Recently, photodynamic therapy (PDT) has gained considerable attention as a promising therapeutic approach for the treatment of psoriasis. Unfortunately, the activation of high mobility group box 1 protein (HMGB1) by PDT triggers innate and adaptive immune responses, which exacerbate skin inflammation. Herein, we combined glycyrrhizic acid (GA), a natural anti-inflammatory compound and immunomodulator derived from the herb Glycyrrhiza uralensis Fisch., with PDT actuated by the photosensitizer chlorin e6 (Ce6) by co-loading them in GA-based lipid nanoparticles coated with a catechol-modified quaternary chitosan salt (GC NPs/QCS-C). GC NPs/QCS-C exhibited high drug loading efficacy, uniform size distribution, an ideal topical adhesive property, enhanced skin retention and penetration in psoriasis-like lesions, and high intracellular uptake in epidermal cells compared with the counterparts. Subsequently, the transdermal administration of GC NPs/QCS-C followed by near-infrared laser radiation in an imiquimod-induced psoriasis-like mouse model significantly ameliorated psoriasis symptoms, promoted the apoptosis of hyperproliferative epidermal cells, and alleviated the inflammatory cascade. The significant therapeutic outcomes of GC NPs/QCS-C were attributed to the synergistic effects of GA and PDT on modulating immune cell recruitment and inhibiting dendritic cell maturation. Our results demonstrated that the topical bio-adhesive nanosystem that combines GA and Ce6 offers a synergistic chemo-phototherapeutic strategy for psoriasis treatment.

Objective:To discusses the variations of 7Be, 137Cs and 210Pb activity concentrations in the air in Beijing from March 16, 2021 to March 31, 2023, and their correlation with temperature, precipitation, relative humidity, barometric pressure, PM10 (only limited to 137Cs) and other meteorological parameters. Methods:A total of 60 aerosol samples were collected using the HRHA01-SFS1000/A ultra-large flowair sampler in the automatic radiation monitoring station. The activity concentrations of 7Be, 137Cs and 210Pb in the aerosol samples were measured by GMX-60 low background anti-Compton high purity germanium gamma spectrometer. Pearson correlation coefficient was used to show the correlation of the relevant parameters. Results:The seasonal mean values of 7Be activity concentration were spring 4.31 mBq/m 3, summer 3.53 mBq/m 3, autumn 3.09 mBq/m 3 and winter 2.45 mBq/m 3, respectively, ranging from 1.17 to 7.79 mBq/m 3, with the overall mean of (3.36±1.33) mBq/m 3. The activity concentration of 137Cs ranged from 0.39 to 8.49 μBq/m 3, with an average of (0.59±1.47) μBq/m 3. The average activity concentrations of 210Pb were spring 0.53 mBq/m 3, summer 0.44 mBq/m 3, autumn 0.72 mBq/m 3 and winter 0.75 mBq/m 3, respectively, ranging from 0.21 to 1.36 mBq/m 3, with an average of (0.56±0.26) mBq/m 3. The activity concentration of 7Be was correlated with temperature and pressure ( r=0.38, -0.40), the activity concentration of 137Cs was correlated with precipitation ( r=-0.41), and the activity concentration of 210Pb was correlated with temperature and pressure ( r=-0.31, 0.37). The variation of 137Cs activity concentration in the air showed an obvious seasonal pattern, and the peak value generally appears in spring of each year (March to May), which was related to the frequent spring dust in Beijing. The activity concentration of 210Pb in the air was affected by coal combustion heating in winter, and has a peak value during November to March. Conclusions:The activity concentrations of 7Be, 137Cs and 210Pb in the air in Beijing are within the normal range, showing a seasonal trend.

