RESUMEN
Some studies have demonstrated the effects of particulate matter (PM) on chronic rhinosinusitis with nasal polyps (CRSwNP) development, as well as the therapeutic role of retinoic acid (RA) in nasal polypogenesis. However, the immunologic effect of PM in innate lymphoid cells (ILCs) and the exact mechanism of the therapeutic effect of RA remain unclear. Therefore, the present study investigated the effects of fine-dust-induced inflammation in CRSwNP and the mechanisms of the therapeutic effect of RA. PM2.5 exposure exacerbated pathological damage in the nasal mucosa of mice with nasal polyps (NP) via upregulation of type 2 inflammation. Additionally, PM2.5 exposure increased the expression of type 2 cytokines and epithelial-cell-derived cytokines (IL-33 and IL-25) significantly, as well as the ILC populations in human-NP-derived epithelial cells (HNECs). Moreover, RA supplementation significantly increased the expression of ILCreg in Lin-CD45+CD127+ cells, which in turn increased the levels of the anti-inflammatory cytokine IL-10. The findings suggest that PM2.5 exposures could aggravate the CRSwNP type 2 inflammation, and RA treatment may ameliorate fine-dust-induced inflammation by modulating the innate immune response.
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Inmunidad Innata , Pólipos Nasales , Humanos , Animales , Ratones , Linfocitos , Inflamación/tratamiento farmacológico , Citocinas , Polvo , Mucosa Nasal , Material Particulado/toxicidadRESUMEN
BACKGROUND: Intestinal barrier dysfunction caused by the disrupted balance of group 3 innate lymphoid cells (ILC3)/group 1 innate lymphoid cells (ILC1) is a significant feature in the pathogenesis of inflammatory bowel disease (IBD). Activation of aryl hydrocarbon receptor (AhR) signaling contributes to the maintenance of ILC3/ILC1 balance. Wogonin, a natural flavonoid from Scutellaria baicalensis Georgi, can repair intestinal mucosal damage of IBD. However, it remains unclear if wogonin can exert a therapeutic effect by activating the AhR pathway to regulate the plasticity of ILC3/ILC1. PURPOSE: In this study, we investigated the immunomodulatory effects of wogonin on IBD and its potential mechanisms in vitro and in vivo. STUDY DESIGN AND METHODS: Chronic colitis was induced by four cycles of 2 % DSS treatment in mice. 20 mg kg-1/day wogonin was administrated by oral gavage and mice were treated intraperitoneally with 10 mg kg-1/2 days CH223191 to block the AhR pathway. Colon tissues were processed for histopathological examination and evaluation of the epithelial barrier function by immunohistochemistry. The activation of the AhR pathway and the plasticity of ILC3/ILC1 were determined by western blot and flow cytometry. Then, we also detected the intestinal microflora and their metabolites by 16 s sequencing and non-targeted Metabolomics analysis. Furthermore, an in vitro culture system consisting of MNK3 cells and NCM460 cells, and a CETSA assay were performed to confirm the molecular mechanism. RESULTS: Wogonin ameliorated histological severity of the colon, decreased the secretion of inflammatory factors, and increased tight junction proteins in colitis mice. These effects are associated with the tendency of conversion from ILC3 to ILC1 prevented by wogonin, which was offset by AhR antagonist CH223191. In addition, wogonin exerted the curative effect by altering gut microbiota to produce metabolites such as Kynurenic acid, and 1H-Indole-3-carboxaldehyde as AhR endogenous ligands. In vitro data further verified that wogonin as an exogenous ligand directly binds to the structural domain of AhR by CETSA. Also, the supernatant of MNK-3 cells stimulated with wogonin enhanced expression of Occludin and Claudin1 in NCM460 cells induced by LPS. CONCLUSION: Cumulatively, our study illustrated that wogonin improved the outcomes of DSS-induced chronic colitis via regulating the plasticity of ILC3/ILC1. Its specific mechanism is to binding to AhR directly, and to activate the AhR pathway indirectly by altering the tryptophan metabolisms of gut microbiota.
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Colitis , Flavanonas , Inmunidad Innata , Linfocitos , Ratones Endogámicos C57BL , Receptores de Hidrocarburo de Aril , Transducción de Señal , Flavanonas/farmacología , Receptores de Hidrocarburo de Aril/metabolismo , Animales , Ratones , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Linfocitos/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Inmunidad Innata/efectos de los fármacos , Masculino , Scutellaria baicalensis/química , Mucosa Intestinal/efectos de los fármacos , Humanos , Modelos Animales de Enfermedad , Sulfato de Dextran , Microbioma Gastrointestinal/efectos de los fármacos , Colon/efectos de los fármacosRESUMEN
The gut health-promoting properties of saponin-rich Polygonatum cyrtonema Hua (FP) fermented with Lactobacillus plantarum P9 were explored in a dextran sulfate sodium (DSS)-induced colitis mouse model. FP supplementation effectively inhibited DSS-induced physiological alteration and impaired immune responses by reducing the disease activity index (DAI) score and restoring the T helper (Th) 1/Th2 and regulatory T (Treg)/Th17 ratios. In addition, FP supplementation protected the gut barrier function against DSS-induced damage via upregulation of zonula occludens (ZO)-1 and occludin and downregulation of pro-inflammatory cytokines, including interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), IL-18, and the granulocyte-macrophage colony-stimulating factor (GM-CSF). This study further elucidated the potential mechanisms underlying the FP-mediated suppression of the plasticity of type 3 innate lymphoid cells (ILC3) and subsequent macrophage polarization. Therefore, the FP supplementation effectively restored mucosal immune homeostasis and enhanced gut integrity. In addition, it suppressed the growth of Escherichia-Shigella and Enterococcus and promoted the enrichment of probiotics and short-chain fatty acid-producing microbes, such as Romboutsia, Faecalibaculum, and Blautia. In conclusion, P. cyrtonema Hua fermented with L. plantarum P9 might be a promising dietary intervention to improve gut health by sustaining overall gut homeostasis and related gut integrity.
