Baicalin is a natural active ingredient isolated from Scutellariae Radix that can cross the blood-brain barrier and exhibits neuroprotective effects on multiple central nervous system diseases. ...However, the mechanism behind the neuroprotective effects remains unclear. In this study, rat models of spinal cord injury were established using a modified Allen's impact method and then treated with intraperitoneal injection of Baicalin. The results revealed that Baicalin greatly increased the Basso, Beattie, Bresnahan Locomotor Rating Scale score, reduced blood-spinal cord barrier permeability, decreased the expression of Bax, Caspase-3, and nuclear factor κB, increased the expression of Bcl-2, and reduced neuronal apoptosis and pathological spinal cord injury. SH-SY5Y cell models of excitotoxicity were established by application of 10 mM glutamate for 12 hours and then treated with 40 µM Baicalin for 48 hours to investigate the mechanism of action of Baicalin. The results showed that Baicalin reversed tight junction protein expression tendencies (occludin and ZO-1) and apoptosis-related protein expression (Bax, Bcl-2, Caspase-3, and nuclear factor-κB), and also led to up-regulation of PI3K and Akt phosphorylation. These effects on Bax, Bcl-2, and Caspase-3 were blocked by pretreatment with the PI3K inhibitor LY294002. These findings suggest that Baicalin can inhibit blood-spinal cord barrier permeability after spinal cord injury and reduce neuronal apoptosis, possibly by activating the PI3K/Akt signaling pathway. This study was approved by Animal Ethics Committee of Xi'an Jiaotong University on March 6, 2014.
Glycogen synthase kinase 3β (GSK-3β) is a ubiquitous serine/threonine protein kinase involved in a number of signaling pathways. Previous studies have demonstrated a role for GSK-3β in the synaptic ...plasticity underlying dopamine-associated behaviors and diseases. Drug sensitization is produced by repeated exposure to the drug and is thought to reflect neuroadaptations that contribute to addiction. However, the role of GSK-3β in cocaine-induced behavior sensitization has not been examined. The present study investigated the effects of chronic cocaine exposure on GSK-3β activity in the nucleus accumbens (NAc) and determined whether changes in GSK-3β activity in the NAc are associated with cocaine-induced locomotor sensitization. We also explored whether blockade of GSK-3β activity in the NAc inhibits the initiation and expression of cocaine-induced locomotor sensitization in rats using systemic or brain region-specific administration of the GSK-3β inhibitors lithium chloride (LiCl) and SB216763. GSK-3β activity in the NAc core, but not NAc shell, increased after chronic cocaine (10 mg/kg, i.p.) administration. The initiation and expression of cocaine-induced locomotor sensitization was attenuated by systemic administration of LiCl (100 mg/kg, i.p.) or direct infusion of SB216763 (1 ng/side) into the NAc core, but not NAc shell. Collectively, these results indicate that GSK-3β activity in the NAc core, but not NAc shell, mediates the initiation and expression of cocaine-induced locomotor sensitization, suggesting that GSK-3β may be a potential target for the treatment of cocaine addiction.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
This study was aimed to evaluate the risk factors of recurrence and the value of nodal involvement in patients with serous borderline ovarian tumors (SBOT).
Two hundred twenty-five patients who ...underwent surgery and were diagnosed with SBOT were retrospectively studied. Univariate and multivariate analyses were used to assess the risk factors for recurrence. Patients' clinical pathologic characteristics were compared between the patients who presented lymph node involvement and those who did not. The significant values of lymph condition influencing 5-year disease-free survival were also evaluated by statistical analysis.
Both univariate and multivariate analyses showed that risk factors for recurrence were micropapillary (P = 0.021), fertility-preserving surgery (P = 0.014), and laparoscopic approach (P = 0.009). Of these 112 patients on whom lymphadenectomy was performed, 17 cases showed lymph node positive, whereas the remaining 95 patients did not. Significant differences in terms of lymph node numbers (P < 0.0001), invasive implant (P = 0.022), and International Federation of Gynecology and Obstetrics staging (P < 0.0001) were observed between the 2 groups of lymphatic node involved or not. Kaplan-Meier curves of 5-year disease-free survival revealed that there were no significant differences either between groups of lymphatic node involved or not (P = 0.778) and groups of removed nodes whether more than 10 or not (P = 0.549).
Micropapillary, fertility-preserving, and laparoscopic approach were factors significantly affecting the recurrence of SBOT by both univariate and multivariate analysis. Lymph node metastasis did not seem to be correlated to a worse prognosis of SBOT.
