RESUMEN

Psoriasis is a chronic, recurrent, and inflammatory skin disease. Topical agents, which can avoid the adverse effects of systemic treatment, are the first-choice therapy for patients with mild-to-moderate psoriasis. Hederacoside C (HSC) with anti-inflammatory properties has been used to treat some inflammatory diseases. We speculated that HSC might also be effective for psoriasis treatment. However, topical application of HSC for psoriasis treatment is challenging because of its low water solubility and poor skin permeability. Therefore, it is important to effectively deliver HSC percutaneously using certain biomaterials. Here we constructed a hydroxypropyl-ß-cyclodextrin-coated liposome gel formulation for the loading and percutaneously delivering of HSC, referred to as HSC-Lipo@gel. The characterization, stability, release properties, and mechanical or transdermal features of the HSC-Lipo@gel were evaluated. Its therapeutic potential was also demonstrated using mouse models of IMQ-induced psoriasis. We found that HSC-Lipo@gel effectively improved the skin permeability of HSC with the property of good stability and sustained release. Importantly, HSC-Lipo@gel showed higher efficacy than HSC@gel without liposomes in alleviating psoriatic skin lesions. It attenuated epidermal hyperplasia and suppressed expression of IL-17A, TNF-α, IL-6, and IL-23 in lesional skin. Interestingly, HSC-Lipo@gel reduced the expression of CC chemokine ligand 17 (CCL17), but not CCL22, in the skin. Especially, HSC-Lipo@gel inhibited CCL17 expression by skin dendritic cells while increasing regulatory T cells (Tregs) in both skin and draining lymph nodes of psoriatic mice. Administration of CCL17 resulted in severe skin lesions and reduced CD4+FoxP3+ Tregs in psoriatic mice previously treated with HSC-Lipo@gel. Finally, HSC or HSC-Lipo also suppressed the CCL17 production by dendritic cells in vitro. Therefore, HSC-Lipo@gel alleviated psoriasiform skin inflammation by increasing cutaneous Tregs via downregulation of the expression of CCL17, but not CCL22. Thus, HSC-Lipo@gel may be a stable, highly permeable, and effective system for topical treatment of psoriasis.

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Phytoplankton has been used as a paradigm for studies of coexistence of species since the publication of the "paradox of the plankton." Although there are a wealth of studies about phytoplankton assemblages of lakes, reservoirs and rivers, our knowledge about phytoplankton biodiversity and its underlying mechanisms in mountain headwater stream ecosystems is limited, especially across regional scales with broad environmental gradients. In this study, we collected 144 phytoplankton samples from the Xijiang headwater streams of the Pearl River across low altitude (< 1,000 m) located in Guangxi province, intermediate altitude (1,000 m < altitude <2,000 m) in Guizhou province and high altitude (> 2,000 m) in Yunnan province of China. Our study revealed high phytoplankton diversity in these streams. Freshwater phytoplankton, including cyanobacteria, Bacillariophyta, Chlorophyta, Rhodophyta, Chrysophyta, Euglenophyta, Glaucophyta, Phaeophyta and Cryptophyta, were all detected. However, phytoplankton alpha diversity exhibited a monotonic decreasing relationship with increasing altitude. High altitudes amplified the "isolated island" effect of headwater streams on phytoplankton assemblages, which were characterized by lower homogeneous selection and higher dispersal limitation. Variability and network vulnerability of phytoplankton assemblages increased with increasing altitudes. Our findings demonstrated diversity, variability and co-occurrence patterns of phytoplankton assemblages linked to environmental factors co-varying with altitude across regional scales.

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Chewing areca nuts is popular in China. Areca alkaloids are the major toxic compounds in areca nuts. In this study, the levels of four areca alkaloids (i.e. arecoline, arecaidine, guvacoline and guvacine) in 119 areca nut samples were analyzed and 3030 areca nut consumption questionnaires were collected to investigate the exposure to areca alkaloids in the Chinese populations through areca nut chewing. The levels of arecoline, arecaidine, guvacoline and guvacine in different areca nut products were 0.46-4.97 mg/g, 0.57-7.51 mg/g, 0.08-1.44 mg/g and 0.03-8.48 mg/g, respectively. Chewing fresh areca fruits was the main source of arecoline and the total areca alkaloids exposure. The estimated daily intake (EDI) of arecoline and the total areca alkaloids for the Chinese populations were 1.126 and 2.625 mg/kg BW/day for average exposure, 4.411 and 9.739 mg/kg BW/day for high exposure (P95th). The EDI varied with age and gender. The young male population (≤ 34 years) had the highest EDI than other populations. Concentrated and focused efforts are required to educate the general public, especially the young male population, about the risks of areca nut chewing to reduce exposure to areca alkaloids of the Chinese population. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-024-05966-6.

