Dose-effect Relationship Research Articles

Pollution Characteristics of Different Components of PM2.5 in Taiyuan during 2017–2020 Wintertime and Their Toxicity Effects on HepG2 Cells

Fine particulate matter (PM2.5) is a common pollutant, and its health risk has attracted much attention. Studies have shown that PM2.5 exposure is associated with liver disease. The composition of PM2.5 is complex, and its hepatotoxic effects and lipid metabolism process are not well understood. In this study, we detected the concentrations of PM2.5 and its components (metals and polycyclic aromatic hydrocarbon (PAHs)) in the winter in Taiyuan, Shanxi Province, China, from 2017 to 2020 and then assessed the health risks. We also investigated the effects of different components (whole particles (WP), water-soluble particles (WSP), organic particles (OP)) of PM2.5 on the cytotoxicity and lipid metabolism in human liver cell line (HepG2) after 24 h of treatment. The changes in cytotoxicity indexes (LDH, IL-6, reactive oxygen species (ROS)) and lipids (triglyceride (TG), free fatty acid (FFA)) were measured after 24 h. The mRNA expression of lipid metabolism-related factors (SREBP1, CD36, MTTP) was determined by real-time quantitative RT-qPCR. Finally, the correlation between metals and PAHs with higher PM2.5 content in 4 years and biomarkers was analyzed. The results showed that: (1) The PM2.5 pollution was severe in Taiyuan during winter in 2017 and the subsequent four years. The calculation results of the metal enrichment factor (EF) value and PAHs characteristic ratio of PM2.5 showed that PM2.5 pollution sources differed in different years. (2) Exposure to metals and PAHs in PM2.5 did not cause a non-carcinogenic risk. Metals had no cancer risk, while PAHs inhaled in PM2.5 in 2017 and 2018 had a potential cancer risk. The atmospheric PM2.5 pollution in Taiyuan has had a downward trend, but the PAHs in the PM2.5 of 2017–18, when the pollution is relatively serious, have a potential carcinogenic risk. (3) WP, OP and WSP inhibited cell survival rate from 2017 to 2020, and OP had higher cytotoxicity at the same concentration. (4) WP, OP and WSP increased the levels of LDH, IL-6, TNF-α, ROS, MDA, TG and FFA, and inhibited SOD activity in a dose-effect relationship. The organic components in PM2.5 are more toxic to HepG2 cells and affect the expression of lipid metabolism-related factors at the transcriptional level. (5) The mRNA expressions of factors related to lipid synthesis, uptake, oxidation and output were up-regulated after treatment with PM2.5 and its components, suggesting a lipid metabolism disorder. (6) The biomarkers were associated with certain metals (Zn, Pb, Cu and Cr) and PAHs in PM2.5. These suggested that PM2.5- and PM2.5-bound organic matter caused HepG2 cytotoxicity and affected lipid metabolism.

The Cytotoxic Effects of Fine Particulate Matter (PM2.5) from Different Sources at the Air-Liquid Interface Exposure on A549 Cells.

The health of humans has been negatively impacted by PM2.5 exposure, but the chemical composition and toxicity of PM2.5 might vary depending on its source. To investigate the toxic effects of particulate matter from different sources on lung epithelial cells (A549), PM2.5 samples were collected from residential, industrial, and transportation areas in Nanjing, China. The chemical composition of PM2.5 was analyzed, and toxicological experiments were conducted. The A549 cells were exposed using an air-liquid interface (ALI) exposure system, and the cytotoxic indicators of the cells were detected. The research results indicated that acute exposure to different sources of particulate matter at the air-liquid interface caused damage to the cells, induced the production of ROS, caused apoptosis, inflammatory damage, and DNA damage, with a dose-effect relationship. The content of heavy metals and PAHs in PM2.5 from the traffic source was relatively high, and the toxic effect of the traffic-source samples on the cells was higher than that of the industrial- and residential-source samples. The cytotoxicity of particulate matter was mostly associated with water-soluble ions, carbon components, heavy metals, PAHs, and endotoxin, based on the analysis of the Pearson correlation. Oxidative stress played an important role in PM2.5-induced biological toxicity.

