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Frontiers in Public Health 2024Pesticides are widely used in agricultural activities. Although pesticide use is known to cause damage to the human body, its relationship with thyroid function remains...
BACKGROUND
Pesticides are widely used in agricultural activities. Although pesticide use is known to cause damage to the human body, its relationship with thyroid function remains unclear. Therefore, this study aimed to investigate the association between pesticide exposure and thyroid function.
METHODS
The Chinese database used included 60 patients with pyrethroid poisoning and 60 participants who underwent health checkups between June 2022 and June 2023. The NHANES database included 1,315 adults enrolled from 2007 to 2012. The assessed pesticide and their metabolites included 2,4-dichlorophenoxyacetic acid (2,4-D), 4-fluoro-3-phenoxybenzoic acid (4F3PB), para-nitrophenol (PN), 3-phenoxybenzoic acid (3P), and trans-dichlorovinyl-dimethylcyclopropane carboxylic acid (TDDC). The evaluated indicators of thyroid function were measured by the blood from the included population. The relationship between pesticide exposure and thyroid function indexes was investigated using linear regression, Bayesian kernel machine regression (BKMR), restricted cubic spline (RCS), and weighted quantile sum (WQS) models.
RESULTS
The Chinese data showed that pesticide exposure was negatively correlated with the thyroid function indicators FT4, TT4, TgAb, and TPOAb (all < 0.05). The BKMR model analysis of the NHANES data showed that the metabolic mixture of multiple pesticides was negatively associated with FT4, TSH, and Tg, similar to the Chinese database findings. Additionally, linear regression analysis demonstrated positive correlations between 2,4-D and FT3 ( = 0.041) and 4F3PB and FT4 ( = 0.003), whereas negative associations were observed between 4F3PB and Tg ( = 0.001), 4F3PB and TgAb ( = 0.006), 3P and TgAB ( = 0.006), 3P and TPOAb ( = 0.03), PN and TSH ( = 0.003), PN and TT4 ( = 0.031), and TDDC and TPOAb ( < 0.001). RCS curves highlighted that most pesticide metabolites were negatively correlated with thyroid function indicators. Finally, WQS model analysis revealed significant differences in the weights of different pesticide metabolites on the thyroid function indexes.
CONCLUSION
There is a significant negative correlation between pesticide metabolites and thyroid function indicators, and the influence weights of different pesticide metabolites on thyroid function indicators are significantly different. More research is needed to further validate the association between different pesticide metabolites and thyroid disease.
Topics: Humans; Pesticides; Male; Female; Middle Aged; China; Adult; Thyroid Gland; Nutrition Surveys; Thyroid Function Tests; Environmental Exposure; Databases, Factual; Aged; 2,4-Dichlorophenoxyacetic Acid; East Asian People
PubMed: 38939562
DOI: 10.3389/fpubh.2024.1378027 -
Frontiers in Microbiology 2024This study aimed to explore whether G423 could improve growth performance and lipid metabolism of broilers by the modulation of gut microbiota and metabolites. A total...