RESUMEN

Psoriasis is an autoinflammatory dermatosis, while methotrexate (MTX) is an immunosuppressant used to treat psoriasis. However, conventional immunosuppressants may cause various side effects. Acupuncture has potential benefits in treating psoriasis based on its anti-inflammatory effects. However, the immune mechanisms underlying its effects remain unclear. In this study, imiquimod-induced psoriatic mice were used to investigate the effects and mechanisms of electroacupuncture (EA) and, in particular, its joint treatment with MTX. We found that treatment with either EA or MTX ameliorated psoriasiform skin lesions, improved skin pathology and reduced proinflammatory cytokines in the skin, while joint treatment with both EA and MTX further alleviated the skin lesions and inflammation compared to either one alone. Moreover, percentages of CD4+ IL-17A+ Th17 cells in the skin and lymph nodes were decreased by EA or MTX and further lowered by combined EA+MTX treatment. Similarly, EA or MTX also reduced their RORγt expression. On the contrary, CD4+ FoxP3+ Treg frequency in psoriatic mice was augmented by EA or MTX and further increased by the joint treatment. However, depleting Tregs mostly reversed the therapeutic effects of EA or EA plus MTX. Additionally, the phosphorylated NF-κB (p65) expression was suppressed by treatment with EA, MTX or better with EA+MTX. Meanwhile, the anti-inflammatory effects of EA plus MTX were offset by an NF-κB agonist. Thus, this study has revealed that EA cooperates with MTX to balance Th17/Treg responses and to ameliorate psoriasiform skin inflammation through suppressing NF-κB activation. Our findings may be implicated for treating human psoriasis.

Asunto(s)

Electroacupuntura , Imiquimod , Metotrexato , Psoriasis , Piel , Linfocitos T Reguladores , Células Th17 , Animales , Psoriasis/inmunología , Psoriasis/tratamiento farmacológico , Psoriasis/terapia , Psoriasis/inducido químicamente , Células Th17/inmunología , Células Th17/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Electroacupuntura/métodos , Piel/patología , Piel/efectos de los fármacos , Piel/inmunología , Ratones , Modelos Animales de Enfermedad , Citocinas/metabolismo , Ratones Endogámicos C57BL , Humanos , FN-kappa B/metabolismo , Terapia Combinada , Masculino , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/metabolismo

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Hyperuricemia (HUA) is one of the most common chronic diseases today, with a prevalence exceeding 14 % in both the United States and China. Current clinical treatments for HUA focus on promoting uric acid (UA) excretion and inhibiting UA production, but often neglect the strain on the liver and kidneys. The fruit of Alpinia oxyphylla (A. oxyphylla) is known to improve renal function, regulate metabolism, and exhibit anti-inflammatory effects; however, its effectiveness and mechanisms in treating HUA are not well understood. In this study, HUA mice induced by potassium oxonate and adenine were treated with A. oxyphylla polysaccharide (AFP) for 21 days. The levels associated with HUA were quantified using assay kits to evaluate the impact of AFP on HUA. Serum metabolomics and 16S rRNA sequencing were used to investigate the mechanisms by which AFP ameliorates HUA. The results showed that AFP treatment reduced abnormal biochemical levels, including UA, blood urea nitrogen, and creatinine, in HUA mice. AFP inhibited UA synthesis by regulating pyrimidine metabolism and the metabolism of alanine, aspartate and glutamate, reduced kidney inflammation, and promoted UA excretion by regulating intestinal flora. Thus, AFP appears to be an effective agent for alleviating HUA symptoms.

