Protective effect of trans-nerolidol on vascular endothelial cell injury induced by lipopolysaccharides / Efectos protectores del trans-nerolidol en lesiones inducidas por lipopolisacáridos en células endoteliales vasculares

This article aimed to discuss the protection of trans - nerolidol on vascular endothelial cells (ECs) injured by lipopolysac charides. ECs were divided into four groups: normal, model, low and high dose trans - nerolidol treatment groups. The cell survival rate and the contents of NO in the cell culture supernatant were determined. The protein expression and transcript level of pe roxisome proliferator - activated receptor - γ (PPARγ), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) were determined by western blotting and RT - PCR respectively. Compared with the normal group, cell livability, protein e xpression and mRNA transcript level of PPARγ and eNOS decreased, NO contents, protein expression and mRNA transcript tlevel of iNOS increased in model group significantly. Compared with model group, all the changes recovered in different degree in treatmen t groups. Hence, it was concluded that trans - nerolidol can alleviate the ECs injuryby the regulation of iNOS/eNOS through activating PPARγ in a dose - dependent manner

Este artículo tiene como objetivo discutir la protección del trans - nerolidol en las células endoteliales vasculares (CE) dañadas por lipopolisacáridos. Las CE se di vidieron en cuatro grupos: normal, modelo, grupos de tratamiento con trans - nerolidol de baja y alta dosis. Se determinó la tasa de supervivencia de las células y los contenidos de óxido nítrico (NO) en el sobrenadante del cultivo celular. La expresión de p roteínas y el nivel de transcripción del receptor activado por proliferadores de peroxisomas - γ (PPARγ), el óxido nítrico sint et asa endotelial (eNOS) y el óxido nítrico sint et asa inducible (iNOS) se determinaron mediante western blot y RT - PCR, respectivamen te. En comparación con el grupo normal, la viabilidad celular, la expresión de proteínas y el nivel de transcripción de PPARγ y eNOS disminuyeron, los contenidos de NO, la expresión de proteínas y el nivel de transcripción de iNOS aumentaron significativam ente en el grupo modelo. En comparación con el grupo modelo, todos los cambios se recuperaron en diferentes grados en los grupos de tratamiento. Por lo tanto, se concluyó que el trans - nerolidol puede aliviar el daño en las CE regulando iNOS/eNOS a través d e la activación de PPARγ de manera dependiente de la dosis.

CALD1 facilitates epithelial-mesenchymal transition progression in gastric cancer cells by modulating the PI3K-Akt pathway.

BACKGROUND: CALD1 has been discovered to be abnormally expressed in a variety of malignant tumors, including gastric cancer (GC), and is associated with tumor progression and immune infiltration; however, the roles and mechanisms of CALD1 in epithelial-mesenchymal transition (EMT) in GC are unknown. AIM: To investigate the role and mechanism of CALD1 in GC progression, invasion, and migration. METHODS: In this study, the relationship between CALD1 and GC, as well as the possible network regulatory mechanisms of CALD1, was investigated by bioinformatics and validated by experiments. CALD1-siRNA was synthesized and used to transfect GC cells. Cell activity was measured using the CCK-8 method, cell migration and invasive ability were measured using wound healing assay and Transwell assay, and the expression levels of relevant genes and proteins in each group of cells were measured using qRT-PCR and Western blot. A GC cell xenograft model was established to verify the results of in vitro experiments. RESULTS: Bioinformatics results showed that CALD1 was highly expressed in GC tissues, and CALD1 was significantly higher in EMT-type GC tissues than in tissues of other types of GC. The prognosis of patients with high expression of CALD1 was worse than that of patients with low expression, and a prognostic model was constructed and evaluated. The experimental results were consistent with the results of the bioinformatics analysis. The expression level of CALD1 in GC cell lines was all higher than that in gastric epithelial cell line GES-1, with the strongest expression found in AGS and MKN45 cells. Cell activity was significantly reduced after CALD1-siRNA transfection of AGS and MKN45 cells. The ability of AGS and MKN45 cells to migrate and invade was reduced after CALD1-siRNA transfection, and the related mRNA and protein expression was altered. According to bioinformatics findings in GC samples, the CALD1 gene was significantly associated with the expression of members of the PI3K-AKT-mTOR signaling pathway as well as the EMT signaling pathway, and was closely related to the PI3K-Akt signaling pathway. Experimental validation revealed that upregulation of CALD1 increased the expression of PI3K, p-AKT, and p-mTOR, members of the PI3K-Akt pathway,while decreasing the expression of PTEN; PI3K-Akt inhibitor treatment decreased the expression of PI3K, p-AKT, and p-mTOR in cells overexpressing CALD1 (still higher than that in the normal group), but increased the expression of PTEN (still lower than that in the normal group). CCK-8 results revealed that the effect of CALD1 on tumor cell activity was decreased by the addition of the inhibitor. Scratch and Transwell experiments showed that the effect of CALD1 on tumor cell migration and invasion was weakened by the addition of the PI3K-Akt inhibitor. The mRNA and protein levels of EMT-related genes in AGS and MKN45 cells were greatly altered by the overexpression of CALD1, whereas the effect of overexpression of CALD1 was significantly weakened by the addition of the PI3K-Akt inhibitor. Animal experiments showed that tumour growth was slow after inhibition of CALD1, and the expression of some PI3K-Akt and EMT pathway proteins was altered. CONCLUSION: Increased expression of CALD1 is a key factor in the progression, invasion, and metastasis of GC, which may be associated with regulating the PI3K-Akt pathway to promote EMT.