Lipophagy, the selective engulfment of lipid droplets (LDs) by autophagosomes for lysosomal degradation, is critical to lipid and energy homeostasis. Here we show that the lipid transfer protein ORP8 is located on LDs and mediates the encapsulation of LDs by autophagosomal membranes. This function of ORP8 is independent of its lipid transporter activity and is achieved through direct interaction with phagophore-anchored LC3/GABARAPs. Upon lipophagy induction, ORP8 has increased localization on LDs and is phosphorylated by AMPK, thereby enhancing its affinity for LC3/GABARAPs. Deletion of ORP8 or interruption of ORP8-LC3/GABARAP interaction results in accumulation of LDs and increased intracellular triglyceride. Overexpression of ORP8 alleviates LD and triglyceride deposition in the liver of ob/ob mice, and Osbpl8-/- mice exhibit liver lipid clearance defects. Our results suggest that ORP8 is a lipophagy receptor that plays a key role in cellular lipid metabolism.
Animals ; Mice ; Lipid Droplets ; Autophagy ; Autophagosomes ; Homeostasis ; Triglycerides

Bacterial antitumor therapy has great application potential given its unique characteristics, including genetic manipulation, tumor targeting specificity and immune system modulation. However, the nonnegligible side effects and limited efficacy of clinical treatment limit their biomedical applications. Engineered bacteria for therapeutic applications ideally need to avoid their accumulation in normal organs and possess potent antitumor activity. Here, we show that macrophage-mediated tumor-targeted delivery of Salmonella typhimurium VNP20009 can effectively reduce the toxicity caused by administrating VNP20009 alone in a melanoma mouse model. This benefits from tumor-induced chemotaxis for macrophages combined with their slow release of loaded strains. Inspired by changes in the tumor microenvironment, including a decrease in intratumoral dysfunctional CD8⁺ T cells and an increase in PDL1 on the tumor cell surface, macrophages were loaded with the engineered strain VNP-PD1nb, which can express and secrete anti-PD1 nanoantibodies after they are released from macrophages. This novel triple-combined immunotherapy significantly inhibited melanoma tumors by reactivating the tumor microenvironment by increasing immune cell infiltration, inhibiting tumor cell proliferation, remodeling TAMs to an M1-like phenotype and prominently activating CD8⁺ T cells. These data suggest that novel combination immunotherapy is expected to be a breakthrough relative to single immunotherapy.

Objective:To investigate the role and mechanism of sodium valproate (VPA) in cardiac and cerebral injuries after cardiopulmonary resuscitation (CPR) in pigs.Methods:Twenty-five healthy male domestic pigs, weighing (37±3) kg, were randomly divided into the sham group ( n=6), CPR group ( n=10), and CPR+VPA group ( n=9). Cardiac arrest was induced by alternating current delivered via a pacing catheter in the right ventricle and untreated for 9 min, and then CPR was performed for 6 min, in which this procedure was used to establish the animal model of cardiac arrest and CPR. At 5 min after resuscitation, a dose of 150 mg/kg of VPA was infused with a pump via the femoral vein in 1 h in the CPR+VAP group. At 1 h, 2 h, 4 h and 24 h after resuscitation, blood samples were drawn from the femoral vein, and then used to measure the serum concentrations of cardiac troponin I (cTnI), creatine kinase MB (CKMB), neuron specific enolase (NSE), and S100B protein (S100B) by ELISA. At 24 h after resuscitation, the animals were euthanized, and then tissue specimens in the left myocardium and brain cortex were rapidly harvested to detect the expression levels of C/EBP homologous protein (CHOP), caspase 12, and caspase 3 by Western blot, and the rate of apoptotic cells was detected by TUNEL. Continuous variables were compared with one way analysis of variance among the three groups. Results:(1) After resuscitation, cardiac and cerebral injury biomarkers including cTnI, CKMB, NSE, and S100B in serum were significantly increased in the CPR and CPR+VPA groups compared with the Sham group (all P<0.05). The serum concentrations of cTnI and NSE starting 1 h after resuscitation and the serum concentrations of CKMB and S100B starting 2 h after resuscitation were significantly decreased in the CPR+VPA group compared to the CPR group (all P<0.05). (2) Those proteins related to cell apoptosis mediated by endoplasmic reticulum stress, including CHOP, caspase 12, and caspase 3, were significantly increased, and meanwhile apoptosis index was markedly elevated after resuscitation in the CPR and CPR+VPA groups compared with the Sham group (all P<0.05). Nevertheless, the expression levels of CHOP, caspase 12, and caspase 3 were significantly decreased, and cell apoptosis was markedly reduced in the heart and brain after resuscitation in the CPR+VPA group compared to the CPR group (all P<0.05). Conclusions:VPA can alleviate cardiac and cerebral injuries after CPR in pigs, and its mechanism may be possibly related to the inhibition of cell apoptosis mediated by endoplasmic reticulum stress.

