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Background: The relationship between the intake of dietary fatty acids (FA) and bone mineral density (BMD) has been the subject of prior investigations. However, the outcomes of these studies remain contentious. The objective of this research is to examine the link between dietary FA consumption among adolescents and BMD. Methods: This study utilized high-quality data from the National Health and Nutrition Examination Survey database, spanning 2011 to 2018, to explore the association between dietary fatty acids and bone health indicators in adolescents, including BMD and bone mineral content (BMC). Analyses were performed using weighted multivariate linear regression models, incorporating detailed subgroup analysis. Results: The study included 3440 participants. Analysis demonstrated that intake of saturated fatty acids (SFA) was positively correlated with total BMD, left arm BMD, total BMC, and left arm BMC. Monounsaturated fatty acid (MUFA) intake was positively correlated with BMC across most body parts, though it showed no correlation with BMD. Intake of polyunsaturated fatty acids (PUFA) was significantly inversely correlated with both BMD and BMC in most body parts. Additionally, subgroup analysis indicated that variables such as sex, age, standing height, and race significantly influenced the correlation between FA intake and BMD. Conclusions: Our study indicates that dietary intake of SFA may benefit to BMD in adolescents, in contrast to PUFA and MUFA. Therefore, we recommend that adolescents maintain a balanced intake of SFA to promote optimal bone mass development while preserving metabolic health.
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Densidad Ósea , Ácidos Grasos , Encuestas Nutricionales , Humanos , Densidad Ósea/efectos de los fármacos , Adolescente , Femenino , Masculino , Niño , Ácidos Grasos/administración & dosificación , Adulto Joven , Grasas de la Dieta/administración & dosificación , Estudios TransversalesRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Blumea balsamifera (L.) DC. (BB), the source of Blumea balsamifera oil (BBO), is an aromatic medicinal plant, renowned for its pharmacological properties and its traditional use in Southeast Asian countries such as China, Thailand, Vietnam, Malaysia, and the Philippines for centuries. Traditionally, BB has been used as a raw herbal medicine for treating various skin conditions like eczema, dermatitis, athlete's foot, and wound healing for skin injuries. AIM OF THE STUDY: This research aimed to explore the inhibitory effects of BBO on skin aging using two models: in vitro analysis with human dermal fibroblasts (HDF) under UVB-induced stress, and in vivo studies on UVA-induced dorsal skin aging in mice. The study sought to uncover the mechanisms behind BBO's anti-aging effects, specifically, its impact on cellular and tissue responses to UV-induced skin aging. MATERIALS AND METHODS: We applied doses of 10-20 µL/mL of BBO to HDF cells that had been exposed to UVB radiation to simulate skin aging. We measured cell viability, and levels of reactive oxygen species (ROS), SA-ß-gal, pro-inflammatory cytokines, and matrix metalloproteinases (MMPs). In addition, we investigated the involvement of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-κB) signaling pathways in mediating the anti-aging effects of BBO. Histopathological and biochemical analyses were conducted in a mouse model to examine the effects of BBO on UV-induced photoaging. RESULTS: UV exposure accelerated aging, and caused cellular damage and inflammatory responses through ROS-mediated pathways. In HDF cells, BBO treatment countered the UVB-induced senescence, and the recovery of cell viability was correlated to notable reductions in SA-ß-gal, ROS, pro-inflammatory cytokines, and MMPs. Mechanistically, the anti-aging effect of BBO was associated with the downregulation of the JNK/NF-κB signaling pathways. In the in vivo mouse model, BBO exhibited protective capabilities against UV-induced photoaging, which were manifested by the enhanced antioxidant enzyme activities and tissue remodeling. CONCLUSIONS: BBO effectively protects fibroblasts from UV-induced photoaging through the JNK/NF-κB pathway. Recovery from photoaging involves an increase in dermal fibroblasts, alleviation of inflammation, accelerated synthesis of antioxidant enzymes, and slowed degradation of ECM proteins. Overall, BBO enhances the skin's defensive capabilities against oxidative stress, underscoring its potential as a therapeutic agent for oxidative stress-related skin aging.