Application of clinical value assessment of treatment protocols in guideline development: taking the WFAS Clinical Practice Guideline of Acupuncture and Moxibustion for Migraine as an example. / 治疗方案临床价值评估在指南制定中的应用.

To enhance the clinical applicability of guidelines and provide more effective guidance for clinical practice, a clinical value assessment was conducted during the development of the World Federation of Acupuncture-Moxibustion Societies (WFAS) Clinical Practice Guideline of Acupuncture and Moxibustion for Migraine, which involved the evaluation of 59 acupuncture and moxibustion treatment protocols from randomized controlled trials (RCTs). This article introduced the methodology, content and results of the clinical value assessment of RCT-based acupuncture and moxibustion treatment protocols, which involved the integration of historical and contemporary medical evidence and expert consensus. It served as a methodological reference for the future development of acupuncture and moxibustion clinical practice guidelines.

New treatment for gastric duplication cyst: Endoscopic ultrasonography-guided fine-needle aspiration combined with lauromacrogol sclerotherapy: A case report.

BACKGROUND: Gastric duplication cysts are very rare disease that are mainly diagnosed by endoscopic ultrasonographic fine-needle aspiration biopsy. In the past, this disease was usually treated with traditional surgery and rarely with minimally invasive endoscopic surgery. However, minimally invasive endoscopic therapy has many advantages, such as no skin wound, organ preservation, postoperative pain reduction, early food intake, fewer postoperative complications, and shorter post-procedure hospitalization. CASE SUMMARY: We report a case of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) combined with lauromacrogol sclerotherapy for pyloric obstruction due to gastric duplication cysts. CONCLUSION: EUS-FNA combined with lauromacrogol sclerotherapy provides a new option for the treatment of gastrointestinal duplication cysts.

Neoadjuvant docetaxel, oxaliplatin plus capecitabine versus oxaliplatin plus capecitabine for patients with locally advanced gastric adenocarcinoma: long-term results of a phase III randomized controlled trial.