Asunto(s)

Alpinia , Frutas , Microbioma Gastrointestinal , Hiperuricemia , Polisacáridos , Ácido Úrico , Animales , Alpinia/química , Hiperuricemia/tratamiento farmacológico , Ácido Úrico/sangre , Ratones , Polisacáridos/farmacología , Polisacáridos/química , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Frutas/química , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , ARN Ribosómico 16S/genética , Nitrógeno de la Urea Sanguínea , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Pirimidinas

RESUMEN

Being the first line of defense, intestinal mucosal immunity serves as in maintaining immune homeostasis among organisms. This study investigated the impact of the areca inflorescence polysaccharide (AFP) on intestinal mucosal immunity and elucidated the mechanisms responsible for the immunomodulatory effects of AFP. The immunosuppression mouse model was established using the cyclophosphamide. The intestinal mucosal status was evaluated based on the intestinal integrity, chemical and mucosal immune barriers, and intestinal flora. According to the findings, AFP enhances intestinal integrity by up-regulating the expression of tight junction proteins and reinforcing the chemical barrier through increased mucin-2, ß-defensins, and SIgA expression and secretion. Furthermore, AFP restores the mucosal immune barrier by regulating immune cells within Peyer's patches and lamina propria. AFP also reverses the intestinal flora balance and regulates its metabolism. Additionally, AFP effectively modulates the immune response in the spleen and peripheral blood. Together, these results indicated that AFP repairs mucosal damage and restores mucosal immunity, thereby preserving the immune homeostasis of organisms.

Asunto(s)

Homeostasis , Inmunidad Mucosa , Mucosa Intestinal , Polisacáridos , Animales , Polisacáridos/farmacología , Ratones , Inmunidad Mucosa/efectos de los fármacos , Homeostasis/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Inflorescencia , Microbioma Gastrointestinal/efectos de los fármacos , Masculino

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Pseudomonas fragi (P. fragi) is usually detected in low-temperature meat products, and seriously threatens food safety and human health. Therefore, the study investigated the antibacterial mechanism of linalool against P. fragi from membrane damage and metabolic disruption. Results from field-emission transmission electron microscopy (FETEM) and atomic force microscopy (AFM) showed that linalool damage membrane integrity increases surface shrinkage and roughness. According to Fourier transform infrared (FTIR) spectra results, the components in the membrane underwent significant changes, including nucleic acid leakage, carbohydrate production, protein denaturation and modification, and fatty acid content reduction. The data obtained from amino acid metabolomics indicated that linalool caused excessive synthesis and metabolism of specific amino acids, particularly tryptophan metabolism and arginine biosynthesis. The reduced activities of glucose 6-phosphate dehydrogenase (G6PDH), malate dehydrogenase (MDH), and phosphofructokinase (PFK) suggested that linalool impair the respiratory chain and energy metabolism. Meanwhile, genes encoding the above enzymes were differentially expressed, with pfkB overexpression and zwf and mqo downregulation. Furthermore, molecular docking revealed that linalool can interact with the amino acid residues of G6DPH, MDH and PFK through hydrogen bonds. Therefore, it is hypothesized that the mechanism of linalool against P. fragi may involve cell membrane damage (structure and morphology), disturbance of energy metabolism (TCA cycle, EMP and HMP pathway) and amino acid metabolism (cysteine, glutamic acid and citrulline). These findings contribute to the development of linalool as a promising antibacterial agent in response to the food security challenge.

RESUMEN

PURPOSE: This research evaluates the effect of balloon pulmonary angioplasty (BPA) on cardiac electrophysiological changes in patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Involving a retrospective analysis of 39 CTEPH patients (average age 61 ± 11), who had at least two BPAs and paired ECGs pre- and post-surgery, we examined changes in ECG indicators of right ventricular hypertrophy and their correlation with hemodynamic results. RESULTS: BPA yielded marked improvements in cardiac function and hemodynamics. ECG parameters, specifically the Lewis criteria and Butler-Leggett score, correlated strongly with hemodynamics and were predictive of a mean pulmonary arterial pressure (mPAP) ≥ 35mmHg. Notably, QRS complex axis normalization was observed in 25 patients, with 14 fully normalizing (range - 30° to + 90°). The qR pattern in V1 vanished in 9 cases, and 75% of the patients in qR pattern in V1 group had QRS complex electrical axis completely returned to normal range. The qR V1 group had higher mPAP and pulmonary vascular resistance (PVR), and lower cardiac output and index compared to the non-qR V1 group, alongside a higher Butler-Leggett score. CONCLUSIONS: BPA enhances cardiac function and hemodynamics in CTEPH patients, with certain ECG measures such as Lewis criteria and Butler-Leggett score reflecting the severity of hemodynamic impairment. The reversal of QRS axis deviation and the disappearance of the qR pattern in lead V1 may serve as valuable indicators for assessing post-BPA satisfaction in CTEPH patients.