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Asteraceae , Fibroblastos , Envejecimiento de la Piel , Rayos Ultravioleta , Animales , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Humanos , Fibroblastos/efectos de los fármacos , Fibroblastos/efectos de la radiación , Ratones , Asteraceae/química , Aceites de Plantas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Supervivencia Celular/efectos de los fármacos , Piel/efectos de los fármacos , Piel/efectos de la radiación , Piel/patología , Piel/metabolismo , Masculino , FN-kappa B/metabolismo , FemeninoRESUMEN
Nanoplastics (NPs) pollution has become a global environmental problem, raising numerous health concerns. However, the cardiotoxicity of NPs exposure and the underlying mechanisms have been understudied to date. To address this issue, we comprehensively evaluated the cardiotoxicity of polystyrene nanoplastics (PS-NPs) in both healthy and pathological states. Briefly, mice were orally exposed to four different concentrations (0 mg/day, 0.1 mg/day, 0.5 mg/day, and 2.5 mg/day) of 100-nm PS-NPs for 6 weeks to assess their cardiotoxicity in a healthy state. Considering that individuals with underlying health conditions are more vulnerable to the adverse effects of pollution, we further investigated the cardiotoxic effects of PS-NPs on pathological states induced by isoprenaline. Results showed that PS-NPs induced cardiomyocyte apoptosis, cardiac fibrosis, and myocardial dysfunction in healthy mice and exacerbated cardiac remodeling in pathological states. RNA sequencing revealed that PS-NPs significantly upregulated homeodomain interacting protein kinase 2 (HIPK2) in the heart and activated the P53 and TGF-beta signaling pathways. Pharmacological inhibition of HIPK2 reduced P53 phosphorylation and inhibited the activation of the TGF-ß1/Smad3 pathway, which in turn decreased PS-NPs-induced cardiotoxicity. This study elucidated the potential mechanisms underlying PS-NPs-induced cardiotoxicity and underscored the importance of evaluating nanoplastics safety, particularly for individuals with pre-existing heart conditions.
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Cardiotoxicidad , Poliestirenos , Proteínas Serina-Treonina Quinasas , Proteína smad3 , Factor de Crecimiento Transformador beta1 , Proteína p53 Supresora de Tumor , Regulación hacia Arriba , Animales , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Proteína smad3/metabolismo , Proteína smad3/genética , Cardiotoxicidad/etiología , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Poliestirenos/toxicidad , Regulación hacia Arriba/efectos de los fármacos , Masculino , Transducción de Señal/efectos de los fármacos , Ratones , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Apoptosis/efectos de los fármacos , Ratones Endogámicos C57BL , Nanopartículas/toxicidad , Miocardio/metabolismo , Miocardio/patologíaRESUMEN
Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.
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Microbioma Gastrointestinal , Metanfetamina , Reproducción , Testículo , Animales , Metanfetamina/toxicidad , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Testículo/efectos de los fármacos , Testículo/patología , Reproducción/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Ratones Endogámicos C57BL , Estimulantes del Sistema Nervioso Central/toxicidad , Trasplante de Microbiota FecalRESUMEN
Organophosphorus flame retardants (OPFRs), such as 2-ethylhexyl diphenyl phosphate (EHDPHP), are ubiquitously used, leading to pervasive environmental contamination and human health risks. While associations between EHDPHP and health issues such as disruption of hormones, neurotoxic effects, and toxicity to reproduction have been recognized, exposure to EHDPHP during perinatal life and its implications for the intestinal health of dams and their pups have largely been unexplored. This study investigated the intestinal toxicity of EHDPHP and the potential for which inulin was effective. Dams were administered either an EHDPHP solution or a corn oil control from gestation day 7 (GD7) to postnatal day 21 (PND21), with inulin provided in their drinking water. Our results indicate that inulin supplementation mitigates damage to the intestinal epithelium caused by EHDPHP, restores mucus-secreting cells, suppresses intestinal hyperpermeability, and abates intestinal inflammation by curtailing lipopolysaccharide leakage through reshaping of the gut microbiota. A reduction in LPS levels concurrently inhibited the inflammation-associated TLR4/NF-κB pathway. In conclusion, inulin administration may ameliorate intestinal toxicity caused by EHDPHP in dams and pups by reshaping the gut microbiota and suppressing the LPS/TLR4/NF-κB pathway. These findings underscore the efficacy of inulin as a therapeutic agent for managing health risks linked to EHDPHP exposure.
