Study on active components and mechanism of shikonin in prevention and treatment of blood heat syndrome / 中国药理学通报

Aim To systematically evaluate the heat-clearing mechanism of Arnebiae Radix on two mouse models of blood heat syndrome. Methods The drug-forming molecules were screened by comprehensive network pharmacology methods, and the correlation between drug efficacy and related factors and targets was evaluated on the mouse model of short effect blood heat syndrome constructed by 2, 4-dinitrophenol (DNP) and the mouse model of severe blood heat syndrome (heat stroke) constructed by high temperature combined with lipopolysaccharide (LPS). Results A total of 277 shikonin related targets were collected, mainly involving biological processes such as inflammatory reaction, oxidation reaction and coagulation reaction. Shikonin, a representative compound, significantly improved the main syndromes of mice with blood heat syndrome, reduced the levels of inflammatory factors IL-1β, IL-6 and TNF-α in the two models, and reduced the contents of oxidative damage indexes LPO and MDA, and the two showed correlation. The main mechanism was to inhibit the expression of NF-ΚB p65 and up-regulate the expression of Nrf2. Conclusions Shikonin plays a pharmacological role in the prevention and treatment of blood heat syndrome by inhibiting inflammation and improving antioxidant capacity, which provides a pharmacological basis for shikonin in the prevention and treatment of blood heat syndrome.

Vitrectomy with fovea-sparing versus complete internal limiting membrane peeling for myopic traction maculopathy: A Meta-analysis / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the efficacy and safety of foveal-sparing internal limiting membrane peeling(FSIP)or complete internal limiting membrane peeling(CMIP)for the treatment of myopic traction maculopathy(MTM)during vitrectomy.METHODS: CNKI, Wanfang, VIP, PubMed, Embase, Cochrane Library, and Web of Science were searched from January 1th 2000 to July 1th 2022, and studies that compared FSIP and CMIP for MTM were collected. The change and recovery rate of best corrected visual acuity(BCVA), incidence of full-thickness macular hole(FTMH), change of central foveal thickness(CFT)and the rate of complete reattachment.RESULTS: A total of 484 eyes from 12 literatures were included, with 203 eyes in the FSIP group and 281 eyes in the CMIP group. The results of Meta-analysis showed that FSIP group were superior to the CMIP group in the mean change of BCVA(SMD=0.52, 95%CI: 0.20～0.85, P=0.002), the improvement rate of BCVA(RR=1.50, 95%CI: 1.22～1.85, P=0.0002)and the incidence of postoperative FTMH(RR=0.23, 95%CI: 0.10～0.54, P=0.0008). There was no statistical difference between the two surgical methods in terms of mean change in CFT(SMD=0.04, 95%CI: -0.19～0.26, P=0.75)and the rate of complete reattachment(RR=1.12, 95%CI: 0.94～1.32, P=0.20).CONCLUSION: FSIP have similar anatomical outcomes compared to CMIP, but FSIP resulted in better visual acuity and lower incidence of postoperative FTMH.

Gonioscopy-assisted transluminal trabeculotomy for secondary high intraocular pressure after vitrectomy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the clinical efficacy of gonioscopy-assisted transluminal trabeculotomy(GATT)for secondary high intraocular pressure after vitrectomy.METHODS: A retrospective study was conducted on 10 patients(15 eyes)with secondary high intraocular pressure(IOP)after vitrectomy treated with GATT in Department of Ophthalmology, Chengdu First People's Hospital from January 2019 to May 2022. The best-corrected visual acuity(BCVA), IOP, number of IOP-lowering drugs, and complications before operation and at 1d, 1wk, 1, 3 and 6mo after operation were recorded, and the surgical success rate was analyzed.RESULTS:There was no difference in BCVA before and 6mo after operation(Z=0, P=1). The mean IOP decreased from 28.33±9.48mmHg to 17.47±3.78(1d), 18.8±3.29(1wk), 19.13±3.62(1mo), 20.31±3.66(3mo)and 18.03±3.23mmHg(6mo; all P<0.05). The average medication used before surgery was 2(2, 4), and the average medication used 6mo after surgery was 1(0, 2), which was significantly decreased(P<0.001). The total success rate of surgery at 1d, 1wk, 1, 3 and 6mo after surgery was 87%(13 eyes), 93%(14 eyes), 87%(13 eyes), 73%(11 eyes)and 93%(14 eyes)respectively. The main postoperative complications were transient hyphema(10 eyes, 67%)and transient elevated IOP(5 eyes, 33%). No complications seriously affecting the vision occurred.CONCLUSION: GATT is safe and effective in the treatment of secondary high intraocular pressure after vitrectomy.

