Saturated free fatty acid sodium palmitate-induced lipoapoptosis by targeting glycogen synthase kinase-3ß activation in human liver cells.

BACKGROUND: Elevated serum saturated fatty acid levels and hepatocyte lipoapoptosis are features of nonalcoholic fatty liver disease (NAFLD). AIM: The purpose of this study was to investigate saturated fatty acid induction of lipoapoptosis in human liver cells and the underlying mechanisms. METHODS: Human liver L02 and HepG2 cells were treated with sodium palmitate, a saturated fatty acid, for up to 48 h with or without lithium chloride, a glycogen synthase kinase-3ß (GSK-3ß) inhibitor, or GSK-3ß shRNA transfection. Transmission electron microscopy was used to detect morphological changes, flow cytometry was used to detect apoptosis, a colorimetric assay was used to detect caspase-3 activity, and western blot analysis was used to detect protein expression. RESULTS: The data showed that sodium palmitate was able to induce lipoapoptosis in L02 and HepG2 cells. Western blot analysis showed that sodium palmitate activated GSK-3ß protein, which was indicated by dephosphorylation of GSK-3ß at Ser-9. However, inhibition of GSK-3ß activity with lithium chloride treatment or knockdown of GSK-3ß expression with shRNA suppressed sodium palmitate-induced lipoapoptosis in L02 and HepG2 cells. On a molecular level, inhibition of GSK-3ß expression or activity suppressed sodium palmitate-induced c-Jun-N-terminal kinase (JNK) phosphorylation and Bax upregulation, whereas GSK-3ß inhibition did not affect endoplasmic reticulum stress-induced activation of unfolded protein response. CONCLUSIONS: The present data demonstrated that saturated fatty acid sodium palmitate-induced lipoapoptosis in human liver L02 and HepG2 cells was regulated by GSK-3ß activation, which led to JNK activation and Bax upregulation. This finding indicates that GSK-3ß inhibition may be a potential therapeutic target to control NAFLD.

Synthesis of three cisplatin-conjugated asymmetric porphyrin photosensitizers for photodynamic therapy.

Photodynamic therapy provides a promising solution for treating various cancer types. In this study, three distinct asymmetric porphyrin-cisplatin complex photosensitizers (ZnPt-P1, ZnPt-P2, and ZnPt-P3) were synthesized, each having unique side chains. Through a set of experiments involving singlet oxygen detection and density functional theory, ZnPt-P1 was demonstrated to have excellent efficacy, exceeding that of ZnPt-P2 and ZnPt-P3. Notably, ZnPt-1 showed significant phototoxicity while maintaining low dark toxicity when tested on HepG2 cells. Additionally, further examination revealed that ZnPt-P1 had the capability to generate reactive oxygen species within cancer cells when exposed to light irradiation. Taken together, these results highlight the potential of ZnPt-P1 as a photosensitizer for use in photodynamic therapy. This study contributes to enhancing cancer treatment methodologies and provides insights for the future development of innovative drugs for photosensitization.

[Expression of TEKT4 protein decreases in the ejaculated spermatozoa of idiopathic asthenozoospermic men].

OBJECTIVE: To investigate the role of the TEKT4 protein in the pathogenesis of idiopathic asthenozoospermia. METHODS: We separated and purified the ejaculated sperm from idiopathic asthenozoospermia patients and normozoospermic men by Percoll discontinuous density gradients, and detected the distribution and the expressions of TEKT4 mRNA and TEKT4 protein by RT-PCR and Western blot. RESULTS: RT-PCR revealed that the expression of TEKT4 mRNA was significantly lower in the sperm of the idiopathic asthenozoospermia patients than in those of the normozoospermic men (0.59 +/- 0.13 vs 0.75 +/- 0.15, t = 4.325, P < 0.05), and Western blot confirmed the results of RT-PCR (0.48 +/- 0.14 vs 0.69 +/- 0.13, t = 5.939, P < 0.05). CONCLUSION: The expression of TEKT4 is significantly decreased in the ejaculated sperm of idiopathic asthenozoospermia patients, which might be one of the causes of idiopathic asthenozoospermia.

