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Multicenter international clinical trials demonstrated the clinical safety and efficacy by using stem cell educator therapy to treat type 1 diabetes (T1D) and other autoimmune diseases. Previous studies characterized the peripheral blood insulin-producing cells (PB-IPC) from healthy donors with high potential to give rise to insulin-producing cells. PB-IPC displayed the molecular marker glucose transporter 2 (GLUT2), contributing to the glucose transport and sensing. To improve the clinical efficacy of stem cell educator therapy in the restoration of islet ß-cell function, we explored the GLUT2 expression on PB-IPC in recent onset and longstanding T1D patients. In the Food and Drug Administration (FDA)-approved phase 2 clinical studies, patients received one treatment with the stem cell educator therapy. Peripheral blood mononuclear cells (PBMC) were isolated for flow cytometry analysis of PB-IPC and other immune markers before and after the treatment with stem cell educator therapy. Flow cytometry revealed that both recent onset and longstanding T1D patients displayed very low levels of GLUT2 on PB-IPC. After the treatment with stem cell educator therapy, the percentages of GLUT2+CD45RO+ PB-IPC were markedly increased in these T1D subjects. Notably, we found that T1D patients shared common clinical features with patients with other autoimmune and inflammation-associated diseases, such as displaying low or no expression of GLUT2 on PB-IPC at baseline and exhibiting a high profile of the inflammatory cytokine interleukin (IL)-1ß. Flow cytometry demonstrated that their GLUT2 expressions on PB-IPC were also markedly upregulated, and the levels of IL-1ß-positive cells were significantly downregulated after the treatment with stem cell educator therapy. Stem cell educator therapy could upregulate the GLUT2 expression on PB-IPC and restore their function in T1D patients, leading to the improvement of clinical outcomes. The clinical data advances current understanding about the molecular mechanisms underlying the stem cell educator therapy, which can be expanded to treat patients with other autoimmune and inflammation-associated diseases.
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Diabetes Mellitus Tipo 1 , Transportador de Glucosa de Tipo 2 , Células Secretoras de Insulina , Insulina , Humanos , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/sangre , Transportador de Glucosa de Tipo 2/metabolismo , Transportador de Glucosa de Tipo 2/genética , Células Secretoras de Insulina/metabolismo , Masculino , Femenino , Insulina/metabolismo , Adulto , Leucocitos Mononucleares/metabolismo , Persona de Mediana Edad , Trasplante de Células MadreRESUMEN
Objective: The objective of this research is to investigate the relationship between dietary glycine consumption and the prevalence of hypertension, hyperlipidemia, and overweight or obesity in economically disadvantaged areas of northern China using a cross-sectional study design. Methods: A cross-sectional study involving 774 participants utilized a web-based dietary questionnaire (IDQC) and underwent physical measurements. Data analysis was conducted using IBM SPSS Statistics software (Version 21). Participants were stratified into four groups based on quartiles of their dietary glycine intake: Q1 (<1.32), Q2 (1.32-1.82), Q3 (1.82-2.26), and Q4 (>2.26). Continuous variables were reported as mean ± standard deviation and compared using ANOVA or the Kruskal-Wallis test, while categorical variables were presented as frequencies (%) and compared using the chi-square test. Finally, multivariable logistic regression with p-value of less than 0.05 was considered statistically significant. Results: Significant differences in dietary glycine intake were observed between the highest quartile group (Q4) and the lowest quartile group (Q1), with corresponding dominance ratios of 0.590 (95% CI, 0.360-0.966), 0.547 (95% CI, 0.327-0.913), and 0.547 (95% CI, 0.353-0.850) for the risk of hypertension, hyperlipidemia, and overweight/obesity, respectively. Furthermore, no significant correlation was found between dietary glycine intake and hypertension or hyperlipidemia within each sex and age subgroup. Conclusion: There exists a potential correlation between increased dietary glycine intake and reduced prevalence of hypertension, hyperlipidemia, and overweight/obesity. However, additional research is necessary to validate this finding through larger-scale studies conducted at a population level.