The weight-adjusted-waist index predicts all-cause and cardiovascular mortality in general US adults

Abstract Background The authors examined the relationship between Weight-adjusted Waist Index (WWI) and all-cause and cardiovascular mortality among adults in the US. Methods This prospective cohort study included 26,882 individuals who participated in the National Health and Nutrition Examination Survey (NHANES) from 2005 through 2014. WWI was calculated as waist circumference divided by the square root of weight. The main outcomes of this study were all-cause mortality and cardiovascular mortality. Mortality status and cause of death were determined by NHANES-linked National Death Index records through December 31, 2015. Cox proportional hazard models and Kaplan-Meier analysis were used to estimate Hazard Ratios (HR) and 95% CIs for mortality for all causes and cardiovascular diseases. Results A total of 26,882 participants with a mean WWI of 10.89 ± 0.01, of whom 49.23% were male. The average follow-up time was 68.95 ± 1.07 months, and 1870 participants were determined as deceased (4.99%), including 349 cardiovascular death (0.88%). The Kaplan-Meier analysis demonstrated a significant difference in all-cause and cardiovascular mortality between patients with WWI <11.33 and ≥11.33 (both log-rank testp < 0.0001). The fully adjusted Cox proportional hazard model indicated that a higher WWI level (≥ 11.33) was associated with an increased 95% risk for cardiovascular mortality (HR = 1.95, 95% CI 1.30‒2.93) and 68% risk for all-cause death (HR = 1.68, 95% CI 1.41‒2.00) compared with the counterparts. Conclusions Elevated WWI levels were associated with a higher risk of cardiovascular mortality and all-cause mortality independently.

Clinical problems and outcome indicators in the expert consensus determined by the Delphi method of 5-aminolevulinic acid photodynamic therapy for the treatment of oral potential malignant diseases / 口腔疾病防治

Objective@#To determine the clinical problems and outcome indicators that need to be included in the expert consensus of 5-aminolevulinic acid (ALA) photodynamic therapy in the treatment of oral potential malignant diseases. @*Methods@# Based on the relevant literature, the clinical problems and outcome indicators were drafted during the meeting. The Delphi method was used for expert consultation and expert opinion collection. The average and standard deviation of the voting results were calculated to determine the importance of the indicators, and the positive coefficient, variation coefficient and coordination coefficient were calculated for quality control. @* Results@#In the first round of the Delphi method, 12 outcome indicators (the main reference elements include photon integral flux, power density, illumination time, and spot diameter were identified; the specific parameters are photon integral flux of 100 J/cm2 and power density of 100-600 mW/cm2. A diode laser of (630 ± 5) nm wavelength should be chosen. The analgesic regimen is local anesthesia supplemented by hypothermia and intermittent laser irradiation before treatment. Lesions with hyperkeratotic require pretreatment. The concentration of ALA administered was set at 20%. Eight clinical problems (main reference elements of photodynamic irradiation dose, specific parameters, choice of light source, evaluation criteria of efficacy, prevention of adverse effects, dosing concentration, whether oral potentially malignant diseases with hyperkeratosis should be pretreated, administration of photosensitizers) were included according to the literature and expert discussion. In the second round, 89 experts completed the questionnaire and gave very important evaluations of 9 outcome indicators (the main reference elements included photon integral flux, power density and illumination time; the specific parameters were a photon integral flux of 100 J/cm 2 and a power density of 100-600 mW/cm2). A diode laser of (630 ± 5)nm wavelength should be chosen. The concentration of ALA administered was set at 20%. Six clinical problems (main reference elements of photodynamic irradiation dose, specific parameters, choice of light source, evaluation criteria of efficacy, dosing concentration, administration of photosensitizers), and the remaining 3 were given important evaluations, with good consistency.@*Conclusion@# In this study, the irradiation dose, mode of administration and concentration, evaluation criteria of efficacy, prevention of adverse effects and pretreatment regimen of ALA photodynamic therapy for oral potentially malignant diseases determined by the Delphi method had good agreement among experts.