Self-assembly-induced luminescence of Eu3+-complexes and application in bioimaging.

Design and engineering of highly efficient emitting materials with assembly-induced luminescence, such as room-temperature phosphorescence (RTP) and aggregation-induced emission (AIE), have stimulated extensive efforts. Here, we propose a new strategy to obtain size-controlled Eu3+-complex nanoparticles (Eu-NPs) with self-assembly-induced luminescence (SAIL) characteristics without encapsulation or hybridization. Compared with previous RTP or AIE materials, the SAIL phenomena of increased luminescence intensity and lifetime in aqueous solution for the proposed Eu-NPs are due to the combined effect of self-assembly in confining the molecular motion and shielding the water quenching. As proof of concept, we also show that this system can be further applied in bioimaging, temperature measurement and HClO sensing. The SAIL activity of the rare-earth (RE) system proposed here offers a further step forward on the roadmap for the development of RE light conversion systems and their integration in bioimaging and therapy applications.

[Expression of SEPT4 protein in the ejaculated sperm of idiopathic asthenozoospermic men].

OBJECTIVE: To investigate the role of the SEPT4 protein in the pathogenesis of idiopathic asthenozoospermia. METHODS: Samples of ejaculated sperm from idiopathic asthenozoospermia patients and normozoospermic men were separated and purified by Percoll discontinuous density gradients, the distribution and expression of SEPT4 in the sperm samples were determined by immunocytochemistry, and the expressions of SEPT4 mRNA and SEPT4 protein were detected by RT-PCR and Western blot. RESULTS: Immunocytochemistry showed that the expression of SEPT4, located in the annulus, was significantly reduced in the sperm of the idiopathic asthenozoospermia patients (t = 3.452, P < 0.01). RT-PCR revealed that the expression of SEPT4 mRNA was significantly lower in the sperm of the idiopathic asthenozoospermia patients than in those of the normozoospermic men (t = 3.521, P < 0.05). Western blot confirmed the results of RT-PCR (t = 5.872, P < 0.05). CONCLUSION: The expression of SEPT4 is significantly decreased in the ejaculated sperm of idiopathic asthenozoospermia patients, which might be one of the causes of idiopathic asthenozoospermia.

[CatSper1 protein and idiopathic asthenozoospermia].

OBJECTIVE: To investigate the role of the cation channel of sperm 1 (CatSper1) protein in the pathogenesis of idiopathic asthenozoospermia. METHODS: Sperm samples from patients with idiopathic asthenozoospermia were separated by Percoll discontinuous density gradients, and the distribution and expression of the CatSper1 protein were determined by immunocytochemistry. Western blotting was used to detect the different expressions of CatSper1 in the ejaculated sperm from the normal control, mild asthenozoospermia, moderate asthenozoospermia and severe asthenozoospermia groups, followed by statistical analyses. RESULTS: The expression of CatSper1, located in the principle piece of the sperm tail, was reduced significantly in the samples from the idiopathic asthenozoospermia patients as compared with the normal controls (t = 2.188, P = 0.042). The relative contents of the CatSper1 protein in the sperm of the control, mild asthenozoospermia, moderate asthenozoospermia and severe asthenozoospermia groups were 0.806 +/- 0.266, 0.669 +/- 0.207, 0.505 +/- 0.214 and 0.295 +/- 0.162, respectively, significantly decreased in the asthenozoospermia patients in comparison with the normal controls (P <0.05). There was a positive correlation between the percentage of progressively motile sperm and the relative content of the CatSper1 protein (r = 0.633, P = 0.000). CONCLUSION: The decreased or abnormal expression of the CatSper1 protein may be a factor involved in the pathogenesis of idiopathic asthenozoospermia.

