The effects of antioxidant supplementation on short-term mortality in sepsis patients.

Background: The occurrence and development of sepsis are related to the excessive production of oxygen free radicals and the weakened natural clearance mechanism. Further dependable evidence is required to clarify the effectiveness of antioxidant therapy, especially its impact on short-term mortality. Objectives: The purpose of this systematic review and meta-analysis was to evaluate the effect of common antioxidant therapy on short-term mortality in patients with sepsis. Methods: According to PRISMA guidelines, a systematic literature search on antioxidants in adults sepsis patients was performed on PubMed/Medline, Embase, and the Cochrane Library from the establishment of the database to November 2023. Antioxidant supplements can be a single-drug or multi-drug combination: HAT (hydrocortisone, ascorbic acid, and thiamine), ascorbic acid, thiamine, N-acetylcysteine and selenium. The primary outcome was the effect of antioxidant treatment on short-term mortality, which included 28-day mortality, in-hospital mortality, intensive care unit mortality, and 30-day mortality. Subgroup analyses of short-term mortality were used to reduce statistical heterogeneity and publication bias. Results: Sixty studies of 130,986 sepsis patients fulfilled the predefined criteria and were quantified and meta-analyzed. Antioxidant therapy reduces the risk of short-term death in sepsis patients by multivariate meta-analysis of current data, including a reduction of in-hospital mortality (OR = 0.81, 95% CI 0.67 to 0.99; P = 0.040) and 28-day mortality (OR = 0.81, 95% CI 0.69 to 0.95]; P = 0.008). Particularly in subgroup analyses, ascorbic acid treatment can reduce in-hospital mortality (OR = 0.66, 95% CI 0.90 to 0.98; P = 0.006) and 28-day mortality (OR = 0.43, 95% CI 0.24 to 0.75; P = 0.003). However, the meta-analysis of RCTs found that antioxidant therapy drugs, especially ascorbic acid, did substantially reduce short-term mortality(OR = 0.78, 95% CI 0.62 to 0.98; P = 0.030; OR = 0.57, 95% CI 0.36 to 0.91; P = 0.020). Conclusions: According to current data of RCTs, antioxidant therapy, especially ascorbic acid, has a trend of improving short-term mortality in patients with sepsis, but the evidence remains to be further demonstrated.

Adsorption of phosphate onto agricultural waste biochars with ferrite/manganese modified-ball-milled treatment and its reuse in saline soil.

Agricultural waste biochar was widely used to absorb phosphorus (P) from eutrophicated water and soil remediation. However, the research on the reuse of the sorbed P on biochar in infertile saline soil is insufficient. Biochars derived from four kinds of agricultural wastes (cotton straws from two origins, maize stalk, and rice husk) were modified and applied to adsorb phosphate in waste water and then be reused in saline soil in this study. The co-modified method combining ball milling and metal coated treatment obtained the higher specific surface area (SSA) of ferrite/manganese modified-ball-milled biochars (Fe/Mn-BMBCs) (226.5-331.5 m2 g-1) than that of pristine biochars (14.02-30.35 m2 g-1) and ferrite/manganese modified biochar (Fe/Mn-BC) (223.7 m2 g-1), which could improve the pore structure of metal modified biochar. The phosphate adsorption capacity (qmax) of Fe/Mn-BMBCs with rich functional groups and high SSA were 44.0-53.8 mg g-1, which was 4.47-5.82 times higher than that of pristine biochars. Fe/Mn-BMBCs showed efficiently adsorption performance at low pH and high temperature. The application of BC to saline soil could promote the availability of P in saline soil. P-loaded biochars could afford P as a nutrient to promote the growth of lettuce (Lactuca sativa L.) in saline soil. The lettuce fresh weight in Fe/Mn-BMBC-P2 treated soil was 8.21 times higher than that grew in control check (CK) treatment. As a P element provider, P-loaded biochars not only improve saline soil fertility and crop productivity, but also convert the agricultural wastes and P in eutrophicated waters to the sustainable resource.

Evidence of temperature-controlled dissolved inorganic nitrogen distribution in a shallow lake.

Dissolved inorganic nitrogen (DIN) plays an important role in aquatic ecosystems as an available source of nitrogen (N). Despite recent advances in our understanding of the effects of climate change on DIN in coastal waters, shallow high-latitude lakes exposed to large seasonal temperature differences have received limited research attention. Therefore, in the present study, Baiyangdian Lake (BYDL) was selected as the study area, as a typical high latitude shallow lake in North China. Based on water and sediment samples collected in spring, summer and winter seasons, DIN accumulation in sedimentary pore water and DIN diffusion fluxes at the sediment-water interface were quantified under different temperature conditions. Correlation analysis was used to establish the effects of temperature on DIN concentration and diffusion in different media. Results show that the diffusion of DIN at the lake sediment-water interface exhibited a strongly positive relationship with temperature, suggesting that high temperature conditions lead to greater DIN release from sediments. Cold temperatures cause DIN accumulation in sedimentary pore water, providing sufficient substrate for N-related bacteria in the sediment under cold temperature conditions. Temperature controls the vertical distribution of DIN by affecting its migratory diffusion and transformation at the sediment-water interface. These findings are valuable for understanding the impact of climate change on the distribution of N in inland shallow lakes, especially in high latitude shallow lakes subjected to large seasonal temperature differences throughout the year.

