Search Results (38)

Cannabis sativa L. shows potent anti-inflammatory activity, resulting in an interesting pharmacological option for pain management. The aim of the study was to evaluate the association between pharmacogenetics, neurological and inflammatory biomarkers, and cannabinoid plasma exposure in patients treated with cannabis. A total of 58 patients with a diagnosis of neuropathic and chronic pain treated with medical cannabis were analyzed. Cannabis was administered as a decoction (n = 47) and as inhaled cannabis (n = 11): 30 patients were treated with cannabis with high THC, while 28 patients were treated with cannabis with reduced THC (plus CBD). Cannabinoid plasma concentrations were obtained with UHPLC-MS/MS. Allelic discrimination was assessed by real-time PCR. Inflammation biomarkers (e.g., interleukin-10) were analyzed by ELISA, neurofilaments light chain (NFL), and brain-derived neurotrophic factor (BDNF) by Single Molecule Array. A statistically significant difference in IL-10 (p = 0.009) and BDNF (p = 0.004) levels was observed comparing patients treated with decoction and inhaled cannabis. BDNF and NFL results correlated with cannabinoid concentrations. Concerning genetics, the COMT 680 T>C genetic variant influences cannabinoid plasma levels, including Δ9-THC (p = 0.017). Conclusions: This study shows a possible impact of some genetic variants on cannabinoid plasma exposure, other than a possible role of medical cannabis on inflammation-related and neuronal impairment factor levels. Further studies in larger cohorts are required. Full article

Objectives: Metabolic dysfunction-associated steatohepatitis (MASH) lacks effective therapies. This study aimed to evaluate the therapeutic potential of compound 3d, a novel elafibranor derivative, focusing on its dual mechanisms of PPAR pathway activation and p38 MAPK signaling inhibition. Methods: Integrated in vitro and in vivo approaches were employed. In vitro, free fatty acid (FFA)-induced lipid accumulation in L02 hepatocytes and lipopolysaccharides (LPSs)-stimulated inflammatory responses in RAW264.7 macrophages were used to evaluate lipid metabolism and anti-inflammatory effects. In vivo, a high-fat diet (HFD)-induced MASH model in C57BL/6 mice assessed serum biochemical parameters (triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), alanine aminotransferase (ALT), aspartate transaminase (AST), tumor necrosis factor-α (TNF-α), nitric oxide (NO), and interleukin-6 (IL-6)), liver histopathology (H&E, Oil Red O, Masson staining), and proteomic profiling. Gut microbiota composition was analyzed via 16S rRNA sequencing. Western blotting quantified PPAR isoforms (γ/δ), downstream targets (Acox1, EHHADH, Acaa1), and p38 MAPK pathway proteins (p-p38, caspase-8, Bcl-2). Results: In vitro, 3d significantly reduced lipid accumulation (reduction in TG, p < 0.01) and inflammation (decrease in ALT activity, p < 0.05) in hepatocytes, while suppressing LPSs-induced TNF-α (63% reduction), NO (51% decrease), and IL-6 (48% reduction) in macrophages (p < 0.01). In vivo, 3d (30 mg/kg) lowered serum TG (39% decrease), TC (32% reduction), LDL-C (45% decline), and TNF-α (57% reduction) in HFD-fed mice (p < 0.05 vs. model), normalized AST/ALT levels, and ameliorated hepatic steatosis, ballooning, and fibrosis. Proteomics demonstrated PPARγ/δ activation (2.3–3.1-fold upregulation of Acox1, EHHADH, Acaa1; p < 0.001) and p38 MAPK pathway inhibition (54% reduction in p-p38, 61% decrease in caspase-8; 1.8-fold increase in Bcl-2; p < 0.01). Gut microbiota analysis revealed enrichment of beneficial taxa (Lactobacillus: 2.7-fold increase; Bifidobacterium: 1.9-fold rise) and reduced pathogenic Proteobacteria (68% decrease, p < 0.05). Conclusions: Compound 3d alleviates MASH via PPAR-mediated lipid metabolism enhancement and p38 MAPK-driven inflammation/apoptosis suppression, with additional gut microbiota modulation. These findings highlight 3d as a multi-target therapeutic candidate for MASH. Full article