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ETHNOPHARMACOLOGICAL RELEVANCE: Ecliptea herba, a traditional Chinese herbal medicine for hair loss, was first recorded in the Tang Dynasty's 'Qian Jin Yue Ling', of which the active ingredients and mechanisms of action in the treatment of chemotherapy-induced hair loss remain poorly investigated. AIM OF THE STUDY: To investigate the effects of the petroleum ether extract of Eclipta (PEE) on alopecia and follicle damage and elucidate its potential therapeutic mechanisms using the integration of network pharmacology, bioinformatics, and experimental validation. MATERIALS AND METHODS: UPLC-MS was used to analyse the chemical composition of PEE. A network pharmacology approach was employed to establish the 'components-targets-pathways' network of PEE to explore potential therapeutic pathways and targets. Molecular docking was used for validation, and the mechanism of PEE in treating chemotherapy-induced alopecia (CIA) was elucidated using in vitro and in vivo on CIA models. RESULTS: UPLC-MS analysis of PEE revealed 185 components, while network pharmacology and molecular docking analyses revealed potential active compounds and their target molecules, suggesting the involvement of core genes, such as TP53, ESR1, AKT1, IL6, TNF, and EGFR. The key components included wedelolactone, dimethyl-wedelolactone, luteoloside, linarin, and hispidulin. In vivo, PEE promoted hair growth, restored the number of hair follicles, and reduced follicle apoptosis. Conversely, in vitro, PEE enhanced cell viability, reduced apoptosis, and protected HaCaT cells from damage induced by 4-hydroperoxycyclophosphamide (4-HC). CONCLUSIONS: PEE alleviated hair follicle damage in CIA mice by inhibiting the P53/Fas pathway, which may be associated with inhibiting hair follicle cell apoptosis. This study provides a novel therapeutic strategy for treating cyclophosphamide-induced hair loss.
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Alopecia , Eclipta , Transducción de Señal , Animales , Humanos , Masculino , Ratones , Alcanos , Alopecia/inducido químicamente , Alopecia/tratamiento farmacológico , Antineoplásicos/farmacología , Antineoplásicos/toxicidad , Apoptosis/efectos de los fármacos , Ciclofosfamida/toxicidad , Eclipta/química , Células HaCaT , Folículo Piloso/efectos de los fármacos , Folículo Piloso/metabolismo , Simulación del Acoplamiento Molecular , Farmacología en Red , Extractos Vegetales/farmacología , Extractos Vegetales/química , Transducción de Señal/efectos de los fármacos , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Purpose: This study aimed to explore the expression of CX3CL1 induced by lipopolysaccharide (LPS) in oral squamous cell carcinoma (OSCC) and its impact on biological characteristics such as invasion and migration, taking the foundation for new targets for the treatment and prognosis of OSCC. Methods: This study utilized a variety of techniques, including bioinformatics, molecular biology, and cell experiments, to investigate the expression of CX3CL1 and its receptor CX3CR1 in OSCC patients' cancer tissues or OSCC cell lines. Extracting, organizing, and analyzing the TCGA database on the expression of CX3CL1 and its receptor CX3CR1 in cancer tissues and corresponding paracancerous normal tissues of OSCC patients by bioinformatics methods. The expression of CX3CL1 in cancerous and normal tissues of OSCC patients was verified by IHC, and the changes in mRNA and protein expression of CX3CL1 and its receptor CX3CR1 in OSCC cell lines were detected before and after lipopolysaccharide LPS stimulation by RT-PCR, ELISA, and WB. Changes in cell biological behavior by overexpression of CX3CL1 in OSCC cell lines were detected by CCK-8, Transwell, scratch healing assay, and cloning assay. The effects of overexpressing cell lines on the AKT pathway and Epithelial-mesenchymal Transition (EMT)-related protein expression before and after LPS stimulation were detected by Western Blot. Results: (1) CX3CL1 and its receptor CX3CR1 were found to be downregulated in OSCC tissues of patients or OSCC cell lines. (2) After LPS stimulation, CX3CL1 gene expression increased in both OSCC cell lines, while CX3CR1 expression remained unchanged. (3) OSCC cell lines overexpressing CX3CL1 showed changes in cell biological characteristics, including decreased proliferation, invasion, migration, and stemness, which were more pronounced after LPS stimulation. (4) Overexpression of CX3CL1 in OSCC cell lines decreased EMT-related protein expression and AKT phosphorylation. On the contrary were promoted by LPS stimulation. Conclusion: CX3CL1 and CX3CR1 are downregulated in OSCC cancer tissues and cell lines compared to adjacent normal tissues and cells. LPS stimulation increases CX3CL1 expression in OSCC cell lines, suggesting that inflammation may induce CX3CL1 expression and that the CX3CL1 gene may play an important role in OSCC progression. Overexpression of CX3CL1 inhibits OSCC cell proliferation, migration, invasion, and stemness, suggesting that CX3CL1 plays a critical role in suppressing OSCC development. CX3CL1 suppresses OSCC invasion and migration by affecting EMT progression and AKT phosphorylation, and partially reverse the process that LPS causes and affects the development of OSCC.