Assessment of no-observed-effect-levels for DNA adducts formation by genotoxic carcinogens in fetal turkey livers

For genotoxic carcinogens, covalent binding to DNA is a critical initiating event in tumorigenesis. The present research investigated dose-effect relationships of three genotoxic carcinogens representing different structural classes, 2-acetylaminofluorene (2-AAF), benzo[a]pyrene (B[a]P) and quinoline (QUI), to assess the existence of no-observed-effect-levels (NOELs) for the formation of DNA adducts. Carcinogens were administered into the air sac of fertilized turkey eggs over wide dose ranges in three daily injections on days 22 to 24 of incubation. DNA adducts were measured in the fetal turkey livers by the 32P-nucleotide postlabeling (NPL) assay. B[a]P and QUI produced DNA adducts in a dosage-related manner and exhibited NOELs at 0.65 and 0.35 mg/kg bw/day, respectively. In contrast, 2-AAF formed DNA adducts at all tested dosages down to 0.005 mg/kg bw/day. Benchmark dose (BMD) analysis identified the potencies of 2-AAF and QUI to be similar, while B[a]P was the least potent compound. Overall, findings in fetal turkey livers demonstrated that exposure levels to genotoxic compounds that do not result in DNA adducts can exist but are not evident with all carcinogens of this type. The use of mechanistic dose-effect studies for genotoxic endpoints can provide critical information for prioritization of concerns for risk assessment.

Evaluation of Dose-Response Relationship of Permeation Enhancer Isopropyl Myristate Release on Drug Release: Release Enhancement Efficiency and Molecular Mechanism.

The objective of this study is to investigate the dose-response relationship between various concentrations of permeation enhancers (PEs) and their ability to enhance drug release from a polymer matrix, utilizing an innovative parameter known as release enhancement efficiency (K). Additionally, the molecular mechanism underlying dynamic enhancement was also examined. Isopropyl myristate (IPM) was used as model enhancer and zolmitriptan (ZOL) was used as model drug to investigate dose-effect relationship in pressure sensitive adhesives (PSA). The release behavior of the PEs was determined by LC-MS/MS and verified by confocal laser scanning microscopy (CLSM). The enhancing effect of the PE on ZOL release was evaluated through in vitro release experiments and further validated by pharmacokinetics study. And the molecular mechanism was characterized with thermal analysis (DSC), Fourier transform infrared spectroscopy (FT-IR) and molecular dynamics simulation. K was 0.156, 0.286 and 0.279 at 3%, 6% and 9% IPM concentrations, indicating that the enhancement efficiency reached the maximum when the 6% IPM was applied. According to the mechanism research results, the fluidity of PSA increased linearly with the increase of IPM concentrations, but the interaction between IPM and ZOL reached its strongest point at 6%. In summary, the increase of K value (from 0 to 6% IPM content) was caused by the synergy of increased mobility of PSA and interaction (dipole-dipole and hydrogen-bond) among three components, and when the above two actions were in antagonistic, K no longer increased (6-9% IPM content).

Dose-effect relationship of different acupuncture courses on chronic insomnia disorder: study protocol for a randomized controlled trial.

Chronic insomnia disorder (CID) is increasing in prevalence year by year, is long lasting, and potentially risky. Acupuncture has been widely used in the clinical management of this condition. However, there is still a lack of direct evidence on the dose-effect relationship between different acupuncture courses and clinical efficacy. To identify this relationship, we will design a randomized controlled trial to clarify the difference in efficacy of different acupuncture courses for CID. This is a prospective, parallel, single center randomized controlled trial. Two hundred and one participants with CID will be randomly divided into three groups (Group A, Group B, and Group C). The three groups will be given acupuncture therapy for 4, 6, and 8 weeks, three sessions per week, with at least 1 day between sessions. Follow-up will continue until the third month after the end of treatment. The primary outcome is the Insomnia Severity Index (ISI), and secondary outcomes include percentage of ISI < 8 points, the Pittsburgh Sleep Quality Index (PSQI), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Fatigue Severity Scale (FSS), medication use, and safety. This study is expected to provide direct evidence for the optimal treatment cycle of acupuncture for CID, as well as to facilitate health economic evaluation. https://clinicaltrials.gov/, identifier [ChiCTR2300073711].