We have demonstrated a facile and green way to synthesize dendritic mesoporous silica nanoparticles (DMSNs) on an ultra-large scale (kg) with cetyltrimethylammonium bromide (CTAB) and an anionic ...surfactant as dual templates free of organic solvents. In contrast to its co-template role in tuning the packing parameter of the surfactant molecule organization, the anionic surfactant herein acts as a more strongly competitive counterion against the adsorption of negatively charged silicate oligomers (I − ) on the micelles. Based on the new understanding of the interaction between the cationic–anionic surfactant ionic pairs and the silicate oligomers, we proposed a dual template synergistically controlled micelle self-aggregated model to understand the formation mechanism of dendritic MSNs where the anionic surfactant stabilized micelles or micelle blocks are basic self-assembling building units for the formation of center-radial pore channel networks. By using one-pot in situ isomorphous substitution, the metal Ti atom can be easily incorporated into the silica frameworks of DMSNs, and the obtained Ti-DMSN catalyst shows a superior catalytic performance in the epoxidation of cyclohexene over the typical mesoporous Ti-MCM-41 silicas.
Considering low photoluminescence quantum yield (PLQY < 5%) of blue emissive CsPbCl3 bulk crystal and the high toxicity of Pb2+, it is significant to explore new single crystalline lead-free ...perovskites with highly efficient blue light emission. Herein, two new zero-dimensional (0D) hybrid indium halides of H2EP2InCl6·Cl·H2O·C3H6O and H3AEPInCl6··H2O (EP = 1-ethylpiperazine, AEP = N-aminoethyl piperazine) were prepared. Remarkably, these 0D indium halides display unusual blue light emissions (about 430 nm) with a highest PLQY of 13.44%. To the best of our knowledge, this work represents one of the first higher energy blue light emitters in hybrid indium perovskites, which would advance the research on lead-free hybrid halides for next-generation luminescent materials.
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IJS, KILJ, NUK, PNG, UL, UM
Increasing evidences showed that ovulatory dysfunction, possibly caused by luteinized unruptured follicular follicle syndrome (LUFS), is one of the reasons for endometriosis-related infertility. The ...present study was conducted to explore the potential effect of elevated progesterone in follicular fluid (FF) on ovulation in endometriosis. A prospective study including 50 ovarian endometriosis patients and 50 control patients with matched pairs design was conducted with alterations in FF and peritoneal fluid (PF) components identified by metabolomics analyses and differentially expressed genes in granulosa cells (GCs) identified by transcriptome analysis. Patients with endometriosis exhibited a significantly higher progesterone level in serum, FF, and PF. Granulosa cells from endometriosis patients revealed decreased expression of HPGD, COX-2, and suppressed NF-KB signaling. Similarly, progesterone treatment in vitro downregulated HPGD and COX2 expression and suppressed NF-KB signaling in granulosa tumor-like cell line KGN (Bena Culture Collection, China) and primarily cultured GCs, as manifested by decreased expressions of IL1R1, IRAK3, reduced pIKBα/IKBα ratio, and nucleus translocation of p65. On the contrary, TNF-α treatment increased expression of IL1R1, IRAK3, pIKBα, p65, and HPGD in GCs. One potential p65 binding site was identified in the promoter region of HPGD by chromatin immunoprecipitation. In conclusion, we found that intrafollicular progesterone might downregulate HPGD and COX-2 in GCs via suppressing the NF-KB signaling pathway, shedding light on the mechanism underlying the endometriosis-related ovulatory dysfunction. Summary Sentence Endometriosis showed repression of NF-KB pathway and downregulation of HPGD and COX2, which may be involved in ovulation by participating in the metabolism of prostaglandin E2 (PGE2), in GCs due to elevated progesterone in FF.
The treatment of diabetic wounds remains a major challenge in clinical practice, with chronic wounds characterized by multiple drug‐resistant bacterial infections, angiopathy, and oxidative damage to ...the microenvironment. Herein, a novel in situ injectable HA@MnO2/FGF‐2/Exos hydrogel is introduced for improving diabetic wound healing. Through a simple local injection, this hydrogel is able to form a protective barrier covering the wound, providing rapid hemostasis and long‐term antibacterial protection. The MnO2/ε‐PL nanosheet is able to catalyze the excess H2O2 produced in the wound, converting it to O2, thus not only eliminating the harmful effects of H2O2 but also providing O2 for wound healing. Moreover, the release of M2‐derived Exosomes (M2 Exos) and FGF‐2 growth factor stimulates angiogenesis and epithelization, respectively. These in vivo and in vitro results demonstrate accelerated healing of diabetic wounds with the use of the HA@MnO2/FGF‐2/Exos hydrogel, presenting a viable strategy for chronic diabetic wound repair.
