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In recent years, nanocellulose (NC) has gained significant attention due to its remarkable properties, such as adjustable surface chemistry, extraordinary biological properties, low toxicity and low density. This review summarizes the preparation of NC derived from lignocellulosic biomass (LCB), including cellulose nanofibrils (CNF), cellulose nanocrystals (CNC), and lignin-containing cellulose nanofibrils (LCNF). It focuses on examining the impact of non-cellulosic components such as lignin and hemicellulose on the functionality of NC. Additionally, various surface modification strategies of NC were discussed, including esterification, etherification and silylation. The review also emphasizes the progress of NC application in areas such as Pickering emulsions, food packaging materials, food additives, and hydrogels. Finally, the prospects for producing NC from LCB and its application in food-related fields are examined. This work aims to demonstrate the effective benefits of preparing NC from lignocellulosic biomass and its potential application in the food industry.
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Targeting the stimulator of interferon genes (STING) pathway is a promising strategy to overcome primary resistance to immune checkpoint inhibitors in non-small cell lung cancer with the STK11 mutation. We previously found metformin enhances the STING pathway and thus promotes immune response. However, its low concentration in tumors limits its clinical use. Here, we constructed high-mesoporous Mn-based nanocarrier loading metformin nanoparticles (Mn-MSN@Met-M NPs) that actively target tumors and respond to release higher concentration of Mn2+ ions and metformin. The NPs significantly enhanced the T cells to kill lung cancer cells with the STK11 mutant. The mechanism shows that enhanced STING pathway activation promotes STING, TBKI, and IRF3 phosphorylation through Mn2+ ions and metformin release from NPs, thus boosting type I interferon production. In vivo, NPs in combination with a PD-1 inhibitor effectively decreased tumor growth. Collectively, we developed a Mn-MSN@Met-M nanoactivator to intensify immune activation for potential cancer immunotherapy.
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Atherosclerosis (AS) is a common clinical sickness and the major pathological basis of ischemic cardiocerebrovascular diseases (CCVDs). The pathogenesis of AS involves a variety of risk factors, and there is a lack of effective preventive and curative drugs that can completely treat AS. In recent years, with the improvement of people's living standards and changes in dietary habits, the morbidity and mortality rates of AS are on the rise, and the age of onset tends to be younger. The formation of AS is closely related to a variety of factors, and the main factors include lipid metabolism disorders, endothelial damage, inflammation, unstable plaques, etc. Epigallocatechin gallate (EGCG), as one of the main components of catechins, has a variety of pharmacological effects, and its role in the prevention of AS and the protection of cardiovascular and cerebral blood vessels has been highly valued. Recent epidemiological investigations and various in vivo and ex vivo experiments have shown that EGCG is capable of resisting atherosclerosis and reducing the morbidity and mortality of AS. In this paper, we reviewed the anti-AS effects of EGCG and its mechanisms in recent years, including the regulation of lipid metabolism, regulation of intestinal flora disorders, improvement of vascular endothelial cell functions, inhibition of inflammatory factors expression, regulation of inflammatory signaling pathways, inhibition of matrix metalloproteinase (MMP) expression, and inhibition of platelet aggregation, which are helpful for the prevention of cardiocerebrovascular diseases.