[Changes in the expression of Dlx5, Msx2, and Dlx5/Msx2 in hPDLSCs loaded with cyclic tensile stress].

OBJECTIVE: To investigate the changes in the expression of Dlx5 and Msx2 in human periodontal ligament stem cells (hPDLSCs) loaded with cyclic tensile stress. METHODS: hPDLSCs were subjected to cyclic tensile stress (0.5 Hz, 3000 microm strain) for 3, 6, 12, 24 h through a four-point bending strain system. The expressions of Dlx5 and Msx2 mRNA were determined by real time PCR. RESULTS: Strong expressions of Dlx5 and Msx2 were found in the periodontal fibroblasts of the tension side 20 minutes after mechanical loading. The expression of Dlx5 mRNA decreased over time with the stress. The expression of Msx2 mRNA increased over time with the stress. CONCLUSION: Both Dlx5 and Msx2 are sensitive to mechanical stress. Cyclic tensile stress may induce differentiating of hPDLSCs towards mineralized tissue cells by promoting Dlx5 mRNA expression and decreasing Msx2 expression.

[Differences in maxillary growth vector of skeletal class I with various vertical growth types before and after growth spurts].

OBJECTIVE: To identify the differences in maxillary growth vector with different vertical skeletal patterns of skeletal class I before and after growth spurts. METHODS: One hundred and ninety four cases with different vertical skeletal patterns of skeletal class I were selected and categorized into six groups according to their vertical skeletal patterns and cervical vertebral stages: cervical vertebral maturation stage (CVMS)1,2-horizontal pattern (n=30); CVMS1,2-average pattern (n=32); CVMS1, 2-vertical pattern (n=33); CVMS5, 6-horizontal pattern (n=34); CVMS5, 6-average pattern (n=29); and CVMS5, 6-vertical pattern (n=36). Lateral cephalograms were taken on all of the cases. The angle SN-C axis (theta) and angel PP-C axis (alpha) were measured. RESULTS: (1) The skeletal class I with a vertical growth pattern had larger angle SN-C axis than those with a horizontal or average growth pattern before growth spurts (P(average-vertical) < 0.05, P(horizontal-vertical) < 0.001). (2) The skeletal class I with a vertical growth pattern had the largest angle SN-C axis after growth spurts, followed by those with an average growth pattern. Those with a horizontal growth pattern had the smallest angle SN-C axis. The differences were statistically significant (P(horizontal-average) < 0.05, P(horizontal-vertical) < 0.001, P(average-vertical) < 0.001). (3) The skeletal class I with the same vertical growth pattern had slightly larger angle SN-C axis after growth spurts than before growth spurts, but without statistical significance. (4) The skeletal class I had relatively stable angle PP-C axis and no significant differences were found before and after growth spurts or among those with various vertical skeletal facial types. CONCLUSION: The magnitude of angle SN-C axis is closely associated with vertical growth patterns and is weakly influenced by maxillofacial growth and development.

[Expression of Galectin-9 and Tim-3 in lungs of mice with asthma].

OBJECTIVE: To study the expression of Galectin-9 and Tim-3 in lungs of mice with asthma and the effect of rosiglitazone (PPAR-γ agonist) on their expression. METHODS: Fortyfive BALB/c SPF female mice were randomized into control group and asthma groups with and without rosiglitazone intervention. After ovalbumin stimulation and rosiglitazone intervention the pathological changes of the lung tissues were observed. Galectin-9 and Tim-3 mRNA levels in lung tissues were determined using RT-PCR. The levels of IL-4 and IFN-γ in peripheral blood were measured using ELISA. RESULTS: The expression of Galectin-9 and Tim-3 mRNA of lung tissues in the untreated asthma group increased significantly compared with the control and the rosiglitazone treated groups (P<0.05). A significantly increased blood expression of IL-4 and a significantly decreased blood expression of IFN-γ were found in the untreated asthma group compared with the control and the rosiglitazone-treated groups (P<0.05). The expression of Galectin-9 and Tim-3 mRNA was positively correlated with blood IL-4 level (r=0.792, r=0.794 respectively; P<0.05), but negatively correlated with blood IFN-γ level (r=-0.692, r=-0.757 respectively; P<0.05). CONCLUSIONS: Galectin-9 and Tim-3 mRNA levels in lungs increase in mice with asthma and significantly correlate with the levels of blood Th1/Th2 cytokines. This suggests that Galectin-9 and Tim-3 are closely related to inflammatory process in asthma. Rosiglitazone treatment may decrease the expression of Galectin-9 and Tim-3.