Afforestation has been considered to be the cost-effective way to sequestrate carbon (C) dioxide from the atmosphere in the soils, while concurrent responses of soil inorganic C (SIC) and soil organic C (SOC), and their turnover are still not well-defined. During the C cycle, inorganic C is enriched in heavy isotopes (¹³C), while organic C, due to photosynthetic fractionation, is enriched in light isotopes (¹²C). This leads to distinct C isotope fractionation in terrestrial ecosystems. In this study, 72 paired soils (0–20 cm) from poplar shelterbelts and adjacent farmland sites were collected in six regions (Zhaozhou, Fuyu, Dumeng, Zhaodong, Lanling, and Mingshui) of northeastern China. Five soil fractions of dissolved organic C (DOC), particulate organic matter (POM), sand and stable aggregates (S + A), silt and clay (S + C), and resistant SOC (rSOC) and bulk soils were used in C content assay and the natural δ¹³C determination. The results showed that, compared with SOC, poplar shelterbelts resulted in SIC accrual in the soils across all six sites; however, only half of the six sites showed SOC accrual, indicating an ambiguous effect of afforestation on SOC. The natural δ¹³C method could identify the SOC turnover owing to the C isotopic discrimination. The δ¹³C–SOC-derived turnover ratio was 23%. When SIC was included in the δ¹³C measurement, bulk soils and four soil fractions (S + C, S + A, rSOC, DOC) showed a 2%–10% lower turnover percentage than the δ¹³C–SOC-derived turnover ratios. The SIC inclusion resulted in the dependency of δ¹³C–TC (TC = SIC + SOC) values on SOC (negative, R²: 0.21–0.44) and SIC content (positive, R²: 0.39–0.63). By contrast, when SIC was excluded, the δ¹³C–SOC values were independent of them (R² < 0.18). Redundancy ordination analysis manifested that more SOC in the soils, together with more POM and farming uses would be accompanied with the lower δ¹³C values. Moreover, forest characteristics (e.g., age and density) and farmland backgrounds (e.g., crop history and distance between forest and farmland) could explain differences in δ¹³C-related features. Our results highlighted that SIC in natural δ¹³C determination underestimated the C turnover ratio in general. However, SIC storage should be included in the soil C sequestration evaluation owing to a general SIC accrual pattern across regions when compared with those of SOC. Full article

Air pollution can induce diseases and increase the risks of death, and it also has close links with climate change. Carbonaceous matter is an important component of aerosols, but studies quantifying the source apportionment of carbonaceous compositions in different-sized aerosols from a stable carbon isotopic perspective remain scarce. In this study, fine (particulate size < 2.5 μm) and coarse (particulate size 2.5~10 μm) particles were collected from December 2021 to February 2022 (winter) and from June to August 2022 (summer) in the tropical city of Haikou; the concentrations of water-soluble inorganic ions (WSIIs) and total carbonaceous matter (TC) and the stable carbon isotope of TC (δ¹³C-TC) values in both fine and coarse particles were analyzed. Higher concentrations of TC, SO₄²⁻, NO₃⁻, and NH₄⁺ but lower δ¹³C-TC values in fine particles than those in coarse particles in both winter and summer indicated that combustion-related emissions dominate fine particulate TC sources. The δ¹³C-TC values coupled with the stable isotope mixing model in R (SIAR) results showed that combustion-related emissions contributed 77.5% and 76.6% to the TC of fine particles in winter and summer, respectively. Additionally, the lowest δ¹³C-TC values were observed in summertime fine particles; plant physiological activity was identified as an important source of fine particulate TC in summer and contributed 12.4% to fine particulate TC. For coarse particles, higher δ¹³C-TC values and Ca²⁺ and Na⁺ concentrations but lower TC concentrations implied significant contributions from natural emissions (29.2% in winter and 44.3% in summer) to coarse particulate TC. This study underscores that instead of fossil fuels and biomass, clean energy can decrease 45–78% of aerosol TC at Haikou. In addition, our results also provide a dataset for making environmental policy and optimizing the energy structure, which further favors the sustainable development of air quality. Full article