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Aterosclerose , Catequina , Metabolismo dos Lipídeos , Catequina/análogos & derivados , Catequina/farmacologia , Catequina/uso terapêutico , Humanos , Aterosclerose/tratamento farmacológico , Aterosclerose/prevenção & controle , Metabolismo dos Lipídeos/efeitos dos fármacos , Animais , Microbioma Gastrointestinal/efeitos dos fármacosRESUMO
Helminths serve as principal regulators in modulating host immune responses, and their excretory-secretory proteins are recognized as potential therapeutic agents for inflammatory bowel disease. Nevertheless, our comprehension of the mechanisms underlying immunoregulation remains restricted. This investigation delves into the immunomodulatory role of a secretory protein serpin (Emu-serpin), within the larval stage of Echinococcus multilocularis. Our observations indicate that Emu-serpin effectively alleviates dextran sulfate sodium-induced colitis, yielding a substantial reduction in immunopathology and an augmentation of anti-inflammatory cytokines. Furthermore, this suppressive regulatory effect is concomitant with the reduction of gut microbiota dysbiosis linked to colitis, as evidenced by a marked impediment to the expansion of the pathobiont taxa Enterobacteriaceae. In vivo experiments demonstrate that Emu-serpin facilitates the expansion of M2 phenotype macrophages while concurrently diminishing M1 phenotype macrophages, alongside an elevation in anti-inflammatory cytokine levels. Subsequent in vitro investigations involving RAW264.7 and bone marrow macrophages reveal that Emu-serpin induces a conversion of M2 macrophage populations from a pro-inflammatory to an anti-inflammatory phenotype through direct inhibition. Adoptive transfer experiments reveal the peritoneal macrophages induced by Emu-serpin alleviate colitis and gut microbiota dysbiosis. In summary, these findings propose that Emu-serpin holds the potential to regulate macrophage polarization and maintain gut microbiota homeostasis in colitis, establishing it as a promising candidate for developing helminth therapy for preventing inflammatory diseases.
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Colite , Disbiose , Echinococcus multilocularis , Microbioma Gastrointestinal , Macrófagos , Serpinas , Animais , Camundongos , Serpinas/metabolismo , Colite/microbiologia , Macrófagos/imunologia , Macrófagos/metabolismo , Echinococcus multilocularis/imunologia , Proteínas de Helminto/metabolismo , Células RAW 264.7 , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Citocinas/metabolismo , Camundongos Endogâmicos C57BL , FemininoRESUMO
Introduction: The precise detection of weeds in the field is the premise of implementing weed management. However, the similar color, morphology, and occlusion between wheat and weeds pose a challenge to the detection of weeds. In this study, a CSCW-YOLOv7 based on an improved YOLOv7 architecture was proposed to identify five types of weeds in complex wheat fields. Methods: First, a dataset was constructed for five weeds that are commonly found, namely, Descurainia sophia, thistle, golden saxifrage, shepherd's purse herb, and Artemisia argyi. Second, a wheat weed detection model called CSCW-YOLOv7 was proposed to achieve the accurate identification and classification of wheat weeds. In the CSCW-YOLOv7, the CARAFE operator was introduced as an up-sampling algorithm to improve the recognition of small targets. Then, the Squeeze-and-Excitation (SE) network was added to the Extended Latent Attention Networks (ELAN) module in the backbone network and the concatenation layer in the feature fusion module to enhance important weed features and suppress irrelevant features. In addition, the contextual transformer (CoT) module, a transformer-based architectural design, was used to capture global information and enhance self-attention by mining contextual information between neighboring keys. Finally, the Wise Intersection over Union (WIoU) loss function introducing a dynamic nonmonotonic focusing mechanism was employed to better predict the bounding boxes of the occluded weed. Results and discussion: The ablation experiment results showed that the CSCW-YOLOv7 achieved the best performance among the other models. The accuracy, recall, and mean average precision (mAP) values of the CSCW-YOLOv7 were 97.7%, 98%, and 94.4%, respectively. Compared with the baseline YOLOv7, the improved CSCW-YOLOv7 obtained precision, recall, and mAP increases of 1.8%, 1%, and 2.1%, respectively. Meanwhile, the parameters were compressed by 10.7% with a 3.8-MB reduction, resulting in a 10% decrease in floating-point operations per second (FLOPs). The Gradient-weighted Class Activation Mapping (Grad-CAM) visualization method suggested that the CSCW-YOLOv7 can learn a more representative set of features that can help better locate the weeds of different scales in complex field environments. In addition, the performance of the CSCW-YOLOv7 was compared to the widely used deep learning models, and results indicated that the CSCW-YOLOv7 exhibits a better ability to distinguish the overlapped weeds and small-scale weeds. The overall results suggest that the CSCW-YOLOv7 is a promising tool for the detection of weeds and has great potential for field applications.