Using a convenient mixed injection, an HA@MnO2/FGF‐2/Exos hydrogel dressing covering the diabetic wound tightly can be rapidly formed. The positive quaternary ammonium groups in the graft play a long‐term antibacterial role. The MnO2/e‐PL nanosheet acts as a nanoenzyme to catalyze the conversion from H2O2 to O2. The released ExosM2@miR‐223 simulate long‐lasting angiogenesis and the released FGF‐2 accelerates epithelization efficiently.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The relationship between subjective and objective health is complex and not always matched. Although frailty and self-rated health (SRH) have been separately associated with adverse outcomes, their ...joint effects remained unclear.
Participants were 5 300 adults ≥60 years from the China Health and Retirement Longitudinal Study in 2011. Frailty, measured by the validated physical frailty phenotype approach, was classified as nonfrail, prefrail, and frail. SRH was categorized into 3 groups: excellent/very good/good, fair, and poor/very poor. We used the Cox models to examine the independent and joint association of frailty and SRH with mortality. We used the interaction approach to determine whether the association of SRH with mortality differed by frailty. Subgroup analyses were conducted by depression and cognitive impairment.
About 8.1% of frail participants reported excellent/very good/good health; 21.2% of the nonfrail reported poor/very poor health. Prefrailty and frailty were associated with a 1.63- and 2.38-fold increase in the hazard of mortality than the nonfrail, respectively, after adjusting for SRH. Reporting fair and poor/very poor health was associated with a 29% and 100% increase in the hazard of mortality, respectively, after adjusting for frailty. No significant interaction was found. Prefrail and frail older adults with excellent/very good/good health had a similar mortality as the nonfrail with poor/very poor SRH. The association of SRH with mortality was less pronounced among individuals with depression or cognitive impairment.
SRH is a potential marker of resilience among people living with frailty that may be a target for ameliorating health risks induced by frailty.
Background: Vascular resistance and flow rate during hypothermic machine perfusion (HMP) of kidneys is correlated with graft function. We aimed to determine the effects of increasing HMP pressure ...versus maintaining the initial pressure on kidney transplantation outcomes.
Methods: We retrospectively reviewed the data of 76 primary transplantation patients who received HMP-preserved kidneys from 48 donors after cardiac death between September 1, 2013, and August 31, 2015. HMP pressure was increased from 30 to 40 mmHg (1 mmHg = 0.133 kPa) in kidneys with poor flow and/or vascular resistance (increased pressure IP group; 36 patients); otherwise, the initial pressure was maintained (constant pressure group; 40 patients). Finally, the clinical characteristics and transplantation outcomes in both groups were assessed.
Results: Delayed graft function (DGF) incidence, 1-year allograft, patient survival, kidney function recovery time, and serum creatinine level on day 30 were similar in both groups, with improved flow and resistance in the IP group. Among patients with DGF, kidney function recovery time and DGF duration were ameliorated in the IP group. Multivariate logistic regression analysis revealed that donor hypertension (odds ratio OR: 1.43, 95% confidence interval CI: 1.02-2.06, P = 0.035), donor terminal serum creatinine (OR: 1.27, 95% CI: 1.06-1.62, P = 0.023), warm ischemic time (OR: 3.45, 95% CI: 1.97-6.37, P = 0.002), and terminal resistance (OR: 3.12, 95% CI: 1.76-6.09, P = 0.012) were independent predictors of DGF. Cox proportional hazards analysis showed that terminal resistance (hazard ratio: 2.06, 95% CI: 1.32-5.16, P = 0.032) significantly affected graft survival.
Conclusion: Increased HMP pressure improves graft perfusion but does not affect DGF incidence or 1-year graft survival.
With the development of metal-based drugs, Ru(II) compounds present potential applications of PDT (photodynamic therapy) and anticancer reagents. We herein synthesized two naphthyl-appended ruthenium ...complexes by the combination of the ligand with naphthyl and bipyridyl. The DNA affinities, photocleavage abilities, and photocytotoxicity were studied by various spectral methods, viscosity measurement, theoretical computation method, gel electrophoresis, and MTT method. Two complexes exhibited strong interaction with calf thymus DNA by intercalation. Production of singlet oxygen (1O2) led to obvious DNA photocleavage activities of two complexes under 365 nm light. Furthermore, two complexes displayed obvious photocytotoxicity and low dark cytotoxicity towards Hela, A549, and A375 cells.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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