Model-based meta-analysis using latent variable modeling to set benchmarks for new treatments of systemic lupus erythematosus.

Several investigational agents are under evaluation in systemic lupus erythematosus (SLE) clinical trials but quantitative frameworks to enable comparison of their efficacy to reference benchmark treatments are lacking. To benchmark SLE treatment effects and identify clinically important covariates, we developed a model-based meta-analysis (MBMA) within a latent variable model framework for efficacy end points and SLE composite end point scores (BILAG-based Composite Lupus Assessment and Systemic Lupus Erythematosus Responder Index) using aggregate-level data on approved and investigational therapeutics. SLE trials were searched using PubMed and www.clinicaltrials.gov for treatment name, SLE and clinical trial as search criteria that resulted in four data structures: (1) study and investigational agent, (2) dose and regimen, (3) baseline descriptors, and (4) outcomes. The final dataset consisted of 25 studies and 81 treatment arms evaluating 16 different agents. A previously developed (K Goteti etal. 2022) SLE latent variable model of data from placebo arms (placebo + standard of care treatments) was used to describe aggregate SLE end points over time for the various SLE placebo and treatment arms in a Bayesian MBMA framework. Continuous dose-effect relationships using a maximum effect model were included for anifrolumab, belimumab, CC-220 (iberdomide), epratuzumab, lulizumab pegol, and sifalimumab, whereas the remaining treatments were modeled as discrete dose effects. The final MBMA model was then used to benchmark these compounds with respect to the maximal efficacy on the latent variable compared to the placebo. This MBMA illustrates the application of latent variable models in understanding the trajectories of composite end points in chronic diseases and should enable model-informed development of new investigational agents in SLE.

Mechanism of the adverse outcome of Chlorella vulgaris exposure to diethyl phthalate: Water environmental health reflected by primary producer toxicity

As a ubiquitous contaminant in aquatic environments, diethyl phthalate (DEP) is a major threat to ecosystems because of its increasing utilization. However, the ecological responses to and toxicity mechanisms of DEP in aquatic organisms remain poorly understood. To address this environmental concern, we selected Chlorella vulgaris (C. vulgaris) as a model organism and investigated the toxicological effects of environmentally relevant DEP concentrations at the individual, physiological, biochemical, and molecular levels. Results showed that the incorporation of DEP significantly inhibited the growth of C. vulgaris, with inhibition rates ranging from 10.3 % to 83.47 %, and disrupted intracellular chloroplast structure at the individual level, while the decrease in photosynthetic pigments, with inhibition rates ranging from 8.95 % to 73.27 %, and the imbalance of redox homeostasis implied an adverse effect of DEP at the physio-biochemical level. Furthermore, DEP significantly reduced the metabolic activity of algal cells and negatively altered the cell membrane integrity and mitochondrial membrane potential. In addition, the apoptosis rate of algal cells presented a significant dose–effect relationship, which was mainly attributed to the fact that DEP pollutants regulated Ca2+ homeostasis and further increased the expression of Caspase-8, Caspase-9, and Caspase-3, which are associated with internal and external pathways. The gene transcriptional expression profile further revealed that DEP-mediated toxicity in C. vulgaris was mainly related to the destruction of the photosynthetic system, terpenoid backbone biosynthesis, and DNA replication. Overall, this study offers constructive understandings for a comprehensive assessment of the toxicity risks posed by DEP to C. vulgaris.