Clinical observation on the treatment of adult glaucoma by stab incision glaucoma surgery / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To observe the safety and efficacy of stab incision glaucoma surgery(SIGS)in the treatment of adult glaucoma.METHODS: A series of retrospective case studies were carried out from June 2018 to November 2020, the clinical data of 55 cases with 70 eyes of glaucoma treated with SIGS in our hospital were collected. Following up at 6mo after operation, the intraocular pressure(IOP), bleb and postoperative complications were observed.RESULTS: Among the included patients, 30 eyes were performed SIGS alonely, 40 eyes were performed SIGS combined with phacoemulsification. Among them, the operation of 33 eyes(47%)was completely successful, the operation of 28 eyes(40%)was partially successful, and the operation of 9 eyes(13%)were failed. The mean preoperative IOP under medication was 31.82±13.16mmHg, and at 1wk, 1, 3 and 6mo after operation, the mean IOP(14.97±5.25, 17.94±5.24, 18.43±4.74, 17.37±3.36)mmHg were all significantly lower than before operation, and the number of IOP-lowering drugs used at 6mo after operation [0(0, 1)] was significantly lower than before operation [3(2, 3)](P&#x003C;0.001). At 6mo after operation, the filtering blebs' shape of the patients: 30 eyes(43%)of type I(functional bleb), 31 eyes(44%)of type Ⅱ(functional bleb), 7 eyes(10%)of type Ⅲ(flat bleb)and 2 eyes(3%)of type IV(encapsulated vesicular bleb)were included. During the follow-up period, 2 eyes had hyphema in anterior chamber, 4 eyes had inflammatory reaction in anterior chamber, 3 eyes had low IOP, shallow anterior chamber and excessive filtration, 1 eye had malignant glaucoma, 1 eye had endophthalmitis, 1 eye had choroidal detachment, 1 eye had choroidal detachment, and 9 eyes had scarring of filtering blebs.CONCLUSION: SIGS is effective in the treatment of primary open angle glaucoma, primary angle-closure glaucoma and some secondary glaucoma without serious complications.

The mechanism by which Peganum harmala L. inhibits high glucose-induced tube formation in endothelial cells / 药学学报

The study investigates the mechanism by which Peganum harmala L. (Luotuopeng, LTP) inhibits tube formation in retinal vascular endothelial cells. Tube formation was induced by treatment of retinal vascular endothelial cells with glucose. The cells were divided into a normal group, model group, and an LTP group. The total length of tube formation was measured. The active components, targets, and pathway by which LTP acts in the treatment of diabetic retinopathy was explored by network pharmacology. The mRNA expression levels of targets [extracellular signal-regulated kinase 2 (ERK2), phosphoinositide 3 kinase catalytic alpha polypeptide (PIK3CA), serine/threonine-protein kinase 1 (AKT1)] related to the mitogen-activated protein kinase (MAPK) signaling pathway and vascular endothelial growth factor (VEGF) signaling pathway was measured by real-time PCR. The results of tube formation indicated that compared with the normal group, the total tube length increased in the model group (P < 0.01); after the treatment with LTP, the total tube length decreased compared with the model group (P < 0.01). Network pharmacology revealed that the targets of LTP included PIK3CA, AKT1, and ERK2, and the pathways involved the MAPK signaling pathway and the VEGF signaling pathway. Real-time PCR indicated that compared with the normal group, the mRNA expression levels of ERK2, PIK3CA and AKT1 were elevated in the model group (P < 0.05); after treatment with LTP, the mRNA expression levels of ERK2, PIK3CA and AKT1 decreased compared with the model group (P < 0.05). LTP may inhibit retinal vascular endothelial cell tube formation by regulating the MAPK signaling pathway and the VEGF signaling pathway. This study confirms the multi-targets and multi-pathways of LTP and provides a basis for its use in the treatment of diabetic retinopathy．

Cardioprotective effect of taurine and ß-alanine against cardiac disease in myocardial ischemia and reperfusion-induced rats