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Natural products with antibacterial activity are highly desired globally to combat against multidrug-resistant (MDR) bacteria. Antibacterial peptide (ABP), especially cyclic ABP (CABP), is one of the abundant classes. Most of them were isolated from microbes, demonstrating excellent bactericidal effects. With the improved proteolytic stability, CABPs are normally considered to have better druggability than linear peptides. However, most clinically-used CABP-based antibiotics, such as colistin, also face the challenges of drug resistance soon after they reached the market, urgently requiring the development of next-generation succedaneums. We present here a detail review on the novel naturally-occurring CABPs discovered in the past decade and some of them are under clinical trials, exhibiting anticipated application potential. According to their chemical structures, they were broadly classified into five groups, including (i) lactam/lactone-based CABPs, (ii) cyclic lipopeptides, (iii) glycopeptides, (iv) cyclic sulfur-rich peptides and (v) multiple-modified CABPs. Their chemical structures, antibacterial spectrums and proposed mechanisms are discussed. Moreover, engineered analogs of these novel CABPs are also summarized to preliminarily analyze their structure-activity relationship. This review aims to provide a global perspective on research and development of novel CABPs to highlight the effectiveness of derivatives design in identifying promising antibacterial agents. Further research efforts in this area are believed to play important roles in fighting against the multidrug-resistance crisis.
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Antibacterianos , Péptidos Cíclicos , Péptidos Cíclicos/química , Péptidos Cíclicos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Relación Estructura-Actividad , Humanos , Péptidos Antimicrobianos/química , Péptidos Antimicrobianos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Productos Biológicos/química , Productos Biológicos/farmacologíaRESUMEN
Background: Rice starch has high digestibility due to its large carbohydrate content. Synergistic modification of hot-melt extrusion (HME) and additives such as flavonoids, hydrocolloids, proteins, lipids, and other additives has the tendency to retard the rate of starch hydrolysis. Hence, the current investigation aimed to study the combined effect of the HME-assisted addition of nobiletin (NOB, 0, 2, 4, and 6%) on the multi-scale structures, interactions, thermal, and digestibility characteristics of rice starch. Methods: The study employed density functional theory calculations and an infrared second derivative of an Fourier-transform infrared (FTIR) spectrometer to analyze the interactions between NOB and starch. The physicochemical properties of the starch extrudates were characterized by FTIR, 13C nuclear magnetic resonance, X-ray diffraction, and differential scanning calorimetry, while the digestibility was evaluated using an in vitro digestion model. Results: HME was found to disrupt the crystalline structure, helix structure, short-ordered structure, and thermal properties of starch. The interaction between NOB and starch involved hydrophobic interactions and hydrogen bonds, effectively preventing the molecular chains of starch from interacting with each other and disrupting their double helix structure. The addition of NOB led to the formation of a highly single-helical V-type crystalline structure, along with the formation of ordered structural domains. Consequently, the combined treatment significantly enhanced the ordered structure and thermal stability of starch, thus effectively leading to an increase in resistant starch and slowly digestion starch. Discussion: The study underscores that synergistic modification of HME and NOB holds promise for enhancing both the nutritional value and functional properties of rice starch. These findings offer valuable insights for developing high-quality rice starch products with broader applications.