Tibetan mineral-herbal medicine Zuotai alleviates the depressive-like behaviors in chronic restraint-stressed mice while regulating stress hormone, inflammation and monoamine

Introduction:Zuotaiis an ancient mineral-herbal mixture containing β-HgS in Tibetan medicine. It is used to treat nervous system diseases, similar to Chinese medicine cinnabar and Indian Ayurveda medicineRasasindura. However, one of the key problems faced byZuotaiis that its indications are ambiguous. Our previous study found thatZuotaiexhibited the activity of ameliorating depressive-like behaviors in a chronic mild stress model. However, due to the inherent limitations of animal models in simulating human disease, clear results often require more than one model for confirmation.Methods:Therefore, another depression model, chronic restraint stressed (CRS) mice, was used to validate the antidepression effect ofZuotai. Prophylactic treatment was conducted for 21 consecutive days while mice were subjected to chronic restraint stress.Results:It was observed thatZuotaiand β-HgS alleviated anhedonia, behavioral despair, stereotype behavior, and reduced exploratory and spontaneous movement in CRS mice.Zuotaiand β-HgS also reversed the increases of stress hormone corticosterone (Cort) in serum and pro-inflammatory cytokines in serum and brain, and increased the serotonin in cortex in CRS mice, with positive dose-effect relationship. The number of Ki67-positive cells in the dentate gyrus and the level of brain-derived neurotrophic factor (BDNF) in the hippocampus were slightly elevated in CRS mice treated withZuotai; however, there was no statistically significant difference. AlthoughZuotaiincreased the total Hg concentration in main organs, the levels remained below those needed to result in observed adverse effect, at least for kidney and liver; andZuotaishowed no observed adverse effect on the brain histopathology, the cell proliferation in dentate gyrus, as well as the hippocampal and cortical organ coefficients.Conclusion:Zuotaiexhibited the alleviation of depressive-like behaviors in CRS mice, accompanying with ameliorating stress hormone, peripherical and cerebral inflammation, and monoamine neurotransmitter.

Airborne bacteria viability and air quality: a protocol to quantitatively investigate the possible correlation by an atmospheric simulation chamber

Abstract. Biological particulate matter or bioaerosol are a subset of atmospheric aerosol. They influence climate, air quality, and health via several mechanisms which often are poorly understood. In particular, the quantitative study of possible relationship between bioaerosol viability and air quality or meteorological conditions is an open and relevant issue. The difficulty of retrieving such possible correlations by analyses of data collected during in-field campaigns can benefit of targeted experiments conducted in well-controlled conditions inside atmospheric simulation chambers (ASCs). ChAMBRe (Chamber for Aerosol Modelling and Bio-aerosol Research) is an ASC in Genoa (Italy) designed and built to perform experimental research on bioaerosol. In this article, we focus on bacteria viability. A multi-step protocol was developed and thoroughly tested to cultivate a suitable bacteria population (E. coli), nebulize and inject in a chamber of viable cells, expose and monitor the viability variation inside ChAMBRe, hold at selected conditions, and finally incubate and count the concentration of viable bacteria. The whole procedure showed an estimated lifetime of total (T) and viable (V) E. coli of about 153 and 32 min, respectively and a V : T lifetime ratio of 40±5 min when ChAMBRe is held in a reference baseline condition. The coefficient of variation of 13 % shows how sensitive the protocol is also to changes in viability when the bacteria are exposed to other (e.g. polluted) conditions. First results showing a viability reduction observed exposing the E. coli strain to NOx concentrations and solar irradiation are presented and discussed. The present results pave the way for systematic studies aimed at the definition of dose–effect relationship for several bacteria strains under different conditions of atmospheric pollutants.