To meet the current demand for lead-free piezoelectric ceramics, a novel sol-gel synthesis route is presented for the preparation of Ba_0.85Ca_0.15Ti_0.9Zr_0.1O₃ doped with cerium (Ce = 0, 0.01, and 0.02 mol%) and vanadium (V = 0, 0.3, and 0.4 mol%). X-ray diffraction patterns reveal the formation of a perovskite phase (space group P4mm) for all samples after calcination at 800 °C and sintering at 1250, 1350, and 1450 °C, where it is proposed that both dopants occupy the B site. Sintering studies show that V doping allows the sintering temperature to be reduced to at least 1250 °C. Undoped BCZT samples sintered at the same temperature show reduced functional properties compared to V-doped samples, i.e., d₃₃ values increase by an order of magnitude with doping. The dissipation factor tan δ decreases with increasing sintering temperature for all doping concentrations, while the Curie temperature T_C increases for all V-doped samples, reaching 120 °C for high-concentration co-doped samples. All results indicate that vanadium doping can facilitate the processing of BCZT at lower sintering temperatures without compromising performance while promoting thermal property stability. Full article

Bacground and Objectives: The objective of this study is to investigate how different therapies modulating insulin resistance, either causally or consequently, affect metabolic parameters in treatment-naïve subjects with T2DM. Subjects and Methods: A total of 212 subjects were assigned to receive either a tight Japanese diet (n = 65), pioglitazone at doses ranging from 15–30 mg/day (n = 70), or canagliflozin at doses ranging from 50–100 mg/day (n = 77) for a duration of three months. Correlations and changes (Δ) in metabolic parameters relative to insulin resistance were investigated. Results: Across these distinct therapeutic interventions, ΔHOMA-R exhibited significant correlations with ΔFBG and ΔHOMA-B, while demonstrating a negative correlation with baseline HOMA-R. However, other parameters such as ΔHbA1c, ΔBMI, ΔTC, ΔTG, Δnon-HDL-C, or ΔUA displayed varying patterns depending on the treatment regimens. Participants were stratified into two groups based on the median value of ΔHOMA-R: the lower half (X) and upper half (Y). Group X consistently demonstrated more pronounced reductions in FBG compared to Group Y across all treatments, while other parameters including HbA1c, HOMA-B, TC, TG, HDL-C, non-HDL-C, TG/HDL-C ratio, or UA exhibited distinct regulatory responses depending on the treatment administered. Conclusions: These findings suggest that (1) regression to the mean is observed in the changes in insulin resistance across these therapies and (2) the modulation of insulin resistance with these therapies, either causally or consequentially, results in differential effects on glycemic parameters, beta-cell function, specific lipids, body weight, or UA. Full article

In this study, we conducted an 8-week feeding trial to investigate the effects of replacing fish oil (FO) with coconut oil (CO) on the growth performance, blood components, tissue fatty acid (FA) profile, and mRNA levels of genes related to lipid metabolism in the liver of the orange-spotted grouper (Epinephelus coioides). Five isolipidic and isoproteic diets were formulated through increasing the CO levels (0, 25%, 50%, 75%, and 100%, respectively). Triplicate groups of twenty-five fish (initial wet weight of about 22.4 g/fish) were fed one of the diets twice daily to apparent satiety. The 25% CO diet had the highest growth rate and feed utilization, and the 100% CO diet exhibited a comparable growth and feed utilization with that of the control diet, indicating a suitable FO substitute. Moreover, the hepatosomatic index, intraperitoneal fat rate, liver lipid content, as well as the serum HDL-C content and ALT activity had positive linear and/or quadratic responses, but the serum TC and LDL-C contents exhibited the opposite trend, with an increasing CO inclusion level. The FA profile in the liver and muscle generally mirrored the FA profile in the feed. Furthermore, the mRNA levels of the fas, acc, g6pd, srebp-1c, and δ6fad genes in the liver had positive linear and/or quadratic responses, but the mRNA levels of elovl 4 and elovl 5 had the opposite trend, with increasing dietary CO inclusion levels. When compared with the control diet, 25% and 50% CO diets up-regulated the mRNA levels of cpt 1, while the 75% and 100% CO diets down-regulated its mRNA levels. The hsl and atgl were down-regulated through the addition of dietary CO. The mRNA level of lpl was not affected by dietary treatments. Results showed that CO could completely replace FO without affecting growth performance, but high CO will lead to the significant liver lipid deposition and lower LC-PUFAs contents of fish flesh. Full article