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Soil salinization is a major abiotic stress factor that negatively impacts plant growth, development, and crop yield, severely limiting agricultural production and economic development. Cotton, a key cash crop, is commonly cultivated as a pioneer crop in regions with saline-alkali soil due to its relatively strong tolerance to salt. This characteristic renders it a valuable subject for investigating the molecular mechanisms underlying plant salt tolerance and for identifying genes that confer salt tolerance. In this study, focus was placed on examining a salt-tolerant variety, E991, and a salt-sensitive variety, ZM24. A combined analysis of transcriptomic data from these cotton varieties led to the identification of potential salt stress-responsive genes within the glutathione S-transferase (GST) family. These versatile enzyme proteins, prevalent in animals, plants, and microorganisms, were demonstrated to be involved in various abiotic stress responses. Our findings indicate that suppressing GhGSTF9 in cotton led to a notably salt-sensitive phenotype, whereas heterologous overexpression in Arabidopsis plants decreases the accumulation of reactive oxygen species under salt stress, thereby enhancing salt stress tolerance. This suggests that GhGSTF9 serves as a positive regulator in cotton's response to salt stress. These results offer new target genes for developing salt-tolerant cotton varieties.
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Arabidopsis , Regulação da Expressão Gênica de Plantas , Gossypium , Proteínas de Plantas , Plantas Geneticamente Modificadas , Tolerância ao Sal , Arabidopsis/genética , Gossypium/genética , Plantas Geneticamente Modificadas/genética , Tolerância ao Sal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Salino/genética , Espécies Reativas de Oxigênio/metabolismo , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Estresse Fisiológico/genética , Plantas Tolerantes a Sal/genéticaRESUMO
BACKGROUND: The dynamic interplay between tyrosine kinase inhibitors (TKIs) and the tumor immune microenvironment (TME) plays a crucial role in the therapeutic trajectory of non-small cell lung cancer (NSCLC). Understanding the functional dynamics and resistance mechanisms of TKIs is essential for advancing the treatment of NSCLC. METHODS: This study assessed the effects of short-term and long-term TKI treatments on the TME in NSCLC, particularly targeting epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations. We analyzed changes in immune cell composition, cytokine profiles, and key proteins involved in immune evasion, such as laminin subunit γ-2 (LAMC2). We also explored the use of aspirin as an adjunct therapy to modulate the TME and counteract TKI resistance. RESULTS: Short-term TKI treatment enhanced T cell-mediated tumor clearance, reduced immunosuppressive M2 macrophage infiltration, and downregulated LAMC2 expression. Conversely, long-term TKI treatment fostered an immunosuppressive TME, contributing to drug resistance and promoting immune escape. Differential responses were observed among various oncogenic mutations, with ALK-targeted therapies eliciting a stronger antitumor immune response compared with EGFR-targeted therapies. Notably, we found that aspirin has potential in overcoming TKI resistance by modulating the TME and enhancing T cell-mediated tumor clearance. CONCLUSIONS: These findings offer new insights into the dynamics of TKI-induced changes in the TME, improving our understanding of NSCLC challenges. The study underscores the critical role of the TME in TKI resistance and suggests that adjunct therapies, like aspirin, may provide new strategies to enhance TKI efficacy and overcome resistance.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Inibidores de Proteínas Quinases , Microambiente Tumoral , Microambiente Tumoral/efeitos dos fármacos , Humanos , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Animais , Camundongos , Resistencia a Medicamentos Antineoplásicos , Feminino , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inibidores , Linhagem Celular Tumoral , MutaçãoRESUMO
BACKGROUND: A score to predict the association between unexplained osteoporosis and an underlying systemic Mastocytosis (SM) is lacking. OBJECTIVE: This study aimed at identifying criteria able to predict the diagnosis of SM without skin involvement and provide an indication for bone marrow (BM) assessment. METHODS: We included 139 adult patients with unexplained osteoporosis and suspected SM. After BM evaluation, 63 patients (45.3 %) were diagnosed with SM, while the remaining 76 patients (54.7 %) negative for clonal mast cell (MC) disorders, constituted our control group. Univariate and multivariate analysis identified three independent predictive factors: age (<54 years: +1 point, >64 years: -1 point), serum basal tryptase (sBT) levels >19 ng/mL (+2 points) and vertebral fractures (+2 points). RESULTS: These variables were used to build the OSTEO-score, able to predict the diagnosis of SM before BM assessment with a sensitivity of 73.5 % and a specificity of 67.1 %. Patients with a score < 3 had a lower probability of having SM compared to patients with a score ≥ 3 (28.5 % and 71.4 %, respectively, p < 0.0001). When sBT levels were corrected for the presence of hereditary alpha-tryptasemia (HαT) using the BST calculater (https://bst-calculater.niaid.nih.gov/) recently published [1,2], the sensitivity of ΗαT-adjusted OSTEO-score increased to 87.8 %, and the specificity reached 76.1 %. Also, the positive predictive value of a score ≥ 3 increased to 85.2 %. CONCLUSIONS: Further studies are needed to validate these results and characterize the role of tryptase genotyping in patients with unexplained osteoporosis in reducing the risk of misdiagnosing patients with SM. Our proposed scoring model allows the identification of patients with the highest probability of having SM, avoiding unnecessary BM studies.