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Colitis , Polygonatum , Animales , Ratones , Dextranos , Inmunidad Innata , Linfocitos , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Homeostasis , Interleucina-1beta , Sulfatos , SodioRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Citrullus colocynthis (L.) Schrad is a member of the Cucurbitaceae plant family which has been used in traditional medicine for the treatment of lung diseases such as asthma and bronchitis. AIM OF THE STUDY: The study was conducted to investigate antiproliferative and immunomodulating effects of C. colocynthis and isolated cucurbitacins on human T lymphocytes and lung epithelial cells in order to evaluate their potential in the treatment of airway diseases. MATERIALS AND METHODS: Different concentrations of an ethanolic extract of C. colocynthis fruits and cucurbitacins B (CuB), E (CuE) and E-glucopyranoside (CuE-Glu) were analysed for their cytotoxicity and immunomodulatory potential on Peripheral Blood Mononuclear Cells (PBMCs) of healthy donors and on the epithelial lung cancer cell line A549. Viability and proliferation were tested using WST1 and CFSE assays. Flow cytometric analysis of AnnexinV/PI staining was used to investigate cell death through apoptosis/necrosis. Effects on regulatory mechanisms of T lymphocytes, such as CD69 and CD25 marker activation, cytokine production of the cytokines interleukin 2 (IL2), tumor necrosis factor α (TNFα) and interferon γ (IFNy) were also analysed via flow cytometry. Influences on the activator protein 1 (AP1), nuclear factor of activated T-cells (NFAT) or nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFκB) pathways were analysed in the Jurkat reporter cell line. Cytokine secretion in A549 cells stimulated with virus-like particles was analysed using the bead-based Legendplex™ assay. RESULTS: Non-toxic concentrations of C. colocynthis and CuE-Glu showed dose-dependent effects on viability and proliferation in both T lymphocytes and A549 cells. The extracts inhibited lymphocyte activation and suppressed T cell effector functions, which was also shown by lower production of cytokines IL2, TNFα and IFNy. A dose dependent inhibition of the pathways NFκB, NFAT and AP1 in Jurkat cells could be observed. In A549 cells, especially CuE and CuE-Glu showed inhibitory effects on cytokine production following a simulated viral infection. Unglycosylated cucurbitacins were more effective in suppressing the immune function in lymphocytes than glycosylated cucurbitacins, however this activity is limited to cytotoxic concentrations. CONCLUSION: In our study we could confirm the immunmodulating effect of C. colocynthis and cucurbitacins B, E and E-glucopyranoside in vitro by suppression of different pathways of inflammation and T cell proliferation. Activity in a lung cell model using a virus-like stimulation shows promise for further research regarding cucurbitacins in airway diseases.
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Citrullus colocynthis , Citrullus , Triterpenos , Humanos , Cucurbitacinas/farmacología , Interleucina-2 , Leucocitos Mononucleares , Factor de Necrosis Tumoral alfa , Extractos Vegetales/farmacología , Linfocitos , PulmónRESUMEN
Type 2 diabetic kidney disease (T2DKD) is a common microvascular complication of type 2 diabetes mellitus (T2DM), and its incidence is significantly increasing. Microinflammation plays an important role in the development of T2DKD. Based on this, this study investigated the value of inflammatory markers including neutrophil-lymphocyte ratio (NLR), high-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1) in the prediction of T2DKD. This was a cross-sectional survey study. A total of 90 patients with T2DM, who were hospitalized in the nephrology and endocrinology departments of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from June 2021 to January 2022, were included and divided into three groups (A1, A2, A3) according to the urinary albumin-to-creatinine ratio (UACR). Observe and compare the basic information, clinical and laboratory data, and the inflammatory markers NLR, hs-CRP, MCP-1. Results revealed that high levels of NLR (OR = 6.562, 95% CI 2.060-20.902, P = 0.001) and MCP-1 (OR = 1.060, 95% CI 1.026-1.095, P < 0.001) were risk factors in the development of T2DKD. Receiver operating characteristic curve analysis showed that the area under curve of NLR and MCP-1 in diagnosing T2DKD were 0.760 (95% CI 0.6577-0.863, P < 0.001) and 0.862 (95% CI 0.7787-0.937, P < 0.001). Therefore, the inflammatory markers NLR and MCP-1 are risk factors affecting the development of T2DKD, which of clinical value may be used as novel markers of T2DKD.
