Pseudolaric acid B suppresses NSCLC progression through the ROS/AMPK/mTOR/autophagy signalling pathway.

Pseudolaric acid B (PAB), an acid isolated from the roots of Pseudolarix kaempferi gorden, has shown antitumour effects through multiple mechanisms of action. The objective of this study was to investigate the anticancer effect of PAB on non-small cell lung cancer (NSCLC) and its underlying mechanism. In our experiments, we observed that PAB decreased cell viability, inhibited colony formation, induced cell cycle arrest, impeded scratch healing, and increased apoptosis in H1975 and H1650 cells. Additionally, PAB treatment enhanced the fluorescence intensity of MDC staining in NSCLC cells, upregulated the protein expression of microtubule-associated protein light chain 3 II (LC3 II), and downregulated the expression of sequestosome 1 (SQSTM1/P62). Combined treatment with PAB and chloroquine (CQ) increased the protein expression levels of LC3 II and P62 while decreasing the apoptosis of H1975 and H1650 cells. Moreover, treatment with PAB led to significant mTOR inhibition and AMPK activation. PAB combined with compound C (CC) inhibited autophagy and apoptosis. Furthermore, PAB treatment increased intracellular reactive oxygen species (ROS) levels in NSCLC cells, which correlated with the modulation of the AMPK/mTOR signalling pathway and was associated with autophagy and apoptosis. Finally, we validated the antitumour growth activity and mechanism of PAB in vivo using athymic nude mice bearing H1975 tumour cells. In conclusion, our findings suggest that PAB can induce apoptosis and autophagic cell death in NSCLC through the ROS-triggered AMPK/mTOR signalling pathway, making it a promising candidate for future NSCLC treatment.

Detection of human serum albumin using a rare-earth nanosheet fluorescent probe based on intensity and lifetime signals.

Human serum albumin (HSA) is an important biomarker for early disease diagnosis. Therefore, the detection of HSA in biological samples is important. In this study, for the sensitive detection of HSA, a fluorescent probe based on Eu(III)-doped yttrium hydroxide nanosheets was designed and sensitized by α-thiophenformyl acetone trifluoride as an antenna. The morphology and structure of the as-prepared nanosheet fluorescent probe were studied by transmission electron microscopy and atomic force microscopy. A detailed investigation of the fluorescence properties of the as-obtained nanosheet probe revealed that the Eu(III) emission intensity was linearly and selectively enhanced by the consecutive addition of HSA. Furthermore, the lifetime signal of this probe was enhanced with increasing concentration. The sensitivity of the nanosheet probe to HSA is discussed based on the results of ultraviolet-visible, fluorescence, and infrared spectral analyses, the findings demonstrate that the nanosheet fluorescent probe we prepared is a highly sensitive and selective tool for detecting HSA concentration with a high intensity and a large lifetime change.

Associations between functional constipation and non-IgE-mediated food allergy in infants and children

Background: The non-IgE-mediated food allergy (non-IgE-FA) is less prevalent than IgE-mediated food allergy, and their relationship with functional constipation (FC) needs to be clarified. Methods: A total of 305 infants and children with constipation treated in the Department of Pediatric Gastroenterology, Children’s Hospital of Nanjing Medical University, from July 2020 to December 2021 were included in this study. Four cases with organic lesions were excluded. Among 301 diagnosed with FC, according to ROME IV criteria, 81 cases with allergy-related indicators were further evaluated for food allergy by food-specific IgG antibody test, allergen- specific IgE antibody detection, skin prick test, and food avoidance and reintroduction. Results: A total of 45 cases with FC were diagnosed with food allergy, and the incidence rate was 15%. Among the 45 patients, 35 cases (77.8%) had FC with non-IgE-FA. The main clinical symptoms or signs included anal fissure, abdominal pain, and pain during defecation. The most prevalent allergic foods were cow’s milk, eggs, fish, and shrimp. Ten (22.2%) cases reported FC with mixed food allergy, including both non-IgE-mediated and IgE-mediated food allergy. This study focused on non-IgE-mediated food allergy–related FC. Conclusion: Our results showed that the incidence of food allergy in infants and children with FC was 15%, which was mainly mediated by non-IgE-FA. The main clinical symptoms or signs in these cases included anal fissure, abdominal pain, and pain during defecation, and the main allergens included milk, eggs, fish, and shrimp (AU)

Associations between functional constipation and non-IgE-mediated food allergy in infants and children.