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Compuestos de Bifenilo , Microbioma Gastrointestinal , Fosfatos , Embarazo , Femenino , Humanos , Fosfatos/farmacología , FN-kappa B , Lipopolisacáridos , Inulina/farmacología , Receptor Toll-Like 4/metabolismo , InflamaciónRESUMEN
Prenatal exposure to methamphetamine (METH) is an issue of global concern due to its adverse effects on offspring, particularly its impact on liver health, an area still not fully understood. Inulin, a recognized prebiotic, is thought to potentially ameliorate these developmental disorders and toxic injuries in progeny. To investigate the effects of prenatal METH exposure on the liver and the role of gut microbiota, we established a murine model, the subjects of which were exposed to METH prenatally and subsequently treated with inulin. Our findings indicate that prenatal METH exposure causes liver damage in offspring, as evidenced by a decreased liver index, histopathological changes, diminished glycogen synthesis, hepatic dysfunction, and alterations in mRNA profiles. Furthermore, it impairs the antioxidant system and induces oxidative stress, possibly due to changes in cecal microbiota and dysregulation of bile acid homeostasis. However, maternal inulin supplementation appears to restore the gut microbiota in offspring and mitigate the hepatotoxic effects induced by prenatal METH exposure. Our study provides definitive evidence of METH's transgenerational hepatotoxicity and suggests that maternal inulin supplementation could be an effective preventive strategy.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Microbioma Gastrointestinal , Metanfetamina , Efectos Tardíos de la Exposición Prenatal , Embarazo , Femenino , Ratones , Animales , Humanos , Metanfetamina/toxicidad , Inulina/farmacología , Suplementos Dietéticos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & controlRESUMEN
Perfluorooctanoic acid (PFOA) is a widely used industrial compound that has been found to induce intestinal toxicity. However, the underlying mechanisms have not been fully clarified and effective interventions are rarely developed. Inulin, a prebiotic, has been used as a supplement in human daily life as well as in gastrointestinal diseases and metabolic disorders. In this study, male mice were exposed to PFOA with or without inulin supplementation to investigate the enterotoxicity and potential intervention effects of inulin. Mice were administered PFOA at 1 mg/kg/day, PFOA with inulin at 5 g/kg/day, or Milli-Q water for 12 weeks. Histopathological analysis showed that PFOA caused colon shortening, goblet cell reduction, and inflammatory cell infiltration. The expression of the tight junction proteins ZO-1, occludin and claudin5 significantly decreased, indicating impaired barrier function. According to the RNA-sequencing analysis, PFOA exposure resulted in 917 differentially expressed genes, involving 39 significant pathways, such as TNF signaling and cell cycle pathways. In addition, the protein expression of TNF-α, IRG-47, cyclinB1, and cyclinB2 increased, while Gadd45γ, Lzip, and Jam2 decreased, suggesting the involvement of the TNF signaling pathway, cell cycle, and cell adhesion molecules in PFOA-associated intestinal injury. Inulin intervention alleviated PFOA-induced enterotoxicity by activating the PI3K/AKT/mTOR signaling pathway and increasing the protein expression of Wnt1, ß-catenin, PI3K, Akt3, and p62, while suppressing MAP LC3ß, TNF-α, and CyclinE expression. These findings suggested that PFOA-induced intestinal injury, including inflammation and tight junction disruption, was mitigated by inulin through modifying the PI3K/AKT/mTOR signaling pathways. Our study provides valuable insights into the enterotoxic effects of PFOA and highlights the potential therapeutic role of inulin.
