | ID: wpr-921678

ABSTRACT

Heat-processed Gynostemma pentaphyllum has strong biological activity, and saponins are the main components. To investigate the changes of saponins in G. pentaphyllum before and after heat processing, the present study determined and analyzed the content of nine saponins in G. pentaphyllum from Zhangzhou of Fujian and Jinxiu of Guangxi by ultra-high performance liquid chromatography with quadrupole ion-trap mass spectrometry(UPLC-Q-Trap-MS). The separation of the analytes was performed on an ACQUITY UPLC BEH C_(18) column(2.1 mm×50 mm, 1.7 μm) at 30 ℃, with acetonitrile and 0.1% formic acid in water as the mobile phase by gradient elution, and the flow rate was 0.3 mL·min~(-1). Quantitative analysis was performed using electrospray ionization source(ESI) in the multiple reaction-monitoring(MRM) mode. The results showed that the content of saponins with biological activities increased after heat processing. Specifically, gypenoside L, gypenoside LI, damulin A, damulin B, ginsenoside Rg_3(S), and ginsenoside Rg_3(R) in G. pentaphyllum produced in Zhangzhou of Fujian increased by 7.369, 8.289, 12.155, 7.587, 0.929, and 1.068 μg·g~(-1), respectively, while the content of ginsenoside Rd, gypenoside LVI, and gypenoside XLVI, which were abundant in the raw materials, decreased by 0.779, 19.37, and 9.19 μg·g~(-1), respectively. The content of gypenoside L, gypenoside LI, damulin A, damulin B, ginsenoside Rg_3(S), and ginsenoside Rg_3(R) in G. pentaphyllum produced in Jinxiu of Guangxi increased by 0.100, 0.161, 0.317, 0.228, 3.280, and 3.395 μg·g~(-1), respectively, while the content of ginsenoside Rd, gypenoside LVI, and gypenoside XLVI in the raw materials was reduced by 1.661, 0.014, and 0.010 μg·g~(-1), respectively. The results suggest that heat processing is an effective way to transform rare gypenosides. Furthermore, it is found that there are great differences in the content of gypenosides in different regions.


Subject(s)
China , Chromatography, High Pressure Liquid , Gynostemma , Hot Temperature , Saponins
10.
Article in Chinese | WPRIM | ID: wpr-910113

ABSTRACT

Objective:To evaluate the value of shear wave elastography (SWE) and salivary gland ultrasound scoring(SGUS) system in the diagnosis of salivary glands lesions in patients with Sj?gren′s syndrome(SS) and to compare the diagnostic efficiency of the two methods.Methods:From June 2019 to November 2020, Fifty-eight patients with suspected SS were selected from the Affiliated Changzhou No.2 People′s Hospital of Nanjing Medical University. According to the 2002 American-European Consensus Group classification standard, the enrolled patients were divided into two groups: SS group (47 cases) and non-SS group(11 cases). According to symptom duration, SS group was divided into the ≤5 years group (29 cases) and the >5 years group (18 cases). Meanwhile, 40 healthy volunteers were enrolled in this study as normal control group. The diagnostic value of salivary gland ultrasound scoring system and Young′s modulus in SS were analyzed.Results:The differences in Young′s modulus of parotid gland and submandibular gland between SS group and non-SS group (or control group) were statistically significant (all P<0.05). The ultrasound score of SS group was significantly higher than that of non-SS group and control group (all P<0.05). SGUS and Young′s modulus were not significantly different between different course groups (all P>0.05). The areas under ROC curve of the mean Young′s value in parotid and submandibular gland and the SGUS were 0.801, 0.829 and 0.676, respectively. The comparison of the area under the curve between the Young′s modulus of the parotid and submandibular glands and the ultrasound score was statistically significant (all P<0.05). Conclusions:SWE and Ultrasonography scoring system have certain value in the diagnosis of salivary gland lesions in SS, and can provide important reference information for clinical diagnosis from different perspectives. The diagnostic efficiency of SWE for salivary glands lesions in patients with SS is better than that of SGUS scoring system.

