Tanshinone IIA improves Alzheimer's disease via RNA nuclear-enriched abundant transcript 1/microRNA-291a-3p/member RAS oncogene family Rab22a axis.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative condition characterized by oxidative stress and neuroinflammation. Tanshinone IIA (Tan-IIA), a bioactive compound isolated from Salvia miltiorrhiza plants, has shown potential neuroprotective effects; however, the mechanisms underlying such a function remain unclear. AIM: To investigate potential Tan-IIA neuroprotective effects in AD and to elucidate their underlying mechanisms. METHODS: Hematoxylin and eosin staining was utilized to analyze structural brain tissue morphology. To assess changes in oxidative stress and neuroinflammation, we performed enzyme-linked immunosorbent assay and western blotting. Additionally, the effect of Tan-IIA on AD cell models was evaluated in vitro using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Genetic changes related to the long non-coding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1)/microRNA (miRNA, miR)-291a-3p/member RAS oncogene family Rab22a axis were assessed through reverse transcription quantitative polymerase chain reaction. RESULTS: In vivo, Tan-IIA treatment improved neuronal morphology and attenuated oxidative stress and neuroinflammation in the brain tissue of AD mice. In vitro experiments showed that Tan-IIA dose-dependently ameliorated the amyloid-beta 1-42-induced reduction of neural stem cell viability, apoptosis, oxidative stress, and neuroinflammation. In this process, the lncRNA NEAT1 - a potential therapeutic target - is highly expressed in AD mice and downregulated via Tan-IIA treatment. Mechanistically, NEAT1 promotes the transcription and translation of Rab22a via miR-291a-3p, which activates nuclear factor kappa-B (NF-κB) signaling, leading to activation of the pro-apoptotic B-cell lymphoma 2-associated X protein and inhibition of the anti-apoptotic B-cell lymphoma 2 protein, which exacerbates AD. Tan-IIA intervention effectively blocked this process by inhibiting the NEAT1/miR-291a-3p/Rab22a axis and NF-κB signaling. CONCLUSION: This study demonstrates that Tan-IIA exerts neuroprotective effects in AD by modulating the NEAT1/miR-291a-3p/Rab22a/NF-κB signaling pathway, serving as a foundation for the development of innovative approaches for AD therapy.

Prognostic Value of Pentraxin-3 Change After Primary Percutaneous Coronary Intervention in Patients with ST-Segment Elevation Myocardial Infarction.

Purpose: So far, ST-segment elevation myocardial infarction (STEMI) is still the main cause of morbidity and mortality of cardiovascular diseases worldwide. Recent studies showed that pentraxin-3 (PTX3) was related to the early diagnosis and prognosis of coronary heart disease. This study aimed to investigate the dynamical change of PTX3 after primary percutaneous coronary intervention (pPCI) in STEMI patients and its prognostic value. Patients and methods: In this prospective cohort study, a total of 350 patients were enrolled. The plasma level of PTX3 was measured at admission, 24-hour and 5-day after pPCI. The primary endpoint was the incidence of major adverse cardiac cerebral events (MACCEs) during 1-year follow-up. Results: Compared with the admission, PTX3 levels were significantly increased at 24 hours, and decreased at 5 days after pPCI in the whole cohort. PTX3 levels at these three time points were not significantly different between the patients with and without MACCEs. Notably, the change in PTX3 from admission to post-pPCI 24-hour (ΔPTX3) was higher in patients with MACCEs (112.83 vs 17.94 ng/dl, P = 0.001). The ROC curves showed that the cut-off value was 29.22 ng/dl and the area under curves was 0.622 (95% CI: 0.554-0.690, p = 0.001). Multivariable cox regression models revealed that the high ΔPTX3 group was an independent predictor of MACCEs (adjusted HR = 2.010, 95% CI = 1.280-3.186, p = 0.003). The higher ΔPTX3 group had significantly higher incidences of revascularization (HR = 2.094, 95% CI: 1.056-4.150, p = 0.034) and composite MACCEs (HR = 2.219, 95% CI: 1.425-3.454, p < 0.001). However, the change of PTX3 level from admission to post-pPCI 5-day had no independently predictive value. Conclusion: The higher increase of PTX3 level 24-hour after pPCI appeared to have a potential value in independently predicting the incidence of 1-year MACCEs in STEMI patients, especially for coronary revascularization.

