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"Zhang, Kai-Xin"
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المحتويات : كلنا في البداية جدد-لا نستغني عن الملح-الخطيئة الأصلية-الباب الخفي-السرعة-روح عيد الميلاد-قمر يقطر منه الماء-قيمة الحب أغلى-السعادة التي لا حدود لها-الحزن-محيط أرض نصف قطرها خمسمائة متر-في طرف السماء الغربي مفكرة تتحدث عن شينجانغ-الزمان والمكان والشخصية-الحب بلغ شيخوخته-الزهور العظام الشقة المبنية بالطوب الطيني-النصف الأول خذلان والنصف الآخر امتلاك-أنجبت ولدا-الحانة التي اعتدت الخروج منها ... وموضوعات أخرى.
Book
Danggui Shaoyao San Alleviates Early Cognitive Impairment in Alzheimer's Disease Mice Through IRS1/GSK3β/Wnt3a‐β‐Catenin Pathway
Introduction Alzheimer's disease (AD) is a neurodegenerative disease characterized by Amyloid plaques and neurofibrillary tangles. We explored the potential mechanism by which Danggui Shaoyao San (DSS) modulates central glucose metabolism via the insulin receptor substrate 1 (IRS1)/glycogen synthase kinase‐3β (GSK3β)/Wnt3a‐β‐catenin pathway, thereby exerting protective effects on cognitive functions. Methods In vitro, HT22 cells were induced with streptozotocin (STZ) to investigate the impact of GSK3β on pathway transduction. The active components in the DSS stock solution were validated using mass spectrometry. Subsequently, an AD model in C57BL/6J mice was established through STZ injection into both ventricles. The success of the model was validated behaviorally and pathologically. The Morris Water Maze (MWM) test, immunohistochemistry, Western blotting, quantitative reverse transcription‐PCR, and 18F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) were employed to evaluate the influence of DSS on memory and pathological changes in AD. Results The DSS stock solution, rich in active components, ameliorated the memory deficits in AD mice in the MWM. In vitro, GSK3β exhibited regulatory control over Wnt and β‐catenin, with GSK3β inhibition mitigating β‐amyloid and tau redundancies at protein and gene levels, facilitating signal transduction. In vivo, DSS impacted key targets in the IRS1/GSK3β/Wnt3a‐β‐catenin pathway, mitigated senile plaques resulting from amyloid β (Aβ) deposition and neurofiber tangles induced by tau hyperphosphorylation, and alleviated the decline in central glucose metabolism observed in FDG‐PET. Conclusions Our findings suggest that DSS potentially confers cognitive protection by alleviating central hypoglycemia through the IRS1/GSK3β/Wnt3a‐β‐catenin pathway. This may serve as a promising therapeutic avenue for AD. In vitro, HT22 cells were induced with streptozotocin to investigate the impact of GSK3β on pathway transduction. The active components in the DSS stock solution were validated using mass spectrometry. Subsequently, an AD model in C57BL/6J mice was established through streptozotocin injection into both ventricles. The success of the model was validated behaviorally and pathologically. The Morris Water Maze test, immunohistochemistry, Western blotting, quantitative reverse transcription‐PCR, and 18F‐fluorodeoxyglucose‐positron emission tomography (FDG‐PET) were employed to evaluate the influence of DSS on memory and pathological changes in AD. DSS potentially confers cognitive protection by alleviating central hypoglycemia through the IRS1/GSK3β/Wnt3a‐β‐catenin pathway.
Journal Article
Correlation Between Regulation of Intestinal Flora by Danggui‐Shaoyao‐San and Improvement of Cognitive Impairment in Mice With Alzheimer's Disease
Purpose The abnormal central glucose metabolism in Alzheimer's disease (AD) is related to the brain–gut axis. This study aims to explore the target of Danggui‐Shaoyao‐San (DSS) in improving cognitive impairment. Method This study analyzed the differences in mice intestinal flora by 16S rRNA sequencing. The cognitive protective effects of DSS were observed through the Morris water maze and the new object recognition. The mitigation effects of DSS on Aβ and p‐tau, regulatory effects on glucose metabolism targets, and intestinal structure effects were observed through brain and colon slices staining. The differences in neural ultrastructure were compared by transmission electron microscopy. Finding The results showed that DSS affected the composition of intestinal dominant bacteria and bacteria genera and regulated the abundance of intestinal bacteria in AD mice. DSS improved the behavior of AD mice, alleviated the deposition of AD pathological products in the brain and colon, regulated the expression of glycometabolism‐related proteins, and improved the colon barrier structure and neural ultrastructure in the brain of mice with AD. Conclusion Our findings suggest that DSS may affect AD central glucose metabolism and improve cognition by regulating the gut–brain axis. DSS regulated the gut microbiota of AD mice, improved the cognition of AD mice, reduced the deposition of pathological products of AD in the brain and colon, regulated the expression of proteins related to glucose metabolism, and improved the brain–colon barrier structure and neural ultrastructure of AD mice.