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Mastocitose Sistêmica , Osteoporose , Humanos , Mastocitose Sistêmica/complicações , Mastocitose Sistêmica/sangue , Mastocitose Sistêmica/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , Triptases/sangue , Medula Óssea/patologiaRESUMO
OBJECTIVE: To analyze the risk factors associated with colorectal adenoma and to investigate the associations of metabolism-related fatty liver disease (MAFLD) with obesity, colorectal adenoma and high-risk adenoma. METHODS: A total of 1395 subjects were enrolled and divided into a colorectal adenoma group (593 subjects) and a control group (802 subjects) according to the inclusion and exclusion criteria. The characteristics of patients in the colorectal adenoma group and the control group were compared by the chi-square test. Univariate and multivariate logistic analyses were used to analyze independent risk factors and associations with different MAFLD subtypes. Colorectal adenoma characteristics and the proportion of patients with high-risk colorectal adenoma were also compared. RESULTS: High-density lipoprotein (HDL-C) was significantly lower in patients in the colorectal adenoma group than in those in the control group (P < 0.001). Logistic regression analysis revealed that age, obesity status, central obesity status, hypertension status, diabetes status, fatty liver status, smoking history, BMI, waist circumference, triglyceride level, HDL-C level, fasting blood glucose level and degree of hepatic steatosis were all independent risk factors for colorectal adenoma. Notably, MAFLD was associated with a significantly increased risk of colorectal adenoma in patients with central obesity (P < 0.001). In addition, obesity, central obesity, diabetes, fatty liver and degree of hepatic steatosis were all shown to be independent risk factors for high-risk colorectal adenoma. In addition, a greater proportion of MAFLD patients with central obesity than those without central obesity had high-risk colorectal adenoma. CONCLUSION: MAFLD and central obesity are independently associated with the development of colorectal adenoma. MAFLD with central obesity is associated with an increased risk of colorectal adenoma and high-risk adenoma.
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Adenoma , Neoplasias Colorretais , Obesidade Abdominal , Humanos , Masculino , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/epidemiologia , Feminino , Adenoma/epidemiologia , Pessoa de Meia-Idade , Obesidade Abdominal/complicações , Obesidade Abdominal/epidemiologia , Fatores de Risco , Idoso , Fígado Gorduroso/complicações , Fígado Gorduroso/epidemiologia , Adulto , Modelos Logísticos , Estudos de Casos e Controles , Circunferência da CinturaRESUMO
Honey is well-known as a food product that is rich in active ingredients and is very popular among consumers. Free amino acids (FAAs) are one of the important nutritional components of honey, which can be used not only as a nutritional indicator of honey but also as an indicator of plant source identification. In this study, the contents of 20 FAAs in seven types of honey from 11 provinces in China were examined for the first time. The 20 FAAs were analyzed by ultra-performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS). By analyzing 93 honey samples from seven types of honey, the FAAs were found to range from 394.4 mg/kg (linden honey) to 1771.7 mg/kg (chaste honey). Proline ranged from 274.55 to 572.48 mg/kg, and methionine was only present in some of the linden honey, chaste honey, acacia honey, and rape honey. Evaluated by amino acid principal component analysis, multifloral grassland honey had the highest overall evaluation score, acacia and jujube honey were the most similar, while chaste honey was the least similar to the other types of honey. In addition, DNA was extracted from 174 Xinjiang grassland honey samples and different plant leaves for PCR and sequencing to identify the species of nectar plants. As a result, 12 families and 25 species of honey plants were identified. The results confirmed the diversity of FAAs in dissimilar types and sources of honey. This study provides a reference for expanding honey quality standards and verifying the authenticity of honey.