Identification of vasospasm biomarkers for cerebral hemorrhage via bio-informatics analysis.

BACKGROUND: The incidence of cerebral hemorrhage has rapidly increased over time, and vascular dysfunction has a significant influence on the pathogenesis and outcome of these patients. This is also the case for vasospasm in cerebral hemorrhage, but there is no method to assess this. We conducted this study to find molecular biomarkers of vasospasm in cerebral hemorrhage patients. METHODS: Raw data of GSE37924 was downloaded from the Gene Expression Omnibus (GEO) database, including 66 samples with cerebral vasospasm and 62 samples without cerebral vasospasm. Differentially expressed genes (DEGs) between samples with cerebral vasospasm and those without cerebral vasospasm were analyzed using the limma package in R software. To determine the functions of DEGs, we conducted functional enrichment analysis of DEGs through the clusterProfiler package in R. The protein-protein interaction (PPI) network of DEGs was constructed through STRING (https://string-db.org/) and generated via Cytoscape software. To understand the correlation between DEGs and immune-related genes, immune-related cerebral vasospasm genes were obtained via intersecting immune-related genes and cerebral vasospasm DEGs. We also compared the infiltration of 28 immune cells between cases with cerebral vasospasm and those without cerebral vasospasm. Finally, we constructed a model to perform the validation experiments. RESULTS: Of the DEGs, there were 24 upregulated and 21 downregulated genes in the vasospasm samples compared to the no-vasospasm samples. Functional enrichment analysis showed that these genes play key roles in several biological processes and signaling pathways such as the bone morphogenetic protein (BMP) signaling pathway, cellular response to BMP stimulus, natural killer cell chemotaxis, negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway, MHC protein complex binding, and receptor ligand activity, among others. CCL4, HLA-DQA1, IGF2, NTS, and so on were the significant immune-related genes. Furthermore, the immune cell infiltration results showed that there were differences between patients with vasospasm and those without vasospasm. Finally, we found that CCL4 had significantly higher expression in patients with vasospasm than those without vasospasm. CONCLUSIONS: CCL4 is an important regulator of vascular dysfunction in cerebral hemorrhage.

The Involvement of the Chemokine RANTES in Regulating Luminal Acidification in Rat Epididymis.

Background: A complex interplay between different cell types in the epithelium leads to activation of the luminal acidifying capacity of the epididymis, a process that is crucial for sperm maturation and storage. Basal cells sense the luminal angiotensin II (ANG II) and stimulate proton secretion in clear cells through nitric oxide (NO). Our previous study has shown the chemokine regulated upon activation normal T-cell expressed and secreted (RANTES) was expressed in the F4/80 positive macrophages of human epididymis. The objective of this study was to explore the involvement of RANTES in regulating the luminal acidification in the rat epididymis. Methods: The role of RANTES was investigated by in vivo perfusion with recombinant RANTES, Met-RANTES, and PBS of different pH values. Furthermore, rats vasectomy was performed to alter the epididymal luminal pH. RIA was used to measure the tissue homogenate ANG II concentration. Real time-PCR and western blot were employed to examine the expression levels of AGTR2, RANTES, CCR1, CCR5, and iNOS in epididymis. Results: RANTES was restricted to the basal macrophages of epididymal ducts and co-localized with its receptors CCR1 and CCR5. Both V-ATPase and iNOS were up-regulated in the cauda epididymis after perfused with recombinant RANTES, while the antagonist Met-RANTES perfusion led to a complete abrogation of the increased expression of V-ATPase in the apical membrane of clear cells and iNOS in macrophages. Upon alkaline perfusion, RANTES expression was significantly increased and the apical accumulation of V-ATPase in the clear cells was induced in the cauda epididymis. The luminal pH in the cauda epididymis increased after vasectomy. The concentration of the ANG II and the expression levels of AGTR2, RANTES, CCR1, CCR5, and iNOS dropped in the cauda epididymis following vasectomy. Conclusion: Upon the activation of basal cells, RANTES might induce the NO release from macrophages by interacting with its receptors, which increases proton secretion by adjacent clear cells. Thus, RANTES is possible to participate in the crosstalk among basal cells, macrophages and clear cells for the fine control of an optimum acidic luminal environment that is critical for male fertility.

Biomarkers and potential pathogenesis of colorectal cancer-related ischemic stroke.