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Humanos , Proteína C-Reactiva/análisis , Quimiocina CCL2/orina , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/orina , Linfocitos/química , Neutrófilos/química , Estudios Retrospectivos , Curva ROCRESUMEN
BACKGROUND: Asthma affects 3% of the global population, leading to over 0.25 million deaths. Due to its complexity, asthma is difficult to cure or prevent, and current therapies have limitations. This has led to a growing demand for alternative asthma treatments. We found rosmarinic acid (RosA) as a potential new drug candidate from natural medicine. However, RosA has poor bioavailability and remains mainly in the gastrointestinal tract after oral administration, suggesting the involvement of gut microbiota in its bioactivity. PURPOSE: To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis. METHODS: We used 16S rRNA gene sequencing and metabolites analysis to investigate RosA's modulation of gut microbiota. Techniques of molecular biology and metabolomics were employed to study the pharmacological mechanism of RosA. Cohousing was used to confirm the involvement of gut microbiota in RosA-induced improvement of allergic asthma. RESULTS: RosA decreased cholate levels from spore-forming bacteria, leading to reduced 5-hydroxytryptamine (5-HT) synthesis, bronchoconstriction, vasodilation, and inflammatory cell infiltration. It also increased short-chain fatty acids (SCFAs) levels, facilitating the expression of intestinal tight junction proteins to promote intestinal integrity. SCFAs upregulated intestinal monocarboxylate transporters (MCTs), thereby improving their systemic delivery to reduce Th2/ILC2 mediated inflammatory response and suppress eosinophil influx and mucus production in lung. Additionally, RosA inhibited lipopolysaccharide (LPS) production and translocation, leading to reduced TLR4-NFκB mediated pulmonary inflammation and oxidative stress. CONCLUSIONS: The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiota-derived 5-HT, SCFAs, and LPS, achieving a combined synergistic effect. RosA is a safe, effective, and reliable drug candidate that could potentially replace glucocorticoids for asthma treatment.
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Asma , Ácido Rosmarínico , Humanos , Inmunidad Innata , ARN Ribosómico 16S/genética , Lipopolisacáridos , Serotonina , Linfocitos , Asma/tratamiento farmacológico , Asma/metabolismo , Pulmón/metabolismo , Ácidos Grasos Volátiles/metabolismoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Cang-ai volatile oil (CAVO) is an aromatic Chinese medicine with potent antibacterial and immune regulatory properties. While CAVO has been used to treat upper respiratory tract infections, depression, otomycosis, and bacterial infections in the skin, its effect on psoriasis is unknown. AIM OF THE STUDY: This study explores the effect and mechanism of CAVO in psoriasis intervention. MATERIAL AND METHODS: The effect of CAVO on the expression of IL-6 and IL-1ß was assessed in TNF-α-induced HaCaT cells using enzyme-linked immunosorbent assay (ELISA). Mice were given imiquimod (IMQ) and administered orally with different CAVO doses (0.03 and 0.06 g/kg) for 5 days. The levels of inflammatory cytokines related to group-3 innate lymphoid cells (ILC3s) in the skin were assessed using hematoxylin and eosin (H&E) staining, ELISA, and western blotting (WB). The frequency of ILC3s in mice splenocytes and skin cells was evaluated using flow cytometry. RESULTS: The results demonstrated that CAVO decreased the expression of IL-6 and IL-1ß in TNF-α- induced HaCaT cells. CAVO significantly reduced the severity of psoriatic symptoms in IMQ-induced mice. The expression of inflammatory cytokines in the skin, such as IL-1ß, IL-6, IL-8, IL-22, IL-23, and IL-17 A were decreased, whereas IL-10 levels were increased. The mRNA expressions of TNF-α, IL-23 A, IL-23 R, IL-22, IL-17 A, and RORγt were down-regulated in skin tissues. CAVO also decreased the levels of NF-κB, STAT3, and JAK2 proteins. CONCLUSIONS: CAVO potentially inhibits ILC3s activation to relieve IMQ-induced psoriasis in mice. These effects might be attributed to inhibiting the activation of NF-κB, STAT3, and JAK2 signaling pathways.