Journal Article
Temporal Effects of Disease Signature Genes and Core Mechanisms in the Hyperacute Phase of Acute Ischemic Stroke: A Bioinformatics Analysis and Experimental Validation
Background: The pathophysiological progression during the hyperacute phase of acute ischemic stroke (AIS) critically determines clinical outcomes. Identification of phase-specific biomarkers and elucidation of their temporal regulatory mechanisms are pivotal for optimizing therapeutic interventions.Methods: Disease signature genes and their mechanisms of action were screened based on the Gene Expression Omnibus database. This involved the use of differentially expressed gene screening, weighted gene co-expression network analysis, Mfuzz analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes enrichment analysis, support vector machines, random forest algorithms, and gene set enrichment analysis. The expression of disease-characteristic genes and their related mechanisms were further validated in both in vivo and in vitro models.Results: Six hyperacute-phase signature genes (Pip5k1c, Nlgn2, Fzd2, Cd86, Agpat1, and Degs2) were identified in the hyperacute phase of AIS. In light of the gene effect mechanism, the regulation of the neuroinflammatory response and apoptosis by the TLR2/TLR4/NF-κB pathway was monitored in the hyperacute phase of AIS at three times: 3, 6, and 12 h. The results indicated a progressively intensified neuroinflammatory response and the fluctuating growth of early apoptosis changes.Conclusion: This study systematically identifies hyperacute-phase-specific biomarkers in AIS and delineates their temporal regulatory logic. The time-course dynamics of neuronal apoptosis and inflammatory regulation in the hyperacute phase of AIS were monitored. The observed biphasic apoptotic pattern provides mechanistic insights for developing chronologically targeted therapies, such as timed inhibition of TLR4/CD86 during 0–3 h to block inflammatory initiation, or administration of Agpat1 agonists at 3–6 h to stabilize mitochondrial function. These findings help alleviate the current ‘molecular blind spot’ in early stroke diagnosis and intervention.
Journal Article
Metabolic engineering of β-carotene biosynthesis in Yarrowia lipolytica
ObjectiveCarotenoids, as potent antioxidant compounds, have gained extensive attention, especially in human health. In this study, the combination of CRISPR/Cas9 integration strategy and fermenter cultivation was utilized to obtain efficient β-carotene-producing Yarrowia lipolytica cell factories for potential industrial application.ResultsThe introduction of the genes of Mucor circinelloides, encoding phytoene dehydrogenase (carB) and bifunctional phytoene synthase/lycopene cyclase (carRP), contributed to the heterologous production of β-carotene in Y. lipolytica XK2. Furthermore, β-carotene production was efficiently enhanced by increasing the copy numbers of the carB and carRP genes and overexpressing of GGS1, ERG13, and HMG, the genes related to the mevalonate (MVA) pathway. Thus, the optimized strain overexpressed a total of eight genes, including three copies of carRP, two copies of carB, and single copies of GGS1, HMG, and ERG13. As a consequence, strain Y. lipolytica XK19 accumulated approximately 408 mg/L β-carotene in shake flask cultures, a twenty-four-fold increase compared to the parental strain Y. lipolytica XK2.Conclusions4.5 g/L β-carotene was obtained in a 5-L fermenter through a combination of genetic engineering and culture optimization, suggesting a great capacity and flexibility of Y. lipolytica in the production of carotenoids.