AIM: To investigate the specific biomarkers and potential pathogenesis of colorectal cancer-related ischemic stroke (CRCIS). METHODS: A retrospective study was conducted on CRCIS patients (colorectal cancer patients with ischemic stroke without conventional stroke risk factors) registered at seven centers between January 2007 and December 2017. Clinical data and laboratory and imaging findings were compared with age- and sex- matched patients with colorectal cancer (CRC) without ischemic stroke that were admitted to the same hospital during the same period. Univariate and multivariate analyses were performed to analyze the independent risk factors for CRCIS. A receiver operator characteristic curve was configured to calculate the optimal cut-off value of the products of the independent risk factors for CRCIS. RESULTS: A total of 114 CRCIS patients and 114 CRC patients were included. Multiple lesions in multiple vascular territories were common in CRCIS patients (71, 62.28%). The levels of plasma D-dimer, carcinoembryonic antigen (CEA), cancer antigen 125, and neutrophil count were significantly higher in CRCIS patients than in CRC patients. Multiple logistic regression analysis revealed that plasma D-dimer levels [odds ratio (OR) = 1.002, 95% confidence interval (CI): 1.001-1.003, P < 0.001], CEA levels (OR = 1.011, 95%CI: 1.006-1.015, P < 0.001), and neutrophil count levels (OR = 1.626, 95%CI: 1.268-2.087, P < 0.001) were independent risk factors for CRCIS. In addition, receiver operator characteristic curve revealed that the area under curve for the products of plasma D-dimer, CEA, and neutrophil count was 0.889 ± 0.022 (95%CI: 0.847-0.932, P < 0.001), and the optimal cut-off value for the product was 252.06, which was called the CRCIS Index, with a sensitivity of 86.0% and specificity of 79.8%. CONCLUSION: Hypercoagulability induced by elevated CEA and neutrophils may be an important cause of CRCIS. The CRCIS index, which serves as a biomarker of CRCIS, needs further study.

[Experiment on pruning of Cistanche deserticola inoculated in artificial Haloxylon ammodendron forest].

At present, the objective of cutting and pruning Cistanche deserticola is to harvest in successive years and enhance the harvesting yield and quality of C. deserticola in the process of the artificial cultivating C. deserticola. An experiment was conducted focusing on cutting and pruning C. deserticola in artificial forests of Haloxylon ammodendron drip-irrigated with saline water at the hinter-land of the Taklimakan desert, according to different growth stages and lengths. The results were following: (1) The effect of cutting on C. deserticola was similar to that of pruning, which resulted in three kinds of morphological types, not related to the bloom and size of C. deserticola. (2) The growth forms were diversified after pruning. Among them, there had sprouting new body, died or maintaining life with no sprouting, mildewed on its surface layer, etc. However, some of new bodies were sprouting from the lower part of the old body. The death rate of bloomed C. deserticola was higher than that of the underground, and the death rate of the 40 cm in stubble height for C. deserticola was higher than those with the stubble height of 20 cm and 5 cm. (3) Most of the diameter of living C. deserticola after pruning was increasing, but some of them changed little. (4) The mildew and rot of C. deserticola and the broken of the roots of the H. ammodendron and the fallen of the point of the inoculated when it was dug, which would cause the death of the C. deserticola. On the other, the yield-increasing effect and the economic benefit of the techniques of the pruning of Cistanche would need further research and evaluate. Therefore, the application of this technique needs to be cautious.

[Effect of shifting sand burial on evaporation reduction and salt restraint under saline water irrigation in extremely arid region].