QLTI-07. DOSE-EFFECT RELATIONSHIP OF DEXAMETHASONE ON OUTCOMES OF BRAIN METASTASES

Abstract BACKGROUND Dexamethasone is commonly used to manage peritumoral edema and alleviate neurologic symptoms in patients with intracranial tumors. The optimal dexamethasone dose for brain metastases is unknown and widely variable. Recent literature reports the most common regimen is 4 mg four times daily. However, the half-life of dexamethasone is 35-54 hours, suggesting that such frequent dosing may be unnecessary. We explored the dose-effect relationship of dexamethasone on brain metastases patient outcomes to improve quality of care. METHODS We retrospectively identified 100 patients (1/1/2016 – 12/31/2022) with brain metastases who were treated with dexamethasone and had adequate follow-up. All patients received standard oncologic care including chemotherapy, radiotherapy, and/or surgical intervention. We evaluated the association between dexamethasone dosing regimens (&amp;lt; 4 mg twice daily versus &amp;gt; 4 mg three times daily), clinical outcomes (performance status, clinical and radiographic response to corticosteroids, survival), and dexamethasone adverse effects during the acute presentation and at first neuro-oncologic follow-up. RESULTS Seventy-two patients received less frequent dexamethasone dosing (&amp;lt; 4 mg twice daily), while 28 received more frequent dexamethasone dosing (&amp;gt; 4 mg three times daily). Patients with higher frequency dexamethasone dosing were more likely to have radiographic evidence of midline shift (p &amp;lt; 0.001), compression of ventricles (p &amp;lt; 0.001), and herniation (p = 0.0020) at presentation. Those with more frequent dosing more often demonstrated radiographic response to dexamethasone (67.9% vs. 45.8%, p = 0.0323), but there were no differences in symptomatic improvement, Karnofsky Performance Status, seizure reduction, survival, or the frequency of adverse events (e.g., hyperglycemia, hypertension, infection, psychosis) between the two cohorts. CONCLUSIONS These results suggest that for most patients with brain metastases, less frequent dexamethasone dosing may lead to clinical outcomes that are similar to those patients who received more frequent dosing. However, higher doses of dexamethasone can be considered for those with more concerning radiologic features.

NCOG-39. DOSE-EFFECT RELATIONSHIP OF DEXAMETHASONE ON OUTCOMES OF PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA

Abstract BACKGROUND Dexamethasone is commonly used for symptomatic management in primary central nervous lymphoma (PCNSL). The optimal dosing scheme for dexamethasone is unknown and practice patterns widely vary among clinicians. In this study, we explored the dose-effect relationship of dexamethasone on PCNSL outcomes to better influence quality care for these patients. METHODS We retrospectively identified 24 Mayo Clinic patients (1/1/2018 – 12/31/2022) with pathologically confirmed PCNSL who received dexamethasone. All patients otherwise received standard oncologic care including methotrexate-based systemic chemotherapy and/or radiotherapy. The association between dexamethasone dosing regimens and clinical outcomes (performance status, clinical and radiographic response, survival) in addition to potential adverse effects were evaluated in the acute phase of presentation and at first post-treatment oncology follow up. RESULTS Nine patients received less frequent dexamethasone dosing (4 mg twice daily or less), while 15 received more frequent dexamethasone dosing (4 mg four times daily). Fourteen patients received dexamethasone prior to biopsy, 2 of which (1 in each cohort) had a non-diagnostic biopsy and required a second procedure 3 weeks to 3 months later to confirm PCNSL diagnosis. There were no statistically significant differences in time to diagnosis from presentation or clinical and radiographic improvement including Karnofsky Performance Status, reduction in seizures, or survival between the two cohorts. Additionally, there were no differences in the frequency of adverse events (e.g., hyperglycemia, hypertension, infection, psychosis) between the two dosing regimens. CONCLUSIONS These results suggest that more frequent dexamethasone dosing is not associated with better clinical outcomes in the symptomatic management of PCNSL. Twice daily or less frequent dosing can be considered without compromising patient outcomes.

Promotion of a quality standard for Paris polyphylla var. yunnanensis based on the efficacy-oriented effect-constituent index

Multi-component determination and bioassays used for the quality control of traditional Chinese medicine (TCM) may have certain shortcomings. The effect-constituent index (ECI) is a quality evaluation index weighted by chemical composition analysis and effect detection. This index can be established by the dose-effect relationship of the active ingredients in TCM. In this study, Paris polyphylla var. yunnanensis (PY) was selected as the representative drug. Chemical evaluation and bioactivity evaluation were combined to establish the ECI, to compensate for the deficiency of a single evaluation method to some extent, and can be related to the efficacy of PY, in order to improve its quality standard. The ECI not only reflects the contribution of component content to the quality of PY, but also relates to clinical efficacy and reflects the influence of different components on the biological activity. Moreover, this study provided a reference method for the quality control of other TCMs.