Asunto(s)

Angioplastia de Balón , Electrocardiografía , Hipertensión Pulmonar , Embolia Pulmonar , Humanos , Estudios Retrospectivos , Persona de Mediana Edad , Masculino , Angioplastia de Balón/métodos , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/cirugía , Hipertensión Pulmonar/terapia , Femenino , Embolia Pulmonar/fisiopatología , Embolia Pulmonar/complicaciones , Anciano , Enfermedad Crónica , Hemodinámica/fisiología , Arteria Pulmonar/fisiopatología , Arteria Pulmonar/cirugía

RESUMEN

OBJECTIVES: Ground-glass nodules-featured lung cancer have been identified in some teenagers in recent years. This study aims to investigate the characteristics and surgical outcomes of these patients and explore proper management strategy. METHODS: Patients aged ≤20 with incidentally diagnosed lung cancer were retrospectively reviewed from February 2016 to March 2023. Based on lymph node evaluation status, these patients were divided into non-lymph node evaluation and lymph node evaluation groups. The clinical and pathological characteristics were analysed. RESULTS: A total of 139 teenage patients were included, with an obviously increased cases observed from 2019, corresponding to the COVID-19 pandemic. The median age of the 139 patients was 18 years (range 12-20). Eighty-five patients had pure ground-glass nodules, while others had mixed ground-glass nodules. The mean diameter of nodules was 8.87 ± 2.20 mm. Most of the patients underwent wedge resection (64%) or segmentectomy (31.7%). Fifty-two patients underwent lymph node sampling or dissection. None of these patients had lymph node metastasis. The majority of lesions were adenocarcinoma in situ (63 cases) and minimally invasive adenocarcinoma (72 cases), while four lesions were invasive adenocarcinoma. The median follow-up time was 2.46 years, and none of these patients experienced recurrence or death during follow-up. The lymph node evaluation group had longer hospital stays (P < 0.001), longer surgery time (P < 0.001), and greater blood loss (P = 0.047) than the non-lymph node evaluation group. CONCLUSIONS: The COVID-19 pandemic significantly increased the number of teenage patients incidentally diagnosed with lung cancer, presenting as ground-glass nodules on CT scans. These patients have favourable surgical outcomes. We propose a management strategy for teenage patients, and suggest that sub-lobar resection without lymph node dissection may be an acceptable surgical procedure for these patients.

Asunto(s)

Adenocarcinoma del Pulmón , COVID-19 , Neoplasias Pulmonares , Neumonectomía , Humanos , Masculino , Adolescente , Femenino , Estudios Retrospectivos , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , COVID-19/epidemiología , Adulto Joven , Adenocarcinoma del Pulmón/cirugía , Adenocarcinoma del Pulmón/patología , Neumonectomía/métodos , Niño , SARS-CoV-2 , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Escisión del Ganglio Linfático

RESUMEN

The functional properties of protein are affected by their aggregation behavior and morphology. In this study, the self-assembled coconut protein aggregates with specific morphology, including small amorphous aggregates (WLA), spherical-like aggregates (SLA) and rod-like aggregates (RLA), were regulated to form. The self-assembled process resulted in a decrease in fluorescence intensity and an increase in the surface hydrophobicity of coconut protein. Fucoidan was added to improve the stability of protein solutions, and the interfacial adsorption behavior was evaluated by dilatational rheology analysis. The results showed that the aggregation state of coconut protein affected its ability to reduce surface tension, and the interfacial layers mainly exhibited elastic property at oil-water interface (tanφ < 0.5). For macroscale analysis, the emulsions based on self-assembled coconut protein exhibited smaller droplet size, better rheological properties and centrifugal stability, especially WLA and RLA. This study may provide a reference to inspire the utilization of self-assembled coconut protein in the food industry.