This study aimed to explore whether G423 could improve growth performance and lipid metabolism of broilers by the modulation of gut microbiota and metabolites. A total of 640 1-day-old AA broilers were randomly divided into 4 groups [Control (CON), Lac_L, Lac_H, and ABX]. Average daily gain (ADG), average daily feed intake (ADFI), feed conversion ratio (FCR), breast muscle, thigh muscle, and abdominal fat pad were removed and weighed at 42 days of age. Serum was obtained by centrifuging blood sample from jugular vein (10 mL) for determining high-density lipoprotein (HDL), total cholesterol (TC), low-density lipoprotein (LDL), and triglyceride (TG) using ELISA. The ileal contents were harvested and immediately frozen in liquid nitrogen for 16S rRNA and LC-MS analyses. Then, the results of 16S rRNA analysis were confirmed by quantitative polymerase chain reaction (qPCR). Compared with the CON group, FCR significantly decreased in the Lac_H group ( < 0.05) in 1-21 days; ADG significantly increased and FCR significantly decreased in the Lac_H group ( < 0.05) in 22-42 days. 42 days weight body and ADG significantly increased in the Lac_H group ( < 0.05) in 42 days. Abdominal fat percentage was significantly decreased by G423 ( < 0.05), the high dose of G423 significantly decreased the serum of TG, TC, and LDL level ( < 0.05), and the low dose of G423 significantly decreased the serum of TG and TC level ( < 0.05). A significant difference in microbial diversity was found among the four groups. Compared with the CON group, the abundance rates of in the Lac_H group were significantly increased ( 0.05). The global and overview maps and membrane transport in the Lac_L, Lac_H, and ABX groups significantly changed versus those in the CON group ( < 0.05). The results of LC-MS demonstrated that could significantly improve the levels of some metabolites (6-hydroxy-5-methoxyindole glucuronide, 9,10-DiHOME, -Acetyl-l-phenylalanine, and kynurenine), and these metabolites were involved in four metabolic pathways. Among them, the pathways of linoleic acid metabolism, phenylalanine metabolism, and pentose and glucuronate interconversions significantly changed ( < 0.05). G423 could ameliorate growth performance and lipid metabolism of broilers by the modulation of gut microbiota and metabolites.
PubMed: 38939183
DOI: 10.3389/fmicb.2024.1381756 -
Biochemistry and Biophysics Reports Sep 2024Prostacyclin or prostaglandin I (PGI), a metabolite of arachidonic cyclooxygenase pathway, has been demonstrated as an effector of adipocyte differentiation. However,...
Prostacyclin or prostaglandin I (PGI), a metabolite of arachidonic cyclooxygenase pathway, has been demonstrated as an effector of adipocyte differentiation. However, due to its instability in biological fluid, it is difficult to evaluate the role of PGI in regulating adipocyte differentiation in different stages in culture. Therefore, this study aimed to establish a simple and rapid method for the production of monoclonal antibody against 6-Keto PGFα, a stable PGI metabolite, and its quantification to determine the role of PGI in culture medium. Eight-week-old female BALB/c mice were immunized with the hapten of 6-Keto PGFα and BSA for several weeks until a higher antibody titer (absorbance value > 0.9 at 1000-times dilution) against 6-Keto PGFα was found. Then, fusion of antibody-producing spleen lymphocytes with SP-2 myeloma cells and thymocytes was performed and cultured in HAT-medium supplemented with hypoxanthine, aminopterin, and thymine. Specific antibody-producing cells (M2-A4-B8-D10) against 6-Keto PGFα were identified and separated. A standard ELISA calibration curve was developed with 100% reactivity for 6-Keto-PGF 1 α ranging from 0.26 pg to 6.44 ng corresponding to 90% and 10% of the maximum binding capacity for the immobilized antigen respectively. This method can easily be applied to monitor PGI regulation in different stages of cultured adipocytes to reveal the regulatory roles of PGI in maintaining homeostasis and adipocyte differentiation.
PubMed: 38939124
DOI: 10.1016/j.bbrep.2024.101748 -
Przeglad Gastroenterologiczny 2024is a common medicinal plant widely cultivated in tropical regions of the world. The outer seed coat of , obtained by cleaning the seeds, contains soluble and insoluble... (Review)
Review
The role and therapeutic effectiveness of seed husk (psyllium husk) in the prevention and non-pharmacological treatment of gastrointestinal diseases. Part 1. Clinical use of psyllium husk in the treatment of irritable bowel syndrome, ulcerative colitis, and colorectal cancer.
is a common medicinal plant widely cultivated in tropical regions of the world. The outer seed coat of , obtained by cleaning the seeds, contains soluble and insoluble fibre in a ratio of 7:3, making products containing husk an ideal source of health-beneficial fibre. The results of clinical trials demonstrate the therapeutic efficacy of psyllium husk for various gastrointestinal disorders. It has also been documented that psyllium ingestion exhibits antioxidant, immunomodulatory, antiproliferative, anticancer, and antiviral effects. Such pleiotropic effects of husk are related to the presence in its composition of arabinoxylan, which forms a gel in an aqueous environment, as well as bioactive compounds and their metabolites. This article presents the evidence available in the literature on the therapeutic potential and possible mechanisms of action of psyllium in the treatment of irritable bowel syndrome and ulcerative colitis, and prevention of colorectal cancer.