For decades in China, carbon neutrality policies have spurred the establishment of northern margin mangroves as artificial blue carbon ecosystems. However, there has been limited research on the impact of plantation and invasion on the stocks and sources of soil carbon and nitrogen in rehabilitated coastal wetlands. Non-native Kandelia obovata afforestation began on Ximen Island, Zhejiang, China, where Spartina alterniflora invasion had also occurred decades ago. Soil cores were collected from both mangrove and salt marsh habitats with depths from 0 to 50 cm and were analyzed for total carbon (TC), soil organic carbon (SOC), total nitrogen (TN), and the isotope of carbon and nitrogen in sediments. The results indicated that there were no significant differences in the TC, SOC, and C/N ratio between the K. obovata and the S. alterniflora, but there were significant differences in TN, isotope δ¹³C, and δ¹⁵N. The SOC content of both ecosystems in the 0–20 cm layer was significantly higher than that in the 30–50 cm layer. Our study has shown that the main sources of carbon and nitrogen for mangroves and salt marshes are different, especially under the impact of external factors, such as tidal waves and aquaculture. These findings provide insight into the ecological functioning of subtropical coastal wetlands and an understanding of the biogeochemical cycles of northern margin mangrove ecosystems. Full article

Glucose and lipid metabolism regulation by the peroxisome proliferator-activated receptors (PPARs) has been extensively reported. However, the role of their polymorphisms remains unclear. Objective: To determine the relation between PPAR-γ2 rs1801282 (Pro12Ala) and PPAR-β/δ rs2016520 (+294T/C) polymorphisms and metabolic biomarkers in adults with type 2 diabetes (T2D). Materials and Methods: We included 314 patients with T2D. Information on anthropometric, fasting plasma glucose (FPG), HbA1c and lipid profile measurements was taken from clinical records. Genomic DNA was obtained from peripheral blood. End-point PCR was used for PPAR-γ2 rs1801282, while for PPAR-β/δ rs2016520 the PCR product was digested with Bsl-I enzyme. Data were compared with parametric or non-parametric tests. Multivariate models were used to adjust for covariates and interaction effects. Results: minor allele frequency was 12.42% for PPAR-γ2 rs1801282-G and 13.85% for PPAR-β/δ rs2016520-C. Both polymorphisms were related to waist circumference; they showed independent effects on HbA1c, while they interacted for FPG; carriers of both PPAR minor alleles had the highest values. Interactions between FPG and polymorphisms were identified in their relation to triglyceride level. Conclusions: PPAR-γ2 rs1801282 and PPAR-β/δ rs2016520 polymorphisms are associated with anthropometric, glucose, and lipid metabolism biomarkers in T2D patients. Further research is required on the molecular mechanisms involved. Full article

To understand the sources and migration pattern of PM_2.5 in the Yangtze River Delta (YRD), China, the total carbon (TC) and total nitrogen (TN) concentrations and the corresponding stable isotope ratios (δ¹³C_TC and δ¹⁵N_TN) were determined in aerosol samples simultaneously collected from August 2014 to April 2015 at three different locations (Shanghai, Ningbo, Nanjing). Ningbo and Shanghai are geographically closer, the research results precisely divide Nanjing and the other two cities into two categories. Nanjing has a higher proportion of nitrogen in PM_2.5 (13.2–15.3%) than Shanghai and Ningbo (8.6–12.6%), and the correlation analysis shows that nitrogen components (mainly ammonium nitrogen) might be the main driving force for the formation of PM_2.5. The isotopes were proven to be sensitive sensors to reflect the impact of special events on PM_2.5. For example, compared to other seasons, δ¹³C_TC in autumn in the three cities are relatively depleted, indicating an input from biomass combustion to PM_2.5 at this time. On New Year’s Eve, three cities simultaneously observed enriched δ¹³C_TC due to the burning of fireworks. During the Qingming Festival, abnormally depleted nitrogen isotope ratios were observed, reflecting the vehicle exhaust pollution caused by people’s short travel. Isotopes are also used to trace the transport process of PM_2.5. Postponing the sampling date in Nanjing by one day increased the linear fit (r²) of δ¹³C_TC between Nanjing and Ningbo from 0.03 to 0.75, while that of δ¹⁵N_TN improved from 0.16 to 0.63, which means PM_2.5 might transport from Nanjing to Shanghai and Ningbo, and the transfer time takes one day. Full article