BACKGROUND: The present study analyzed the synergistic protective effect of ß-alanine and taurine against myocardial ischemia/reperfusion. Myocardial infarct size, lipid peroxidation, and levels of glutathione peroxidase (Gpx), superoxide dismutase (SOD), reduced glutathione (GSH), catalase, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), reactive oxygen species (ROS), apoptosis, and the mRNA and protein expression of Janus kinase 2 (JAK2) and signal transducer and activator 3 of transcription (STAT3) were determined. The molecular docking was carried out by using AutoDock 4.2.1. RESULTS: Combined treatment with ß-alanine and taurine reduced myocardial infarct size, lipid peroxidation, inflammatory marker, ROS levels, and apoptosis and increased Gpx, SOD activity, GSH, and catalase activity. Furthermore, combined treatment significantly reduced JAK2 and STAT3 mRNA and protein expression compared with the control. The small molecule was docked over the SH2 domain of a STAT3, and binding mode was determined to investigate the inhibitory potential of ß-alanine and taurine. ß-Alanine bound to SH2 domain with ΔG of -7.34 kcal/mol and KI of 1.91 µM. Taurine bound to SH2 domain with ΔG of -7.38 kcal/mol and KI of 1.95 µM. CONCLUSION: Taken together, these results suggest that the combined supplementation of ß-alanine and taurine should be further investigated as an effective therapeutic approach in achieving cardioprotection in myocardial ischemia/reperfusion.

Fatigue correlates with sleep disturbances in Parkinson disease / 中华医学杂志(英文版)

BACKGROUND@#Many Parkinson disease (PD) patients complain about chronic fatigue and sleep disturbances during the night. The objective of this study is to determine the relationship between fatigue and sleep disturbances by using polysomnography (PSG) in PD patients.@*METHODS@#Two hundred and thirty-two PD patients (152 with mild fatigue and 80 with severe fatigue) were recruited in this study. Demographic information and clinical symptoms were collected. Fatigue severity scale (FSS) was applied to evaluate the severity of fatigue, and PSG was conducted in all PD patients. FSS ≥4 was defined as severe fatigue, and FSS <4 was defined as mild fatigue. Multivariate logistic regression and linear regression models were used to investigate the associations between fatigue and sleep disturbances.@*RESULTS@#Patients with severe fatigue tended to have a longer duration of disease, higher Unified Parkinson Disease Rating Scale score, more advanced Hoehn and Yahr stage, higher daily levodopa equivalent dose, worse depression, anxiety, and higher daytime sleepiness score. In addition, they had lower percentage of rapid eye movement (REM) sleep (P = 0.009) and were more likely to have REM sleep behavior disorder (RBD) (P = 0.018). Multivariate logistic regression analyses found that the presence of RBD and proportion of REM sleep were the independent predictors for fatigue. After the adjustment of age, sex, duration, body mass index, severity of disease, scores of Hamilton Rating Scale for Depression, Hamilton Anxiety Rating Scale, and other sleep disorders, proportion of REM sleep and degree of REM sleep without atonia in patients with PD were still associated with FSS score.@*CONCLUSION@#Considering the association between fatigue, RBD, and the altered sleep architecture, fatigue is a special subtype in PD and more studies should be focused on this debilitating symptom.

Clinical effects of clomiphene citrate combined with low molecular weight heparin calcium in the treatment of patients with polycystic ovary syndrome infertility / 中国实用妇科与产科杂志

OBJECTIVE: To discuss the clinical effects of clomiphene citrate combined with low molecular weight heparin calcium in the treatment of patients with polycystic ovarian syndrome(PCOS)infertility. METHODS: A total of 105 patients with PCOS infertility who were admitted to the Outpatient Department of Women and Children's Hospital of Qingdao University from September 2016 to April 2018 were taken as research subjects.They were randomly divided into observation group(57 cases)and control group(48 cases).The control group received clomiphene citrate for ovulation treatment,the observation group was given clomiphene citrate combined with low molecular weight heparin calcium for ovulation treatment,and the endometrial receptivity changes,pregnancy rate and the incidence of adverse reactions of patients were compared between the two groups.RESULTS: In the observation group,the endometrial thickness,blood flow index(FI),endometrial spiral arterial blood flow resistance index(RI)and pulsatility index(PI)decreased,and the pregnancy rate was better than that in the control group;the difference was statistically significan(t P0.05).CONCLUSION: Clomiphene citrate combined with low molecular weight heparin calcium in the treatment of polycystic ovary syndrome infertility can improve the treatment efficiency,and is safe and reliable.It is worthy of clinical promotion.