PubMed: 38939069
DOI: 10.5114/pg.2024.139209 -
Research (Washington, D.C.) 2024Short-chain fatty acids (SCFAs) have been increasingly evidenced to be important bioactive metabolites of the gut microbiota and transducers in controlling diverse...
Short-chain fatty acids (SCFAs) have been increasingly evidenced to be important bioactive metabolites of the gut microbiota and transducers in controlling diverse psychiatric or neurological disorders via the microbiota-gut-brain axis. However, the precise mechanism by which brain SCFAs extert multiple beneficial effects is not completely understood. Our previous research has demonstrated that the acetyl-coenzyme A synthetase short-chain family member 2 (ACSS2) is a novel target of the rapid and long-lasting antidepressant responses. Here, we show that micromolar SCFAs significantly augment both total cellular and nuclear ACSS2 to trigger tryptophan hydroxylase 2 (TPH2) promoter histone acetylation and its transcription in SH-SY5Y cells. In chronic-restraint-stress-induced depression mice, neuronal ACSS2 knockdown by stereotaxic injection of adeno-associated virus in the hippocampus abolished SCFA-mediated improvements in depressive-like behaviors of mice, supporting that ACSS2 is required for SCFA-mediated antidepressant responses. Mechanistically, the peroxisome-proliferator-activated receptor gamma (PPARγ) is identified as a novel partner of ACSS2 to activate TPH2 transcription. Importantly, PPARγ is also responsible for SCFA-mediated antidepressant-like effects via ACSS2-TPH2 axis. To further support brain SCFAs as a therapeutic target for antidepressant effects, d-mannose, which is a naturally present hexose, can significantly reverse the dysbiosis of gut microbiota in the chronic-restraint-stress-exposure mice and augment brain SCFAs to protect against the depressive-like behaviors via ACSS2-PPARγ-TPH2 axis. In summary, brain SCFAs can activate ACSS2-PPARγ-TPH2 axis to play the antidepressive-like effects, and d-mannose is suggested to be an inducer of brain SCFAs in resisting depression.
PubMed: 38939042
DOI: 10.34133/research.0400 -
Frontiers in Cellular and Infection... 2024In recent years, a growing body of research has confirmed that the gut microbiota plays a major role in the maintenance of human health and disease. A gut microbiota... (Review)
Review
In recent years, a growing body of research has confirmed that the gut microbiota plays a major role in the maintenance of human health and disease. A gut microbiota imbalance can lead to the development of many diseases, such as pregnancy complications, adverse pregnancy outcomes, polycystic ovary syndrome, endometriosis, and cancer. Short-chain fatty acids are metabolites of specific intestinal bacteria and are crucial for maintaining intestinal homeostasis and regulating metabolism and immunity. Endometriosis is the result of cell proliferation, escape from immune surveillance, and invasive metastasis. There is a strong correlation between the anti-proliferative and anti-inflammatory effects of short-chain fatty acids produced by gut microbes and the development of endometriosis. Given that the mechanism of action of gut microbiota and Short-chain fatty acids in endometriosis remain unclear, this paper aims to provide a comprehensive review of the complex interactions between intestinal flora, short-chain fatty acids and endometriosis. In addition, we explored potential microbial-based treatment strategies for endometriosis, providing new insights into the future development of diagnostic tests and prevention and treatment methods for endometriosis.