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Caprilatos , Fluorocarburos , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Humanos , Masculino , Ratones , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Inulina/farmacología , Factor de Necrosis Tumoral alfa/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND: Oxaliplatin (Oxa) is the first-line chemotherapy drug for colorectal cancer (CRC), and Oxa resistance is crucial for treatment failure. Prostaglandin F2α synthase (PGF2α) (PGFS), an enzyme that catalyzes the production of PGF2α, is involved in the proliferation and growth of a variety of tumors. However, the role of PGFS in Oxa resistance in CRC remains unclear. AIM: To explore the role and related mechanisms of PGFS in mediating Oxa resistance in CRC. METHODS: The PGFS expression level was examined in 37 pairs of CRC tissues and paracancerous tissues at both the mRNA and protein levels. Overexpression or knockdown of PGFS was performed in CRC cell lines with acquired Oxa resistance (HCT116-OxR and HCT8-OxR) and their parental cell lines (HCT116 and HCT8) to assess its influence on cell proliferation, chemoresistance, apoptosis, and DNA damage. For determination of the underlying mechanisms, CRC cells were examined for platinum-DNA adducts and reactive oxygen species (ROS) levels in the presence of a PGFS inhibitor or its products. RESULTS: Both the protein and mRNA levels of PGFS were increased in the 37 examined CRC tissues compared to the adjacent normal tissues. Oxa induced PGFS expression in the parental HCT116 and HCT8 cells in a dose-dependent manner. Furthermore, overexpression of PGFS in parental CRC cells significantly attenuated Oxa-induced proliferative suppression, apoptosis, and DNA damage. In contrast, knockdown of PGFS in Oxa-resistant HCT116 and HCT8 cells (HCT116-OxR and HCT8-OxR) accentuated the effect of Oxa treatment in vitro and in vivo. The addition of the PGFS inhibitor indomethacin enhanced the cytotoxicity caused by Oxa. Treatment with the PGFS-catalyzed product PGF2α reversed the effect of PGFS knockdown on Oxa sensitivity. Interestingly, PGFS inhibited the formation of platinum-DNA adducts in a PGF2α-independent manner. PGF2α exerts its protective effect against DNA damage by reducing ROS levels. CONCLUSION: PGFS promotes resistance to Oxa in CRC via both PGF2α-dependent and PGF2α-independent mechanisms.
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Neoplasias Colorrectales , Platino (Metal) , Humanos , Oxaliplatino/farmacología , Oxaliplatino/uso terapéutico , Platino (Metal)/farmacología , Platino (Metal)/uso terapéutico , Aductos de ADN/farmacología , Aductos de ADN/uso terapéutico , Especies Reactivas de Oxígeno , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , ARN Mensajero/metabolismo , Prostaglandinas , Resistencia a Antineoplásicos/genética , Línea Celular TumoralRESUMEN
Increases in the prevalence of food allergy and vitamin D deficiency have been observed in recent years. The association between vitamin D levels and food allergy remains to be fully elucidated, and research focused on the prevalence of vitamin D insufficiency in infants with food protein-induced gastrointestinal disease in Chengdu, Sichuan is lacking. Thus, the present study aimed to determine the prevalence and clinical characteristics of serum 25 hydroxyvitamin D [25-(OH)D] insufficiency and sufficiency in infants with food protein-induced gastrointestinal disease. The present study also aimed to identify the potential predisposing factors of 25-(OH)D insufficiency. The present retrospective study analyzed data obtained from Chengdu Women's and Children's Central Hospital spanning between June 2021 and February 2022. Children with a confirmed diagnosis of food protein-induced gastrointestinal disease were enrolled in the present study. Blood indicators, including serum 25-(OH)D, serum total immunoglobulin E (IgE), specific IgE against allergens, and hemoglobin were measured during the course of the disease. Clinical characteristics of patients and blood examination results were obtained from the hospital electronic database. A total of 361 patients were included in the study group and 45 healthy individuals were included in the control group. The results of the present study demonstrated that serum 25-(OH)D levels of infants with protein-induced gastrointestinal disease were significantly lower compared with the control group. Notably, female participants with higher serum total IgE levels exhibited insufficient serum 25-(OH)D levels. However, the results of the logistic regression analysis revealed no predisposing factors associated with serum 25-(OH)D insufficiency. In conclusion, infants with food protein-induced gastrointestinal disease may exhibit a higher risk of low serum 25-(OH)D levels and this risk may be greater in females with higher total IgE.