Journal Article
Research Progress of Baihe Gujin Decoction in the Treatment of Lung Cancer
Baihe Gujin decoction is one of the most commonly used decoction in traditional Chinese medicine for the treatment of lung cancer. It can nourish yin and moisten the lung as well as prevent phlegm from forming and stop coughing. On the one hand, Baihe Gujin decoction is characterized with extensive application, proven efficacy, a long history, and high safety. On the other hand, Baihe Gujin decoction can induce apoptosis of tumor cells, improve immune function and inhibit inflammation. The main anti-tumor components of this include kaempferol, quercetin, isorhamnetin, glycyrrhizin and β-sitosterol. Clinically, Baihe Gujin decoction can improve the adverse reactions caused by radiotherapy, chemotherapy and immunotherapy for lung cancer, enhance the quality of life of patients, and prolong their survival time. At present, there are a large number of clinical and basic researches on the treatment of lung cancer with Baihe Gujin decoction. In this paper, we mainly discussed the treatment of lung cancer with Baihe Gujin decoction through analyzing basic and clinical researches at home and abroad in the past 20 years. Through the discussion, we aimed to probe deeper into Baihe Gujin decoction for the treatment of lung cancer, thereby providing a broader idea for clinical diagnosis and treatment of lung cancer.
Journal Article
Effect of NaCl-stressed Bacillus thuringiensis (Bt) cotton on the feeding behaviors and nutritional parameters of Helicoverpa armigera
Saline-alkali soil is an arable land resource on which transgenic Bacillus thuringiensis (Bt) cotton has been planted on a large scale in accordance with food security strategies. There are, however, concerns about the insecticidal effects of Bt cotton on target insect pests. In this study, a Bt cotton variety, GK19, and its nontransgenic parent variety, Simian-3, were used as experimental models for investigating the effect of the expression of exogenous insecticidal proteins in Bt cotton under NaCl stress on the feeding behavior and nutritional parameters of Helicoverpa armigera. The results showed that the expression of exogenous insecticidal proteins in GK19 was significantly inhibited under NaCl stress. However, the feeding, crawling, resting and spinning down behavior of the 5th instar H. armigera larvae on GK19 Bt cotton, as well as the amount of food consumed and feces produced by these larvae, did not markedly differ under different NaCl concentrations. In contrast, the mean relative growth rate (MRGR), relative growth rate (RGR), approximate digestibility (AD), efficiency of conversion of ingested food (ECI) and efficiency of conversion of digested food (ECD) of the larvae markedly decreased in response to NaCl stress. Under the same concentration of NaCl, the nutritional parameters of the bollworm larvae on GK19 Bt cotton or Simian-3 nontransgenic cotton were different. However, the interaction between salt stress and cotton variety had no significant effect on the feeding behavior or nutritional parameters of H. armigera larvae. These results may provide a scientific basis for determining the effect of exogenous insecticidal protein expression in Bt cotton under NaCl stress on H. armigera and can therefore be useful for the effective application of Bt cotton in saline-alkali soils to prevent and control H. armigera.
Journal Article
Synergistic effects and flame-retardant mechanism of aluminum diethyl phosphinate in combination with melamine polyphosphate and aluminum oxide in epoxy resin
In this work, the melamine polyphosphate (MPP) and aluminum oxide (Al2O3) were used to investigate their synergistic effects with aluminum diethyl phosphinate (AlPi) on enhancing the flame retardancy of epoxy resins (EP). The results indicated that low loadings of only 3.2 mass% AlPi, 1.6 mass% MPP and 0.2 mass% Al2O3 can make EP get high LOI value of 33.5% and UL-94 V-0 rating. The results also showed that the multi-component system of AlPi, MPP and Al2O3 in appropriate mixing ratio had good smoke suppression effect. The total smoke production of flame-retarded EP was decreased by as much as 64% compared with EP. Joint analysis by multiple techniques of cone calorimeter test, thermogravimetric analysis (TGA), Fourier infrared spectra (FTIR), X-ray photoelectron spectroscopy and TGA coupling FTIR was shown that the flame-retardant mechanisms of the flame-retarded EP by loading of AlPi, MPP and Al2O3 were proposed as synergistic mechanism in gas and condensed phase. The excellent flame retardancy of EP/AlPi/MPP/Al2O3 composite was improved by the formation of protective char layer from the high valence phosphorus compounds in the residual char.
