RNA interfering (RNAi) using short interfering RNA (siRNA) is becoming a promising approach for cancer gene therapy. However, owing to the lack of safe and efficient carriers, the application of RNAi for clinical use is still very limited. In this study, we have developed cadmium sulphoselenide/Zinc sulfide quantum dots (CdSSe/ZnS QDs)-based nanocarriers for in vitro gene delivery. These CdSSe/ZnS QDs are functionalized with polyethyleneimine (PEI) to form stable nanoplex (QD-PEI) and subsequently they are used for siRNA loading which specially targets human telomerase reverse transcriptase (TERT). High gene transfection efficiency (>80%) was achieved on two glioblastoma cell lines, U87 and U251. The gene expression level (49.99 ± 10.23% for U87, 43.28 ± 9.66% for U251) and protein expression level (51.58 ± 7.88% for U87, 50.69 ± 7.59% for U251) of TERT is observed to decrease substantially after transfecting the tumor cells for 48 h. More importantly, the silencing of TERT gene expression significantly suppressed the proliferation of glioblastoma cells. No obvious cytotoxicity from these QD-PEI nanoplexes were observed over at 10 times of the transfected doses. Based on these results, we envision that QDs engineered here can be used as a safe and efficient gene nanocarrier for siRNA delivery and a promising tool for future cancer gene therapy applications.
OBJECTIVE To explore the surgical management and its results of intercondylar fractures of the humerus through approach of osteotomy of olecranon (AOO) with dual steel plate. METHODS From June 2001 to March 2007, 38 patients of intercondylar fractures of humerus were treated surgically through AOO, and the fracture was reduced and fixed with dual steel plate. There were 24 males and 14 females with a mean age of 37 years (range 19 to 48 years). All cases were closed fractures. The fractures were classified according AO included 12 cases of C1, 20 cases of C2 and 6 cases of C3. The time from injured to operation was 6 hours to 14 days (means 7 days). RESULTS These 38 patients were followed up from 5 months to 2 years (average 12 months). The wound healing of one patient was below the mark. After the treatment of change dressings, the wound healed. Of these 38 patients, no loosening or breakage of internal fixation occurred. All the osteotomies healed in 15 weeks averagely (range 12 to 22 weeks). According to Cassebaum scoring system, the results were excellent in 15 cases, good in 17 cases, fair in 5 cases and poor in 1 case. CONCLUSION The technique of dual steel plate for the treatment intercondylar fractures of the humerus through approach of osteotomy of olecranon (AOO) offers many advantages, such as sufficient exposure easy, stable fixation and earlier exercise. Functional exercise in the early period is the crucial factor of enhancing the therapeutic effect.
Amidst the burgeoning interest in rotating magnetic fields (RMF) within biological research, there remains a notable gap in the scientific evidence concerning the long-term safety of RMF. Thus, this study aimed to investigate the safety of protracted exposure to a 0.2 T, 4 Hz RMF over 10 months in mice. Two-month-old female C57BL/6 mice were randomly allocated to either the RMF group (exposed to 0.2 T, 4 Hz real RMF) or the SHAM group (exposed to 0 T, 4 Hz sham RMF). Throughout the experiment, the murine weekly body weights were recorded, and their behavioral traits were assessed via open field tests. In the final month, a comprehensive evaluation of the murine overall health was conducted, encompassing analyses of blood parameters, histomorphological examination of major organs, and skeletal assessments using X-ray and micro-CT imaging. The murine immune system and lipid metabolism were evaluated through immunochip analysis and metabolomics. Notably, no discernible adverse effects with RMF exposure were observed. Murine body weight, locomotor behavior, organ histomorphology, and skeletal health remained unaffected by RMF. Blood analysis revealed subtle changes in hormone and lipid levels between the SHAM and RMF groups, yet these differences did not reach statistical significance. Moreover, RMF led to elevated serum interleukin-28 (IL-28) levels, albeit within the normal range, and modest alterations in serum lipid metabolites. Conclusively, mice exposed to the 0.2 T, 4 Hz RMF for 10 months displayed no significant signs of chronic toxicity, indicating its potential clinical application as a physical therapy.
Objective To study the effect of implantation of bone marrow mesenchymal stem cells(MSCs)on infarcted myocardium. Methods Twenty-four Guizhou Xiang porcine were equally divided into an experimental group and a control group randomly.3 mL bone marrow was extracted from the posterior superior iliac spine.MSCs were cultured according to the methods of Wakitani's.After being co-cultured with 5-azacytidine for 24 h,these cells were labeled with bromodeoxyuridine.Autologus MSCs were implanted into the acute myocardial infarct site both via the distal segment of the ligated left anterior descending artery and topical injection.Specimens and muscle strip were harvested at 3 and 6 weeks after MSCs implantation for morphologic examinations and contractile force study. Results The structure in the experimental group appeared in an orderly arrangement as compared with that in the control group.The collagenous fibers fused less and the basic structures appeared in an orderly arrangement in the experimental group as showed by VG staining.The contractile force in the experimental group was better than that in the control group(P0.001). Conclusion After being implanted into infarct myocardium,MSCs showed the ability of structural preservation of myocardial tissue and improvement of the contractile perfor-(mance) in the infarcted myocardium.