The Taklimakan Desert Highway Shelterbelt is drip-irrigated with high saline groundwater (2.58-29.70 g x L(-1)), and shifting sand burial and water-salt stress are most common and serious problems in this region. So it is of great importance to study the effect of shifting sand burial on soil moisture evaporation, salt accumulation and their distribution for water saving, salinity restraint, and suitable utilization of local land and water resources. In this study, Micro-Lysimeters (MLS) were used to investigate dynamics of soil moisture and salt under different thicknesses of sand burial (1, 2, 3, 4, and 5 cm), and field control experiments of drip-irrigation were also carried out to investigate soil moisture and salt distribution under different thicknesses of shifting sand burial (5, 10, 15, 20, 25, 30, 35, and 40 cm). The soil daily and cumulative evaporation decreased with the increase of sand burial thickness in MLS, cumulative evaporation decreased by 2.5%-13.7% compared with control. And evaporative inhibiting efficiency increased with sand burial thickness, evaporative inhibiting efficiency of 1-5 cm sand burial was 16.7%-79.0%. Final soil moisture content beneath the interface of sand burial increased with sand burial thickness, and it increased by 2.5%-13.7% than control. The topsoil EC of shifting sand in MLS decreased by 1.19-6.00 mS x cm(-1) with the increasing sand burial thickness, whereas soil salt content beneath the interface in MLS increased and amplitude of the topsoil salt content was higher than that of the subsoil. Under drip-irrigation with saline groundwater, average soil moisture beneath the interface of shifting sand burial increased by 0.4% -2.0% compare with control, and the highest value of EC was 7.77 mS x cm(-1) when the sand burial thickness was 10 cm. The trend of salt accumulation content at shifting sand surface increased firstly, and then decreased with the increasing sand burial thickness. Soil salt contents beneath the interface of shifting sand burial were much lower than that of shifting sand surface. 35 cm was the critical sand burial thickness for water-saving and salt restraint. In summary, sand burial had obvious inhibition effects on soil evaporation and salt accumulation, so maybe it could be used to save water and reduce salt accumulation in arid shifting desert areas.

[Variation characteristics of soil microbial activities in the Tarim Desert Highway shelter forests, Xinjiang of Northwast China].

By the methods of Biolog, fumigation extraction, and colorimetric titration, this paper determined the soil carbon sources metabolic intensities, microbial biomass, and enzyme activities in the Tarim Desert Highway shelter-forests with different plantation times, and analyzed the variation characteristics of soil microbial activities in these shelter forests. With the increasing planting years of the shelter forests, the soil microbial metabolic activities (AWCD) and microbial diversity indices enhanced obviously, but the AWCD values in different soil layers had no significant differences. The soil catalase activity among the forests had no significant difference, but the soil cellulase and sucrase activities varied significantly. The soil microbial biomass carbon and nitrogen increased with the increasing planting years of the shelter forests, having a significant difference among the forests, but the microbial biomass phosphorus had no significant difference. The AWCD values had significant correlations with soil available nutrient contents, but less correlations with soil bulk density and moisture content. It was suggested that under the present management patterns and climate conditions, the soil metabolic activities in the Tarim Desert Highway shelter forests would be improved continuously with the increasing planting years of the forests.

[Effects of stumping on Calligonum mongolicum shelterbelt growth and soil moisture and salt distribution along Tarim Desert Highway, Xinjiang of Northwest China].

In order to ensure the stability and sustainability of the Calligonum mongolicum shelterbelt along Tarim Desert Highway, the aged C. mongolicum was stumped to investigate its growth and soil moisture and salt distribution. After stumping twice, C. mongolicum grew rapidly in its height, crown width, maximum basal diameter, and sprout number. Three years after stumping, the average height of the sprouts exceeded the control (no stumping), and the crown width and maximum basal diameter was 92.0% and 73.0% of the control, respectively. The fresh mass of the branches and assimilating branches, their dry mass, and the total fresh mass and dry mass of the aboveground parts reached 80.0%, 115.0%, 80.0%, 116.0%, 93.5%, and 88.0% of the control, respectively. Four years after stumping, the aboveground biomass surpassed the control. Comparing with the control, stumping increased the soil moisture content significantly and decreased the soil salt concentration. It was suggested that, to stump the aged C. mongolicum repeatedly could increase the soil moisture content and decrease the soil salt concentration in root zone, and effectively promote the rejuvenation and renewing of C. mongolicum.

Implantation of Ommaya reservoir in extremely low weight premature infants with posthemorrhagic hydrocephalus: a cautious option.

OBJECTIVE: This study aims to evaluate effects and complications of the implantation of Ommaya reservoir in premature infants with posthemorrhagic hydrocephalus (PHH). METHODS: The effects and complications of the implantation of Ommaya reservoir in seven premature infants with PHH were retrospectively analyzed. Intracapsular puncture of the reservoir was performed for draining cerebrospinal fluid. RESULTS: Seven extremely low-weight premature infants with PHH (birthweight less than 1,000 g) were treated with the placement of an Ommaya reservoir. Ommaya reservoirs in five infants were removed, but were retained in two infants. Two premature infants had to undergo ventriculoperitoneal (VP) shunt. Postsurgical major complications (including skin dehiscence, cerebrospinal fluid (CSF) infection, ventricular hemorrhage, and CSF leak) occurred in 57% of all patients. Three infants of skin dehiscence and CSF leak occurred. Two infants of CSF infection occurred, as well as one clinically significant secondary hemorrhage. Six infants survived, and one died. CONCLUSION: The implantation of Ommaya reservoir is a cautious option of treating low-weight premature infants with PHH because of a relatively high complication rate. However, VP shunt surgery may be avoided in some infants.