11.
Article in Chinese | WPRIM | ID: wpr-837492

ABSTRACT

Objective To explore the risk factors and early intervention methods of obesity in children aged 5-14 years in Xuzhou. Methods Children from 3 urban areas were randomly selected from Xuzhou City for physical measurement. The children were divided into obese group and normal group based on 2 standard deviations of WHO standard weight. A questionnaire survey was used to assess the risk factors for obesity in children aged 5 to 14, and early intervention measures were put forward. Results The detection rate of obese children in this group was 53.00%. Single factor analysis showed that breastfeeding, supplementary food addition at 4 and 6 months, fast eating, preference for dessert, drinks and fried foods, sleep time <8h/d, dislike of sports, daily TV watching time ≥ 2h / d, obesity of father and mother, mother's education level, and parents' obesity cognition were related to obesity in children aged 5-14 (P <0.05) . Logistic regression analysis revealed that artificial feeding, fast eating, deep frying, sweet drinks, mother's education, father's obesity and mother's obesity were high risk factors of children's obesity. Conclusion The incidence of obesity in children aged 5-14 years old in Xuzhou was high. Early feeding mode, children's preference for fried desserts, parents' obesity and mother's education level were the main risk factors for children's obesity. It is suggested that communities promote more health education on children’s obesity.

12.
Journal of Integrative Medicine ; (12): 319-325, 2020.
Article in English | WPRIM | ID: wpr-829096

ABSTRACT

OBJECTIVE@#Sorafenib has been extensively used for the treatment of advanced hepatocellular carcinoma (HCC), and Chinese herbal medicine has also been used to manage advanced HCC. The present work evaluates the effectiveness and safety of Jiedu (JD) Granule, a compound of traditional Chinese herbal medicine, side-by-side with sorafenib for the treatment of advance HCC.@*METHODS@#Patients with advanced HCC receiving treatment with JD Granule or sorafenib were enrolled from December 2014 to March 2018. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS) and safety. Propensity score matching (PSM) analysis was used to control for possible selection bias from the study group allocation process.@*RESULTS@#Of the 325 patients included, 161 received JD Granule and 164 received sorafenib. No significant differences were found in OS or PFS among patients receiving JD Granule compared to sorafenib (P > 0.05). Median OS of the two study groups was 6.83 months (95% confidence interval [CI]: 5.83-9.47) in the group receiving JD Granule and 8 months (95% CI: 6.67-9.80) in the group receiving sorafenib, with half-, 1- and 2-year survival rates of 53.6%, 31.2% and 13.2% vs 60.1%, 35.5% and 14.2%, respectively. Even after PSM, the median survival time did not differ between the JD Granule group (9.03 months; 95% CI: 6.37-14.2) and the sorafenib group (7.93 months; 95% CI: 6.5-9.97), with comparable half-, 1- and 2-year survival rates. The most common adverse events (AEs) were diarrhea (13.7%) and fatigue (5.6%) in the JD Granule group, and hand-foot skin reaction (46.3%) and diarrhea (36.6%) in the sorafenib group. The JD Granule was more cost-effective than sorafenib treatment for advanced HCC.@*CONCLUSION@#Compared to sorafenib, JD Granule was more cost-effective and caused fewer AEs for the treatment of Chinese patients with advanced HCC.

13.
Acta Pharmaceutica Sinica B ; (6): 812-824, 2020.
Article in English | WPRIM | ID: wpr-828842

ABSTRACT

Peritoneal adhesions are fibrous tissues that tether organs to one another or to the peritoneal wall and represent the major cause of postsurgical morbidity. Enterolysis at repeat surgeries induces adhesion reformation that is more difficult to prevent than primary adhesion. Here we studied the preventive effects of different approaches of berberine treatment for primary adhesion, and its effects on adhesion reformation compared to Interceed. We found the primary adhesion was remarkably prevented by berberine through intraperitoneal injection 30 min before abrasive surgery (pre-berberine) or direct addition into injured cecum immediately after the surgery (inter-berberine). Rats with adhesion reformation had a more deteriorative collagen accumulation and tissue injury in abrasive sites than rats with primary adhesion. The dysregulated TIMP-1/MMP balance was observed in patients after surgery, as well as adhesion tissues from primary adhesion or adhesion reformation rats. Inter-berberine treatment had a better effect for adhesion reformation prevention than Interceed. Berberine promoted the activation of MMP-3 and MMP-8 by directly blocking TIMP-1 activation core, which was reversed by TIMP-1 overexpression in fibroblasts. In conclusion, this study suggests berberine as a reasonable approach for preventing primary adhesion formation and adhesion reformation.