The need to guarantee the geographical origin of food samples has become imperative in recent years due to the increasing amount of food fraud. Stable isotope ratio analysis permits the characterization and origin control of foodstuffs, thanks to its capability to discriminate between products having different geographical origins and derived from different production systems. The Framework 6 EU-project “TRACE” generated hydrogen (²H/¹H), carbon (¹³C/¹²C), nitrogen (¹⁵N/¹⁴N), and sulphur (³⁴S/³²S) isotope ratio data from 227 authentic beef samples. These samples were collected from a total of 13 sites in eight countries. The stable isotope analysis was completed by combining IRMS with a thermal conversion elemental analyzer (TC/EA) for the analysis of δ(²H) and an elemental analyzer (EA) for the determination of δ(¹³C), δ(¹⁵N), and δ(³⁴S). The results show the potential of this technique to detect clustering of samples due to specific environmental conditions in the areas where the beef cattle were reared. Stable isotope measurements highlighted statistical differences between coastal and inland regions, production sites at different latitudes, regions with different geology, and different farming systems related to the diet the animals were consuming (primarily C3- or C4-based or a mixed one). Full article

A major ocean response to tropical cyclone (TC) wind is the mixing of warm sea-surface water with cool subsurface water, which decreases the sea-surface temperature (SST). The decreased SST (δT) under the TC (rather than the cooled water in the wake after the storm has passed) modifies the storm’s intensity and is of interest to TC intensity studies. Here, the author shows that δT (non-dimensionalized by some reference temperature) is linearly related to Ψ, a dimensionless (nonlinear) function of TC and ocean parameters: the TC maximum wind, radius, and translation speed, as well as the ocean’s 26 °C and 20 °C isothermal depths (Z₂₆ and Z₂₀). The Ψ can be estimated from observations. The modelled δT is validated against sea-surface cooling observed by satellites, δT_o, for typhoons during the May–December 2015 period in the western North Pacific. The result yields a best-fit, linear relation between δT_o and Ψ that explains ~60% of the observed variance: r² ≈ 0.6 (99% confidence). Tests show that the cube of the TC maximum wind and the ocean’s Z₂₆ account for 46% and 7%, respectively, of the observed variance, indicating their predominant influence on TC-induced cooling. Contributions from other parameters are less but not negligible. Full article

Absence seizures are hyperexcitations within the cortico-thalamocortical (CTC) network, however the underlying causative mechanisms at the cellular and molecular level are still being elucidated and appear to be multifactorial. Dysfunctional feed-forward inhibition (FFI) is implicated as one cause of absence seizures. Previously, we reported altered excitation onto parvalbumin-positive (PV⁺) interneurons in the CTC network of the stargazer mouse model of absence epilepsy. In addition, downstream changes in GABAergic neurotransmission have also been identified in this model. Our current study assessed whether dysfunctional FFI affects GABA_A receptor (GABA_AR) subunit expression in the stargazer primary somatosensory cortex (SoCx). Global tissue expression of GABA_AR subunits α1, α3, α4, α5, β2, β3, γ2 and δ were assessed using Western blotting (WB), while biochemically isolated subcellular fractions were assessed for the α and δ subunits. We found significant reductions in tissue and synaptic expression of GABA_AR α1, 18% and 12.2%, respectively. However, immunogold-cytochemistry electron microscopy (ICC-EM), conducted to assess GABA_AR α1 specifically at synapses between PV⁺ interneurons and their targets, showed no significant difference. These data demonstrate a loss of phasic GABA_AR α1, indicating altered GABAergic inhibition which, coupled with dysfunctional FFI, could be one mechanism contributing to the generation or maintenance of absence seizures. Full article