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BACKGROUND: Gastric cancer (CC) is a disease with high incidence and mortality rate. Immunotherapy is an important method for gastric cancer while lack of effective predictor. Integrins play an important role in the development. We aimed to explore the predictive value of ß1 integrin (ITGB1) as a predictor of immunnotherapy in gastric cancer. METHODS: Differential expression analysis was conducted using the Gene Expression Profiling Interactive Analysis (GEPIA) 2.0 and GEO databases. GEPIA data were used to evaluate the prognostic value of ITGB1 in gastric cancer (GC). Transcriptomic and clinical data of GC and normal tissues were downloaded from The Cancer Genome Atlas database, and the TIMER database was used to evaluate the association between ITGB1 and immune infiltration. Time-dependent receiver operating characteristic (ROC) curve analysis was used to determine the prognostic value of ITGB1. To verify ITGB1 expression at the protein level, immunohistochemical staining was conducted. In addition, to analyze the correlation of ITGB1 with PD-1 and PD-L1, we examined levels of PD-1 and PD-L1 by IHC and determined the predictive value of ITGB1 for anti-PD-1 therapy in GC by ROC curve analysis. RESULTS: Compared with normal tissues, analysis of GEPIA and data at protein levels showed significantly higher expression of ITGB1 in GC. In addition, higher expression of ITGB1 was associated with worse pathological G-staging and tumor T-staging, which suggested that ITGB1 is a risk factor for poor prognosis in GC. The level of ITGB1 expression was positively correlated with CD8 + T cells, neutrophils, macrophages, and dendritic cells. ITGB1 expression was also correlated with PD-L1 expression, and this was further verified at the protein level by immunohistochemical analysis. The area under the ROC curve was 0.808. CONCLUSION: ITGB1 may be a promising prognostic biomarker and effective predictor for anti-PD-1 therapy in GC. TRIAL REGISTRATION: Retrospectively registered.
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Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Antígeno B7-H1/genética , Perfilación de la Expresión Génica , Linfocitos T CD8-positivosRESUMEN
Organophosphorus flame retardants (OPFRs), including 2-ethylhexyl diphenyl phosphate (EHDPHP), are prevalent in everyday life due to their broad usage in fields such as healthcare, electronics, industry, and sports. These compounds, added to polymers through physical mixing, can leach into the environment, posing a risk to humans through direct contact or the food chain. Despite known associations with health issues like endocrine disruption, neurotoxicity, and reproductive toxicity, the implications of perinatal EHDPHP exposure on both mothers and offspring are still unclear. This study aimed to investigate the neuroinflammatory effects of EHDPHP and the potential mitigating role of inulin. Pregnant C57 mice were administered either a corn oil control or an EHDPHP solution (300 µg/kg bw/d) from gestation day 7 (GD7) to postnatal day 21 (PND21). Concurrently, mice were provided either regular drinking water or water supplemented with 1% inulin. We found that EHDPHP significantly increased the serum levels of IL-1ß, IL-6, and MDA, but decreased SOD levels in both mothers and pups. These effects were reversed by inulin supplementation. RNA-sequencing revealed that EHDPHP induced inflammation and oxidative stress through the TLR4/NF-κB pathway, which was mitigated by inulin. In conclusion, inulin ameliorated EHDPHP-induced neuroinflammation and oxidative stress in both mothers and offspring, highlighting its potential therapeutic role.
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Retardadores de Llama , Fosfatos , Embarazo , Ratones , Humanos , Femenino , Animales , Organofosfatos/toxicidad , Inulina , Enfermedades Neuroinflamatorias , Estrés Oxidativo , Retardadores de Llama/toxicidadRESUMEN
Polystyrene microplastics (PS-MPs) have emerged as a concerning pollutant in modern society due to their widespread production and usage. Despite ongoing research efforts, the impact of PS-MPs on mammalian behavior and the mechanisms driving these effects remain incompletely elucidated. Consequently, effective strategies for prevention have yet to be developed. To fill these gaps, C57BL/6 mice were orally administered with 5 µm PS-MPs for 28 consecutive days in this study. The open-field test and the elevated plus-maze test were performed to evaluate the anxiety-like behavior, 16S rRNA sequencing and untargeted metabolomics analysis were used to detect the changes of gut microbiota and serum metabolites. Our results indicated that PS-MPs exposure activated hippocampal inflammation and induced anxiety-like behavior in mice. Meanwhile, PS-MPs disturbed the gut microbiota, impaired the intestinal barrier, and aroused peripheral inflammation. Specifically, PS-MPs increased the abundance of pathogenic microbiota Tuzzerella, while lowered the abundance of probiotics Faecalibaculum and Akkermansia. Interestingly, eliminating the gut microbiota protected against the deleterious effects of PS-MPs on intestinal barrier integrity, reduced the levels of peripheral inflammatory cytokines, and ameliorated anxiety-like behavior. Additionally, green tea's primary bioactive constituent, epigallocatechin-3-gallate (EGCG), optimized gut microbial composition, improved intestinal barrier function, reduced peripheral inflammation, and exerted anti-anxiety effects by inhibiting the hippocampal TLR4/MyD88/NF-κB signaling cascade. EGCG also remodeled serum metabolism, especially modulated purine metabolism. These findings suggested that gut microbiota participates in PS-MPs-induced anxiety-like behavior by modulating the gut-brain axis, and that EGCG could serve as a potential preventive strategy.