BACKGROUND: Neoadjuvant chemotherapy with docetaxel, oxaliplatin, and capecitabine (DOX regimen) is rarely used in Eastern countries and its efficacy and safety in advanced gastric cancer have not been reported. In this open-label, randomized, controlled trial, the authors aimed to assess the clinical efficacy of neoadjuvant chemotherapy using the DOX and oxaliplatin plus capecitabine (XELOX) regimens, in comparison to surgery alone. MATERIALS AND METHODS: Three hundred patients younger than 60 years with potentially resectable advanced gastric cancer (cT3-4, Nany, M0) were enrolled in this randomized controlled clinical trial between November 2014 and June 2018. The primary endpoint of the study was the pathological complete response (pCR) rate. Secondary endpoints included 3-year overall survival (OS), 3-year disease-free survival. RESULTS: In total, 280 patients (93 in the DOX group, 92 in the XELOX group, and 95 in the surgery group) were included in the per-protocol analysis. The DOX group demonstrated a significantly higher pCR rate compared to the XELOX group (16.1 vs. 4.3%, P =0.008). For patients with intestinal type, the DOX group exhibited significantly higher rates of both pCR and major pathological response compared to the XELOX group ( P =0.007, P <0.001). The 3-year OS rates of the DOX group, the XELOX group and the surgery group were 56.9, 44.6, and 34.7%, respectively. The 3-year disease-free survival rates were 45.2, 40.2, and 28.4%, respectively. The neoadjuvant DOX regimen demonstrated a significant improvement in the 3-year OS of patients compared to the neoadjuvant XELOX regimen ( P =0.037). CONCLUSION: The neoadjuvant DOX regimen has shown the potential to increase the pCR rate and improve the prognosis of patients with advanced gastric cancer who are under 60 years old.

Effectiveness of Acupuncture for Prophylactic Treatment of Migraine: A Systematic Review and Bayesian Network Meta-Analysis.

It is aimed to evaluate the effectiveness and provide evidence-based medical support for acupuncture as a prophylactic treatment for migraines. Randomized controlled trials (RCTs) from inception to April 2022 are included in 14 databases. Pairwise meta-analysis is conducted using STATA software V14.0, while Windows Bayesian Inference Using Gibbs Sampling (WinBUGS V.1.4.3) is applied to generate Bayesian Network Meta-analysis (NMA) using Markov chain Monte Carlo algorithm. Forty RCTs are included, with 4405 participants. The effectiveness of six acupuncture techniques, three types of prophylactic drugs, and psychotherapy are compared and ranked. Acupuncture outperformed prophylactic drugs in terms of diminishing visual analog scale (VAS) score, migraine attack frequency, and days during the treatment and at the 12-week follow-up. At the 12-week follow-up, the effectiveness of various interventions is ranked as follows: manual acupuncture (MA) > electroacupuncture (EA) > calcium antagonists (CA) in reducing VAS score; MA > EA > CA in reducing migraine attack frequency; MA > EA > ß-receptor blocker and CA in reducing headache attack days. Acupuncture is a promising treatment for migraine prevention. The best option of acupuncture for improving various migraine outcomes has changed over time. However, the quality of included trials and NMA inconsistency limited the credibility of the conclusion.

[Surgical treatment for ipsilateral femoral neck and shaft fracture].

OBJECTIVE: To retrospectively analyze efficacy of single structure internal fixation and double structure internal fixation in the treatment of ipsilateral femoral shaft and neck fracture, and analyze their indications. METHODS: From June 2015 to December 2020, 21 patients with ipsilateral femoral shaft and femoral neck fracture were treated, including 14 males and 7 females, aged 23 to 69 years old with an average of(38.1±12.9) years old. According to different femoral shaft fracture sites, some patients were fixed with cephalomedullary implant for both femoral neck and the femoral shaft(single structure, InterTan or PFNA Ⅱ), some patients were fixed with cannulated screws for the femoral neck and a retrograde locking nail for the femoral shaft (dual structure), and postoperative function and complications were recorded during follow-up. In 10 cases of single-structure fixation, the femoral necks were all basicervical fractures, and the femoral shaft fractures were located in the proximal isthmus;11 cases were double-structure fixation, 9 cases in 11 were basal type of femoral neck, 2 cases in 11 were neck type, and the femoral shaft fractures were located in the isthmus and the distal isthmus. RESULTS: All patients were followed up for 12 to 27 months. No femoral head necrosis, deformity, delay or nonunion occurred in the patients with single-structure fixation, and no delayed union or nonunion occurred in femoral shaft fractures;At the final follow-up, Harris score of patients with single-structure fixation was 91.8±4.1, with 8 cases were excellent and 2 cases were good. The fractures of patients with dual-structure fixation achieved good union without femoral head necrosis, except 1 case of femoral shaft fracture had delayed union;At the final follow-up, Harris score of patients with dual-structure fixation was 92.4±5.9, 7 cases were excellent, 3 cases were good, and 1 case was fair. CONCLUSION: Good reduction and fixation is the key to the treatment of such fractures. Both the single-structure fixation and the dual-structure fixation are good methods, and it should be selected according to the locations of femoral shaft and femoral neck fractures. Single-structure fixation is a good choice for femoral shaft fractures located at the proximal isthmus and basal femoral neck fractures. For isthmus and distal femoral shaft fractures combined with ipsilateral femoral neck fractures, dual-structure fixation is recommended.