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Interleucina-17 , Psoriasis , Animales , Ratones , Imiquimod , Interleucina-17/genética , Interleucina-17/metabolismo , FN-kappa B/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Inmunidad Innata , Interleucina-6/metabolismo , Linfocitos/metabolismo , Piel , Psoriasis/inducido químicamente , Psoriasis/tratamiento farmacológico , Citocinas/metabolismo , Interleucina-23/metabolismo , Ratones Endogámicos BALB C , Modelos Animales de EnfermedadRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Yanghe Decoction (JWYHD) is modified Yanghe Decoction (YHD). YHD historically utilized as a potent medicinal solution for addressing chronic inflammatory conditions, holds promising therapeutic potential in the treatment of asthma. However, the mechanisms underlying JWYHD's effects on allergic asthma remain unclear. AIM OF THE STUDY: To investigate the therapeutic effect as well as the underlying mechanisms of JWYHD on asthmatic mice. MATERIALS AND METHODS: The ovalbumin (OVA)-induced mouse model was utilized, followed by the administration of JWYHD to allergic asthmatic mice. Subsequently, inflammatory cells in the bronchoalveolar lavage fluid (BALF) and lung tissues were conducted. The levels of various cytokines including interleukin (IL)-4, IL-5, IL-13, IL-33, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in BALF, as well as the total immunoglobulin E (IgE) content in serum, were assessed. Lung function and tissue pathology examinations were performed to assess the protective impacts of JWYHD. The chemical components of JWYHD and its lung prototype compounds (referred to the chemical components present in JWYHD that were observed in the lung) were explored by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). RNA-seq analysis revealed the regulation mechanisms of JWYHD treating asthma. Furthermore, the effect of JWYHD on type 2 innate lymphoid cells (ILC2s) in asthmatic mice was detected by flow cytometry and Smart-RNA-seq analysis. Then molecular docking analysis was used to show the interaction between identified compounds and key targets. RESULTS: JWYHD significantly attenuated the airway inflammation of asthmatic mice, reduced the levels of inflammatory cells in BALF, as well the levels of the cytokines IL-4, IL-5, IL-13, IL-33, and TNF-α in BALF and IgE in serum. Airway hyperresponsiveness (AHR) and lung inflammation infiltration were also alleviated by JWYHD. Moreover, RNA-seq analysis revealed that JWYHD attenuated airway inflammation in asthmatic mice via regulating immunity. Flow cytometry confirmed that JWYHD could inhibit ILC2 responses. ILC2 Smart-RNA-seq analysis showed that JWYHD impaired the inflammation reaction-related signaling pathways in ILC2s, and neuropilin-1 (Nrp1), endothelial transcription factor 3 (GATA3) and interleukin 1 receptor like protein 1 (ST2) might be the key targets. The molecular docking analysis investigating the connection between the primary targets and JWYHD's prototype compounds in the lung demonstrated that liquiritin apioside, icariin, glycyrrhizic acid, and uralsaponin B, identified through UPLC-Q-TOF/MS, exhibited significant affinity in binding to the mentioned key targets. CONCLUSION: Our results suggested that the mechanism of JWYHD in treating asthma might be related to limiting ILC2 responses. Our findings provided some pharmacological evidence for the clinical application of JWYHD in the treatment of asthma.
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Asma , Medicamentos Herbarios Chinos , Inmunidad Innata , Ratones , Animales , Interleucina-33 , Interleucina-13 , Interleucina-5 , Simulación del Acoplamiento Molecular , Linfocitos/metabolismo , Pulmón , Inflamación/tratamiento farmacológico , Inflamación/patología , Citocinas/metabolismo , Líquido del Lavado Bronquioalveolar , Inmunoglobulina E , Ovalbúmina/farmacología , Ratones Endogámicos BALB C , Modelos Animales de EnfermedadRESUMEN
AIMS: This study combines traditional Chinese medicine polysaccharides with nanomaterials to enhance drug bioavailability and immunological activity. BACKGROUND: The study of polysaccharide preparation, structure identification, pharmacological activity, and mechanism of action is deepening, but the research combined with the new drug delivery system is relatively weak, so the application of polysaccharides is still facing great limitations. In order to prolong the action time of polysaccharides and improve their bioavailability, liposome has become the most promising delivery carrier. OBJECTIVES: The purpose of this study was to optimize the preparation process of Portulaca oleracea L. polysaccharides liposomes (POL-PL) and evaluate the immunoactivity in vitro. METHODS: POL-PL was prepared by reverse evaporation, and the preparation process was optimized using the response surface methodology. The characteristic analysis of POL-PL was detected by the indicators including morphology, particle size, zeta potential, encapsulation efficiency, release, and stability. The effects of POL-PL on the proliferation and immunological activity of mouse spleen lymphocytes and RAW264.7 cells were evaluated in vitro. RESULTS: POL-PL is highly homogeneous in morphology and particle size, and its sustained release improves the bioavailability of Portulaca oleracea L. polysaccharides (POL-P). Moreover, POL-PL treatment significantly enhanced the proliferation and phagocytic activity of RAW264.7 cells and increased the secretion of IL-6, TNF-α, IL-1ß, and NO. CONCLUSION: This study suggested that POL-PL were prepared successfully by reverse evaporation method, and POL-PL had immunoenhancing activity in vitro. The results provided a theoretical basis for further application of POL-PL.
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Liposomas , Polisacáridos , Portulaca , Portulaca/química , Animales , Ratones , Polisacáridos/química , Polisacáridos/farmacología , Polisacáridos/aislamiento & purificación , Células RAW 264.7 , Proliferación Celular/efectos de los fármacos , Tamaño de la Partícula , Linfocitos/efectos de los fármacos , Linfocitos/inmunología , Ratones Endogámicos BALB C , Células CultivadasRESUMEN
Apitherapy is a form of alternative medicine that utilizes products from the western honeybee (Apis mellifera), including honey, propolis, and honeybee venom, to improve the health status of human patients by altering host immunity. An added benefit of these products is that they are nutraceuticals and relatively inexpensive to aquire. Currently, little is known about the use of honeybee products in veterinary species, as well as their impact on host immunity. In the present in vitro study, honey, propolis, and honeybee venom were co-cultured with enriched canine, equine, and chicken peripheral blood lymphocytes (PBLs) with cell proliferation, cell viability/apoptosis, and cellular morphology evaluated. Concanavalin A (Con A) and dexamethasone were used as stimulatory and suppressive controls, respectively. Honeybee products' effects on the three veterinary species varied by product and the species. Honey stimulated the PBLs proliferation in all three species but also displayed some increased cytotoxicity. Propolis stimulated proliferation in canine and equine PBLs, however, it suppressed proliferation in the chicken PBLs. Honeybee venom was the strongest PBL stimulant for all three species and in the equine, surpassed the stimulant response of Con A and yet, enhanced PBL cell viability post culture. In summary, the results of this preliminary in vitro study show that these three honeybee products do impact lymphocyte proliferation and viability in dogs, horses, and chickens, and that more research both in vitro and in vivo will be necessary to draw conclusions regarding their future use as immune stimulants or inhibitors.