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Paroxysmal kinesigenic dyskinesia (PKD) represents the most prevalent form of paroxysmal dyskinesia, characterized by recurrent and transient attacks of involuntary movements triggered by a sudden voluntary action. In this study, whole-exome sequencing was conducted on a cohort of Chinese patients to identify causal mutations. In one young female case, a de novo CACNA1B variant (NM_000718.3:exon3:c.479C > T:p.S160F) was identified as the causative lesion. This finding may broaden the phenotypic spectrum of CACNA1B mutations and provide a prospective cause of primary PKD. Additionally, a novel start-loss variant (NM_000682.7:c.3G > A) within ADRA2B further denied its association with benign adult familial myoclonic epilepsy, and a KCNQ2 E515D variant that was reported as a genetic susceptibility factor for seizures had no damaging effect in this family. In sum, this study established a correlation between CACNA1B and primary PKD, and found valid evidence that further negates the pathogenic role of ADRA2B in benign adult familial myoclonic epilepsy.
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This report presents a case of Charcot-Marie-Tooth dominant intermediate D (CMTDID), a rare subtype of Charcot-Marie-Tooth disease, in a 52 years-old male patient. The patient exhibited mobility impairment, foot abnormalities (pes cavus), and calf muscle atrophy. Whole exome sequencing and Sanger sequencing suggested that a novel variant (NM_000530.8, c.145C>A/p.His49Asn) of MPZ may be the genetic lesion in the patient. The bioinformatic program predicted that the new variant (p.His49Asn), located at an evolutionarily conserved site of MPZ, was neutral. Our study expands the variant spectrum of MPZ and the number of identified CMTDID patients, contributing to a better understanding of the relationship between MPZ and CMTDID.
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The Asian yellow pond turtle (Mauremys mutica) is widely traded in China, and its artificial breeding has now become a major industry. However, the insufficient offspring supply and reproductive decline of farmed turtles make the wild turtles more vulnerable. The present study was mainly designed to quantify the fecundity of M. mutica and attempt to screen for good reproductive performance in females. The genetic variability of the population and its genetic structure were also analysed. The parent-offspring relationships of all offspring in four consecutive years were confirmed using sixteen microsatellite loci. The genetic variability between the parents and offspring was low, and offspring of different years also showed little variability. We summarised the reproductive results of all females and counted the annual number of offspring and the variation in the number of offspring. The females were then divided into three types (stable, undulating and levelling off) according to the continuity. We selected seven females with good reproductive ability, which provided 16.94% of the annual contributions, while there were two females that had no offspring in four years. We also analysed the possible reasons for this difference and the importance of carrying out a family survey. This research can provide the basis and materials for the creation of a good reproductive group and the study of the reproductive biology of turtles in M. mutica aquaculture.