Finite element analysis of necessity of reduction and selection of internal fixation for valgus-impacted femoral neck fracture.

This study compared the biomechanical characteristics of different treatment strategies based on finite element analysis. Posterior tilt and valgus angle were measured on X-ray from ten valgus-impacted femoral neck fractures, and 7 finite element models that were generated to compare the stress and displacement. The results showed that in the intact femur, von Mises stress was concentrated at the medial and inferior sides of the femoral neck. In valgus-impacted femoral neck fractures, von Mises stress was at the same locations but was 5.66 times higher than that in the intact femur. When 3 cannulated screws were used for internal fixation, anatomic reduction diminished the stress at the fracture end from 140.6 to 59.14 MPa, although displacement increased from 0.228 to 0.450 mm. When the fracture was fixed with a sliding hip screw (SHS) + cannulated screw, there was less stress at the fracture end and greater displacement with anatomic reduction than that without reduction (stress: 15.9 vs 37.9 MPa; displacement: 0.329 vs 0.168 mm). Therefore, the SHS + cannulated screw has superior biomechanical stability than 3 cannulated screws, and is recommended following anatomic reduction to treat valgus-compacted femoral neck fractures.

Elevated CO2 exacerbates effects of TiO2 nanoparticles on rice (Oryza sativa L.) leaf transcriptome and soil bacteria.

Elevated CO2 affects the plant rhizosphere and can therefore affect the fate and toxicity of soil contaminants. However, little is known about how the effects of nanoparticles on plants and soil bacteria will change under future CO2 levels. A free-air CO2 enrichment system with two CO2 levels (ambient, 390 µmol mol-1; elevated, 590 µmol mol-1) was used to investigate the responses of rice (Oryza sativa L.) and soil bacteria to titanium dioxide nanoparticles (nano-TiO2, 0 and 200 mg kg-1). Results showed that nano-TiO2 alone did not significantly affect rice growth but affected soil bacteria involved in the carbon and sulfur cycles. Elevated CO2 alone increased rice plant biomass and up-regulated genes related to ribosomes, but its combination with nano-TiO2 down-regulated genes related to photosynthesis and photosynthetic antennae. Elevated CO2 also exacerbated the disturbance by nano-TiO2 to soil bacteria involved in carbon and nitrogen cycles, and consequently inhibited the rice growth. These findings provide a reference for the comprehensive evaluation for the risk of soil pollution.

Development of protective agents against ovarian injury caused by chemotherapeutic drugs.

BACKGROUND: Chemotherapy is one of the causes of ovarian injury and infertility. Although assisted reproductive technology helps young female patients with cancer become pregnant, preventing chemotherapy-induced ovarian injury will often possess even more significant benefits. OBJECTIVE: We aimed at demonstrating the hazardous effects and mechanisms of ovarian injury by chemotherapeutic agents, as well as demonstrating agents that protect the ovary from chemotherapy-induced injury. RESULTS: Chemotherapeutic agents cause death or accelerate activation of follicles and damage to the blood vessels in the ovary, resulting in inflammation. These often require drug development to protect the ovaries from injury. CONCLUSIONS: Our findings provide a basis for the development of drugs to protect the ovaries from injury. Although there are many preclinical studies on potential protective drugs, there is still an urgent need for a large number of clinical experiments to verify their potential use.