Objective To evaluate the feasibility, efficacy and safety of new nano material occluder of single rivet type (left-disk with no-hub) in treating ventricular septal defect (VSD) in order to provide experimental basis for clinical application. Methods A total of 26 healthy adult dogs were selected for this study . Under thoracotomy , VSD model was established through fluoroscopically-guided percutaneous puncturing of the right ventricular free wall. The models were randomly and equally divided into the study group(n=13, using nano material VSD occluder) and the control group(n=13, using double-hub nitinol occluder). Every two dogs from each group were sacrificed each time at one, 2, and 3 months after percutaneous closure of VSD with corresponding occluder, the tissue samples were collected and sent for gross examination as well as for the optical and electronic microscopy study;the blood concentration of nickel ion was also determined. The state of endothelialization after implantation of the new type occluder was evaluated, and the complications such as residual shunt and superficial thrombus formation were recorded. The results were analyzed. Results By open chest operation with small incision and percutaneous puncturing of the right ventricular free wall, VSD model was successfully established in all 26 dogs. The success rate of the implantation of the VSD occluder in the study group was 100%, while it was 91.7% in the control group. One, 2, 3 and 6 months after the implantation, the heart specimens of 25 dogs were removed and gross examination showed that neither occluder displacement nor alloy wire fracture occurred in both groups. No thrombus formation or vegetation attached on the disk surface was observed. One month after the procedure , in the study group the bilateral disk surfaces of the occluder were covered with thin layer transparent tissue , which were proved to be composed of the fibrous tissue and endothelial cells through pathologic and electronic microscopy study. Six months after implantation, the superficial tissue of the occluder became further thickened and the occluder edge became fused with the surrounding heart tissue. Conclusion The design of the new VSD nano materials occluder, which has a left-disk with no hub, is very scientific. Compared with double-hub nitinol occluder, the new device can shorten the time of complete endothelialization and effectively occlude the VSD. Therefore, this new nano material occluder has promising prospect in clinical application.

BACKGROUNDThe prevalence of metabolic syndrome (MetS) increased recently and there was still not a screening index to predict MetS. The aim of this study was to estimate whether brachial-ankle pulse wave velocity (baPWV), a novel marker for systemic arterial stiffness, could predict MetS in Chinese community population.

METHODSA total of 2 191 participants were recruited and underwent medical examination including 1 455 men and 756 women from June 2011 to January 2012. MetS was diagnosed according to the criteria of the International Diabetes Federation (IDF). Multiple Logistic regressions were conducted to explore the risk factors of MetS. Receiver operating characteristic (ROC) curve was performed to estimate the ideal diagnostic cutoff point of baPWV to predict MetS.

RESULTSThe mean age was (45.35±8.27) years old. In multiple Logistic regression analysis, the gender, baPWV and smoking status were risk factors to MetS after adjusting age, gender, baPWV, walk time and sleeping time. The prevalence of MetS was 17.48% in 30-year age population in Shanghai. There were significant differences (χ(2) = 96.46, P < 0.05) between male and female participants on MetS prevalence. According to the ROC analyses, the ideal cutoff point of baPWV was 1 358.50 cm/s (AUC = 60.20%) to predict MetS among male group and 1 350.00 cm/s (AUC = 70.90%) among female group.

CONCLUSIONBaPWV may be considered as a screening marker to predict MetS in community Chinese population and the diagnostic value of 1 350.00 cm/s was more significant for the female group.