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Venenos de Abeja , Própolis , Animales , Perros , Humanos , Caballos , Abejas , Apiterapia/veterinaria , Pollos , Própolis/farmacología , Linfocitos , Venenos de Abeja/farmacologíaRESUMEN
Hyperbaric oxygen (HBO) therapy is a well-established method for improving tissue oxygenation and is typically used for the treatment of various inflammatory conditions, including infectious diseases. However, its effect on the intestinal mucosa, a microenvironment known to be physiologically hypoxic, remains unclear. Here, we demonstrated that daily treatment with hyperbaric oxygen affects gut microbiome composition, worsening antibiotic-induced dysbiosis. Accordingly, HBO-treated mice were more susceptible to Clostridioides difficile infection (CDI), an enteric pathogen highly associated with antibiotic-induced colitis. These observations were closely linked with a decline in the level of microbiota-derived short-chain fatty acids (SCFAs). Butyrate, a SCFA produced primarily by anaerobic microbial species, mitigated HBO-induced susceptibility to CDI and increased epithelial barrier integrity by improving group 3 innate lymphoid cell (ILC3) responses. Mice displaying tissue-specific deletion of HIF-1 in RORγt-positive cells exhibited no protective effect of butyrate during CDI. In contrast, the reinforcement of HIF-1 signaling in RORγt-positive cells through the conditional deletion of VHL mitigated disease outcome, even after HBO therapy. Taken together, we conclude that HBO induces intestinal dysbiosis and impairs the production of SCFAs affecting the HIF-1α-IL-22 axis in ILC3 and worsening the response of mice to subsequent C. difficile infection.
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Clostridioides difficile , Infecciones por Clostridium , Microbioma Gastrointestinal , Oxigenoterapia Hiperbárica , Ratones , Animales , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares , Inmunidad Innata , Oxigenoterapia Hiperbárica/efectos adversos , Interleucina-22 , Disbiosis/terapia , Linfocitos , Butiratos/farmacología , Ácidos Grasos Volátiles/farmacología , Antibacterianos/farmacologíaRESUMEN
Objective: This study aims to explore the predictive value of preoperative C-reactive protein (CRP) and other inflammatory biomarkers: platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) for postoperative complications (infection, diarrhea, etc.) in colorectal tumor patients. Methods: A cohort of 109 colorectal tumor patients who underwent surgical resection for colorectal cancer at the hospital from January 2021 to December 2022 were selected as the research subjects. Patients' postoperative complications were tracked, and they were split into the complication group and the non-complication group. All patients underwent preoperative biochemical tests. Serum levels of CRP, PLR, and NLR were compared between the two groups. The relationship between these markers and postoperative complications in colorectal tumor patients was analyzed. A Logistic regression model was established to analyze their impact on postoperative complications, and a Receiver Operating Characteristic (ROC) curve was drawn to assess predictive value. Results: Among the 109 colorectal tumor patients, 31 cases (28.44%) experienced postoperative complications. The complication group had larger tumor diameters and a higher proportion of open surgeries compared to the non-complication group (P < .05). Serum levels of CRP, PLR, and NLR were higher in the complication group compared to the non-complication group (P < .05). Correlation analysis showed that serum CRP, PLR, and NLR values were positively correlated with postoperative complications in colorectal tumor patients (r > 0, P < .05). The Logistic regression model revealed that high serum CRP levels (95%CI: 1.253-2.503), PLR (95%CI: 1.005-1.041), and NLR values (95%CI: 2.702-20.533) were risk factors for postoperative complications in colorectal tumor patients (OR>1, P < .05). The ROC curve demonstrated that serum CRP levels, PLR, and NLR values had certain predictive values for postoperative complications in colorectal tumor patients (AUC=0.811, 0.789, 0.870), the optimal predictive values were obtained when the cut-off values were set at 5.400 mg/L, 142.790, and 2.485, respectively and combined detection showed even higher predictive values (AUC=0.913). At 1 week post-surgery, the patient's CRP levels, PLR value, and NLR value were significantly lower than pre-surgery (P < .05). Conclusion: Preoperative serum CRP, PLR, and NLR values are closely related to postoperative complications in colorectal tumor patients, and they can be used to predict the risk of postoperative complications in colorectal tumor patients. Clinically, early prediction of postoperative complications in patients can be achieved by measuring the aforementioned indicators, allowing for the implementation of appropriate preventive measures such as detoxification and infection control to improve patient outcomes.