An exploration of biomarkers for noise exposure: mitochondrial DNA copy number and micronucleus frequencies in Chinese workers

ABSTRACT Few studies have been conducted that use biomarkers as early warning signals for noise-associated health hazards. To explore potentially effective biomarkers for noise-exposed populations, we recruited 218 noise-exposed male workers in China. We calculated cumulative noise exposure (CNE) through noise intensity and noise-exposed duration. When the model was fully adjusted, ln-transformed relative mitochondrial DNA copy number (mtDNAcn) decreased by 0.014 (95% confidence interval (CI): −0.026, −0.003) units with each 1 dB(A)∙year increase in CNE levels. CNE was further included in the model as a grouping variable, and the results showed a negative dose-effect relationship between relative mtDNAcn and CNE (P-trend = 0.045). However, we did not find a correlation between CNE and micronucleus (MN) frequencies. Our findings suggest that CNE in workers was associated with a decrease in relative mtDNAcn which may provide a potential biomarker for noise and for certain health risk but not with MN frequencies.

Dose-effect relationship of linear accelerator based stereotactic radiotherapy for brain metastases

ObjectiveThe purpose of this study is to reveal the dose-effect relationship of linear accelerator (LINAC)-based stereotactic radiotherapy (SRT) in patients with brain metastases (BM).Materials and methodsThe PubMed, Cochrane, and Web of Science databases were used to identify studies that reported local tumour control after LINAC-based SRT in patients with BMs. Studies of other approaches that could affect local tumour control, such as whole brain radiotherapy, targeted therapy, and immunotherapy, were excluded from the dose-effect relationship analysis. Data extracted included patient and treatment characteristics and tumour local control. Probit model in XLSTAT 2016 was used for regression analysis, and P < 0.05 was set as the statistically significant level.ResultsAfter literature screening, 19 eligible studies involving 1523 patients were included in the probit model regression analysis. There was no significant dose-effect relationship between nominal BED10 and peripheral BED10 versus 12-month local control probability. There were significant dose effect relationships between the centre BED10 and the average BED10 versus the 12-month local control probability, with P values of 0.015 and 0.011, respectively. According to the model, the central BED10 and the average BED10 corresponding to probabilities of 90% 12-month local control were 109.2 GyBED10 (95% confidence interval (CI): 88.7–245.9 GyBED10) and 87.8 GyBED10 (95% CI: 74.3–161.5 GyBED10), respectively. A 12-month local control rate of 86.9% (95% CI: 81.7–89.7%) and 85.5% (95% CI: 81.2–89.2%) can be expected at a centre BED10 of 80 Gy and an average BED10 of 60 Gy, respectively.ConclusionFor patients with BM treated with LINAC-based SRT, more attention should be given to the central and average doses of PTV. A clear definition of the dose prescription should be established to ensure the effectiveness and comparability of treatment.

The Associations of Maternal Blood Hemoglobin and Serum Triglyceride Levels and the Risk of Preterm Delivery.

The abnormal hemoglobin (HGB) and serum lipid concentrations during pregnancy will increase the risk of preterm delivery. Our study aimed to explore the correlation between prenatal HGB and serum lipid levels and preterm delivery. We enrolled 215 mother-infant pairs in a pilot cohort study. The logistic regression model and Restricted Cubic Spline model (RCS) were used to investigate the levels of prenatal blood HGB and serum lipid such as triglyceride (TG), total cholesterol, high-density lipoprotein, low density lipoprotein and preterm delivery. The results showed that moderate levels of prenatal blood HGB (OR=0.28; 95%CI: 0.10, 0.75, p-trend=0.018) and high level of serum TG (OR=0.29; 95%CI: 0.10, 0.84, p-trend=0.022) level were negatively associated with the risk of preterm delivery. The joint effect results showed that compared with lower level of prenatal blood HGB (≤123.13 g/l) and TG (≤3.7 mmol/l), we found that high levels prenatal blood HGB and serum TG (OR=0.32, 95%CI: 0.12, 0.89) had a negative association with the risk of preterm delivery. Moreover, prenatal blood HGB and serum TG levels had negative linear dose-effect relationships with the risk of preterm delivery in overall and girl group (p<0.05). Moderate levels of prenatal blood HGB and high level of serum TG were negatively associated with the risk of preterm delivery. The joint effect of high levels prenatal HGB and prenatal serum TG in the normal range were negatively correlated with preterm delivery. Moreover, the underlying mechanisms should be clarified in future studies.