BACKGROUND: The non-IgE-mediated food allergy (non-IgE-FA) is less prevalent than IgE-mediated food allergy, and their relationship with functional constipation (FC) needs to be clarified. METHODS: A total of 305 infants and children with constipation treated in the Department of Pediatric Gastroenterology, Children's Hospital of Nanjing Medical University, from July 2020 to December 2021 were included in this study. Four cases with organic lesions were excluded. Among 301 diagnosed with FC, according to ROME IV criteria, 81 cases with allergy-related indicators were further evaluated for food allergy by food-specific IgG antibody test, allergen- specific IgE antibody detection, skin prick test, and food avoidance and reintroduction. RESULTS: A total of 45 cases with FC were diagnosed with food allergy, and the incidence rate was 15%. Among the 45 patients, 35 cases (77.8%) had FC with non-IgE-FA. The main clinical symptoms or signs included anal fissure, abdominal pain, and pain during defecation. The most prevalent allergic foods were cow's milk, eggs, fish, and shrimp. Ten (22.2%) cases reported FC with mixed food allergy, including both non-IgE-mediated and IgE-mediated food allergy. This study focused on non-IgE-mediated food allergy-related FC. CONCLUSION: Our results showed that the incidence of food allergy in infants and children with FC was 15%, which was mainly mediated by non-IgE-FA. The main clinical symptoms or signs in these cases included anal fissure, abdominal pain, and pain during defecation, and the main allergens included milk, eggs, fish, and shrimp.

Emerging roles and therapeutic potentials of ferroptosis: from the perspective of 11 human body organ systems.

Since ferroptosis was first described as an iron-dependent cell death pattern in 2012, there has been increasing interest in ferroptosis research. In view of the immense potential of ferroptosis in treatment efficacy and its rapid development in recent years, it is essential to track and summarize the latest research in this field. However, few writers have been able to draw on any systematic investigation into this field based on human body organ systems. Hence, in this review, we provide a comprehensive description of the latest progress in unveiling the roles and functions, as well as the therapeutic potential of ferroptosis, in treating diseases from the aspects of 11 human body organ systems (including the nervous system, respiratory system, digestive system, urinary system, reproductive system, integumentary system, skeletal system, immune system, cardiovascular system, muscular system, and endocrine system) in the hope of providing references for further understanding the pathogenesis of related diseases and bringing an innovative train of thought for reformative clinical treatment.

Dendritic cell vaccines for glioblastoma fail to complete clinical translation: Bottlenecks and potential countermeasures.

Glioblastoma (GBM) is a heterogeneous and invasive WHO grade IV brain tumor. Patients with GBM have a median overall survival (OS) of only 14 to 17 months when treated with surgical resection and chemoradiation. As one of the most promising anti-tumor immunotherapies, dendritic cell (DC) vaccines have demonstrated good efficacy, safety, and tolerability in many clinical trials. However, to date, no Phase III clinical trial has achieved positive endpoints and truly implement clinical development and transformation. Moreover, the survival benefits of DC vaccines for patients with GBM seem to have a delayed effect; therefore, we urgently require strategies to optimize DC vaccines to advance the time point of its survival benefits. Here, we discuss the latest clinical trial progress of DC vaccines in GBM and summarize the benefits and drawbacks of various vaccine design options, as well as the challenges faced in clinical translation. Moreover, we target future combination therapy strategies for DC vaccines in GBM, which provides a new perspective for comprehensively understanding the effectiveness, limitations, and new directions of the development of DC vaccines.

Global Characteristics and Trends in Research on Ferroptosis: A Data-Driven Bibliometric Study.

Ferroptosis, an iron-dependent form of regulated cell death, has drawn an increasing amount of attention since it was first mentioned in 2012 and is found to play a significant role in the treatment of certain diseases. Our study is aimed at analysing the scientific output of ferroptosis research and at driving future research into novel publications. Publications focused on ferroptosis were retrieved from the SCI-EXPANDED database of the Web of Science Core Collection and were screened according to inclusion criteria. CiteSpace V and Microsoft Excel 2016 were used to evaluate and visualize the results, including generating network maps and analysing annual publications, country, category, references and cocited references, and keywords. As of October 1, 2021, a total of 1690 original articles related to ferroptosis were included, and the overall trend of the number of publications rapidly increased. Among the common categories in the field of ferroptosis, the most common category was biochemistry and molecular biology. Worldwide, China and the United States were the leading countries for research production. The retrieved 1690 publications received 44,650 citations, with an average of 26.42 citations per paper (October 1, 2021). By citation analysis, Scott J Dixon's article in 2012 was the most symbolic reference and the earliest publication in the field of ferroptosis, with the highest citation rate (2709 times). Among the most common keywords, most were related to the mechanisms and regulatory networks of ferroptosis. Furthermore, with accumulating evidence demonstrating the role of ferroptosis in cancers and other diseases, inducing ferroptosis in clinical treatment is becoming a new research focus that should be closely monitored.

[Effects of tree species interaction, stand density, and tree size on the productivity of Larix principis-rupprechtii]. / æ ‘ç§ç›¸äº’ä½œç”¨ã€æž—åˆ†å¯†åº¦å’Œæ ‘æœ¨å¤§å°å¯¹åŽåŒ—è½å¶æ¾ç”Ÿäº§åŠ›çš„å½±å“.