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Biomarcadores , Proteína C-Reactiva , Neoplasias Colorrectales , Complicaciones Posoperatorias , Humanos , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/sangre , Proteína C-Reactiva/metabolismo , Proteína C-Reactiva/análisis , Masculino , Femenino , Complicaciones Posoperatorias/sangre , Persona de Mediana Edad , Anciano , Biomarcadores/sangre , Valor Predictivo de las Pruebas , Adulto , Neutrófilos , Estudios Retrospectivos , Linfocitos/metabolismoRESUMEN
Tellimagrandin-I (TL) and camptothin A (CA) are ellagitannins widely found in diverse plant species. Numerous studies demonstrated their significant biological activities, which include antitumor, antioxidant, and hepatoprotective properties. Despite this protective profile, the effects of TL and CA on DNA have not been comprehensively investigated. Thus, the aim of this study was to determine the mutagenic and antimutagenic effects attributed to TL and CA exposure on Salmonella enterica serovar Typhimurium strains using the Ames test. In addition, the cytotoxic and genotoxic effects were examined on human lymphocytes, employing both trypan blue exclusion and CometChip assay. The antigenotoxic effect was determined following TL and CA exposure in the presence of co-treatment with doxorubicin (DXR). Our results from the Ames test indicated that TL or CA did not display marked mutagenic activity. However, TL or CA demonstrated an ability to protect DNA against the damaging effects of the mutagens 4-nitroquinoline-1-oxide and sodium azide, thereby exhibiting antimutagenic properties. In relation to human lymphocytes, TL or CA did not induce significant cytotoxic or genotoxic actions on these cells. Further, these ellagitannins exhibited an ability to protect DNA from damage induced by DOX during co-treatment, indicating their potential beneficial usefulness as antigenotoxic agents. In conclusion, the protective effects of TL or CA against mutagens, coupled with their absence of genotoxic and cytotoxic effects on human lymphocytes, emphasize their potential therapeutic value in chemopreventive strategies.
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Antimutagênicos , Salmonella enterica , Humanos , Salmonella typhimurium/genética , Salmonella enterica/genética , Taninos Hidrolizables/farmacología , Serogrupo , Pruebas de Mutagenicidad , Mutágenos/toxicidad , Antimutagênicos/farmacología , Extractos Vegetales/farmacología , Carcinógenos/farmacología , ADN/farmacología , LinfocitosRESUMEN
This study investigated the effects of fermented rice bran (FRB) on modulating intestinal aryl hydrocarbon receptor (AhR) expression, innate lymphoid cell (ILC)3 populations, the fecal microbiota distribution, and their associations with dextran sodium sulfate (DSS)-induced acute colitis. C57BL/6 mice were assigned to four groups: 1) NC group, normal mice fed the AIN-93M diet; 2) FRB group, normal mice fed a diet supplemented with 5% FRB; 3) NCD group, DSS-treated mice fed AIN-93M; 4) FRBD group, DSS-treated mice fed a 5% FRB-supplemented diet. DSS was administered for 5 d and followed by 5 d for recovery. At the end of the experiment, mice were sacrificed. Their blood and intestinal tissues were collected. Results showed that there were no differences in colonic biological parameters and function between the NC and FRB groups. Similar fecal microbiota diversity was noted between these two groups. Compared to the non-DSS-treated groups, DSS administration led to increased intestinal permeability, enhanced inflammatory cytokine production and disease severity, whereas tight junctions and AhR, interleukin (IL)-22 expressions were downregulated, and the ILC3 population had decreased. Also, gut microbiota diversity differs from the non-DSS-treated groups and more detrimental bacterial populations exist when compared to the FRBD group. FRB supplementation in DSS-treated mice attenuated fecal microbial dysbiosis, decreased intestinal permeability, improved the barrier integrity, upregulated AhR and IL-22 expression, maintained the ILC3 population, and pathologically mitigated colonic injury. These findings suggest enhanced ILC3- and AhR-mediated functions may be partly responsible for the anti-colitis effects of FRB supplementation in DSS-induced colitis.
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Colitis , Oryza , Ratones , Animales , Inmunidad Innata , Dextranos/efectos adversos , Dextranos/metabolismo , Receptores de Hidrocarburo de Aril/metabolismo , Linfocitos , Ratones Endogámicos C57BL , Colitis/metabolismo , Colon/metabolismo , Suplementos Dietéticos , Sulfato de Dextran/toxicidad , Modelos Animales de EnfermedadRESUMEN
Diseases caused by a compromised immune system, characterized by decreased production and diversification of T lymphocytes, such as immunodeficiencies or chronic infections, are becoming increasingly prominent. These diseases lead to increased vulnerability to infections caused by parasites, viruses, bacteria, fungi, and other microorganisms. According to various articles, Trametes versicolor has been used as immunotherapy and cancer treatment due to its polysaccharides, which have shown their value in traditional medicine. However, most of the studies have been done with Asian samples. For this reason, the aim of this study was to evaluate the effect of samples of Mexican T. versicolor on human lymphoid cells. Of various extracts, the one with the best T cell proliferative response was the extract produced by maceration in water at room temperature, but all treatments in aqueous and ethanolic extracts increased the lymphocyte count, showing that extracts of Mexican T. versicolor also have compounds that stimulate T cells. Unfortunately, genetic damage expressed as an increment in micronuclei count was identified, so using these fungus extracts in traditional medicine would require careful control of recommended doses.