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Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening clinical syndrome characterized by a positive feedback loop between cytokine storm and macrophages and lymphocytes overactivation, which could serve as a valid therapeutic target for HLH treatment. In this study, the clinically extensively used JAK1/2 inhibitor ruxolitinib was encapsulated into macrophage membrane-coated nanoparticles (M@NP-R) with high drug-loading efficiency for targeted HLH treatment. In vitro and in vivo studies demonstrated that M@NP-R not only efficiently adsorbed extracellular proinflammation cytokines, like IFN-γ and IL-6 to alleviate the cytokine storm, but also effectively dampened macrophage activation and proliferation by intracellular JAK/STAT signaling pathway inhibition. M@NP-R treatment significantly ameliorated the clinical and laboratory manifestations of HLH in mouse models, including trilineage cytopenia, hypercytokinemia, organomegaly, hepatorenal dysfunction, and tissue inflammation. Importantly, M@NP-R significantly enhanced the survival of the lethal HLH mice. Altogether, M@NP-R successfully blocked the positive feedback loop between the cytokine storm and macrophage overactivation by depleting extracellular inflammatory cytokines and inhibiting the intracellular JAK/STAT signaling pathway, both of which worked synergistically in HLH treatment. As ruxolitinib has already been extensively used in clinics with favorable safety, and M@NP is biodegradable and highly biocompatible, M@NP-R has good prospects for clinical translation.
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Síndrome de Liberación de Citoquinas , Citocinas , Linfohistiocitosis Hemofagocítica , Macrófagos , Nanopartículas , Nitrilos , Pirazoles , Pirimidinas , Animales , Linfohistiocitosis Hemofagocítica/tratamiento farmacológico , Pirazoles/administración & dosificación , Pirazoles/farmacología , Pirimidinas/administración & dosificación , Pirimidinas/farmacología , Ratones , Citocinas/metabolismo , Síndrome de Liberación de Citoquinas/tratamiento farmacológico , Macrófagos/efectos de los fármacos , Activación de Macrófagos/efectos de los fármacos , Ratones Endogámicos C57BL , Transducción de Señal/efectos de los fármacos , Células RAW 264.7 , Modelos Animales de Enfermedad , Masculino , Inhibidores de las Cinasas Janus/farmacología , Inhibidores de las Cinasas Janus/administración & dosificación , HumanosRESUMEN
This study aimed to examine the morphological, physiological, and biochemical alterations occurring in Notopterygium incisum seeds throughout their developmental stages, with the objective of establishing a theoretical foundation for the cultivation of superior quality seeds. The experimental materials utilized in this study were the seeds of N. incisum at various stages of development following anthesis. Through the employment of morphological observation and plant physiology techniques, the external morphology, nutrients, enzyme activity, and endogenous hormones of the seeds were assessed. The results revealed a transition in seed coat color from light green to brown during the growth and development of N. incisum seeds. Additionally, as the seeds matured, a decrease in water content was observed. Conversely, starch content exhibited a progressive increase, while sucrose content displayed fluctuations. At 7 days after anthesis, the soluble sugar content attained its highest level of 4.52 mg·g~(-1), whereas the soluble protein content reached its maximum of 6.00 mg·g~(-1) at 14 days after anthesis and its minimum of 4.94 mg·g~(-1) at 42 days after anthesis. The activity of superoxide dismutase(SOD) exhibited an initial increase, followed by a decrease, and eventually reached a stable state. Conversely, the activities of catalase(CAT) and peroxidase(POD) demonstrated a decrease initially, followed by an increase, and then another decrease. The levels of the four endogenous hormones, namely gibberellin(GA_3), zeatin riboside(ZR), auxin(IAA), and abscisic acid(ABA), in the seeds displayed significant variations, with IAA and ABA exhibiting considerably higher levels compared to the other hormones. The levels of plant growth-promoting hormones, represented by IAA, generally displayed a pattern of initial increase followed by a subsequent decrease during seed development, while the plant growth-inhibiting hormone ABA showed the opposite trend. The findings indicate that the alterations in nutrient composition, antioxidant enzyme activity, and endogenous hormone levels vary throughout the maturation process of N. incisum seeds. These observations hold relevance for the cultivation of N. incisum seeds.