[Roles of FIZZ1 and NOTCH1 in asthma].

OBJECTIVE: To investigate the roles of FIZZ1 and NOTCH1 in the pathogenesis of asthma and the effect of rosiglitazone on airway remodeling. METHODS: Forty-five healthy 6 to 8-week-old Sprague-Dawley rats were randomly divided into a control group and asthma groups with and without rosiglitazone treatment. The paraffin slices of lung tissues were made to assess the histological changes. a-SMA protein, a specific marker of airway remodeling, in lung tissues was measured by immunohistochemistry. FIZZl-mRNA and NOTCH1-mRNA expression in lung tissues was measured by RT-PCR. RESULTS: The characteristic changes of airway remodeling were observed in the untreated asthma group. The histological changes in the airway were less severe in the rosiglitazone treated asthma group. Positive a-SMA staining, FIZZl-mRNA and NOTCH1-mRNA were highly expressed in peribronchial lung sections isolated from the untreated asthma group. Rosiglitazone treatment decreased significantly the expression of a-SMA protein, FIZZl-mRNA and NOTCH1-mRNA compared with the untreated asthma group, but the expression of a-SMA protein, FIZZl-mRNA and NOTCH1-mRNA in the rosiglitazone treated asthma group remained higher than the control group. a-SMA expression was positively correlated with FIZZl-mRNA (r=0.826, P<0.01) and NOTCH1-mRNA expression (r=0.9, P<0.01). FIZZl-mRNA expression was positively correlated with NOTCH1-mRNA expression (r=0.76, P<0.01). CONCLUSIONS: FIZZl and NOTCH1 may induce an increase in a-SMA expression. FIZZl and NOTCH1 play a critical role in the process of airway remodeling. Rosiglitazone treatment may inhibit airway remodeling in asthmatic rats.

Diammonium Porphyrin-Induced CsPbBr3 Nanocrystals to Stabilize Perovskite Films for Efficient and Stable Solar Cells.

Employing all-inorganic perovskite quantum dots (QDs) to treat organic-inorganic perovskite films has been well documented as a serviceable tactic to improve the performance of perovskite solar cells (PSCs). However, the inert molecule-coated QDs with zero-dimensional (0D) structure would limit further enhancement of the efficiency and stability of PSCs. Here, we employ a conductive diammonium porphyrin (ZnPy-NH3Br) to treat CsPbBr3 QDs coated on a three-dimensional perovskite film, thus constructing a stable 0D-two-dimensional perovskite capping layer. The generation of large-scale nanocube crystals by treating CsPbBr3 nanocrystallites with ZnPy-NH3Br in solution demonstrates such an assembly strategy. The formed capping layer can achieve efficient charge transport and separation. As a consequence, the best efficiency of an optimized device is up to 20.0%, which is superior to the control PSCs fabricated without modification (19.1%) and with pure CsPbBr3 QD modification (19.5%). More importantly, the porphyrin-treated CsPbBr3 QD-based devices retain over 65 or 85% of their initial efficiency when placed at 85 °C or 45% humidity tracking for 1000 h, respectively. Also, with the incorporation of QD-Por, the device retained 85% of the original efficiency when illuminated at AM 1.5 G for 450 h. Therefore, this work offered a facile avenue to modify perovskite films for fabricating highly efficient and stable PSCs.