Sleep disturbances can disrupt the overall circadian rhythm. However, the impact of sleep deprivation on the circadian rhythm of the liver and its underlying mechanisms still requires further exploration. In this study, we subjected male mice to 5 days of sleep deprivation and performed liver transcriptome sequencing analysis at various time points within a 24-h period. Subsequently, we monitored the autonomic activity and food intake in these male mice for six days post-sleep deprivation. We observed alterations in sleep-wake and feeding rhythms in the first two days following sleep deprivation. Additionally, we also observed a decrease in 24-h serum-glucose levels. Liver transcriptome sequencing has shown that sleep deprivation induces the rhythmic transcription of a large number of genes, or alters the rhythmic properties of genes, which were then significantly enriched in the carbohydrate, lipid, and protein metabolism pathways. Our findings suggest that under conditions of prolonged sleep deprivation, the expression of metabolic-related genes in the liver was reset, leading to changes in the organism’s metabolic state to ensure energy supply to sustain prolonged wakefulness.
Cancer stem cell is one of the important causes of tumorigenesis as well as a drug target in the treatment of malignant tumor. However, at present, there is no immune vaccine targeting these cells. Octamer-binding transcription factor 4 (OCT4), a marker of embryonic stem cells and germ cells, often highly expresses in the early stages of tumorigenesis and is therefore a good candidate for cancer vaccine development.
Methods:
To identify the optimal carrier and adjuvant combination, we chemically synthesized and linked three different OCT4 epitope antigens to a carrier protein, keyhole limpet hemocyanin (KLH), combined with Toll-like receptor 9 agonist (TLR9).
Results:
Immunization with OCT4-3 + TLR9 produced the strongest immune response in mice. In prevention assays, significant tumor growth inhibition was achieved in BABL/c mice treated with OCT4-3 + TLR9 (P < 0.01). Importantly, the results showed that cytotoxic T lymphocyte activity and the inhibition of tumor growth were enhanced in mice immunized with OCT4-3 combined with TLR9. Meanwhile, multiple cytokines [such as interferon (IFN)-γ (P < 0.05), interleukin (IL)-12 (P < 0.05), IL-2 (P < 0.01), and IL-6 (P < 0.05)] promoting cellular immune responses were shown to be greatly enhanced in mice immunized with OCT4-3 + TLR9. Moreover, we considered safety considerations in terms of the composition of the vaccines to help facilitate the development of effective next-generation vaccines.
Conclusions:
Collectively, these experiments demonstrated that combination therapy with TLR9 agonist induced a tumor-specific adaptive immune response, leading to the suppression of primary tumor growth in testis embryonic carcinoma.
Involving eight electron transfer process and multiple intermediates of nitrate (NO3- ) reduction reaction leads to a sluggish kinetic and low Faradaic efficiency, therefore, it is essential to get an insight into the reaction mechanism to develop highly efficient electrocatalyst. Herein, a series of reduced-graphene-oxide-supported RuCu alloy catalysts (Rux Cux /rGO) are fabricated and used for the direct reduction of NO3- to NH3 . It is found that the Ru1 Cu10 /rGO shows the ammonia formation rate of 0.38 mmol cm-2 h-1 (loading 1 mg cm-2 ) and the ammonia Faradaic efficiency of 98% under an ultralow potential of -0.05 V versus Reversible Hydrogen Electode (RHE), which is comparable to Ru catalyst. The highly efficient activity of Ru1 Cu10 /rGO can be attributed to the synergetic effect between Ru and Cu sites via a relay catalysis, in which the Cu shows the exclusively efficient activity for the reduction of NO3- to NO2- and Ru exhibits the superior activity for NO2- to NH3 . In addition, the doping of Ru into Cu tunes the d-band center of alloy and effectively modulates the adsorption energy of the NO3- and NO2- , which promotes the direct reduction of NO3- to NH3 . This synergetic electrocatalysis strategy opens a new avenue for developing highly efficient multifunctional catalysts.
Objectives To analyze the clinical characteristics and perinatal outcomes of umbilical cord vascular rupture, and to investigate the diagnosis and treatment strategies for reducing adverse perinatal outcomes. Methods Clinical data of patients with a singleton pregnancy with umbilical cord rupture who were admitted to Fujian Maternity and Child Health Hospital were collected. The incidence, related factors, clinical features and perinatal outcomes of umbilical cord rupture were retrospectively analyzed. Results There were eight cases of umbilical cord rupture (incidence rate: 1/8370). Among them, seven were secondary to umbilical cord insertion abnormality, and one may have been related to a relatively short umbilical cord and umbilical cord traction. There were eight cases of abnormal fetal heart rate, two of vaginal bleeding, five of bloody amniotic fluid, five of premature rupture of the membranes, and two of placental abruption. With regard to outcomes, 50% of patients had cesarean section, 12.5% had forceps delivery, and 50% had perinatal mortality. Conclusions Vaginal bleeding, amniotic fluid, fetal heart rate, and umbilical cord insertion should be closely monitored in pregnancy. When abnormal conditions occur, obstetricians should be aware of rupture of the umbilical vessels and terminate pregnancy as soon as possible, which could improve perinatal outcomes.
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