Comparative analysis of a panel of biomarkers related to protein phosphatase 2A between laryngeal squamous cell carcinoma tissues and adjacent normal tissues / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Laryngeal squamous cell carcinoma (LSCC) is the most common type of head and neck squamous cell carcinoma (HNSCC) worldwide. Protein phosphatase 2A (PP2A) dysfunction has been widely reported in a broad range of malignancies due to its distinctive role in miscellaneous cellular processes. However, it is poorly understood whether aberrant alterations of PP2A are involved in the network of oncogenic events in LSCC. Here, we detected a panel of PP2A-associated proteins using western blot in both laryngeal squamous cell carcinoma tissues and paired adjacent normal tissues from patients (Data S1). We found that phospho-PP2A/C (Y307), α4, cancerous inhibitor of protein phosphatase 2A (CIP2A), Akt, ezrin, phospho-ezrin (T567), 14-3-3, and focal adhesion kinase (FAK) showed increased expression levels in carcinoma tissues relative to normal tissues, while phospho-Akt (T308) showed decreased levels. Our study, thus, provides a rationale for targeting PP2A to develop novel therapies and proposes a combination of interrelated biomarkers for the diagnostic evaluation and prognosis prediction in LSCC.

DL-3-n-butylphthalide protects the blood-brain barrier against ischemia/hypoxia injury via upregulation of tight junction proteins / 中华医学杂志(英文版)

Background@#The increased permeability of the blood-brain barrier (BBB) induced by ischemia/hypoxia is generally correlated with alteration of tight junctions (TJs). DL-3-n-butylphthalide (NBP) has been shown to exert neuroprotective effects after ischemic injury. However, few studies have assessed the correlation between NBP and TJs. This study aimed to investigate the potential effect of NBP on the TJ proteins claudin-5, zonula occludens-1 (ZO-1), and occludin during brain ischemia.@*Methods@#A chronic cerebral hypoperfusion (CCH) Sprague-Dawley rat model was established, and NBP (20, 40, or 80 mg/kg, gavage, once a day) treatment was performed for 14 days. NBP (0.1 or 1.0 μmol/L) pre-treatment was applied to an in vitro hypoxia microvascular endothelial cell model (1% O2, 24 h). BBB permeability was assessed by performing the Evans blue assay. The expressions and localization of claudin-5, ZO-1, occludin, phosphorylated/total protein kinase B (p-Akt/Akt), phosphorylated/total glycogen synthase kinase 3β (GSK-3β)/GSK-3β, and β-catenin/β-actin were evaluated by Western blotting or immunofluorescence. Reactive oxygen species (ROS) generation was measured by flow cytometry analysis. TJ ultrastructure was observed by transmission electron microscopy.@*Results@#In CCH rats, treatment with 40 and 80 mg/kg NBP decreased the Evans blue content in brain tissue (9.0 ± 0.9 μg/g vs. 12.3 ± 1.9 μg/g, P = 0.005; 6.7 ± 0.6 μg/g vs. 12.3 ± 1.9 μg/g, P < 0.01), increased the expression of claudin-5 (0.79 ± 0.08 vs. 0.41 ± 0.06, P < 0.01; 0.97 ± 0.07 vs. 0.41 ± 0.06, P < 0.01), and elevated the ZO-1 protein level (P < 0.05) in brain microvascular segments in a dose-dependent manner in comparison with the corresponding values in the model group. There was no significant difference in occludin expression (P > 0.05). In the hypoxia cell model, NBP pre-treatment improved TJ ultrastructure, decreased intracellular ROS level, and increased the expression of claudin-5 (P < 0.01) and ZO-1 (P < 0.01) in comparison with the corresponding values in the hypoxia group. NBP treatment also elevated the relative expression levels of p-Akt/Akt, p-GSK-3β/GSK-3β, and β-catenin/β-actin in comparison with the corresponding values in the hypoxia group (all P < 0.05).@*Conclusion@#NBP improves the barrier function of BBB against ischemic injury by upregulating the expression of TJ proteins, possibly by reducing oxidative stress and activating the Akt/GSK-3β/β-catenin signaling pathway.