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Agaricales , Trametes , Humanos , México , Péptidos y Proteínas de Señalización Intercelular , LinfocitosRESUMEN
OBJECTIVE: This study evaluated the therapeutic effect of hyperbaric oxygen therapy (HBOT) combined with steroid therapy to treat sudden hearing loss and examined the index associated with excellent therapeutic effect. METHODS: We included 109 patients with sudden hearing loss. Patients were divided into the HBOT combination group (59 sides) treated with HBOT and steroid therapy and HBOT noncombination group (50 sides) involving steroid therapy only. The recovery rate of each group was compared according to the severity of hearing loss. Blood samples were evaluated and inflammatory markers, such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), were calculated and compared by severity. We evaluated the usefulness of inflammatory markers for predicting recovery rate, and calculated cutoff values were also evaluated. RESULTS: The HBOT combination group exhibited a higher overall recovery rate than the HBOT noncombination group, particularly in severe cases. However, there was no significant difference in the severity of hearing loss based on various inflammatory markers. NLR and PLR are useful for predicting the effect in patients treated with concomitant HBOT. By setting 2.43 and 146.67 as cutoff values for NLR and PLR, respectively, we observed that lower values resulted in better recovery rates. CONCLUSION: The use of HBOT is effective for severe cases and early blood flow disorders with low NLR and PLR and less inflammation. When determining treatment, not only should the severity of hearing loss be considered, but also the NLR and PLR should be evaluated and examined based on the cutoff values.
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Sordera , Pérdida Auditiva Sensorineural , Pérdida Auditiva Súbita , Oxigenoterapia Hiperbárica , Humanos , Pérdida Auditiva Súbita/tratamiento farmacológico , Oxigenoterapia Hiperbárica/métodos , Pérdida Auditiva Sensorineural/terapia , Linfocitos , Sordera/terapia , Esteroides/uso terapéutico , Estudios RetrospectivosRESUMEN
The incidence of Alzheimer's disease (AD) is higher in people over the age of 65 and in African Americans (AA). Elevated acetylcholinesterase (AChE) activity has been considered a major player in the onset of AD symptoms. As a result, many FDA-approved AD drugs target AChE inhibition to treat AD patients. Hydrogen sulfide (H2S) is a signaling molecule known to downregulate oxidative stress and inflammation. The neutrophil-to-lymphocyte ratio (NLR) in the blood is widely used as a biomarker to monitor inflammation and immunity. This study examined the hypothesis that plasma AChE levels have a negative association with H2S levels and that a positive association exists between levels of NLR, HbA1c, and ROS with the AChE in the peripheral blood. The fasting blood sample was taken from 114 African Americans who had provided written informed consent approved by the IRB. The effect of H2S and high-glucose treatment on AChE activity levels was also investigated in THP-1 human monocytes. There was a significant negative relationship between AChE and the levels of H2S (r = -0.41, p = 0.001); a positive association between the levels of AChE with age (r = 0.26, p = 0.03), NLR (r = 0.23, p = 0.04), ROS (r = 0.23, p = 0.04) and HbA1c levels (r = 0.24, p = 0.04), in AA subjects. No correlation was seen between blood levels of AChE and acetylcholine (ACh). Blood creatinine had a negative correlation (r = -0.23, p = 0.04) with ACh levels. There was a significant effect of H2S on AChE inhibition and of high glucose in upregulating AChE activity in cultured monocytes. This study suggests hyperglycemia and lower H2S status can contribute to an increase in the AChE activity levels. Future clinical studies are needed to examine the potential benefits of supplementation with hydrogen sulfide pro-drugs/compounds in reducing the AChE and the cognitive dysfunctions associated with AD.
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Enfermedad de Alzheimer , Sulfuro de Hidrógeno , Humanos , Sulfuro de Hidrógeno/farmacología , Acetilcolinesterasa/metabolismo , Hemoglobina Glucada , Monocitos/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Regulación hacia Arriba , Neutrófilos/metabolismo , Negro o Afroamericano/genética , Enfermedad de Alzheimer/tratamiento farmacológico , Sulfuros , Linfocitos/metabolismo , Inflamación/tratamiento farmacológico , GlucosaRESUMEN
Interleukin-17 family (IL-17s) comprises six structurally related members (IL-17A to IL-17F); sequence homology is highest between IL-17A and IL-17F, displaying certain overlapping functions. In general, IL-17A and IL-17F play important roles in chronic inflammation and autoimmunity, controlling bacterial and fungal infections, and signaling mainly through activation of the nuclear factor-kappa B (NF-κB) pathway. The role of IL-17A and IL-17F has been established in chronic immune-mediated inflammatory diseases (IMIDs), such as psoriasis (PsO), psoriatic arthritis (PsA), axial spondylarthritis (axSpA), hidradenitis suppurativa (HS), inflammatory bowel disease (IBD), multiple sclerosis (MS), and asthma. CD4+ helper T cells (Th17) activated by IL-23 are well-studied sources of IL-17A and IL-17F. However, other cellular subtypes can also produce IL-17A and IL-17F, including gamma delta (γδ) T cells, alpha beta (αß) T cells, type 3 innate lymphoid cells (ILC3), natural killer T cells (NKT), or mucosal associated invariant T cells (MAIT). Interestingly, the production of IL-17A and IL-17F by innate and innate-like lymphocytes can take place in an IL-23 independent manner in addition to IL-23 classical pathway. This would explain the limitations of the inhibition of IL-23 in the treatment of patients with certain rheumatic immune-mediated conditions such as axSpA. Despite their coincident functions, IL-17A and IL-17F contribute independently to chronic tissue inflammation having somehow non-redundant roles. Although IL-17A has been more widely studied, both IL-17A and IL-17F are overexpressed in PsO, PsA, axSpA and HS. Therefore, dual inhibition of IL-17A and IL-17F could provide better outcomes than IL-23 or IL-17A blockade.