Background. The cause of the worldwide doubling-tripling of testicular cancer rates (TCRs) in recent decades is unknown. Previous cohort studies associated cannabis use with TCR including dose–response relationships but the contribution of cannabis to TCRs at the population level is unknown. This relationship was tested by analyzing annual trends across US states and formally assessed causality. Four US datasets were linked at state level: age-adjusted TCRs from Centers for Disease Control Surveillance Epidemiology and End Results database; drug use data from annual National Survey of Drug Use and Health including 74.1% response rate; ethnicity and median household income data from the US Census Bureau; and cannabinoid concentration data from Drug Enforcement Agency reports. Data was processed in R in spatiotemporal and causal inference protocols. Results. Cannabis-use quintile scatterplot-time and boxplots closely paralleled those for TCRs. The highest cannabis-use quintile had a higher TCR than others (3.44 ± 0.05 vs. 2.91 ± 0.2, mean ± S.E.M., t = 10.68, p = 1.29 × 10⁻²²). A dose–response relationship was seen between TCR and Δ9-tetrahydrocannabinol (THC), cannabinol, cannabigerol, and cannabichromene (6.75 × 10⁻⁹ < p < 1.83 × 10⁻¹⁴²). In a multivariate inverse probability-weighted interactive regression including race and ethnic cannabis exposure (ECE), ECE was significantly related to TCR (β-estimate = 0.89 (95%C.I. 0.36, 2.67), p < 2.2 × 10⁻¹⁶). In an additive geospatiotemporal model controlling for other drugs, cannabis alone was significant (β-estimate = 0.19 (0.10, 0.28), p = 3.4 × 10⁻⁵). In a full geospatial model including drugs, income and ethnicity cannabinoid exposure was significant (cannabigerol: β-estimate = 1.39 (0.024, 2.53), p = 0.0017); a pattern repeated at two spatial and two temporal lags (cannabigerol: β-estimate = 0.71 (0.05, 1.37), p = 0.0.0350; THC: β-estimate = 23.60 (11.92, 35.29), p = 7.5 × 10^–5). 40/41 e-Values > 1.25 ranged up to 1.4 × 10⁶³ and 10 > 1000 fitting causal relationship criteria. Cannabis liberalization was associated with higher TCRs (ChiSqu. = 312.2, p = 2.64 × 10⁻¹¹). Rates of TC in cannabis-legal states were elevated (3.36 ± 0.09 vs. 3.01 ± 0.03, t = 4.69, p = 4.86 × 10⁻⁵). Conclusions. Cannabis use is closely and causally associated with TCRs across both time and space and higher in States with liberal cannabis legislation. Strong dose–response effects were demonstrated for THC, cannabigerol, cannabinol, cannabichromene and cannabidiol. Cannabinoid genotoxicity replicates all major steps to testicular carcinogenesis including whole-genome doubling, chromosomal arm excision, generalized DNA demethylation and chromosomal translocations thereby accelerating the pathway to testicular carcinogenesis by several decades. Full article

Open biomass burning (BB) has contributed severely to the ambient levels of particulate matter of less than 2.5 μm diameter (PM_2.5) in upper northern Thailand over the last decade. Some methods have been reported to identify the sources of burning using chemical compositions, i.e., ions, metals, polycyclic aromatic hydrocarbons, etc. However, recent advances in nuclear techniques have been limited in use due to their specific instrumentation. The aims of this study were to investigate the sources of ambient PM_2.5 in Chiang Mai city using stable carbon (δ¹³C) and nitrogen isotopes (δ¹⁵N). The mean concentrations of total carbon (TC) and total nitrogen (TN) in PM_2.5 were 12.2 ± 5.42 and 1.91 ± 1.07 μg/m³, respectively, whereas δ¹³C and δ¹⁵N PM_2.5 were −26.1 ± 0.77‰ and 10.3 ± 2.86‰, respectively. This isotopic analysis confirmed that biomass burning was the source of PM_2.5 and that C₃ and C₄ plants contributed about 74% and 26%, respectively. These study results confirm that the stable isotope is an important tool in identifying the sources of aerosols. Full article