Topics: Endometriosis; Humans; Female; Gastrointestinal Microbiome; Fatty Acids, Volatile; Animals; Bacteria; Probiotics
PubMed: 38938880
DOI: 10.3389/fcimb.2024.1373004 -
JACS Au Jun 2024Computational study of the effect of drug candidates on intrinsically disordered biomolecules is challenging due to their vast and complex conformational space. Here, we...
Computational study of the effect of drug candidates on intrinsically disordered biomolecules is challenging due to their vast and complex conformational space. Here, we developed a comparative Markov state analysis (CoVAMPnet) framework to quantify changes in the conformational distribution and dynamics of a disordered biomolecule in the presence and absence of small organic drug candidate molecules. First, molecular dynamics trajectories are generated using enhanced sampling, in the presence and absence of small molecule drug candidates, and ensembles of soft Markov state models (MSMs) are learned for each system using unsupervised machine learning. Second, these ensembles of learned MSMs are aligned across different systems based on a solution to an optimal transport problem. Third, the directional importance of inter-residue distances for the assignment to different conformational states is assessed by a discriminative analysis of aggregated neural network gradients. This final step provides interpretability and biophysical context to the learned MSMs. We applied this novel computational framework to assess the effects of ongoing phase 3 therapeutics tramiprosate (TMP) and its metabolite 3-sulfopropanoic acid (SPA) on the disordered Aβ42 peptide involved in Alzheimer's disease. Based on adaptive sampling molecular dynamics and CoVAMPnet analysis, we observed that both TMP and SPA preserved more structured conformations of Aβ42 by interacting nonspecifically with charged residues. SPA impacted Aβ42 more than TMP, protecting α-helices and suppressing the formation of aggregation-prone β-strands. Experimental biophysical analyses showed only mild effects of TMP/SPA on Aβ42 and activity enhancement by the endogenous metabolization of TMP into SPA. Our data suggest that TMP/SPA may also target biomolecules other than Aβ peptides. The CoVAMPnet method is broadly applicable to study the effects of drug candidates on the conformational behavior of intrinsically disordered biomolecules.
PubMed: 38938816
DOI: 10.1021/jacsau.4c00182 -
Journal of Extracellular Biology Jan 2024Extracellular vesicles (EVs) secreted by human-induced pluripotent stem cells (hiPSCs) have great potential as cell-free therapies in various diseases, including...
Extracellular vesicles (EVs) secreted by human-induced pluripotent stem cells (hiPSCs) have great potential as cell-free therapies in various diseases, including prevention of blood-brain barrier senescence and stroke. However, there are still challenges in pre-clinical and clinical use of hiPSC-EVs due to the need for large-scale production of a large quantity. Vertical-Wheel bioreactors (VWBRs) have design features that allow the biomanufacturing of hiPSC-EVs using a scalable aggregate or microcarrier-based culture system under low shear stress. EV secretion by undifferentiated hiPSCs expanded as 3-D aggregates and on Synthemax II microcarriers in VWBRs were investigated. Additionally, two types of EV collection media, mTeSR and HBM, were compared. The hiPSCs were characterized by metabolite and transcriptome analysis as well as EV biogenesis markers. Protein and microRNA cargo were analysed by proteomics and microRNA-seq, respectively. The functional assays of microglia stimulation and proliferation were conducted. HiPSCs expanded as 3-D aggregates and on microcarriers had comparable cell number, while microcarrier culture had higher glucose consumption, higher glycolysis and lower autophagy gene expression based on mRNA-seq. The microcarrier cultures had at least 17-23 fold higher EV secretion, and EV collection in mTeSR had 2.7-3.7 fold higher yield than HBM medium. Microcarrier culture with mTeSR EV collection had a smaller EV size than other groups, and the cargo was enriched with proteins (proteomics) and miRNAs (microRNA-seq) reducing apoptosis and promoting cell proliferation (e.g. Wnt-related pathways). hiPSC-EVs demonstrated the ability of stimulating proliferation and M2 polarization of microglia . HiPSC expansion on microcarriers produces much higher yields of EVs than hiPSC aggregates in VWBRs. EV collection in mTeSR increases yield compared to HBM. The biomanufactured EVs from microcarrier culture in mTeSR have exosomal characteristics and are functional in microglia stimulation, which paves the ways for future in vivo anti-aging study.