Toxicity of triphenyl phosphate toward the marine rotifer Brachionus plicatilis: Changes in key life-history traits, rotifer-algae population dynamics and the metabolomic response.

Triphenyl phosphate (TPhP) is used as a flame retardant that gradually leaks from products into the marine environment and thus may threaten low-trophic-level marine organisms, such as zooplankton. To assess the effect of TPhP on these taxa, we treated the marine rotifer Brachionus plicatilis as a target and examined the changes in key life history parameters and the metabolome after exposure to TPhP at 0.02, 1 and 5 mg/L. Additionally, the rotifer-Phaeocystis population dynamics (a simulation of the prey-predator relationship) were studied under TPhP stress. Our results showed that TPhP at 1 and 5 mg/L reduced the average lifespan and the total offspring number and prolonged the prereproductive time, suggesting damage to survival and fecundity. In the 0.02 mg/L group, no obvious damage occurred in the overall condition of rotifers, but the volume of parental rotifers after the first brood decreased. This implied that rotifers sacrificed somatic growth to reproduction in the initial period of TPhP exposure at the low concentration. All the tested TPhP concentrations altered the rotifer-Phaeocystis population dynamic changes, especially that 1 mg/L TPhP reduced the ability of rotifers to remove this harmful alga, as evidenced by the decrease in the maximum population density of rotifers and the extended time to P. globosa extinction. At the molecular level, metabolomics identified 84 and 206 differentially expressed metabolites, most of which were enriched in glycerophospholipid metabolism, steroid biosynthesis and sphingolipid metabolism. Nile red staining showed a decrease in neutral lipids in rotifers, further indicating a disorder of lipid metabolism induced by TPhP. Moreover, the balance between ROS production and the defense system was disrupted by TPhP, which contributed to its toxicity. This finding will promote the understanding of the ecological risk and mode of action of TPhP in aquatic environments.

Alleviation of Tris(2-chloroethyl) Phosphate Toxicity on the Marine Rotifer Brachionus plicatilis by Polystyrene Microplastics: Features and Molecular Evidence.

As emerging pollutants, microplastics (MPs) and organophosphorus esters (OPEs) coexist in the aquatic environment, posing a potential threat to organisms. Although toxicological studies have been conducted individually, the effects of combined exposure are unknown since MPs can interact with OPEs acting as carriers. In this study, we assessed the response of marine rotifer, Brachionus plicatilis, to co-exposure to polystyrene MPs and tris(2-chloroethyl) phosphate (TCEP) at different concentrations, including population growth, oxidative status, and transcriptomics. Results indicated that 0.1 µm and 1 µm MPs were accumulated in the digestive system, and, even at up to 2000 µg/L, they did not exert obvious damage to the stomach morphology, survival, and reproduction of B. plicatilis. The presence of 1 µm MPs reversed the low population growth rate and high oxidative stress induced by TCEP to the normal level. Some genes involved in metabolic detoxification and stress response were upregulated, such as ABC and Hsp. Subsequent validation showed that P-glycoprotein efflux ability was activated by combined exposure, indicating its important role in the reversal of population growth inhibition. Such results challenge the common perception that MPs aggravate the toxicity of coexisting pollutants and elucidate the molecular mechanism of the limited toxic effects induced by MPs and TCEP.

Wnt signaling in triple-negative breast cancers: Its roles in molecular subtyping and cancer cell stemness and its crosstalk with non-coding RNAs.