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Giberelinas , Reguladores del Crecimiento de las Plantas , Ácido Abscísico , Semillas , Hormonas/metabolismo , Germinación/fisiologíaRESUMEN
Chronic inflammation is critical in the onset and progression of atherosclerosis (AS). The lipopolysaccharide (LPS) level in the circulation system is elevated in AS patients and animal models, which is correlated with the severity of AS. Inspired by the underlying mechanism that LPS could drive the polarization of macrophages toward the M1 phenotype, aggravate inflammation, and ultimately contribute to the exacerbation of AS, LPS in the circulation system was supposed to be the therapeutic target for AS treatment. In the present study, polymyxin (PMB) covalently conjugated to PEGylated liposomes (PLPs) were formulated to adsorb LPS through specific interactions between PMB and LPS. In vitro, the experiments demonstrated that PLPs could adsorb LPS, reduce the polarization of macrophages to M1 phenotype and inhibit the formation of foam cells. In vivo, the study revealed that PLPs treatment reduced the serum levels of LPS and pro-inflammatory cytokines, decreased the proportion of M1-type macrophages in AS plaque, stabilized AS plaque, and downsized the plaque burdens in arteries, which eventually attenuated the progression of AS. Our study highlighted LPS in the circulation system as the therapeutic target for AS and provided an alternative strategy for AS treatment.
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Hemophagocytic lymphohistiocytosis (HLH) is a highly fatal condition with the positive feedback loop between continued immune cell activation and cytokine storm as the core mechanism to mediate multiple organ dysfunction. Inspired by macrophage membranes harbor the receptors with special high affinity for proinflammation cytokines, lipopolysaccharide (LPS)-stimulated macrophage membrane-coated nanoparticles (LMNP) were developed to show strong sponge ability to both IFN-γ and IL-6 and suppressed overactivation of macrophages by inhibiting JAK/STAT signaling pathway both in vitro and in vivo. Besides, LMNP also efficiently alleviated HLH-related symptoms including cytopenia, hepatosplenomegaly and hepatorenal dysfunction and save the life of mouse models. Furthermore, its sponge effect also worked well for five human HLH samples in vitro. Altogether, it's firstly demonstrated that biocompatible LMNP could dampen HLH with high potential for clinical transformation, which also provided alternative insights for the treatment of other cytokine storm-mediated pathologic conditions such as COVID-19 infection and cytokine releasing syndrome during CAR-T therapy.
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Apoptosis is a physiological process that occurs in all cell types of the human body, and it profoundly changes the fate of hair by affecting hair follicle cells. This review outlines the cellular changes, intrinsic biochemical characteristics, and mechanisms underlying apoptosis and summarizes the hair follicle life cycle, including development, cycle stages, and corresponding cellular changes. Finally, the relationship between apoptosis and the hair cycle is discussed and the significance of apoptosis in hair loss conditions and drug treatments is highlighted. Apoptosis induces cellular changes and exhibits distinctive properties through intricate signaling pathways. Hair follicles undergo cyclic periods of growth, regression, and dormancy. Apoptosis is closely correlated with the regression phase by triggering hair follicle cell death and shedding. Regulation of apoptosis in hair follicles plays an essential role in hair loss due to maladies and drug treatments. Mitigating apoptosis can enhance hair growth and minimize hair loss. A comprehensive understanding of the correlation between apoptosis and the hair cycle can facilitate the development of novel treatments to prevent hair loss and stimulate hair regeneration.