PubMed: 38938678
DOI: 10.1002/jex2.133 -
Frontiers in Plant Science 2024Global warming has led to increased environmental stresses on plants, notably drought. This affects plant distribution and species adaptability, with some medicinal...
INTRODUCTION
Global warming has led to increased environmental stresses on plants, notably drought. This affects plant distribution and species adaptability, with some medicinal plants showing enhanced drought tolerance and increased medicinal components. In this pioneering study, we delve into the intricate tapestry of , a medicinal plant renowned for its resilience in arid environments. By fusing a rich historical narrative with cutting-edge analytical methodologies, this research endeavors to demystify the plant's intricate response to drought stress, illuminating its profound implications for medicinal valorization.
METHODS
The methodology includes a comprehensive textual research and resource investigation of , regionalization studies, field sample distribution analysis, transcriptome and metabolome profiling, rhizosphere soil microbiome analysis, and drought stress experiments. Advanced computational tools like ArcGIS, MaxEnt, and various bioinformatics software were utilized for data analysis and modeling.
RESULTS
The study identified significant genetic variations among samples from different regions, correlating with environmental factors, particularly precipitation during the warmest quarter (BIO18). Metabolomic analysis revealed marked differences in metabolite profiles, including shikonin content, which is crucial for the plant's medicinal properties. Soil microbial community analysis showed variations that could impact plant metabolism and stress response. Drought stress experiments demonstrated 's resilience and its ability to modulate metabolic pathways to enhance drought tolerance.
DISCUSSION
The findings underscore the complex interplay between genetic makeup, environmental factors, and microbial communities in shaping 's adaptability and medicinal value. The study provides insights into how drought stress influences the synthesis of active compounds and suggests that moderate stress could enhance the plant's medicinal properties. Predictive modeling indicates future suitable growth areas for , aiding in resource management and conservation efforts. The research contributes to the sustainable development of medicinal resources and offers strategies for improving the cultivation of .
PubMed: 38938629
DOI: 10.3389/fpls.2024.1395046 -
PeerJ 2024Fungal polysaccharides are commonly utilized in the food industry and biomedical fields as a natural and safe immune modulator. Co-culturing is a valuable method for...
Fungal polysaccharides are commonly utilized in the food industry and biomedical fields as a natural and safe immune modulator. Co-culturing is a valuable method for enhancing the production of secondary metabolites. This study used intracellular polysaccharide (IPS) content as a screening index, co-culturing seven different fungi with . The seed pre-culture liquid culture time was selected through screening, and conditions were assessed using single factor experimentation, a Plackett-Burman (PB) design, and response surface methodology (RSM) optimization. RSM optimization was conducted, leading to the measurement of antioxidant capacity. Results indicated that the co-culture of and exhibited the most effective outcome. Specifically, pre-culturing and seed cultures for 2 days and 0 days, respectively, followed by co-culturing, significantly increased IPS content compared to single-strain culturing. Further optimization of co-culture conditions revealed that yeast extract concentration, liquid volume, and inoculum ratio notably influenced IPS content in the order of yeast extract concentration > liquid volume > inoculum ratio. Under the optimal conditions, IPS content reached 69.9626 mg/g, a 17.04% increase from pre-optimization co-culture conditions. Antioxidant capacity testing demonstrated that co-cultured IPS exhibited greater scavenging abilities for DPPH and ABTS free radicals compared to single strain cultures. These findings highlight the potential of co-culturing and to enhance IPS content and improve antioxidant capacity, presenting an effective strategy for increasing fungal polysaccharide production.
Topics: Coculture Techniques; Pleurotus; Antioxidants; Polysaccharides; Fungal Polysaccharides
PubMed: 38938607
DOI: 10.7717/peerj.17571