Potential Defence Mechanisms Triggered by Monosodium Glutamate Sub-Chronic Consumption in Two-Year-Old Wistar Rats.

Monosodium glutamate (MSG) is the sodium salt of glutamic acid (GLA), used as a flavour enhancer. MSG is considered a controversial substance. It is incriminated in disturbing the antioxidant system, but also has beneficial effects, as GLA metabolism plays a crucial role in homeostasis. This study highlights which positive or negative aspects of MSG sub-chronic consumption are better reflected in subjects potentially affected by advanced age. Daily doses of MSG were administered to four groups of two-year-old Wistar rats for 90 days: (I) 185 mg/kg bw, (II) 1500 mg/kg bw, (III) 3000 mg/kg bw and (IV) 6000 mg/kg bw, compared to a MSG non-consumer group. Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, direct and total bilirubin, total cholesterol, triglycerides, creatinine and urea levels were analysed; stomach, liver and kidney samples were subjected to histopathological analysis. Although, in most cases, there were no statistical differences, interesting aspects of the dose-effect relationship were observed. After MSG sub-chronic consumption, the positive aspects of GLA seem to be reflected better than the negative ones. The hormesis effect, with low-level reactive oxygen species' protective effects and GLA metabolism, may represent the hypothesis of a potential defence mechanism triggered by MSG sub-chronic consumption in ageing rats.

Effect of pachymaran on oxidative stress and DNA damage induced by formaldehyde

To further explore the pharmacological effect of pachymaran, this article studied the inhibition of pachymaran on oxidative stress and genetic damage induced by formaldehyde. 40 adult Kunming male mice were randomly divided into four groups with different interventions. One week later, the contents of serum SOD, GR, MDA, DNA–protein crosslink (DPC), 8-hydroxydeoxyguanosine (8-OHDG) and DNA adduct were determined by ELISA. The results showed that there were statistically significant differences in the contents of SOD, GR and MDA among the four groups (P < 0.01). The activity of SOD and GR increased along with the increase of pachymaran dosage (SOD: rs = 0.912, P < 0.01; GR: rs = 0.857, P < 0.01), while the content of MDA showing a significant negative correlation (rs = − 0.893, P < 0.01). There were statistically significant differences in the levels of DPC, 8-OHDG and DNA adduct among the four groups (DPC and DNA adduct: P < 0.01, 8-OHDG: P < 0.05), the concentration decreased along with the increase of pachymaran dosage (DPC: rs = − 0.855, P < 0.01; 8-OHDG:rs = − 0.412, P < 0.05, DNA adduct: γs = − 0.869, P < 0.01). It can be inferred that pachymaran can inhibit oxidative stress and DNA damage induced by formaldehyde with the dose–effect relationship.

Regulation of oxygen-glucose deprivation/reperfusion-induced inflammatory responses and M1-M2 phenotype switch of BV2 microglia by lobetyolin.

To elucidate the protective mechanism of lobetyolin on oxygen-glucose deprivation/reperfusion (OGD/R)-induced damage in BV2 microglial cells. The OGD/R model was established using a chemical modeling method to simulate in vivo brain ischemia in lobetyolin-pretreated BV2 cells. The optimum lobetyolin dosage, chemical concentration, and OGD/R modeling duration were screened. The changes in cell morphology were observed, and the levels of immune response-related factors, including tumor necrosis factor-α (TNF-α), interleukin-6, inducible nitric oxide synthase (iNOS), and cluster of differentiation (CD)206, were detected using the enzyme-linked immunosorbent assay. The expression of chemokine-like-factor-1 (CKLF1), hypoxia-inducible factor (HIF)-1α, TNF-α, and CD206, was detected using western blotting. The gene expression of M1 and M2 BV2 phenotype markers was assessed using quantitative polymerase chain reaction (qPCR). The localization of M1 and M2 BV2 markers was detected using immunofluorescence analysis. The results showed that lobetyolin could protect BV2 cells from OGD/R-induced damage. After OGD/R, CKLF1/C-C chemokine receptor type 4 (CCR4) levels increased in BV2 cells, whereas the CKLF1/CCR4 level was decreased due to lobetyolin pretreatment. Additionally, BV2 cells injured with OGD/R tended to be M1 type, but lobetyolin treatment shifted the phenotype of BV2 cells from M1 type to M2 type. Lobetyolin decreased the expression of TNF-α and HIF-1α but increased the expression of transforming growth factor-β (TGF-β) in BV2 cells, indicating a dose-effect relationship. The qPCR results showed that lobetyolin decreased the expression of CD16, CD32, and iNOS at the gene level and increased the expression of C-C-chemokine ligand-22 and TGF-β. The immunofluorescence analysis showed that lobetyolin decreased CD16/CD32 levels and increased CD206 levels. Lobetyolin can protect BV2 cells from OGD/R-induced damage by regulating the phenotypic polarization of BV2 and decreasing inflammatory responses. Additionally, CKLF1/CCR4 may participate in regulating lobetyolin-induced polarization of BV2 cells via the HIF-1α pathway.