Assessing for Mood and Anxiety Disorders in Parents of Clinically-Referred Children: Laying the Foundation for a Family-Based Approach to Mental Health in Singapore

INTRODUCTION@#Family history of psychopathology is a risk factor for mood and anxiety disorders in children, but little is known about rates of parental psychopathology among treatment-seeking youth with affective disorders in the Asia Pacific region. This study examined patterns of emotional and behavioural problems in parents of clinically-referred youth in Singapore. We hypothesised that parents would have higher rates of affective disorders compared to the Singapore national prevalence rate of 12%.@*MATERIALS AND METHODS@#In this cross-sectional study, 47 families were recruited from affective disorders and community-based psychiatry programmes run by a tertiary child psychiatry clinic. All children had a confirmed primary clinical diagnosis of depression or an anxiety disorder. Parents completed the Mini International Neuropsychiatric Interview (MINI) to assess for lifetime mood and anxiety disorders. They also completed the Adult Self Report (ASR) and Adult Behavior Checklist (ABCL) to assess current internalising and externalising symptoms.@*RESULTS@#Consistent with our hypothesis, 38.5% of mothers and 10.5% of fathers reported a lifetime mood and anxiety disorder. Nearly 1/3 of mothers had clinical/subclinical scores on current internalising and externalising problems. A similar pattern was found for internalising problems among fathers, with a slightly lower rate of clinical/subclinical externalising problems.@*CONCLUSION@#Our findings are consistent with previous overseas studies showing elevated rates of affective disorders among parents - particularly mothers - of children seeking outpatient psychiatric care. Routine screening in this population may help to close the current treatment gap for adults with mood and anxiety disorders.

Role of SIRT1 in hematologic malignancies / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Sirtuin 1 (SIRT1) is a protein deacetylase, which regulates various physiological activities by deacetylating different protein substrates. An increasing number of studies have revealed critical roles of SIRT1 in different aspects of cancers including metabolism, proliferation, genomic instability, and chemotherapy resistance. Depending on the protein targets in a certain oncogenic context, SIRT1 may play a unique role in each individual blood cancer subtype. Our previous work showed that activation of SIRT1 in primitive leukemia cells of acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML) promotes disease maintenance. On the other hand, an SIRT1 agonist was shown to disrupt maintenance of myelodysplastic syndrome (MDS) stem cells and holds promise as a potential therapeutic approach. Herein, we present a concise summary of the different functions of SIRT1 in hematologic malignancies.

DL-3-n-butylphthalide protects the blood-brain barrier against ischemia/hypoxia injury via upregulation of tight junction proteins / 中华医学杂志(英文版)

BACKGROUND@#The increased permeability of the blood-brain barrier (BBB) induced by ischemia/hypoxia is generally correlated with alteration of tight junctions (TJs). DL-3-n-butylphthalide (NBP) has been shown to exert neuroprotective effects after ischemic injury. However, few studies have assessed the correlation between NBP and TJs. This study aimed to investigate the potential effect of NBP on the TJ proteins claudin-5, zonula occludens-1 (ZO-1), and occludin during brain ischemia.@*METHODS@#A chronic cerebral hypoperfusion (CCH) Sprague-Dawley rat model was established, and NBP (20, 40, or 80 mg/kg, gavage, once a day) treatment was performed for 14 days. NBP (0.1 or 1.0 μmol/L) pre-treatment was applied to an in vitro hypoxia microvascular endothelial cell model (1% O2, 24 h). BBB permeability was assessed by performing the Evans blue assay. The expressions and localization of claudin-5, ZO-1, occludin, phosphorylated/total protein kinase B (p-Akt/Akt), phosphorylated/total glycogen synthase kinase 3β (GSK-3β)/GSK-3β, and β-catenin/β-actin were evaluated by Western blotting or immunofluorescence. Reactive oxygen species (ROS) generation was measured by flow cytometry analysis. TJ ultrastructure was observed by transmission electron microscopy.@*RESULTS@#In CCH rats, treatment with 40 and 80 mg/kg NBP decreased the Evans blue content in brain tissue (9.0 ± 0.9 μg/g vs. 12.3 ± 1.9 μg/g, P = 0.005; 6.7 ± 0.6 μg/g vs. 12.3 ± 1.9 μg/g, P  0.05). In the hypoxia cell model, NBP pre-treatment improved TJ ultrastructure, decreased intracellular ROS level, and increased the expression of claudin-5 (P < 0.01) and ZO-1 (P < 0.01) in comparison with the corresponding values in the hypoxia group. NBP treatment also elevated the relative expression levels of p-Akt/Akt, p-GSK-3β/GSK-3β, and β-catenin/β-actin in comparison with the corresponding values in the hypoxia group (all P < 0.05).@*CONCLUSION@#NBP improves the barrier function of BBB against ischemic injury by upregulating the expression of TJ proteins, possibly by reducing oxidative stress and activating the Akt/GSK-3β/β-catenin signaling pathway.