Asunto(s)

Cocos , Emulsiones , Proteínas de Plantas , Polisacáridos , Reología , Cocos/química , Adsorción , Polisacáridos/química , Proteínas de Plantas/química , Emulsiones/química , Interacciones Hidrofóbicas e Hidrofílicas , Agregado de Proteínas , Tensión Superficial

RESUMEN

Direct barrier discharge (DBD) plasma is a potential antibacterial strategy for controlling Fusarium oxysporum (F. oxysporum) in the food industry. The aim of this study was to investigate the inhibitory effect and mechanism of action of DBD plasma on F. oxysporum. The result of the antibacterial effect curve shows that DBD plasma has a good inactivation effect on F. oxysporum. The DBD plasma treatment severely disrupted the cell membrane structure and resulted in the leakage of intracellular components. In addition, flow cytometry was used to observe intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential, and it was found that, after plasma treatment, intracellular ROS accumulation and mitochondrial damage were accompanied by a decrease in antioxidant enzyme activity. The results of free fatty acid metabolism indicate that the saturated fatty acid content increased and unsaturated fatty acid content decreased. Overall, the DBD plasma treatment led to the oxidation of unsaturated fatty acids, which altered the cell membrane fatty acid content, thereby inducing cell membrane damage. Meanwhile, DBD plasma-induced ROS penetrated the cell membrane and accumulated intracellularly, leading to the collapse of the antioxidant system and ultimately causing cell death. This study reveals the bactericidal effect and mechanism of the DBD treatment on F. oxysporum, which provides a possible strategy for the control of F. oxysporum.

Asunto(s)

Membrana Celular , Fusarium , Oxidación-Reducción , Gases em Plasma , Especies Reactivas de Oxígeno , Fusarium/efectos de los fármacos , Membrana Celular/metabolismo , Membrana Celular/efectos de los fármacos , Gases em Plasma/farmacología , Oxidación-Reducción/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Antibacterianos/farmacología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Homeostasis/efectos de los fármacos , Ácidos Grasos/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo

RESUMEN

The pelite samples were collected from drillholes from the Chengmen area of the Fuzhou Basin of Fujian, China to reveal the sediments resource and tectonic environment of these pelites via an analysis of its lithology and geochemistry. The rare earth element distribution pattern of the pelites exhibited a high degree of fractionation between light and heavy rare earth elements, moderate negative Eu anomalies, and positive Ce anomalies, which are consistent with the rare earth element distribution pattern of Minjiang sediments and Fujian soils. Moreover, the variations in trace elements are also generally consistent, indicating a common provenance. The extremely high chemical index of alteration (CIA) and index of chemical variability (ICV) values of the pelites suggest that the source area experienced intense weathering, indicating a subtropical hot and humid climate environment in the source area and the Fuzhou Basin at that time. The source rock attribute discrimination diagrams show that the main source of pelites is felsic igneous rocks. The ratios of REDOX parameters show that during the sedimentary period, the water body in the study area was predominantly in an oxidizing environment. Furthermore, the tectonic background diagrams reveal that the source area underwent geological tectonic evolution processes of active and passive continental margins, marking the transition from the continental margin above the subduction of the ancient Pacific plate to the continental margin extension after subduction cessation.

RESUMEN

Background: Psoriasis is a widespread chronic, immune-mediated skin disease with frequent recurrences, and is extremely harmful to the physical and mental health of patients, causing enormous suffering and exerting considerable economic burdens on the health care system as a whole. In more than a decade of clinical use, the optimized formula of Yinxieling (PSORI-CM01) has consistently demonstrated its effectiveness for treating psoriasis. However, its underlying mechanism remains largely unexplored. Methods: The network pharmacology analysis was conducted to predict the mechanism and protective effect of PSORI-CM01 in treating psoriasis. Subsequently, we collected blood samples from 21 patients with psoriasis as part of a randomized, double-blind, and double-dummy clinical trial for microRNA expression profiling. Finally, it was experimentally confirmed that PSORI-CM01 improved psoriasis by regulating miR-20a-3p and miR-3184-3p expression. Results: As a result of the network pharmacology analysis, PSORI-CM01 improved psoriasis through the regulation of autophagy, cellular apoptosis, cellular proliferation, and anti-inflammatory processes. In the target-miRNA regulatory network, these key targets were mainly associated with the regulation of hsa-miR-20a-3p, hsa-miR-155-5p, has-miR-3184-3p, hsa-miR-328-3p and hsa-miR-124-3p. Based on the microRNA expression profiling results, the PSORI-CM01 treatment group exhibited five up-regulated genes and 16 down-regulated genes compared with the healthy control group. In particular, miR-20a-3p and miR-3184-3p were the primary differentially expressed microRNAs, and they were significantly enriched in the signaling pathways involving autophagy, apoptosis, proliferation, and anti-inflammation. Further experiments confirmed that PSORI-CM01 effectively regulates miR-20a-3p and miR-3184-3p, resulting in increased autophagy. Conclusion: We demonstrated by combining network pharmacology and clinical studies of miRNA expression profiles in PBMCs that PSORI-CM01 effectively modulated miR-20a-3p and miR-3184-3p, leading to an increase in autophagy and a decrease in keratinocyte proliferation.