Triple-negative breast cancers (TNBCs) are now acknowledged as a collection of diseases encompassing distinct histological plasticity, multi-tier molecular heterogeneity, as well as different outcomes. Despite decades of efforts, the molecular subtyping strategy has been theoretical, and target therapies based on molecular alternations barely improve survival rates of TNBC patients, and thus traditional chemotherapy remains the standard of care in clinic. The Wnt signaling is an evolutionarily conserved signaling pathway, playing critical roles in embryogenesis and neoplastic disease. The dysregulation of Wnt signaling pathway endows cancer cells with stem cell-like capacities of self-renewal, cell proliferation and differentiation, thus exerting crucial roles in tumorigenesis and therapy responses. Recently, the gene expression assays and genomic sequencing have demonstrated that the dysregulation of Wnt signaling is associated with progression of TNBCs, particularly with metastasis, relapse and therapy resistance. In this review, we highlight the dysregulation of Wnt signaling in TNBCs and its potential biological roles in molecular subtyping and stemness traits of specific subtypes, as well as its crosstalk with ncRNAs in regulation of the biological features of TNBCs, aiming to update this important oncogenic signaling pathway in TNBCs.

Assessment of Carbon Nanoparticle Suspension Lymphography-Guided Distal Gastrectomy for Gastric Cancer.

Importance: Carbon nanoparticle suspension injection (CNSI) can be used to visualize lymph node (LN) drainage in gastric cancer. The tracing and diagnostic value of carbon nanoparticle suspension lymphography-guided distal gastrectomy for gastric cancer has not been thoroughly reported. Objective: To compare the number of lymph nodes identified in patients with gastric cancer receiving a CNSI vs no injection. Design, Setting, and Participants: This is a retrospective cohort study including patients with clinical T1 to T4 disease who underwent laparoscopic or robotic distal gastrectomy. Data from a cohort of 1225 patients at the Fourth Hospital of Hebei Medical University (Shijiazhuang, China) from November 2019 to February 2021 were analyzed. Patients were divided into the CNSI group and conventional group after 1:1 propensity matching analysis. The mean number of LNs detected was compared between groups, and the diagnostic role of CNSI was analyzed in the CNSI group. Statistical analysis was performed from May to July 2021. Exposure: CNSI was peritumorally injected under an endoscope 1 day before surgery in the CNSI group, and the conventional group did not receive any treatment before surgery. Main Outcomes and Measures: The main outcome was the number of LNs detected. Gastrectomy with systematic D1+ (ie, stations 1, 3, 4sb, 4d, 5, 6, and 7) or D2 (ie, all D1 stations, plus 8a, 9, 11p, and 12a) lymphadenectomy was performed. Black-stained LNs and nonblack-stained LNs were examined separately in the CNSI group. Results: A total of 312 consecutive patients (mean [SD] age, 56.7 [10.4] years; 216 [69.2%] men) who underwent distal gastrectomy were enrolled, including 78 patients in the CNSI group, and another 78 patients determined from 1:1 propensity score matching, making an overall cohort size of 156 patients. The mean (SD) number of LNs detected in the CNSI group was 59.6 (21.4), which was significantly higher than that in the conventional group (30.0 [11.3] LNs; P < .001). In the CNSI group, the mean (SD) number of LNs detected at black-stained LN stations was significantly higher than that at nonstained LN stations (9.2 [6.1] LNs per station vs 3.5 [3.2] LNs per station; P < .001). For black-stained LN stations, the sensitivity was 97.8% (95% CI, 91.6%-99.6%), specificity was 38.1% (95% CI, 34.2%-42.3%), positive predictive value was 20.1% (95% CI, 16.6%-24.2%), and negative predictive value was 99.1% (95% CI, 96.4%-99.8%); for the black-stained LNs, sensitivity was 97.6% (95% CI, 95.3%-98.8%), specificity was 35.4% (95% CI, 33.9%-36.8%), positive predictive value was 11.6% (95% CI, 10.5%-12.8%), and negative predictive value was 99.4% (95% CI, 98.8%-99.7%). Conclusions and Relevance: These findings suggest that CNSI was associated with facilitating the dissection of all positive LNs, which could improve surgical quality. Carbon nanoparticle suspension-guided lymphography may be an alternative to conventional systematic lymphadenectomy for distal gastrectomy.

Endoscopic diagnosis of early-stage primary esophageal small cell carcinoma: Report of two cases.