14.
Acta Pharmaceutica Sinica B ; (6): 878-894, 2020.
Article in English | WPRIM | ID: wpr-828837

ABSTRACT

In this report, a series of novel piperidine-substituted thiophene[3,2-]pyrimidine derivatives were designed to explore the hydrophobic channel of the non-nucleoside reverse transcriptase inhibitors binding pocket (NNIBP) by incorporating an aromatic moiety to the left wing of the lead . The newly synthesized compounds were evaluated for anti-HIV potency in MT-4 cells and inhibitory activity to HIV-1 reverse transcriptase (RT). Most of the synthesized compounds exhibited broad-spectrum activity toward wild-type and a wide range of HIV-1 strains carrying single non-nucleoside reverse transcriptase inhibitors (NNRTI)-resistant mutations. Especially, compound exhibited the most potent activity against wild-type and a panel of single mutations (L100I, K103N, Y181C, Y188L and E138K) with an EC ranging from 6.02 to 23.9 nmol/L, which were comparable to those of etravirine (ETR). Moreover, the RT inhibition activity, preliminary structure-activity relationship and molecular docking were also investigated. Furthermore, exhibited favorable pharmacokinetics (PK) profiles and with a bioavailability of 33.8%. Taken together, the results could provide valuable insights for further optimization and compound holds great promise as a potential drug candidate for the treatment of HIV-1 infection.

15.
Article in English | WPRIM | ID: wpr-827218

ABSTRACT

Lung cancer is the leading cause of cancer death and the most common malignant tumor, the long-term survival of which has stagnated in the past several decades. Pileostegia tomentella Hand. Mazz is a traditional Chinese medicine called "Zhongliuteng" (ZLT) in the pharmacopeia, which has been proved to possess a potent anti-tumor effect on various cancers. In this study, the effects of ZLT N-butanol extraction (ZLTN) and ZLT ethyl acetate extraction (ZLTE) on the viability of non-small cell lung cancer cell (NSCLC) lines H1299 and A549 were evaluated. Here, we firstly reported that ZLTE significantly inhibited H1299 cells growth without affecting the release of lactate dehydrogenase (LDH). In addition, ZLTE induced caspase-dependent apoptosis in a concentration-dependent manner and increased the expression cleaved-PARP and decreased pro-caspase-3, pro-caspase-7, pro-caspase-8, and pro-caspase-9. Moreover, ZLTE increased the level of cellular reactive oxygen species (ROS) in H1299 cells to lead to apoptosis, which was reversed by N-acetyl-cysteine (NAC). Taken together, our results revealed that ZLTE induced caspase-dependent apoptosis via ROS generation, suggesting that ZLTE is a promising herbal medicine for the treatment of NSCLC.

16.
Acta Pharmaceutica Sinica ; (12): 763-772, 2020.
Article in Chinese | WPRIM | ID: wpr-820871

ABSTRACT

West Nile virus is a flavivirus transmitted by culex mosquitoes. People are generally susceptible to it, West Nile virus infection can cause west Nile fever, which can develop West Nile viral encephalitis and even lead to death. There are currently no approved specific antiviral drugs against West Nile virus. Therefore, seeking effective West Nile virus inhibitors is a hot topic in current community of medicinal chemistry. In this article, based on the main targets of West Nile virus, we summarize the new progress research on West Nile virus inhibitors.

17.
Article in Chinese | WPRIM | ID: wpr-942085

ABSTRACT

OBJECTIVE@#Mitochondrial deoxyribonucleic acid (mtDNA) 8344 A>G (m.8344A>G) mutation is the common mutation associated with mitochondrial myoclonus epilepsy with ragged-red fibers (MERRF) syndrome. Herein we report a rare case with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes/MERRF/Leigh (MELAS/MERRF/Leigh) overlap syndrome caused by m.8344A>G mutation.@*METHODS@#The clinical and imaging data of the patient were collected and an open muscle biopsy was carried out. We further employed molecular genetic analyses to detect mtDNA mutation in the proband and his mother. And then a clinical and neuroimaging follow-up was performed.@*RESULTS@#This patient was a 25-year-old male, who developed exercise intolerance since the age of 6. At age 10, he suffered from acute episodes of hemianopia, and cranial magnetic resonance imaging (MRI) showed occipital stroke-like lesions and cranial magnetic resonance spectroscopy (MRS) revealed a lactate peak corresponding to the lesion. After that the patient presented slowly progressive psychomotor decline. He had myoclonic seizures and cerebellar ataxia since the age of 12. At age 21, he was admitted to our hospital because of confusion and cranial MRI revealed symmetrical lesions in bilateral posterior putamen, thalami and midbrain. Then repeated MRI showed progression of original lesions and new frontal multiple stroke-like lesions. Symptomatic and rehabilitation treatment relieved his condition. Follow-up cranial MRI at age 24 showed the lesions in basal ganglia and thalami diminished, and the midbrain lesions even completely vanished. Muscle pathology indicated the presence of numerous scattered ragged-red fibers (RRF), suggestive of a mitochondrial disorder. Polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) detected the m.8344A>G mutation of the MT-TK gene encoding mitochondrial transfer RNA for lysine in the patient's blood. Next generation sequencing (NGS) of the whole mitochondrial genome identified that the proportion of m.8344A>G was 90%, and no other mtDNA mutation was detected. Sanger sequencing further identified this mutation both in the proband and his mother's blood, although the mutation load was much lower in his mother's blood with approximately 10% heteroplasmy.@*CONCLUSION@#The present study is the first to describe a patient with m.8344A>G mutation in association with the MELAS/MERRF/Leigh overlap syndrome, which expands the phenotypic spectrum of the m.8344A>G mutation.