[Effects of thinning on Calligonum arborescens growth and soil water-salt distribution in Tarim Desert Highway shelterbelt, Xinjiang of Northwest China].

In order to understand the effects of thinning on the growth of Calligonum arborescens and the soil water-salt distribution in Tarim Desert Highway shelterbelt, a thinning experiment was conducted on an aged and declined C. arborescens woodland in a demonstration section of the shelterbelt, with the growth of C. arborescens and the soil water-salt distribution monitored. Thinning had no effects on the phenophase of C. arborescens, but after thinning, the growth of the current year plant height, crown width, ground diameter, and new branch length of reserved trees was larger than that of the control, and the increment was in the order of planting space 2 mx 1 m > 1 m x 1 m > the control, with significant differences among the treatments. The assimilation branch surface area in treatments 2 mx 1 m and 1 m x 1 m were 5.97 m2 and 5.22 m2 per plant, respectively, being significantly larger than the control (3.1 m2 per plant). The soil moisture content in 0-160 cm layer was significantly higher in treatments 2 m x 1 m and 1 mx 1 m than in the control, and increased obviously with thinning intensity. The soil salt content was in the order of control > planting space 1 m x 1 m > 2 m x 1 m, and the differences among the treatments were significant. It was suggested that the best reserved plant density after thinning was planting space 2 m x 1 m.

[Effects of the grain size and thickness of dust deposits on soil water and salt movement in the hinterland of the Taklimakan Desert].

By using mcirolysimeter, a laboratory simulation experiment was conducted to study the effects of the grain size and thickness of dust deposits on the soil water evaporation and salt movement in the hinterland of the Taklimakan Desert. Under the same initial soil water content and deposition thickness condition, finer-textured (<0.063 mm) deposits promoted soil water evaporation, deeper soil desiccation, and surface soil salt accumulation, while coarse-textured (0.063-2 mm) deposits inhibited soil water evaporation and decreased deeper soil water loss and surface soil salt accumulation. The inhibition effect of the grain size of dust deposits on soil water evaporation had an inflection point at the grain size 0.20 mm, i. e., increased with increasing grain size when the grain size was 0.063-0.20 mm but decreased with increasing grain size when the grain size was > 0.20 mm. With the increasing thickness of dust deposits, its inhibition effect on soil water evaporation increased, and there existed a logarithmic relationship between the dust deposits thickness and water evaporation. Surface soil salt accumulation had a negative correlation with dust deposits thickness. In sum, the dust deposits in study area could affect the stability of arid desert ecosystem.

[Relationships of soil microbial biomass with soil environmental factors in Tarim Desert highway shelter-forest].

By using correlation analysis, this paper studied the relationships of soil microbial quantity and biomass with soil physical and chemical factors and enzyme activities in highway shelter-forests of Tarim Desert, aimed to approach the interactions between microbes and environmental factors in aeolian sandy soil of extremely arid area. The results showed that soil microbial quantity and biomass in the shelter-forests had an increasing trend with the decrease of soil bulk density and particle size (R < -0.84) and the increase of soil moisture content and porosity (R > 0.85), with the correlation between soil microbial biomass and soil bulk density as the key. Soil microbial quantity and biomass were positively correlated with soil nutrient contents, mainly caused by the correlations of soil actinomycetes and microbial biomass C and P with soil available nutrients. Greater differences (R = 0.51-0.91) were observed in the correlations of soil enzyme activities with soil microbial quantity and biomass, which was mainly determined by the correlations of soil invertase and phosphatase activities with soil actinomycetes and microbial biomass C. The increase of soil salt content was not favorable to the accumulation of soil microbial biomass (R < -0.71), and there was a higher positive correlation (R > 0.63) between soil microbial amount and biomass. In practice, good soil condition should be established in the forestlands of arid area for the development of soil microbes and the promotion of soil matter cycling.