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Fasting heat production (FHP) is used to assess the maintenance net energy requirement of animals. Herein, the FHP of layer-type pullets was estimated. In trial 1, 16 40-day-old Jingfen layer-type pullets were divided into 4 groups of 4 chickens and placed in 4 respiratory chambers. Pullets had free access to feed and water. After 4-d acclimatization, feed was withdrawn, and chickens were measured for FHP for 3 consecutive days. In trial 2, twenty-four 40-day-old pullets were placed in 4 respiratory calorimetry chambers, with 6 pullets per chamber. After 4-d acclimatization, one chamber was randomly selected and all pullets in the chamber was sampled at 5, 25, 50, or 65 h after feed withdrawal. The result showed that FHP declined with fasting time and reached the lowest level between 48 and 72 h. Respiratory quotient was decreased (P < 0.05) between 24 and 48 h compared with that in the first 24 h after fasting. The FHP in the light period showed a significant to decline with fasting time (P < 0.01), whereas the FHP in the dark period was decreased (P < 0.01) 24 h after fasting. Body weight, thigh mass, and abdominal fat decreased (P < 0.05) at 25 h after fasting. Serum glucose were increased (P < 0.01) and while triglycerides were significantly decreased (P < 0.01) at 50 h compared with that at 5 and 25 h time point. The result suggests that the adequate measuring period for FHP for layer-type pullets is from 24 to 48 h after fasting. The FHP of 7-wk-old layer-type pullets was 562.20 kJ/kg of BW0.75/d under a 10-h light and 14-h dark lighting regime.
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Galinhas , Jejum , Animais , Feminino , Termogênese , Peso Corporal , Calorimetria Indireta/veterinária , Ração Animal/análise , Dieta/veterináriaRESUMO
Understanding the neural mechanisms involved in learning processes is crucial for unraveling the complexities of behavior and cognition. Sudden change from the untrained level to the fully-learned level is a pivotal feature of instrumental learning. However, the concept of change point and suitable methods to conveniently analyze the characteristics of sudden change in groups remain elusive, which might hinder a fuller understanding of the neural mechanism underlying dynamic leaning process. In the current study, we investigated the learning processes of mice that were trained in an aversive instrumental learning task, and introduced a novel strategy to analyze behavioral variations in instrumental learning, leading to improved clarity on the concept of sudden change and enabling comprehensive group analysis. By applying this novel strategy, we examined the effects of cocaine and a cannabinoid receptor agonist on instrumental learning. Intriguingly, our analysis revealed significant differences in timing and occurrence of sudden changes that were previously overlooked using traditional analysis. Overall, our research advances understanding of behavioral variation during instrumental learning and the interplay between learning behaviors and neurotransmitter systems, contributing to a deeper comprehension of learning processes and informing future investigations and therapeutic interventions.
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Condicionamento Operante , Camundongos , AnimaisRESUMO
Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing's anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing's pharmacologically significant constituents supports the medicine's anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.
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Medicamentos de Ervas Chinesas , Ratos Sprague-Dawley , Sepse , Animais , Sepse/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacocinética , Masculino , Ratos , Administração IntravenosaRESUMO
OBJECTIVE: Numerous scattered case studies continue to demonstrate a strong correlation between acquired KRAS mutations and epidermal growth factor receptor-tyrosine kinase inhibitor resistance in non-small cell lung cancer. However, the comprehensive understanding of the KRAS pathway following the failure of epidermal growth factor receptor-tyrosine kinase inhibitor therapy remains limited. METHODS: We conducted a retrospective evaluation of the next generation sequencing data from 323 patients with advanced non-small cell lung cancer and EGFR-activating mutations after experiencing progression with epidermal growth factor receptor-tyrosine kinase inhibitor therapy. Our analysis specifically focused on the acquired changes to the KRAS gene. RESULTS: Among the 323 patients with advanced non-small cell lung cancer and EGFR-activating mutations who experienced resistance to epidermal growth factor receptor-tyrosine kinase inhibitor therapy, 14 individuals (4.3%) developed resistance due to acquired KRAS alterations. Of these 14 patients, 10 cases (71.4%) were due to KRAS missense mutations, 1 case (7.2%) was due to KRAS gene fusion and 3 cases (21.4%) were due to KRAS amplification. Notably, we identified one newly demonstrated KRAS gene fusion (KRAS and LMNTD1), one KRAS G13D and one KRAS K117N. The