Asunto(s)

Autofagia , Medicamentos Herbarios Chinos , MicroARNs , Farmacología en Red , Psoriasis , Humanos , Psoriasis/tratamiento farmacológico , Psoriasis/genética , Psoriasis/patología , Autofagia/efectos de los fármacos , MicroARNs/genética , MicroARNs/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Masculino , Método Doble Ciego , Adulto , Femenino , Persona de Mediana Edad , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos

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BACKGROUND: QingChang-XiaoPi Decoction (QCXPY), a Chinese herbal prescription, has been employed in the treatment of ulcerative colitis (UC) in China. However, its molecular mechanism of action in UC remains unclear. PURPOSE: To elucidate the therapeutic effects of QCXPY against UC and reveal its mechanism of action. STUDY DESIGN: We conducted a single-arm observation to evaluate the clinical efficacy of QCXPY in patients with mild-to-moderate UC. Inclusion and exclusion criteria were established to ensure the eligibility of participants, with a focus on excluding patients with specific conditions or complications that could confound the results. METHODS: The expression of inflammatory factors in patients' serum was detected using a Luminex assay. The main components of QCXPY were identified using UHPLC-Q-TOF-MS. Network pharmacology was employed to predict potential therapeutic targets and their mechanisms of action. The efficacy of QCXPY was evaluated using a dextran sulfate sodium (DSS)-induced mouse model. Disease activity index (DAI), histopathological score, cytokine detection by ELISA, T-helper 17 (Th17) cell proportion by flow cytometry, expression of the IL-23/IL-17 axis, and changes in the levels of its downstream effectors were detected by immunohistochemistry, immunofluorescence, and western blotting. RESULTS: QCXPY could alleviate the symptoms of diarrhea, abdominal pain, abdominal distension, and purulent stool in patients with mild-to-moderate UC. Moreover, it reduced the expression of IL-6, IL-17, and IL-23 in serum; alleviated DSS-induced experimental colitis in mice; reduced DAI, pathological scores, and the expressions of IL-6, IL-17, and IL-23 in colon tissue; and decreased the proportion of pathogenic Th17 cells and the expression of STAT3 and phospho-STAT3. CONCLUSION: This study confirmed for the first time that QCXPY could alleviate intestinal symptoms, reduce the levels of serum inflammatory factors, and improve the quality of life of patients with mild-to-moderate UC. Its mechanism of action may involve reducing the secretion of inflammatory cytokines, moderating the pathogenicity of Th17 cells, and inhibiting STAT3 phosphorylation, thereby alleviating intestinal inflammation in UC.

Asunto(s)

Colitis Ulcerosa , Sulfato de Dextran , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Factor de Transcripción STAT3 , Células Th17 , Colitis Ulcerosa/tratamiento farmacológico , Animales , Células Th17/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Humanos , Masculino , Femenino , Adulto , Ratones , Factor de Transcripción STAT3/metabolismo , Persona de Mediana Edad , Interleucina-17/metabolismo , Interleucina-23 , Ratones Endogámicos C57BL , Farmacología en Red , Adulto Joven , Citocinas/metabolismo