BACKGROUND: Primary esophageal small cell carcinoma (PESCC) is a highly aggressive malignancy, and its detailed clinical behaviors have remained virtually unknown. Because of the rapid tumor progression, the diagnosis of esophageal small cell carcinoma at early stage is extremely difficult in clinical practice. Currently, only a handful of PESCC cases have been reported. CASE SUMMARY: Case 1: A 62-year-old man was diagnosed with an esophageal submucosal tumor by endoscopy. Endoscopic ultrasonography showed a 0.8 cm low echo nodule in the muscularis mucosa. As the patient refused to undergo endoscopic resection, neoplasia was detected by endoscopy 1 year later. Case 2: A 68-year-old woman was diagnosed as having an esophageal submucosal tumor by endoscopy at a local hospital. About 2 wk later, we performed endoscopic ultrasonography and found a 1 cm low echo nodule in the muscularis mucosa; the submucosal was thinner than normal but still continuous; mucosal hyperemia and erosion were found on the surface of the tumor. Endoscopic submucosal dissection (ESD) was performed and the histopathological finding showed a small cell carcinoma invading the submucosal layer. CONCLUSION: Early esophageal small cell carcinoma shows submucosal infiltrating growth with a hypoechoic mass in the muscularis mucosa as diagnosed by endoscopic ultrasonography. It is easily misdiagnosed as submucosal masses. Endoscopic manifestations should be identified and pathological biopsies should be employed. ESD may be performed to provide an opportunity for early treatment of PESCC.

Responses of the reproduction, population growth and metabolome of the marine rotifer Brachionus plicatilis to tributyl phosphate (TnBP).

The typical alkyl organophosphorus flame retardant tributyl phosphate (TnBP) can leak from common products into the marine environment, with potential negative effects on marine organisms. However, risk assessments for TnBP regarding zooplankton are lacking. In this study, a marine rotifer, Brachionus plicatilis, was used to analyze the effect of TnBP (0.1 µg/L, environmental concentration; 1 and 6 mg/L) on reproduction, population growth, oxidative stress, mitochondrial function and metabolomics. Mortality increased as the TnBP concentration rose; the 24-h LC50 value was 12.45 mg/L. All tested TnBP concentrations inhibited B. plicatilis population growth, with reproductive toxicity at the higher levels. Microstructural imaging showed ovary injury, the direct cause of reproductive toxicity. Despite elevated glutathione reductase activities, levels of reactive oxygen species and malonyldialdehyde increased under TnBP stress, indicating oxidative imbalance. TnBP induced mitochondrial malformation and activity suppression; the ROS scavenger N-acetylcysteine alleviated this inhibition, suggesting an internal connection. Nontargeted metabolomics revealed 398 and 583 differentially expressed metabolites in the 0.1 µg/L and 6 mg/L treatments relative to control, respectively, which were enriched in the pathways such as biosynthesis of amino acids, purine metabolism, aminoacyl-tRNA biosynthesis. According to metabolic pathway analysis, oxidative stress from purine degradation, mitochondrial dysfunction, disturbed lipid metabolism and elevated protein synthesis were jointly responsible for reproduction and population growth changes. This study echoes the results previously found in rotifer on trade-off among different life processes in response to environmental stress. Our systematic study uncovers the TnBP toxic mode of action.

Feeding behavior toxicity in the marine rotifer Brachionus plicatilis caused by 2,2',4,4'-tetrabromodiphenyl ether (BDE-47): Characteristics and mechanisms.