emergence of acquired KRAS alterations was often accompanied by novel mutations and high tumor mutation burden, with TP53, CNKN2A, PIK3CA, MYC, STK11, CDK4, BRCA2 and ERBB2 being the most frequently observed concurrent mutations. The median progression-free survival and overall survival for the 14 patients were 5.2 and 7.3 months, respectively. Acquired KRAS missense variants were associated with significantly worse progression-free survival compared with other KRAS variant subtypes (P < 0.028). CONCLUSIONS: This study provides significant evidence of the role of acquired KRAS variants in the development of resistance to epidermal growth factor receptor-tyrosine kinase inhibitor therapy. Our results contribute to the growing body of knowledge on the mutational profiles associated with resistance to epidermal growth factor receptor-tyrosine kinase inhibitor treatment. Furthermore, our study highlights the KRAS gene change as a significant mechanism of resistance to epidermal growth factor receptor-tyrosine kinase inhibitor therapy.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos Retrospectivos , Inibidores de Proteínas Quinases/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas , Receptores ErbB/genética , Mutação , Resistencia a Medicamentos Antineoplásicos/genéticaRESUMO
Ulcerative colitis (UC) is a chronic, non-specific inflammatory sickness of the intestinal tract, chiefly implicating the rectum and colon, which is characterized by chronic or subacute diarrhea, mucopurulent stools, and abdominal pain. The pathogeny of UC is still uncertain, and it is thought that multiple factors interact to cause the disease, such as environment, genetics, gut microbes, and immunity. Injuring the intestinal barrier is one of the most significant features of UC and includes mechanical, chemical, immune, and biological barriers. Plenty of research has shown that probiotics, as profitable bacteria in the gut, can play a prominent role in the treatment of UC by improving gut barrier function and modulating gut immunity. Lactobacillus plantarum (L. plantarum), a common probiotic, has made outstanding contributions to food and medicine, and many studies in recent years have shown that L. plantarum has great preventive and therapeutic effects on ulcerative colitis and restores the intestinal barrier. This paper reviews the mechanisms of L. plantarum for improving the intestinal barrier function of UC organisms, mainly including regulating the immune response, inhibiting oxidative stress, raising the expression of tight junction (TJ) proteins, promoting the formation of mucin, improving the composition of gut flora, and raising the levels of short-chain fatty acids (SCFAs), which offers some help for the clinical therapy of UC.
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Colite Ulcerativa , Colite , Lactobacillus plantarum , Humanos , Animais , Camundongos , Colite Ulcerativa/tratamento farmacológico , Lactobacillus plantarum/fisiologia , Função da Barreira Intestinal , Estresse Oxidativo , Fezes , Sulfato de Dextrana , Modelos Animais de Doenças , Colo , Camundongos Endogâmicos C57BLRESUMO
This study aimed to explore the effects of light-emitting diode (LED) light colors on growth, intestinal morphology, and cecal microbiota in broilers. A total of 360 healthy male Arbor Acres (AA) broilers with similar weights were selected and divided into four groups with six replicates in each group and 15 broilers in each replicate: LED white light (W), LED green light (G), LED blue light (B), and LED blue-green composite light (BG). The experimental period was 42 d, the light cycle of each treatment group was 23L:1D (23 h of light, one hour of darkness) from 1 to 3 d, and the light cycle from 4 to 42 d was 16L:8D; light intensity was 20 Lux. The results showed that the average daily feed intake and final weight of broilers receiving the B group were the highest in 21 d and 42 d compared with other groups. The average daily feed intake of the BG group was lower than that of the B group. In the same light color, small intestine villus height grows with age. On days 21 and 42, compared with other groups, the ileal villus height was higher, the crypt depth was lower, and the V/C ratio (villus to crypt ratio) was higher in the BG group. The combination of blue-green composite light was beneficial to increase the content of propionate, isobutyrate, butyrate, isovalerate, and valerate in the cecum of 21-day-old broilers and the content of isobutyrate in the cecum of 42-day-old broilers, and a decrease in cecal short-chain fatty acid concentrations with age. The B group and the BG group had higher abundances of Bacteroidetes at day 21 of age and lower abundances of Phascolarctobacterium at day 42. However, no cecal microbiota differences were detected by the Bonferroni-corrected test. In general, our research results showed that light color could promote the growth of broilers by affecting intestinal morphology, microbiota abundance (needs to be validated by further experiments), and cecal short-chain fatty acid concentrations. And blue and blue-green composite lights are more suitable for broiler growth.