[Relationship between the phenotypes and functions of peripheral blood dendritic cells and the different spleen deficiency syndrome types in patients with chronic hepatitis B].

OBJECTIVE: To study the phenotypes and functions of dendritic cells (DCs) derived from peripheral blood monocytes of chronic hepatitis B (CHB) patients with different traditional Chinese medicine (TCM) syndrome types, and to explore the relationship between TCM syndrome type and DC functions. METHODS: Sixty CHB patients were included in this study. All the CHB patients were divided into spleen deficiency and liver stagnation, spleen deficiency and dampness-heat and deficiency of both spleen and kidney groups according to TCM syndrome diagnosis standard. There were 20 cases in each group, and ten healthy people were included as normal control. The volunteer's peripheral blood was collected for monocyte separation, biochemical test and hepatitis B virus DNA loads detection. DCs were induced and isolated from peripheral blood monocytes, and then the expressions of surface markers CD80, CD86, CD1a and HLA-DR were detected by flow cytometric analysis method. Interleukin-10 (IL-10) production of the DCs was quantified by enzyme-linked immunosorbent assay. RESULTS: The proliferation of DCs in the CHB patients was slower than that in the healthy volunteers (P<0.05). The expressions of DC surface molecules such as CD80, CD86, and CD1a were obviously decreased in the CHB patients as compared with those in the healthy volunteers (P<0.05). More over, expressions of DC surface molecules were different among CHB patients with different TCM syndrome types. The positive expressions of CD80, CD1a, and HLA-DR in the CHB patients with spleen deficiency and liver stagnation were obviously higher than those in the CHB patients with deficiency of both spleen and kidney (P<0.05), and the CD1a expression in the CHB patients with spleen deficiency and dampness-heat was higher than that in the CHB patients with deficiency of both spleen and kidney (P<0.05). In DC culture supernatant, the IL-10 concentration of the CHB patients with deficiency of both spleen and kidney was higher than that of the CHB patients with spleen deficiency and liver stagnation (P<0.05), and the IL-10 concentrations of the CHB patients with different TCM syndrome types were higher than that of the healthy volunteers (P<0.05). CONCLUSION: During the pathogenic course of CHB, the phenotypes and functions of DCs are different in CHB patients with different TCM syndrome types. It suggests that there is a correlation between TCM syndrome type and body immunity function.

[Therapeutic effect and prognosis of interferon therapy after transcatheter arterial chemoembolization in patients with hepatocellular carcinoma associated with hepatitis B virus].

OBJECTIVE: To evaluate the therapeutic effect of interferon therapy after transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma associated with hepatitis B virus. METHODS: Sixty-two patients with advanced primary hepatocellular carcinoma associated with hepatitis B virus was randomly divided into 2 groups. Thirty-one cases were treated with TACE and Interferon. Thirty-one cases with TACE only. HBV DNA, clinical effect, intrahepatic tumor recurrence rate and survival rate were studied. RESULTS: Of the 31 patients in TACE+IFN group, 17 (54.8%) were negative for HBV DNA at the end of treatment. None of TACE group was negative for HBV DNA. The intrahepatic tumor recurrence rate at 1 year and 2 years in TACE+IFN group was 16.1%, 29.0%, compared with 38.7%, 61.3% in TACE group (chi-square = 3.97, chi-square 6.51, P < 0.05). The survival rate in the former was 83.9% and 74.2% respectively, compared with that of 61.3% and 38.7% in the latter (chi-square = 3.97, chi-square = 7.94, P < 0.05). CONCLUSION: Interferon therapy after transcatheter arterial chemoembolization resulted low recurrence and long survival in patients with hepatocellular carcinoma associated with hepatitis B virus. This method showed fewer side effects and should be recommended.