Pure and mixed larch (Larix pricipis-rupprechtii) and birch (Betula platyphylla) plantations in Saihanba area were selected as test objects, with two stand density (200-340 and 880-1100 trees·hm-2) of each stand type. Based on tree size-stratified sampling approach, a total of 668 tree core samples were collected. A linear mixed model was used to analyze the effects of tree species interaction, stand density, and tree size on larch productivity. Results showed that basal area increment of larch was affected by competition, diameter at breast height, tree age, and neighborhood density to different degrees. Overyielding of larch was mainly due to the positive effect of birch on larch growth in the mixed plantation with higher stand density. For mixed plantation with lower stand density, the productivity of those two species was lower than that pure plantation because of a lack of species interaction. Intraspecific competition was the main factor influencing larch productivity. Larch productivity was positively affected by tree size, with the magnitude of tree size effect varying with stand density and species composition. Suitable enhancement of stand density and selection of birch as the mixing tree species could improve productivity of larch.

[Changes of nutrient release and enzyme activity during the decomposition of mixed leaf litter of Larix principis-rupprechtii and broadleaved tree species.] / åŽåŒ—è½å¶æ¾ä¸Žé˜”å¶æ ‘ç§æ··åˆå‡‹è½å¶åˆ†è§£è¿‡ç¨‹ä¸­å »åˆ†é‡Šæ”¾å’Œé ¶æ´»æ€§å˜åŒ–.

Litter is an important contribution to forest soil. Litter decomposition plays an important role in nutrient cycling of forest ecosystem. A field litterbag experiment was conducted to examine the dynamics of decomposition rate, nutrient release and enzyme activity during litter decomposition in the pure forests of Larix principis-rupprechtii (L) and mixed forests, including L and Betula platyphylla (B), L and Quercus mongolica (Q), as well as LBQ, in Saihanba area, Hebei Pro-vince, China. The results showed that the decomposition rate of leaf litter in L forest was significantly lower than that in mixed forests during the 720 d decomposition. The LB had the highest decomposition rate of L leaf litter. All treatments had the same change trend of nutrient contents, with the contents of N and P being increased and that of C, K and C/N being decreased. Contrast to pure leaf litter of L, leaf litter in mixed forests could promote the release of C and K, and inhibit litter N and P release. During the litter decomposition, the activities of catalase, urease and acid phosphatase increased, while that of sucrase decreased in all leaf litter of forests. The decomposition rate of leaf litter was positively correlated with the activities of catalase, urease and acid phosphatase, negatively correlated with that of sucrase. Our results showed that leaf litter mixture of L. principis-rupprechtii, B. platyphylla and Q. mongolica could enhance the litter decomposition of L. principis-rupprechtii, and that enzyme activities were closely related to litter decomposition.

Efficacy and safety of spleen aminopeptide oral lyophilized powder in ameliorating liver injury in infants and children with human cytomegalovirus infection: a single-center study in China.

BACKGROUND: Liver injury is both very common in infants and children and associated with low immune function. This study aimed to investigate the effect of spleen aminopeptide oral lyophilized powder (SAOLP) on liver injury in infants and children with human cytomegalovirus (HCMV) infection. METHODS: In this prospective observational study, 217 infants and children with both liver damage and HCMV infection who were admitted to the Department of Pediatric Gastroenterology, Children's Hospital of Nanjing Medical University between July 2018 and May 2020 were investigated. The median age of patients was 0.75 years (0.36-3.77 years), with 105 male and 112 female participants. All 217 patients received ursodeoxycholic acid (UDCA) and/or reduced glutathione (GDC) therapy. Of these 217 patients, 114 also received SAOLP. Liver function, cellular immunity levels, HCMV antibody titer, and HCMV-DNA load values were measured 1 day before treatment, and on the second and fourth week after treatment. RESULTS: After 4 weeks, patients treated with SAOLP showed median levels of serum alanine aminotransferase (ALT), total bilirubin (TB), and direct bilirubin (DB) which were significantly lower than those seen in patients who did not receive it. In addition, the percentage of CD4+ cells was significantly higher in those treated with SAOLP in comparison to those treated with UDCA and/or GDC alone. The number of positive HCMV-immunoglobin M (IgM) patients was also sharply decreased in the group receiving SAOLP. CONCLUSIONS: The addition of SAOLP to UDCA and/or GDC therapy may significantly relieve liver injury and reduce the jaundice index by enhancing immune function and anti-HCMV infection ability in infants and children.

Fennel-like nanoaggregates based on polysaccharide derivatives and their application in drug delivery.

Biodegradable polymeric nanoparticles, which hold hierarchical morphologies, are of importance for controlled drug delivery. In this work, nanoparticles with fennel-like morphology were prepared from graft copolymers of hydroxyethylcellulose and poly(p-dioxane). The effect of microstructure parameters on the morphological transition of the nano-aggregates was studied and the nanoparticles were investigated as a carrier of hydrophobic drug. The morphology and drug release property of the nanoparticles were found to be related with the degree of substitution and molecular weight of graft chain of the copolymer.