Preclinical efficacy and clinical safety of clinical-grade nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles.

Mesenchymal stromal cell-derived extracellular vesicles (MSC-EVs) turn out to be a promising source of cell-free therapy. Here, we investigated the biodistribution and effect of nebulized human adipose-derived MSC-EVs (haMSC-EVs) in the preclinical lung injury model and explored the safety of nebulized haMSC-EVs in healthy volunteers. DiR-labelled haMSC-EVs were used to explore the distribution of nebulized haMSC-EVs in the murine model. Pseudomonas aeruginosa-induced murine lung injury model was established, and survival rate, as well as WBC counts, histology, IL-6, TNF-α and IL-10 levels in bronchoalveolar lavage fluid (BALF) were measured to explore the optimal therapeutic dose of haMSC-EVs through the nebulized route. Twenty-four healthy volunteers were involved and received the haMSC-EVs once, ranging from 2 × 108 particles to 16 × 108 particles (MEXVT study, NCT04313647). Nebulizing haMSC-EVs improved survival rate to 80% at 96 h in P. aeruginosa-induced murine lung injury model by decreasing lung inflammation and histological severity. All volunteers tolerated the haMSC-EVs nebulization well, and no serious adverse events were observed from starting nebulization to the 7th day after nebulization. These findings suggest that nebulized haMSC-EVs could be a promising therapeutic strategy, offering preliminary evidence to promote the future clinical applications of nebulized haMSC-EVs in lung injury diseases.

Potato Spindle Tuber Viroid RNA-Templated Transcription: Factors and Regulation.

Viroids are circular noncoding RNAs that infect plants. Without encoding any protein, these noncoding RNAs contain the necessary genetic information for propagation in hosts. Nuclear-replicating viroids employ DNA-dependent RNA polymerase II (Pol II) for replication, a process that makes a DNA-dependent enzyme recognize RNA templates. Recently, a splicing variant of transcription factor IIIA (TFIIIA-7ZF) was identified as essential for Pol II to replicate potato spindle tuber viroid (PSTVd). The expression of TFIIIA-7ZF, particularly the splicing event, is regulated by a ribosomal protein (RPL5). PSTVd modulates its expression through a direct interaction with RPL5 resulting in optimized expression of TFIIIA-7ZF. This review summarizes the recent discoveries of host factors and regulatory mechanisms underlying PSTVd-templated transcription processes and raises new questions that may help future exploration in this direction. In addition, it briefly compares the machinery and the regulatory mechanism for PSTVd with the replication/transcription system of human hepatitis delta virus.

Taurine supplementation reduces neuroinflammation and protects against white matter injury after intracerebral hemorrhage in rats.

Intracerebral hemorrhage (ICH) initiates a neuroinflammatory cascade that contributes to substantial neuronal damage and neurological deterioration. Taurine, an abundant amino acid in the nervous system, is reported to reduce inflammatory injury in various central nervous system diseases, but its role and the possible underlying mechanisms in the pathology following ICH remains unclear. This study was designed to evaluate the effect of taurine supplementation on neurological deficits, acute inflammatory responses and white matter injury in a model of ICH in rats. Adult male Sprague-Dawley (SD) rats subjected to collagenase-induced ICH injury were injected intravenously with different concentrations of taurine or vehicle 10 min after ICH and subsequently daily for 3 days. Behavioral studies, brain water content, and assessments of hemorrhagic lesion volume were quantified at day 1 and day 3 post-ICH. Neuronal damage, peri-hematomal inflammatory responses, and white matter injury were determined at 24 h, meanwhile, the content of hydrogen sulfide (H2S) along with the expression of cystathionine-ß-synthase (CBS) and P2X7 receptor (P2X7R) in peri-hematomal tissues was analyzed to investigate the possible anti-inflammatory mechanism of taurine. Treatment with a high dosage of taurine (50 mg/kg) significantly attenuated functional deficits and reduced brain edema and hemorrhagic lesion volume after ICH. Taurine administration also resulted in significant amelioration of neuronal damage and white matter injury. These changes were associated with marked reductions in neutrophil infiltration, glial activation, and expression levels of inflammatory mediators. Moreover, the anti-inflammatory effect of taurine was accompanied by increased H2S content, enhanced CBS expression, and less expression of P2X7R. Our study demonstrated that the high dosage of taurine supplementation effectively mitigated the severity of pathological inflammation and white matter injury after ICH, and the mechanism may be related to upregulation of H2S content and reduced P2X7R expression.