Journal Article
Effects of neural stem cell transplantation on the motor function of rats with contusion spinal cord injuries: a meta-analysis
Objective: To judge the efficacies of neural stem cell (NSC) transplantation on functional recovery following contusion spinal cord injuries (SCIs).
Data sources: Studies in which NSCs were transplanted into a clinically relevant, standardized rat model of contusion SCI were identified by searching the PubMed, Embase and Cochrane databases, and the extracted data were analyzed by Stata 14.0.
Data selection: Inclusion criteria were that NSCs were used in in vivo animal studies to treat contusion SCIs and that behavioral assessment of locomotor functional recovery was performed using the Basso, Beattie, and Bresnahan lo-comotor rating scale. Exclusion criteria included a follow-up of less than 4 weeks and the lack of control groups.
Outcome measures: The restoration of motor function was assessed by the Basso, Beattie, and Bresnahan locomotor rating scale.
Results: We identified 1756 non-duplicated papers by searching the aforementioned electronic databases, and 30 full-text articles met the inclusion criteria. A total of 37 studies reported in the 30 articles were included in the meta-analysis. The meta-analysis results showed that transplanted NSCs could improve the motor function recovery of rats following contusion SCIs, to a moderate extent (pooled standardized mean difference (SMD) = 0.73; 95% confidence interval (CI): 0.47-1.00; P < 0.001). NSCs obtained from different donor species (rat: SMD = 0.74; 95% CI: 0.36-1.13; human: SMD = 0.78; 95% CI: 0.31-1.25), at different donor ages (fetal: SMD = 0.67; 95% CI: 0.43-0.92; adult: SMD = 0.86; 95% CI: 0.50-1.22) and from different origins (brain-derived: SMD = 0.59; 95% CI: 0.27-0.91; spinal cord-derived: SMD = 0.51; 95% CI: 0.22-0.79) had similar efficacies on improved functional recovery; however, adult induced pluripotent stem cell-derived NSCs showed no significant efficacies. Furthermore, the use of higher doses of transplanted NSCs or the administration of immunosuppressive agents did not promote better locomotor function recovery (SMD = 0.45; 95% CI: 0.21-0.70). However, shorter periods between the contusion induction and the NSC transplantation showed slightly higher efficacies (acute: SMD = 1.22; 95% CI: 0.81-1.63; subacute: SMD = 0.75; 95% CI: 0.42-1.09). For chronic injuries, NSC implantation did not significantly improve functional recovery (SMD = 0.25; 95% CI: -0.16 to 0.65).
Conclusion: NSC transplantation alone appears to be a positive yet limited method for the treatment of contusion SCIs.
Journal Article
Chemical and Biological Study of Novel Aplysiatoxin Derivatives from the Marine Cyanobacterium Lyngbya sp
Since 1970s, aplysiatoxins (ATXs), a class of biologically active dermatoxins, were identified from the marine mollusk Stylocheilus longicauda, whilst further research indicated that ATXs were originally metabolized by cyanobacteria. So far, there have been 45 aplysiatoxin derivatives discovered from marine cyanobacteria with various geographies. Recently, we isolated two neo-debromoaplysiatoxins, neo-debromoaplysiatoxin G (1) and neo-debromoaplysiatoxin H (2) from the cyanobacterium Lyngbya sp. collected from the South China Sea. The freeze-dried cyanobacterium was extracted with liquid–liquid extraction of organic solvents, and then was subjected to multiple chromatographies to yield neo-debromoaplysiatoxin G (1) (3.6 mg) and neo-debromoaplysiatoxin H (2) (4.3 mg). They were elucidated with spectroscopic methods. Moreover, the brine shrimp toxicity of the aplysiatoxin derivatives representing differential structural classifications indicated that the debromoaplysiatoxin was the most toxic compound (half inhibitory concentration (IC50) value = 0.34 ± 0.036 µM). While neo-aplysiatoxins (neo-ATXs) did not exhibit apparent brine shrimp toxicity, but showed potent blocking action against potassium channel Kv1.5, likewise, compounds 1 and 2 with IC50 values of 1.79 ± 0.22 µM and 1.46 ± 0.14 µM, respectively. Therefore, much of the current knowledge suggests the ATXs with different structure modifications may modulate multiple cellular signaling processes in animal systems leading to the harmful effects on public health.
Journal Article