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OBJECTIVES: To investigate the potential utility of [18F]fibroblast activation protein inhibitor (FAPI) positron emission tomography/computed tomography (PET/CT) for evaluating pulmonary artery (PA) masses, and compare it with [18F]fluorodeoxyglucose (FDG) PET/CT. METHODS: Participants with clinically suspected PA malignancy were prospectively enrolled and underwent dual-tracer PET/CT ([18F]FAPI-42 and [18F]FDG) imaging. Visual analysis and semi-quantitative parameters were compared between the two types of radiotracers. The tissue specimen underwent immunohistochemical staining to verify FAP expression in the tissue. RESULTS: Thirty-three patients (18 males/15 females; mean age 53.1 ± 15.4 years) were enrolled. All 21 patients with malignant PA masses were FDG-positive (100%), whereas 20 out of 21 patients were FAPI-positive (95.2%). All 12 patients with benign PA masses were both negative in FDG and FAPI PET. The mean maximum standardized uptake value (SUVmax) and target-to-background ratio (TBR) of FAPI and FDG in malignant PA masses were significantly higher than those of benign masses. Although there was no significant difference in SUVmax between FDG and FAPI in malignant PA masses (11.36 vs. 9.18, p = 0.175), the TBR (liver) and TBR (left ventricle) were more favorable for FAPI than for FDG (13.04 vs. 5.17, p < 0.001); (median: 7.75 vs. 2.75, p = 0.007). Immunohistochemical analysis (n = 16) validated that the level of FAP expression corresponded strongly to the uptake of FAPI in PET/CT scans (rs = 0.712, p = 0.002). For clinical management, FAPI PET found more metastatic lesions than FDG PET in 4 patients, with 2 patients upgrading and 1 patient changing treatment decisions. CONCLUSIONS: FAPI PET/CT is feasible in the diagnosis of PA masses. Although not superior to FDG PET/CT, FAPI PET/CT showed better target-to-background contrast. CLINICAL RELEVANCE STATEMENT: This study found that FAPI PET/CT is not superior to FDG PET/CT in diagnosing PA masses, but FAPI PET/CT displays better target-to-background contrast and more positive lesions, which may help improve disease management. KEY POINTS: Pulmonary malignancies lack specificity in clinical manifestations, laboratory tests, and routine imaging examinations. FAPI PET/CT is not diagnostically better than FDG PET/CT but displays better target-to-background contrast and more positive lesions. Dual-tracer PET/CT ([18F]FAPI-42 and [18F]FDG) imaging improves clinical management of pulmonary artery masses.

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Thermal pollution from the cooling system of the nuclear power plants greatly changes the environmental and the ecological conditions of the receiving marine water body, but we know little about their impact on the steady-state transition of marine bacterioplankton communities. In this study, we used high-throughput sequencing based on the 16S rRNA gene to investigate the impact of the thermal pollution on the bacterioplankton communities in a subtropical bay (the Daya Bay). We observed that thermal pollution from the cooling system of the nuclear power plant caused a pronounced thermal gradient ranging from 19.6°C to 24.12°C over the whole Daya Bay. A temperature difference of 4.5°C between the northern and southern parts of the bay led to a regime shift in the bacterioplankton community structure. In the three typical scenarios of regime shifts, the steady-state transition of bacterioplankton community structure in response to temperature increasing was more likely consistent with an abrupt regime shift rather than a smooth regime or a discontinuous regime model. Water temperature was a decisive factor on the regime shift of bacterioplankton community structure. High temperature significantly decreased bacterioplankton diversity and shifted its community compositions. Cyanobium and Synechococcus of Cyanobacteria, NS5 marine group of Bacteroidota, and Vibrio of Gammaproteobacteria were found that favored high temperature environments. Furthermore, the increased water temperature significantly altered the community assembly of bacterioplankton in Daya Bay, with a substantial decrease in the proportion of drift and others, and a marked increase in the proportion of homogeneous selection. In summary, we proposed that seawater temperature increasing induced by the thermal pollution resulted in an abrupt regime shift of bacterioplankton community in winter subtropical bay. Our research might broad our understanding of marine microbial ecology under future conditions of global warming.