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Apoptosis , Folículo Piloso , Humanos , Alopecia/tratamiento farmacológico , Cabello , Muerte CelularRESUMEN
Current chemotherapies for metastatic tumors are seriously restricted by limited drug infiltration and deficient disturbance of metastasis-associated complex pathways involving tumor cell autocrine as well as paracrine loops in the microenvironment (TME). Of note, cancer-associated fibroblasts (CAFs) play a predominant role in shaping TME favoring drug resistance and metastasis. Herein, we constructed a tumor extracellular pH (pHe) sensitive methotrexate-chitosan conjugate (MTX-GC-DEAP) and co-assembled it with quercetin (QUE) to achieve co-delivered nanodrugs (MTX-GC-DEAP/QUE). The pHe sensitive protonation and disassembly enabled MTX-GC-DEAP/QUE for stroma-specific delivery of QUE and positive-charged MTX-GC-DEAP molecular conjugates, thereby achieving deep tumor penetration via the combination of QUE-mediated CAF inactivation and adsorption-mediated transcytosis. On the basis of significantly promoted drug availability, a strengthened "omnidirectional" inhibition of pre-metastatic initiation was generated both in vitro and in vivo from the CAF inactivation-mediated reversion of metastasis-promoting environments as well as the inhibition of epithelial-mesenchymal transition, local and blood vessel invasion via QUE-mediated direct regulation on tumor cells. Our tailor-designed versatile nanodrug provides a deep insight into potentiating multi-faceted penetration of multi-mechanism-based regulating agents for intensive metastasis inhibition.
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Fibroblastos Asociados al Cáncer , Nanopartículas , Línea Celular Tumoral , Fibroblastos Asociados al Cáncer/metabolismo , Transición Epitelial-Mesenquimal , Nanopartículas/uso terapéutico , Microambiente Tumoral/fisiologíaRESUMEN
Anti-virulence strategy has been considered as one of the most promising approaches to combat drug-resistant bacterial infections. Pore-forming toxins (PFTs) are the largest class of bacterial toxins, inflicting their virulence effect through creating pores on the cell membrane. However, current solutions for eliminating PFTs are mostly designed based on their molecular structure, requiring customized design for different interactions. In the present study, we employed erythroliposome (denoted as RM-PL), a biomimetic platform constructed by artificial lipid membranes and natural erythrocyte membranes, to neutralize different hemolytic PFTs regardless of their molecular structure. When tested with model PFTs, including α-hemolysin, listeriolysin O, and streptolysin O, RM-PL could completely inhibit toxin-induced hemolysis in a concentration-dependent manner. In vivo studies further confirmed that RM-PL could efficiently neutralize various toxins and save animals' lives without causing damage to organs or tissues. In addition, we explored the underlying mechanisms of this efficient detoxification ability and found that it was mainly macrophages in the spleen and the liver that took up RM-PL-absorbed toxins through a variety of endocytosis pathways and digested them in lysosomes. In summary, the biomimetic RM-PL presented a promising system for broad-spectrum and powerful toxin neutralization with a mechanism of lysosome-mediated toxin degradation.
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Traditional Chinese medicine (TCM) has accumulated a wealth of ecological wisdom and is regarded as an outstanding cultural and medical resource in China. However, in the context of serious environmental pollution, the potential harm caused by TCM materials (TCMMs) due to toxic heavy metals has seriously affected the sustainable development of TCM. Cadmium (Cd) is an internationally recognized heavy metal contaminant. In this paper, 270 reports on Cd in TCMMs were screened from 1969 publications covering 243 species in 81 families. According to the source of the TCMMs, the data were divided into the following categories: aboveground part, bark, flower and fruit, herb, leaf and rhizome. The temporal dynamics of the Cd content and its correlations with the habitats and categories (parts) of TCMMs were also studied. The results show that 22.05 % of the investigated TCMM samples exceeded the relevant domestic standards (Cd≤0.3 mg/kg), among which the maximum Cd content was 17.75 mg/kg. Myrtaceae and Syzygium aromaticum were the family and species with the highest mean Cd content, respectively. Regarding the source of TCMMs of great concern, the mean Cd content of TCMMs decreased in the order of herb > aboveground part > flower and fruit > leaf > rhizome > bark. In addition, in terms of the spatiotemporal distribution, the spatial distribution of the mean Cd content of TCMMs was significantly higher on the Qinghai-Tibet Plateau, followed by Southwest China. When comparing different times, more serious Cd pollution of TCMMs existed after 2000, and the highest mean Cd content was observed in 2000-2004. In summary, soil acidity must be decreased and the cultivation conditions of Cd-hyperaccumulators such as Ligusticum chuanxiong and Lonicera japonica must be modified, in conjunction with a scientific health risk assessment, to ensure the sustainable development of TCMMs.