Role of X-Box Binding Protein-1 in Fructose-Induced Lipogenesis in HepG2 Cells / 中华医学杂志(英文版)

<p><b>Background</b>A high consumption of fructose leads to hepatic steatosis. About 20-30% of triglycerides are synthesized via de novo lipogenesis. Some studies showed that endoplasmic reticulum stress (ERS) is involved in this process, while others showed that a lipotoxic environment directly influences ER homeostasis. Here, our aim was to investigate the causal relationship between ERS and fatty acid synthesis and the effect of X-box binding protein-1 (XBP-1), one marker of ERS, on hepatic lipid accumulation stimulated by high fructose.</p><p><b>Methods</b>HepG2 cells were incubated with different concentrations of fructose. Upstream regulators of de novo lipogenesis (i.e., carbohydrate response element-binding protein [ChREBP] and sterol regulatory element-binding protein 1c [SREBP-1c]) were measured by polymerase chain reaction and key lipogenic enzymes (acetyl-CoA carboxylase [ACC], fatty acid synthase [FAS], and stearoyl-CoA desaturase-1 [SCD-1]) by Western blotting. The same lipogenesis-associated factors were then evaluated after exposure of HepG2 cells to high fructose followed by the ERS inhibitor tauroursodeoxycholic acid (TUDCA) or the ERS inducer thapsigargin. Finally, the same lipogenesis-associated factors were evaluated in HepG2 cells after XBP-1 upregulation or downregulation through cell transfection.</p><p><b>Results</b>Exposure to high fructose increased triglyceride levels in a dose- and time-dependent manner and significantly increased mRNA levels of SREBP-1c and ChREBP and protein levels of FAS, ACC, and SCD-1, concomitant with XBP-1 conversion to an active spliced form. Lipogenesis-associated factors induced by high fructose were inhibited by TUDCA and induced by thapsigargin. Triglyceride level in XBP-1-deficient group decreased significantly compared with high-fructose group (4.41 ± 0.54 μmol/g vs. 6.52 ± 0.38 μmol/g, P < 0.001), as mRNA expressions of SREBP-1c (2.92 ± 0.46 vs. 5.08 ± 0.41, P < 0.01) and protein levels of FAS (0.53 ± 0.06 vs. 0.85 ± 0.05, P = 0.01), SCD-1 (0.65 ± 0.06 vs. 0.90 ± 0.04, P = 0.04), and ACC (0.38 ± 0.03 vs. 0.95 ± 0.06, P < 0.01) decreased. Conversely, levels of triglyceride (4.22 ± 0.54 μmol/g vs. 2.41 ± 0.35 μmol/g, P < 0.001), mRNA expression of SREBP-1c (2.70 ± 0.33 vs. 1.00 ± 0.00, P < 0.01), and protein expression of SCD-1 (0.93 ± 0.06 vs. 0.26 ± 0.05, P < 0.01), ACC (0.98 ± 0.09 vs. 0.43 ± 0.03, P < 0.01), and FAS (0.90 ± 0.33 vs. 0.71 ± 0.02, P = 0.04) in XBP-1s-upregulated group increased compared with the untransfected group.</p><p><b>Conclusions</b>ERS is associated with de novo lipogenesis, and XBP-1 partially mediates high-fructose-induced lipid accumulation in HepG2 cells through augmentation of de novo lipogenesis.</p>

Research progress on the mechanism and clinical data of IDO inhibitor in reversing the resistance of malignancies to PD-1 antibody by regulating MDSCs / 中国肿瘤临床

PD-1 antibody immunotherapy has been used as a first-line treatment against various malignancies,but resistance to this treatment limits its efficacy.For instance,myeloid derived suppressor cells,myeloid derived suppressor cells induce resistance to PD-1 antibody in a tumor microenvironment.A few combination regimens of an IDO inhibitor plus PD-1 antibody are currently subjected to ongoing clinical trials in the US,and preliminary results have shown that this inhibitor can reverse the resistance of malignancies to PD-1 antibody.This study reviewed the research progress on the resistance mechanism of malignancies to PD-1 antibody and revealed that IDO inhibitor regulates MDSCs to reverse the resistance to PD-1 antibody.This study also described the clinical efficacy of this in-hibitor plus PD-1 antibody.