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Microbioma Gastrointestinal , Animales , Ratones , Ratones Endogámicos C57BL , Microplásticos , Plásticos , Poliestirenos/toxicidad , ARN Ribosómico 16S , Homeostasis , Inflamación/inducido químicamente , MamíferosRESUMEN
Introduction: Burn injury has been shown to lead to changes in the composition of the gut microbiome and cause other damage in patients. However, little is known about how the gut microbial community evolves in individuals who have recovered from burn injury. Methods: In this study, we established a model of deep partial-thickness burn in mice and collected fecal samples at eight time points (pre-burn, 1, 3, 5, 7, 14, 21, and 28 days post-burn) for 16S rRNA amplification and high-throughput sequencing. Results: The results of the sequencing were analyzed using measures of alpha diversity, and beta diversity and taxonomy. We observed that the richness of the gut microbiome declined from day 7 post-burn and that the principal component and microbial community structure varied over time. On day 28 after the burn, the microbiome composition largely returned to the pre-burn level, although day 5 was a turning point for change. Some probiotics, such as the Lachnospiraceae_NK4A136_group, decreased in composition after the burn but were restored in the later recovery period. In contrast, Proteobacteria showed an opposite trend, which is known to include potential pathogenic bacteria. Conclusion: These findings demonstrate gut microbial dysbiosis after burn injury and provide new insights into the burn-related dysbiosis of the gut microbiome and strategies for improving the treatment of burn injury from the perspective of the microbiota.
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Introduction: Depression is a common mental disorder that affects approximately 350 million people worldwide. Much remains unknown about the molecular mechanisms underlying this complex disorder. Sigma-1 receptor (Sig-1R) is expressed at high levels in the central nervous system. Increasing evidence has demonstrated a close association between the Sig-1R and depression. Recently, research has suggested that the gut microbiota may play a crucial role in the development of depression. Methods: Male Sig-1R knockout (Sig-1R KO) and wild-type (WT) mice were used for this study. All transgenic mice were of a pure C57BL/6J background. Mice received a daily gavage of vancomycin (100 mg/kg), neomycin sulfate (200 mg/kg), metronidazole (200 mg/kg), and ampicillin (200 mg/kg) for one week to deplete gut microbiota. Fecal microbiota transplantation (FMT) was conducted to assess the effects of gut microbiota. Depression-like behaviors was evaluated by tail suspension test (TST), forced swimming test (FST) and sucrose preference test (SPT). Gut microbiota was analyzed by 16s rRNA and hippocampal transcriptome changes were assessed by RNA-seq. Results: We found that Sig-1R knockout induced depression-like behaviors in mice, including a significant reduction in immobility time and an increase in latency to immobility in the FST and TST, which was reversed upon clearance of gut microbiota with antibiotic treatment. Sig-1R knockout significantly altered the composition of the gut microbiota. At the genus level, the abundance of Alistipes, Alloprevotella, and Lleibacterium decreased significantly. Gut microbiota dysfunction and depression-like phenotypes in Sig-1R knockout mice could be reproduced through FMT experiments. Additionally, hippocampal RNA sequencing identified multiple KEGG pathways that are associated with depression. We also discovered that the cAMP/CREB/BDNF signaling pathway is inhibited in the Sig-1R KO group along with lower expression of neurotrophic factors including CTNF, TGF-α and NGF. Fecal bacteria transplantation from Sig-1R KO mice also inhibited cAMP/CREB/BDNF signaling pathway. Discussion: In our study, we found that the gut-brain axis may be a potential mechanism through which Sig-1R regulates depression-like behaviors. Our study provides new insights into the mechanisms by which Sig-1R regulates depression and further supports the concept of the gut-brain axis.