Polybrominated diphenyl ether contamination in marine environments has received special attention due to its accumulation and magnification in the marine food web and toxicity to organisms. In the present study, a series of short-term toxicological tests were conducted with the marine rotifer Brachionus plicatilis to assess the effects on ingestion and digestive performance after treatment with 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) at nonlethal concentrations under controlled laboratory conditions and to analyze the possible mechanism. The results showed that with accumulation in rotifers, BDE-47 caused a significant decline in the filtration and feeding rates in a concentration-dependent manner. Moreover, the activities of amylase (AMS) and protease were affected, indicating that BDE-47 impaired ingestion and digestion efficiency. BDE-47 exposure did not lead to abnormal microstructures in the main digestive tract (e.g., cilia around the corona, mastax, stomach, digestive gland and esophagus), but the gastric parietal cells shrank, suggesting nutritional deficiency. BDE-47 prominently induced the occurrence of irregular mitochondria at the cilia root, and mitochondrial and isocitrate dehydrogenase activity declined, indicating mitochondrial dysfunction. Furthermore, the activity of ATPase, which catalyzes ATP hydrolysis, decreased as the BDE-47 concentration rose, implying that BDE-47 retarded rotifer ATP dynamics, inevitably interfering with cilia movement to ingest food. Additionally, a significant decline in acetylcholine esterase activity was observed, which led to a hindrance in neurotransmission involved in food intake and digestion. Altogether, our results demonstrated that nonlethal concentrations of BDE-47 could induce feeding depression in rotifers, which is mainly attributed to stymied energy metabolism and nerve conduction.

Toxic effect and mechanism of tris (1,3-dichloro-2-propyl)phosphate (TDCPP) on the marine alga Phaeodactylum tricornutum.

Tris (1,3-dichloro-2-propyl)phosphate (TDCPP) is an organophosphate-based plasticizer and flame retardant with a high production volume. The ubiquitous distribution and persistence of TDCPP in aquatic environment have led to concerns over its possible toxic effects on aquatic organism. However, data regarding the toxicity of TDCPP on algae are limited, and the molecular mechanism remains largely unknown. Therefore, we determined the growth characteristics, physiological changes and transcriptome profiles of Phaeodactylum tricornutum in response to 4 mg L-1 TDCPP for 24 h. TDCPP caused morphological damage and growth inhibition with an EC50 value of 3.71 mg L-1 at 96 h. A decline in pigments and photosynthetic activity was observed, indicating the occurrence of photosynthesis inhibition. Although the activities of both glutathione peroxidase and glutathione reductase were stimulated, oxidative stress was not relieved in the algal cells, as evidenced by the elevated levels of reactive oxygen species and lipid peroxidation. Transcriptomic analyses revealed 3312 differentially expressed genes (DEGs), and photosynthesis was a key target, as genes related to this process were greatly altered under TDCPP stress. Moreover, some DEGs were also enriched in amino acid metabolism, nitrogen metabolism, nucleotide metabolism and lipid metabolism, implying that TDCPP-induced damage towards algae by various pathways. Additionally, several TFs related to stress signaling were differentially expressed, suggesting roles in the TDCPP stress response. The results will provide critical data to understand the ecological risks and toxic mechanism of OPFRs entering into marine habitat.

Lycium barbarum polysaccharide protects against ethanol-induced spermiotoxicity and testicular degeneration in Immp2l+/- mice.

Studies have indicated that high levels of ethanol exposure impaired spermatogenesis in mice. However, the effects of chronic and low-dose alcohol consumption on susceptible populations remain unclear. The previous studies have confirmed that Immp2l mutant mice (Immp2lTg(Tyr)979Ove or Immp2l-/- ) suffered from increased levels of oxidative stress(OS) and male infertility, heterozygous lmmp2l mice (Immp2l+/- ) showed no altered ROS levels under physiological condition. Lycium barbarum polysaccharide (LBP) significantly scavenge oxygen free radicals and enhance antioxidant enzyme activity. The objectives of present study were to research the effects of chronic and low-dose alcohol-induced damage on Immp2l+/- , explore the protective function of LBP and possible mechanism. The results indicated that chronic ethanol exposure leads to spermatogenic impairment and triggered a toxic effect on germ cell, 10 mg/kg LBP administration improved the quality of spermatozoon, decreased the ratio of apoptotic germ cells and the expression of Col1a1 and Col1a2, while increased the level of TNP2 and RPL31. In conclusion, the study may provide basic knowledge about LBP's important role against ethanol-induced spermiotoxicity and testicular degeneration in Immp2l+/- mice, and the mechanism may be that LBP influenced the state of the spermatogenic epithelium by decreasing the expression of Collagen level leading to alterations in protein biosynthesis during the process of spermatogenesis.