Therapeutic effects of oleanolic acid nanoparticles combined with heparin sodium nanoparticles on liver cancer in vivo and in vitro / 西安交通大学学报(医学版)

Objective To investigate the therapeutic effects of oleanolic acid-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS ) nanoparticles (OPTN ) combined with heparin sodium-loaded PLGA-TPGS nanoparticles (HPTN)on liver cancer,and explore whether OPTN combined with HPTN has a synergistic effect by comparing the results of single medication.Methods Coumarin 6 and eosin were used as fluorescent probes to examine the cellular uptake by human liver cancer HepG2 cell and murine ascitic hepatocarcinoma cell strain with high metastasis potential in the lymphatic system (HCa-F).The in vitro cytotoxic combination effect and apoptosis of HepG2 cells induced by OPTN combined with HPTN were also determined using WST-1 assay and Annexin V-FITC staining. The antitumor effect in vivo was determined by tumor growth inhibition rate and hematoxylin & eosin staining (H & E)method.Results Both OPTN with green fluorescence and HPTN with red fluorescence were found in HepG2 cells and HCa-F cells,suggesting that they had been internalized.The cell cytotoxicity test and Annexin V-FITC staining results showed that OPTN combined with HPTN had a synergistic effect.The therapeutic effect in vivo showed that OPTN combined with HPTN effectively inhibited tumor growth better than the drug alone.Conclusion OPTN combined with HPTN has a synergistic effect in more effectively inhibiting liver cancer better than single medication.

Research progress on the mechanism and clinical data of IDO inhibitor in reversing the resistance of malignancies to PD-1 antibody by regulating MDSCs / 中国肿瘤临床

PD-1 antibody immunotherapy has been used as a first-line treatment against various malignancies,but resistance to this treatment limits its efficacy.For instance,myeloid derived suppressor cells,myeloid derived suppressor cells induce resistance to PD-1 antibody in a tumor microenvironment.A few combination regimens of an IDO inhibitor plus PD-1 antibody are currently subjected to ongoing clinical trials in the US,and preliminary results have shown that this inhibitor can reverse the resistance of malignancies to PD-1 antibody.This study reviewed the research progress on the resistance mechanism of malignancies to PD-1 antibody and revealed that IDO inhibitor regulates MDSCs to reverse the resistance to PD-1 antibody.This study also described the clinical efficacy of this in-hibitor plus PD-1 antibody.

Therapeutic effects of oleanolic acid nanoparticles combined with heparin sodium nanoparticles on liver cancer in vivo and in vitro / 西安交通大学学报(医学版)

Objective To investigate the therapeutic effects of oleanolic acid-loaded polylactic-co-glycolic acid-D-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS ) nanoparticles (OPTN ) combined with heparin sodium-loaded PLGA-TPGS nanoparticles (HPTN)on liver cancer,and explore whether OPTN combined with HPTN has a synergistic effect by comparing the results of single medication.Methods Coumarin 6 and eosin were used as fluorescent probes to examine the cellular uptake by human liver cancer HepG2 cell and murine ascitic hepatocarcinoma cell strain with high metastasis potential in the lymphatic system (HCa-F).The in vitro cytotoxic combination effect and apoptosis of HepG2 cells induced by OPTN combined with HPTN were also determined using WST-1 assay and Annexin V-FITC staining. The antitumor effect in vivo was determined by tumor growth inhibition rate and hematoxylin & eosin staining (H & E)method.Results Both OPTN with green fluorescence and HPTN with red fluorescence were found in HepG2 cells and HCa-F cells,suggesting that they had been internalized.The cell cytotoxicity test and Annexin V-FITC staining results showed that OPTN combined with HPTN had a synergistic effect.The therapeutic effect in vivo showed that OPTN combined with HPTN effectively inhibited tumor growth better than the drug alone.Conclusion OPTN combined with HPTN has a synergistic effect in more effectively inhibiting liver cancer better than single medication.