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Methamphetamine (Meth) abuse can cause severe anxiety disorder and interfere with gut homeostasis. Obeticholic acid (OCA) has emerged as a protective agent against diet-related anxiety that improves gut homeostasis. The potential for OCA to ameliorate Meth-induced anxiety, and the microbial mechanisms involved, remain obscure. Here, C57/BL6 mice were intraperitoneally injected with Meth (15 mg/kg) to induce anxiety-like behavior. 16 S rRNA sequence analysis and fecal microbiome transplantation (FMT) were used to profile the gut microbiome and evaluate its effects, respectively. Orally administered OCA was investigated for protection against Meth-induced anxiety. Results indicated that Meth mediated anxiety-like behavior, aroused hippocampal neuroinflammation through activation of the TLR4/MyD88/NF-κB pathway, weakened intestinal barrier and disturbed the gut microbiome. Specifically, abundance of anxiety-related Rikenella was increased. FMT from Meth-administrated mice also weakened intestinal barrier and elevated serum LPS, inducing hippocampal neuroinflammation and anxiety-like behavior in recipient mice. Finally, OCA pretreatment ameliorated Meth-induced impairment of gut homeostasis by reshaping the microbial composition and improving the intestinal barrier. Meth-induced anxiety-like behavior and hippocampal neuroinflammation were also ameliorated by OCA pretreatment. These preliminary findings reveal the crucial role of gut microbiota in Meth-induced anxiety-like behavior and neuroinflammation, highlighting OCA as a potential candidate for the prevention of Meth-induced anxiety.
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Metanfetamina , Microbiota , Ratones , Animales , Metanfetamina/toxicidad , Enfermedades Neuroinflamatorias , Ansiedad/inducido químicamente , Ansiedad/prevención & controlRESUMEN
Although Polychlorinated biphenyl (PCB) levels are decreased in the environment, the adverse effects of gestational exposure on the mother and offspring cannot be ignored due to the vulnerability of the fetus. In the present study, pregnant Balb/c mice were administered PCB52 (1 mg/kg BW/day) or corn oil vehicle by gavage until parturition. In the dams, PCB52 caused histopathological changes in the liver, higher serum levels of aminotransferase and alanine aminotransferase, and activated apoptosis and autophagy, suggesting hepatotoxicity. Overexpressed indicators of TLR4 pathway were observed in the liver of PCB52-exposed dams, indicated hepatic inflammation. Moreover, PCB52 exposure weakened the intestinal barrier and triggered inflammatory response, which might contribute to the hepatic inflammation by gut-liver axis. In the pups, prenatal PCB52 exposure affected the sex ratio at birth and reduced birth length and weights. Similar to the dams, prenatal PCB52 exposure induced hepatotoxicity in the pups without gender difference. Consistent with the alteration of gut microbiota, intestinal inflammation was confirmed, accompanying the disruption in the intestinal barrier and the activation of apoptosis and autophagy in the PCB52-exposed pups. Intestinal injury might be responsible for hepatotoxicity at least in part. Taken together, these findings suggested that gestational PCB52 exposure induced hepatic and intestinal injury in both maternal and offspring mice by arousing inflammation.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Enfermedades del Sistema Digestivo , Enfermedades Intestinales , Bifenilos Policlorados , Efectos Tardíos de la Exposición Prenatal , Alanina Transaminasa , Animales , Aceite de Maíz , Femenino , Inflamación/inducido químicamente , Ratones , Bifenilos Policlorados/toxicidad , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Receptor Toll-Like 4RESUMEN
Objective: The study aimed to summarize the morphological characteristics of low-grade gastric intraepithelial neoplasia (LGIN) and explore its outcomes and risk factors. Additionally, it aimed to screen the core different expression genes (DEGs) of high-grade gastric intraepithelial neoplasia (HGIN) using bioinformatics methods to identify biomarkers for early gastric cancer outcomes. Methods: The clinical and pathological data of 449 patients with LGIN in the endoscopy center of the Second Hospital of Hebei Medical University from June 2013 to September 2018 were collected for retrospective analysis. The GSE130823 and GSE55696 data sets were selected from the Gene Expression Omnibus database, and the GEO2R tool was used to screen DEGs in HGIN and chronic gastritis tissue types. A DEG functional enrichment analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery. The STRING database was utilized to create a protein-protein interaction network, and the CytoHubba plug-in was used to screen the key genes of HGIN. Results: The incidence of LGIN increased with age, and most of the patients were aged between 45-59 years (P = 0.048). Lesions were found mainly in the cardia, mostly in people aged 60 (P < 0.05). Progression occurred in 42 of 449 patients, with a 9.4% rate of cancer development. Foci larger than 10 mm, ulcerative lesions, and an Helicobacter pylori-positive result were factors affecting the outcome of LGIN (P < 0.05). Seven core genes of HGIN were screened, including MYC, SOX2, CDX2, TBX3, KRT7, CDKN2A, and MUC5AC. Conclusion: The patients with LGIN reflected the potential for developing cancer. A magnifying gastroscope can contribute to the detection of early gastric cancer. Additionally, the MYC, CDX2, and TBX3 genes may act as specific biomarkers of HGIN.