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Metales Pesados , Contaminantes del Suelo , Cadmio/análisis , China , Monitoreo del Ambiente/métodos , Humanos , Medicina Tradicional China , Metales Pesados/análisis , Medición de Riesgo , Suelo , Contaminantes del Suelo/análisisRESUMEN
Rhizosphere soil microbial community and its diversity are important for the structure and functions of medicinal plant ecosystem. In this study, based on high-throughput sequencing, rhizosphere soil microbial diversity, and yield and quality of rhizome and root of Notopterygium incisum cultivated alone(control, CK) and intercropped with Vicia faba(QH) were analyzed, which is expected to lay a basis for optimization of the cultivation mode and ecological production of N. incisum. RESULTS:: showed that the rhizosphere soil bacteria of N. incisum were dominated by Proteobacteria and Bacteroides, with the relative abundance of 50.38%-51.95% and 16.36%-17.02%, respectively. Soil bacterial community at the phylum level was not significantly different between CK and QH. At the genus level, the relative abundance of MND1(3.54%), Spinstomonas(3.50%), Nitrospira(1.53%), and Rhizobacter(1.05%) was significantly higher and that of Gemmatimonas, Candidatus_Solibacter, and Bryophytes was lower in QH treatment than in the CK. The plant height, leaf length, leaf width, and petiole length of N. incisum in QH treatment was significantly increased and the underground biomass rose by 71.43% compared with those in the CK. Thus, intercropping with V. faba promoted the aboveground growth of N. incisum and improved the yield of root and rhizome. Moreover, the content of notopterol and isoimperatorin increased by 37.96% and 4.09% in QH treatment, respectively, indicating that the intercropping with V. faba boosted the accumulation of secondary metabolites in N. incisum. Pearson's correlation analysis showed that the soil bacterial community was mainly influenced by the soil factors including the content of soil available nutrients, soil organic matter, pH value, and soil water. The influence was in the order: total potassium>total nitrogen>pH>organic matter>available potassium>soil water content>available nitrogen>available phosphorus. In conclusion, the intercropping with V. faba altered soil microenvironment and also increased the yield and accumulation of secondary metabolites of N. incisum, which is a promising ecological planting model for N. incisum.
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Apiaceae , Vicia faba , Agricultura , Apiaceae/metabolismo , Ecosistema , Nitrógeno/metabolismo , Raíces de Plantas , Potasio , Rizosfera , Suelo/química , Microbiología del Suelo , Vicia faba/metabolismo , Vicia faba/microbiología , Agua/metabolismoRESUMEN
Due to the special physiological and pathological characteristics of gliomas, most therapeutic drugs are prevented from entering the brain. To improve the poor prognosis of existing therapies, researchers have been continuously developing non-invasive methods to overcome barriers to gliomas therapy. Although these strategies can be used clinically to overcome the bloodâbrain barrier (BBB), the accurate delivery of drugs to the glioma lesions cannot be ensured. Nano-drug delivery systems (NDDS) have been widely used for precise drug delivery. In recent years, researchers have gathered their wisdom to overcome barriers, so many well-designed NDDS have performed prominently in preclinical studies. These meticulous designs mainly include cascade passing through BBB and targeting to glioma lesions, drug release in response to the glioma microenvironment, biomimetic delivery systems based on endogenous cells/extracellular vesicles/protein, and carriers created according to the active ingredients of traditional Chinese medicines. We reviewed these well-designed NDDS in detail. Furthermore, we discussed the current ongoing and completed clinical trials of NDDS for gliomas therapy, and analyzed the challenges and trends faced by clinical translation of these well-designed NDDS.