RESUMEN

Most recurrences of lung cancer (LC) occur within 3 years after surgery, but the underlying mechanism remains unclear. Here, we collect LC tissues with shorter (<3 years, recurrence group) and longer (>3 years, non-recurrence group) recurrence-free survival. By using 16S sequencing, we find that intratumor microbiome diversity is lower in the recurrence group and butyrate-producing bacteria are enriched in the recurrence group. The intratumor microbiome signature and circulating microbiome DNA can accurately predict LC recurrence. We prove that intratumor injection of butyrate-producing bacteria Roseburia can promote subcutaneous tumor growth. Mechanistically, bacteria-derived butyrate promotes LC metastasis by increasing expression of H19 in tumor cells through inhibiting HDAC2 and increasing H3K27 acetylation at the H19 promoter and inducing M2 macrophage polarization. Depletion of macrophages partially abolishes the metastasis-promoting effect of butyrate. Our results provide evidence for the cross-talk between the intratumor microbiome and LC metastasis and suggest the potential prognostic and therapeutic value of the intratumor microbiome.

Asunto(s)

Neoplasias Pulmonares , Microbiota , Humanos , Neoplasias Pulmonares/patología , Butiratos/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Macrófagos

RESUMEN

Lung cancer mortality is exacerbated by late-stage diagnosis. Emerging evidence indicates the potential clinical significance of distinct microbial signatures as diagnostic and prognostic biomarkers across various cancers. However, circulating microbiome DNA (cmDNA) profiles are underexplored in lung cancer (LC). Here, whole-genome sequencing is performed on plasma of LC patients and healthy controls (HCs). Differentially enriched microbial species are identified between LC and HC. A diagnostic model is developed, which has a high sensitivity of 87.7% and achieves an AUC of 93.2% in the independent validation dataset. Crucially, this model demonstrates the capability to detect early-stage LC, achieving a sensitivity of 86.5% for stage I and 87.1% for tumors <1 cm. In addition, we construct a cmDNA model for recurrence, which precisely predicts LC recurrence after surgery. Overall, this study highlights the significant alterations of cmDNA profiles in LC, indicating its potential as biomarkers for early diagnosis and recurrence.

Asunto(s)

Ácidos Nucleicos Libres de Células , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Biomarcadores de Tumor/genética , Detección Precoz del Cáncer , Recurrencia Local de Neoplasia

RESUMEN

In this paper, the effect of monosodium glutamate (MSG) on coconut protein (CP) solubility, surface hydrophobicity, emulsification activity, ultraviolet spectroscopy and fluorescence spectroscopy was investigated. Meanwhile, the changes in the in vitro digestive properties of coconut milk were also further analyzed. MSG treatment altered the solubility and surface hydrophobicity of CP, thereby improving protein digestibility. Molecular docking showed that CP bound to pepsin and trypsin mainly through hydrogen bonds and salt bridges. And MSG increased the cleavable sites of pepsin and trypsin on CP, thus further improving the protein digestibility. In addition, MSG increased the Na+ concentration in coconut milk, promoted flocculation and aggregation between coconut milk droplets, which prevented the binding of lipase and oil droplets and inhibited lipid digestion. These findings may provide new ideas and insights to improve the digestive properties of plant-based milk.

Asunto(s)

Cocos , Digestión , Interacciones Hidrofóbicas e Hidrofílicas , Simulación del Acoplamiento Molecular , Proteínas de Plantas , Glutamato de Sodio , Solubilidad , Glutamato de Sodio/química , Digestión/efectos de los fármacos , Cocos/química , Proteínas de Plantas/química , Tripsina/metabolismo , Tripsina/química , Pepsina A/metabolismo , Pepsina A/química

RESUMEN

Alkali-activated materials (AAMs) possess several advantages, such as high strengths and low carbon emissions. However, their application is hindered due to their significant shrinkage. This study explored the effect of borax-modified sodium silicate activator and metakaolin (MK) on the mechanical properties and drying shrinkage (DS) of alkali-activated slag (AAS) and AAS/MK (AASM) mortars. X-ray diffraction, scanning electron microscopy, and Fourier-transform infrared spectroscopy were used to characterize the hydration products. The results showed that the DS reduction of the AAS mortar was related to decreased Na2O content, a reduction in the proportion of mesopores, and the formation of moisture-retaining borate compounds. The DS reduction of the AASM mortar was attributed to the ultra-fine differential effect induced by MK, reducing the connected pores. The modified activator combined with MK increased the chemically bound water content in the matrix. Additionally, the B-O bond and highly active MK improved compactness of the AASM mortar. The use of borax-modified activators and MK provides a new solution to address the significant shrinkage issue in AAMs. This sets the stage for AAMs to potentially replace OPC, contributing to low-carbon emissions and promoting environmental protection.