A metabolomic perspective on the mechanisms by which environmental pollutants and lifestyle lead to male infertility.

The incidence of male infertility (MI) is rising annually. According to epidemiological studies, environmental pollution (e.g., organic, inorganic, and air pollutants), occupational exposure (e.g., high temperature, organic solvents, and pesticides), and poor lifestyle (e.g., diet, sleep, smoking, alcohol consumption, and exercise) are important non-genetic causative factors of MI. Due to multiple and complex causative factors, the dose-effect relationship, and the uncertainty of pathogenicity, the pathogenesis of MI is far from fully clarified. Recent data show that the pathogenesis of MI can be monitored by the metabolites in serum, seminal plasma, urine, testicular tissue, sperm, and other biological samples. It is considered that these metabolites are closely related to MI phenotypes and can directly reflect the individual pathological and physiological conditions. Therefore, qualitative and quantitative analysis of the metabolome, the related metabolic pathways, and the identification of biomarkers will help to explore the MI-related metabolic problems and provide valuable insights into its pathogenic mechanisms. Here, we summarized new findings in MI metabolomics biomarkers research and their abnormal metabolic pathways triggered by the presented non-genetic risk factors, providing a metabolic landscape of semen and seminal plasma in general MI patients. Then, we compared the similarities and differences in semen and seminal plasma biomarkers between MI patients exposed to environmental and poor lifestyle factors and MI patients in general, and summarized some common biomarkers. We provide a better understanding of the biological underpinnings of MI pathogenesis, which might offer novel diagnostic, prognostic, and precise treatment approaches to MI.

Dose dependence of prenatal fluoride exposure associations with cognitive performance at school age in three prospective studies.

Fluoride may be a developmental neurotoxicant at elevated exposures. We merged new data from a prospective Odense Child Cohort (OCC) with results from two previous birth cohort studies from Mexico and Canada to characterize the dose-effect relationship in greater detail. The OCC contributed 837 mother-child pairs to the total of >1500. We measured creatinine-adjusted urine-fluoride concentrations in maternal urine samples obtained during late pregnancy. Child IQ was determined at age 7 years using an abbreviated version of the Wechsler Intelligence Scales for Children. Findings from the three cohorts were used to calculate the joint benchmark concentration (BMC) and the lower confidence limit (BMCL) after adjustment for covariables. In the OCC, urine-fluoride concentrations varied between 0.08 and 3.04 mg/l (median 0.52 mg/l) but were not significantly associated with full-scale IQ at age 7 years (β = 0.08; 95% confidence interval -1.14 to 1.30 for a doubling in exposure). No difference was apparent between boys and girls. In the OCC, the BMC was 0.92 mg/l, with a BMCL of 0.30 mg/l. The joint analysis of all three cohorts showed a statistically significant association between urine-fluoride and IQ, with a BMC of 0.45 mg/l (BMCL, 0.28 mg/l), slightly higher than the BMC previously reported for the two North American cohorts alone. As the BMCL reflects an approximate threshold for developmental neurotoxicity, the results suggest that pregnant women and children may need protection against fluoride toxicity.