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Anisakidae nematode larvae is one of the most common parasites in wild anadromous Coilia nasus. This study aims to explore the mechanism of the C. nasus immune response to the parasitism of Anisakid nematode larvae. Results found that Anisakid nematode larvae parasitism caused liver injury as evidenced by histomorphology results as well as high levels of aminotransferase and aspertate aminotransferase. Furthermore, Anisakid nematode larvae parasitism induced an immune response in the host, which was characterized by the elevated populations of macrophages and neutrophils in the liver and head-kidney in the Anisakidae-infected group compared to the noninfected group. The expression of immunoglobulin IgM and IgD in the liver and head-kidney was also increased in the Anisakidae-infected group. The Anisakidae-infected group showed higher activity of antioxidant enzymes catalase and superoxide dismutase, which indicates severe oxidative stress, and increased production of pro-inflammatory cytokines, TNF-α, IL-6 as well as MCP-1 in the liver compared with the noninfected group. As a result of inflammation, livers of hosts in the Anisakidae-infected group showed fibrosis, and elevated expression of associated proteins including α-smooth muscle actin, fibronectin, collagen type I and type III compared with the noninfected group. We demonstrated that Anisakid nematode larvae parasitism results in injury and fibrosis in the liver, and triggers immune cell infiltration and inflammation in the liver and head-kidney of C. nasus. Altogether, the results provide a foundation for building an interaction between parasite and host, and will contribute to C. nasus population and fishery resource protection.
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Proteínas de Peces , Peces , Animales , Fibrosis , Proteínas de Peces/metabolismo , Peces/fisiología , Inmunidad , Inflamación/metabolismo , Larva/metabolismo , Hígado/metabolismo , Cirrosis Hepática/metabolismo , Transaminasas/metabolismoRESUMEN
A limited infiltration and the subsequent low effective drug concentration result in poor chemotherapeutic outcomes against tumors, and even further promote tumor resistance and metastatic. Herein, iRGD-modified graphene oxide (GO) nanosheets (IPHG) are developed for the intensive treatment of metastatic tumors using focus-specific penetrated delivery together with photothermal therapy-mediated chemosensitization and photothermal therapy-strengthened integrin targeting-based antimigration. In vitro and in vivo data verified the mechanism of the tumor-selective infiltration of IPHG is based on a rigid 2D structure-associated advantage regarding hemodynamics and endothelial contact, followed by iRGD-endowed transendothelial and intratumoral transport. Once IPHG-DOX-penetrated 4T1 tumors are exposed to near-infrared irradiation, hyperthermia stress and photothermal therapy-elevated effective drug concentrations result in chemosensitization and prominent tumor suppression. Meanwhile, the specific binding of iRGD to integrins and photothermal therapy leads to the synergistic perturbation of cytoskeleton remodeling and subsequent impairment of cell motility and metastasis. The tailored design of IPHG validates a promising paradigm for drug delivery to combat tumor resistance and metastasis resulting from poor target access for single chemotherapy.
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Hipertermia Inducida , Nanopartículas , Neoplasias , Línea Celular Tumoral , Doxorrubicina , Grafito , Humanos , Integrinas , Neoplasias/tratamiento farmacológico , FototerapiaRESUMEN
Metastatic breast cancer is a major cause of cancer-related mortality worldwide. The tumor-specific penetration and triggered drug release for "full-line" inhibition of pre-metastatic initiation are of essential importance in improving mortality rates. Here, a crosslinked, redox-sensitive amphiphilic conjugate (cHLC) was constructed with a combination of features, including hyaluronic acid (HA)-mediated tumor active targeting, lipoic acid (LA) core-crosslinking based bio-stability and reducibility, and lipid raft anchoring-promoted HA-mediated endocytosis through cholesterol (CHO) modification for the penetrated co-delivery of paclitaxel (PTX) and the multi-targeted anti-metastatic agent, silibinin (SB). Resultantly, the nanodrug (cHLC/(PTX + SB)) demonstrated enhanced tumor cytoplasm-selective rapid drug delivery in a 4T1 model both in vitro and in vivo. The released SB efficiently sensitized cells to PTX treatment and inhibited the whole process of pre-metastatic initiation including epithelial-to-mesenchymal transition (EMT), local and blood vessel invasion. The exquisite design of this delivery system provides a deep insight into enhancing focus accessibility of multi-targeted drugs for an efficient inhibition of tumor metastasis.