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Methamphetamine (Meth), an addictive psychostimulant of abuse worldwide, has been a common cause of acute toxic hepatitis in adults. Gut microbiota has emerged as a modulator of host immunity via metabolic pathways. However, the microbial mechanism of Meth-induced hepatic inflammation and effective therapeutic strategies remain unknown. Here, mice were intraperitoneally (i.p.) injected with Meth to induce hepatotoxicity. Cecal microbiome and bile acids (BAs) composition were analyzed after Meth administration. Fecal microbiota transplantation (FMT) technology was utilized to investigate the role of microbiota. Additionally, the protective effects of obeticholic acid (OCA), an agonist of farnesoid X receptor (FXR), were evaluated. Results indicated that Meth administration induced hepatic cholestasis, dysfunction and aroused hepatic inflammation by stimulating the TLR4/MyD88/NF-κB pathway in mice. Meanwhile, Meth disturbed the cecal microbiome and impaired the homeostasis of BAs. Interestingly, FMT from Meth administered mice resulted in serum and hepatic BA accumulation and transferred similar phenotypic changes into the healthy recipient mice. Finally, OCA normalized Meth-induced BA accumulation in both serum and the liver, and effectively protected against Meth-induced hepatic dysfunction and inflammation by suppressing the TLR4/MyD88/NF-κB pathway. This study established the importance of microbial mechanism and its inhibition as a potential therapeutic target to treat Meth-related hepatotoxicity.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Microbioma Gastrointestinal , Metanfetamina , Animales , Ácidos y Sales Biliares/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Homeostasis , Inflamación/tratamiento farmacológico , Hígado , Metanfetamina/toxicidad , Ratones , Ratones Endogámicos C57BL , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/genética , FN-kappa B/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptor Toll-Like 4/metabolismoRESUMEN
Methamphetamine (METH) is a stimulant drug. METH abuse induces hepatotoxicity, although the mechanisms are not well understood. METH-induced hepatotoxicity was regulated by TLR4-mediated inflammation in BALB/c mice in our previous study. To further investigate the underlying mechanisms, the wild-type (C57BL/6) and Tlr4-/- mice were treated with METH. Transcriptomics of the mouse liver was performed via RNA-sequencing. Histopathological changes, serum levels of metabolic enzymes and lipopolysaccharide (LPS), and expression of TLR4-mediated proinflammatory cytokines were assessed. Compared to the control, METH treatment induced obvious histopathological changes and significantly increased the levels of metabolic enzymes in wild-type mice. Furthermore, inflammatory pathways were enriched in the liver of METH-treated mice, as demonstrated by expression analysis of RNA-sequencing data. Consistently, the expression of TLR4 pathway members was significantly increased by METH treatment. In addition, increased serum LPS levels in METH-treated mice indicated overproduction of LPS and gut microbiota dysbiosis. However, antibiotic pretreatment or silencing Tlr4 significantly decreased METH-induced hepatic injury, serum LPS levels, and inflammation. In addition, the dampening effects of silencing Tlr4 on inflammatory pathways were verified by the enrichment analysis of RNA-sequencing data in METH-treated Tlr4-/- mice compared to METH-treated wild-type mice. Taken together, these findings implied that Tlr4 silencing, comparable to antibiotic pretreatment, effectively alleviated METH-induced hepatotoxicity by inhibiting LPS-TLR4-mediated inflammation in the liver.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Metanfetamina , Animales , Antibacterianos , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Inflamación/genética , Inflamación/metabolismo , Lipopolisacáridos/toxicidad , Metanfetamina/toxicidad , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , ARN , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismoRESUMEN
[This corrects the article DOI: 10.3389/fphar.2022.831912.].