Subject(s)
Acidosis, Lactic , Adult , Child , DNA, Mitochondrial/genetics , Humans , Male , Mitochondrial Encephalomyopathies , Mutation , Stroke , Young Adult
18.
Article in Chinese | WPRIM | ID: wpr-865327

ABSTRACT

Objective:To investigate the protective effect of astaxanthin on the retinopathy in rats with type 1 diabetes and related mechanism.Methods:Thirty-six male SPF rats received intraperitoneal injection of 1% streptozotocin (STZ) to prepare type 1 diabetes model.The rats were randomly assigned to the diabetes group, low dose astaxanthin group and high dose astaxanthin group by a random number table.The rats in the low dose astaxanthin group and high dose astaxanthin group received respectively astaxanthin 20 mg/kg and 100 mg/kg by gavage everyday.The rats in the diabetes group received an equal volume of olive oil.Twelve rats received an equal volume of sodium citrate as the control group.Blood glucose and body mass were measured every 2 weeks.After 24 weeks, the retina was digested to make retinal capillary network preparation.The number of pericytes and acelluar strands was compared among the different experimental groups.The relative expressions of anti-inflammatory cytokines in retinal tissue were detected by immunohistochemistry, real-time PCR and Western blot.The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.Results:Body mass of the rats in the low dose astaxanthin group and high dose astaxanthin group was significantly higher than that in the diabetes group (both at P<0.05). Blood glucose levels in the low dose astaxanthin group and high dose astaxanthin group were significantly lower than that in the diabetes group (both at P<0.05). In the control group, main artery was round, uniform, and strongly stained.The vein was lightly stained and had a large diameter.In the diabetes group, retinal arteriovenous trunk and branches appeared tortuous at a low magnification, with capillary network disorder.The morphology of the capillaries showed pathology in the low dose astaxanthin group and high dose astaxanthin group, but the vascular tortuosity, dilatation and stenosis were reduced in comparison with the diabetes group.The number of pericytes was 466.4±23.2, 207.3±31.7, 298.1±27.1 and 312.2±19.5 among different groups, with a significant difference among them ( F=34.420, P=0.047). The number of acelluar strands were 5.2±2.3, 32.9±12.7, 14.5±9.1 and 16.5±3.5 among different groups, with a significant difference among them ( F=47.340, P=0.021). The relative expression of IL-6, TNF-α and caspase-3 mRNA in the low dose astaxanthin group was 0.87±0.23, 0.91±0.34 and 1.07±0.15, the relative expression in the high dose astaxanthin group was 0.81±0.31, 0.85±0.39 and 0.95±0.11, which was significantly decreased in comparison with the diabetes group (1.63±0.47, 1.57±0.53 and 1.51±0.32) (all at P<0.05). The relative expression of IL-6, TNF-α and caspase-3 protein in the low dose astaxanthin group was 0.63±0.33, 0.51±0.14 and 0.60±0.13, the relative expression in the high dose astaxanthin group was 0.69±0.22, 0.49±0.15 and 0.57±0.22, which was significantly decreased in comparison with the diabetes group (all at P<0.05). Conclusions:Astaxanthin may play an important role in protecting pericytes from apoptosis and delaying development and progression of diabetic retinopathy in rats.Additionally, astaxanthin can inhibit release of anti-apoptosis and anti-inflammatory cytokines.