Assessment of anti-cancerous potential of 6-gingerol (Tongling White Ginger) and its synergy with drugs on human cervical adenocarcinoma cells.

The anti-cancerous activity of 6-gingerol extracted from Tongling White Ginger was investigated. 6-Gingerol inhibited the growth of HeLa cells with IC50 (96.32 µM) and IC80 (133.01 µM) and led to morphological changes, induced the cell cycle arrest in G0/G1-phase and ultimately resulted into apoptosis. Among cell cycle-related genes and proteins, the expression of cyclin (A, D1, E1) reduced, while of CDK-1, p21 and p27 showed slight decrease, except cyclin B1 and E1 (protein). Western blotting reported the induction of apoptosis with an increased Bax/Bcl-2 ratio, release of cytochrome c, cleavage of caspase-3, -8, -9 and PRPP in treated cells. 6-Gingerol activated AMPK, but inhibited PI3K/AKT phosphorylation with reduced P70S6K expression and also suppressed the mTOR phosphorylation. 6-Gingerol with 5-FU and Ptx resulted in 83.2% and 52% inhibition respectively, this synergy have stimulated apoptosis proteins more efficiently as compared to 6-Gingerol alone (10.75%) under in vitro conditions.

[Study on identification of wild Dipsacus asper and cultivated Dipsacus asper at different growth years by organization structure].

OBJECTIVE: To study the regular pattern of growing development and the structural changes of the main root of Dipsacus asper; Find the basis for distinguishing between wild and cultivated Dipsacus asper as well as identifying cultivated Dipsacus asper at different growth years. METHODS: Continuous sectional sampling and histological observation was conducted on the main roots of annual and biennial cultivated Dipsacus asper and on the main roots of bolting and non-bolting plants of wild Dipsacus asper; Histological observation was carried out respectively on the main roots of one to four-year-old cultivated Dipsacus asper. RESULTS: It was discovered for the first time that there was structure of growth rings in the main roots of Dipsacus asper. And the ways in which the vessels of the growth rings were arranged differed between wild and cultivated Dipsacus asper, the vessels of growth rings in wild Dipsacus asper were arranged tangentially while those in cultivated Dipsacus asper were arranged as clusters. Pith existed in the upper part of roots of wild Dipsacus asper,while it was not found in the cultivated ones, and this could be adopted as a preliminary method to distinguish the wild Dipsacus asper from cultivatedone. The structures of growth rings in each main root were in consistency from top to bottom, and the thickening of roots mainly depended on the growth of xylem in the first year. There were particular relations and regular patterns between the structure of main roots of one to four-year-old cultivated Dipsacus asper and the ages of their growth, which could serve as the primary basis for identifying their growth years. CONCLUSION: Methods to distinguish wild Dipsacus asper from cultivated ones at different ages by organization structure are established, which could provide the basis for identification of the medicinal material of Dipsacus asper.

N-Acetylcysteine modulates acute lung injury induced by Pseudomonas aeruginosa in rats.

1. In critically ill patients, Pseudomonas aeruginosa-induced pneumonia and the lung injury associated with infection are major causes of mortality. The aim of the present study was to evaluate the protective properties of N-acetylcysteine (NAC) in rats infected with P. aeruginosa and the role of nitric oxide synthases (NOS) protein in this process. 2. Pneumonia was induced in rats by infecting them with P. aeruginosa intratracheally. One group of rats was treated with NAC (150 mg/kg per day, i.p., for 7 days). An untreated group served as the control. Samples were collected both before (0 h) and after infection (24 h). Bacterial loads in lung tissue, the lung wet : dry (W/D) ratio and pulmonary vascular permeability were assessed. Total cell and polymorphonuclear leucocyte cell counts in bronchoalveolar lavage fluid were determined. The expression of inducible (i) NOS and endothelial (e) NOS protein was analysed and correlated with indices of lung injury using Pearson's correlation analysis. 3. Bacterial load, lung injury indices and NOS expression increased after infection. Pretreatment with NAC mitigated lung injury although it did not significantly change bacterial loads. Furthermore, NAC treatment increased eNOS protein expression, but decreased iNOS expression, in lung tissues after infection. The expression of iNOS protein was positively correlated with indices of lung injury, whereas there was a negative correlation between eNOS expression and lung injury indices. 4. N-Acetylcysteine modulated P. aeruginosa-induced lung injury in rats. The results suggest that this effect maybe due to regulation of iNOS and eNOS protein expression by NAC.