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Artritis Psoriásica , Hidradenitis Supurativa , Interleucina-17 , Psoriasis , Humanos , Enfermedad Crónica , Inmunidad Innata , Inflamación , Interleucina-23 , LinfocitosRESUMEN
BACKGROUND: Elevated platelet lymphocyte ratio (PLR) and low body mass index (BMI) are associated with inferior survival in non-small cell lung cancer (NSCLC) patients receiving immunotherapy (IO). We evaluated real-world prognostic utility of PLR, BMI, and albumin level in stage IV NSCLC patients receiving first line (1L) IO. METHODS: We identified 75 stage IV patients who received 1L IO therapy at USC Norris Comprehensive Cancer Center and Los Angeles General Medical Center from 2015 to 2022. The primary outcome was overall survival (OS) from time of IO with attention to pre-treatment BMI < 22, albumin < 3.5 g/dL, and PLR > 180. RESULTS: Median age was 66.5 years with 49 (65.3%) males. 25 (33.3%) had BMI < 22. 45/75 (60%) had PLR > 180. Patients with BMI < 22 had inferior OS (13.1 months (m) vs. 37.4 m in BMI > 28, p-value = 0.042) along with patients with albumin<3.5 g/dL (OS: 2.8 m vs. 14.6 m, p-value = 0.0027), and patients with PLR>180 (OS: 8.7 m vs. 23.0 m, p = 0.028). Composite BMI < 22, PLR > 180 had the worst OS, p-value = 0.0331. Multivariate analysis controlling for age, smoking, gender, PD-L1 tumor proportion score (TPS), and histology (adenocarcinoma, squamous, adenosquamous, and large cell) showed that BMI (HR: 0.8726, 95% CI: 0.7892-0.954) and PLR > 180 (HR: 2.48, 95% CI: 1.076-6.055) were significant in OS mortality risk. CONCLUSION: Patients with a composite of BMI < 22, albumin < 3.5 g/dL, and PLR > 180 had significantly worse OS. This highlights the importance of screening for poor nutritional status and high PLR to better inform stage IV NSCLC patients receiving IO therapy of their prognosis and supportive care. MICROABSTRACT: We evaluated real-world prognostic utility of platelet lymphocyte ratio (PLR), body mass index (BMI), and albumin level in 75 Stage IV NSCLC patients receiving first line IO. Patients with a composite of BMI < 22, albumin < 3.5 g/dL, and PLR > 180 had significantly worse OS. This highlights the importance of screening for poor nutritional status and high PLR to better inform stage IV NSCLC patients of their prognosis and to emphasize supportive care needs.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Masculino , Humanos , Anciano , Femenino , Estado Nutricional , Carcinoma de Pulmón de Células no Pequeñas/terapia , Pronóstico , Neoplasias Pulmonares/terapia , Inmunoterapia , Albúminas , LinfocitosRESUMEN
BACKGROUND: Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa that is mediated by immunoglobulin E (IgE). Xiao-qing-long-tang (XQLT) is a traditional Chinese medicine compound that is widely used to treat respiratory diseases such as AR. However, the underlying mechanism of the effect of XQLT on AR remains unclear. PURPOSE: To elucidate the effect of XQLT on ovalbumin (OVA)-induced AR and the mechanisms of action. METHODS: The therapeutic efficacy of XQLT was evaluated in a well-established OVA-induced AR mouse model. Nasal symptoms were analyzed, type 2 cytokines and OVA-sIgE levels were measured, nasal mucosa tissues were collected for histological analysis, and the changes of Group 2 innate lymphoid cells (ILC2s) and the IL-33/ST2 and JAK/STAT signaling pathways in the nasal mucosa were observed. RESULTS: XQLT significantly alleviated the nasal symptoms and histological damage to the nasal mucosa in AR mice, and reduced the levels of type 2 cytokines and OVA-sIgE. In addition, after XQLT treatment, the numbers of ILC2s in the nasal mucosa of AR mice were reduced, and the mRNA levels of the transcription factors GATA3 and ROR-α were decreased. Moreover, IL-33/ST2 signaling pathway was inhibited. The costimulatory cytokine associated JAK/STAT signaling pathway was also inhibited in ILC2s. CONCLUSION: Our study demonstrated that XQLT regulated ILC2s through the IL-33/ST2 and JAK/STAT pathways to ameliorate type 2 inflammation in OVA-induced AR. These findings suggest that XQLT might be used to treat AR.