19.
Article in Chinese | WPRIM | ID: wpr-826385

ABSTRACT

To investigate the association of pancreatic steatosis with coronary atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Patients with T2DM who underwent coronary computed tomography angiography(CCTA)in our center due to chest pain were enrolled from January 2016 to February 2019. According to the CCTA findings,patients were divided into normal group,mild-to-moderate coronary atherosclerosis group and severe coronary atherosclerosis group. CT attenuation of pancreas and spleen was measured on abdominal non-enhanced CT,and the CT attenuation indexes including the difference between pancreatic and splenic attenuation (P-S) and the ratio of pancreas-to-spleen attenuation (P/S) were calculated. Analysis of variance or Kruskal-Wallis rank test were used to assess differences among each group. Logistic regression analysis was used to analyze the risk factors of severe coronary stenosis. The accuracy of P/S in predicting severe coronary artery stenosis was assessed by receiver operator characteristic (ROC) curve analysis. A total of 173 consecutive T2DM patients were enrolled. These patients included 27 patients with normal coronary artery (15.6%),124 patients with mild to moderate stenosis (71.7%),and 22 patients with severe stenosis (12.7%). There were significant differences in CT attenuation of pancreas (=11.543,=0.003),P-S (=11.152,=0.004) and P/S (=11.327,=0.004) among normal coronary artery group,mild and moderate stenosis group,and severe stenosis group. The CT attenuation of pancreatic head,body,and tail significantly differed in patients with coronary artery stenosis (=14.737,=0.001). After adjusting for confounding factors,multiple Logistic regression showed that P/S (=0.062,95%=0.008-0.487,=0.008) was still significantly associated with the severe coronary artery stenosis. The area under the ROC curve of P/S for the diagnosis of severe coronary artery stenosis was 0.701,and the optimal cutoff point was 0.660. CT attenuation of pancreas and CT attenuation indexes are associated with the severity of coronary stenosis in T2DM patients,suggesting that pancreatic steatosis may be used as one of the indicators for predicting severe coronary artery stenosis.


Subject(s)
Coronary Angiography , Coronary Artery Disease , Coronary Stenosis , Diabetes Mellitus, Type 2 , Humans , Pancreas , Pathology , Predictive Value of Tests
20.
Article in Chinese | WPRIM | ID: wpr-746203

ABSTRACT

Objective To evaluate the factors that may influence the possibility of early hemorrhage after vitrectomy with silicon oil tamponade for proliferative diabetic retinopathy (PDR).Methods Sixty-seven eyes of 60 patients of PDR who received vitrectomy and silicon oil filled in Department of Ophthalmology,China-Japan Friendship Hospital during January 2014 and May 2017 were included in this study.There were 34 males and 26 females,with the mean age of 51.3 ± 12.5 years.Groups were divided depending on the degree of postoperative hemorrhage in 3 days:non-hemorrhage group (NH group) and hemorrhage Group (H group) composed of two sub-group that were called slight hemorrhage (SH) and massive hemorrhage (MH) group.The treatment was conventional 25G or 27G pars plana vitrectomy combined with silicon oil tamponade.Forty eyes received phacoemulsification.The follow-up ranged from 8 to 16 months,with the mean follow-up of 11.2± 5.6 months.The possible related factors of early hemorrhage after vitrectomy with silicon oil tamponade were analyzed.Independent t test,x2 test and Fisher test were used in this study.Results 55 eyes of 48 patients were in the NH group,while 12 eyes of 12 patients were in the H Group.There were statistical significances on the difference of age (t=-3.552,P=0.001),gender (P=0.052),hypertension (P=0.021),HbA1c (t=2.187,P=0.033)and presence of neovascularization of iris (x2=6.414,P=0.011),but there was no difference on diabetes duration (t=-0.451,P=0.654).Of the 12 patients in the H group,7 were in the SH group and 5 were in the MH group.The MH group had a significantly higher HbA1c level (7.8± 1.1)% compared with the SH Group (9.7±0.7)%,the difference was statistical significant (t=-3.256,P=0.009).Higher systolic blood pressure of MH group 186± 7 mmHg (1 mmHg=0.133 kPa) acquired during operation was observed compared with S H Group 153± 18 mmHg,the difference was statistical significant (t=-3.894,P=0.003).There was no statistical significances on the difference of age (t=1.954),gender,hypertension duration (t=-1.787),diabetes duration (t=-1.079),fasting blood-glucose (t=-0.361),diastolic blood pressure during operation (t=-0.811) between the two groups (P>0.05).Conclusions Younger age,history of hypertension,presence of neovascularization of iris,higher level of HbA 1 c may predict greater possibility to cause early hemorrhage after vitrectomy with silicon oil tamponade for PDR.The patients with high level of HbA1c and high systolic pressure during the operation are more likely to undergo massive hemorrhage and secondary glaucoma.

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