Adult ; Ankle Brachial Index ; methods ; Female ; Humans ; Logistic Models ; Male ; Metabolic Syndrome ; diagnosis ; Middle Aged ; ROC Curve

Aim To investigate the possible mecha-nisms of the levels of NO decrease induced apoptosis in human placental trophoblast cells. Methods Human placental trophoblast cells ( HTR-8 ) were cultured in 5 ml DMEM-F12 culture medium with 37℃ 5% CO2 . Then, the old culture medium was discarded and re-placed with 10,100,500,1 000 μmol·L-1 L-NAME, and the group without L-NAME was set as the control group, cultured for 48h. The effects of L-NAME on the survival of cells were detected by methylthiazolyldiphe-nyl tetrazolium bromide ( MTT); the content of NO in cells was tested by nitrate reductive enzymatic;trans-mission electron microscopy, flow cytometry analysis and Annexin-V FITC dyeing were used to test the effects of L-NAME on apoptosis in HTR-8 cells;restore Fe3+ colorimetric assay was applied for detection of to-tal antioxidant capacity ( T-AOC ) , xanthine oxidase for detection of superoxide dismutase ( SOD) activity, and thiobarbituric acid colorimetry for determination of content of MDA. Results Compared with the control group, the survival rate of HTR-8 cells and the levels of NO in 100,500,1 000 μmol·L-1 L-NAME group were significantly reduced(P<0.05,P<0.01). Flow analysis and Annexin-V FITC staining showed that L-NAME could induce cell apoptosis in a dose-dependent manner. The number of cell apoptosis was negatively correlated with the content of NO ( r = -0.5210 ) in HTR-8 cells. Transmission electron microscopy results showed that compared with the control group, the ex-perimental group's cell nucleus shape was irregular, nuclear pyknosis in irregular shape, the chromatin ag-glutination or side the collection, mitochondrial swell-ing or enrichment, crest fracture or dissolved, even vanished, forming the vacuole, especially in 100 μmol ·L-1 L-NAME group, the apoptotic bodies obviously appeared. At the same time, T-AOC, SOD levels in HTR-8 cells decreased ( P <0.05 ) , and the MDA content increased ( P<0.05 ) . The number of cell ap-optosis was negatively correlated with the level of T-AOC ( r= -0.3212 ) , SOD ( r= -0.2779 ) in HTR-8 cells , while positively correlated with the content of MDA(r=0.2807). Conclusion Oxidative stress may play an important role in the levels of NO decrease in-duced apoptosis in human placental trophoblast cells.

BACKGROUND: With the development of biotechnology, the electrophysiology of repairing heart tissues of myocardial infarction or myocardial hypertrophy by using bone marrow mesenchymal stem cell has become a hot spot. OBJECTIVE: To overview the research progress of cardiac electrophysiological characteristics after transplantation of induced differentiation of bone marrow mesenchymal stem cells into cardiomyocytes. METHODS: The databases of PubMed, Springer Link, Science Direct and CNKI were retrieved for papers published from January 2000 to October 2010 with the key words of bone marrow mesenchymal stem cells, cardiac/heart, electrophysiology/electrophysiological characteristics. The relevant articles concerning cardiac electrophysiological characteristics of induce differentiation and transplantation of bone marrow stem cells were collected. RESULTS AND CONCLUSION: Totally 208 papers have been searched. Preliminary screening by reading abstracts to exclude 162 papers that study purpose do not coincident with this review either contents duplicated, and internalized 46 papers at last. Bone marrow mesenchymal stem cells after induced differentiation and transplantation could improve heart function of animal experimental model and myocardial infarction or myocardial hypertrophy patients. Although the cardiomyocyte-like cells from bone marrow mesenchymal stem cells could help to improve heart function, the cardiac electrophysiological characteristics may be influenced by them.

Objective To investigate the effect of acute intervention therapy on the QT dispersions(QTd)and correction QTd(QTcd)in patients with myocardial infarction. Methods112 patients with myocardial infarction who had received acute percutaneous coronary intervention(PCI)as study group,and divided it into three sub-group as Left anterior descending group,Left circumflex group and Right coronary group.70 infarction patients without acute intervention therapy as control group.And 12 lead standard surfaces ECG were recorded at beginning and 24h and 48h.respectively. ResultsAfter the PCI therapy,QTd and QTcd in study group improved significantly.However,QTd and QTcd had no difference among three sub-group. ConclusionThe acute intervention therapy could improve QTd and QTcd in patients with myocardial infarction.The vascular location had no difference in myocardial repolarization.