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Knowledge of tree biomass allocation is fundamental for estimating forest acclimation and carbon stock for global changes in the future. Optimal partitioning theory (OPT) and allometric partitioning theory (APT) are two major patterns of biomass allocation, and occurrences have been tested on taxonomical, ontogenetic, geographic and environmental scales, showing conflicting results and unclear ecophysiological mechanisms. Here, we examine the biomass allocation patterns of two young poplar (Populus) clones varying greatly in drought resistance under different soil water and nitrogen availabilities and the major physiological processes involved in biomass partitioning. We found that Biyu, a drought-sensitive hybrid poplar clone, had significant relations among biomass of leaf, stem and root, showing allometric partitioning. Xiaoye, a drought-tolerant poplar clone native to semi-arid areas, on the contrary, showed tightly regulated biomass allocation following optimal partitioning theory. Biyu had higher nitrate reductase activity in the fine roots, while Xiaoye had higher nitrate reductase activity in the leaves. Biochemical analyses and measurements of fluorescence and gas exchange showed that Xiaoye maintained more stable chloroplast membranes and photosystem electron flow, showing higher water use efficiency and a higher resistance to drought. A nitrogen addition could improve leaf photosynthesis and growth both in Biyu and Xiaoye seedlings under drought conditions. We concluded that the two poplar clones showed different biomass allocation patterns and suggest that the site of nitrate assimilation may play a role in biomass partitioning under varying water and nitrogen availabilities. [ABSTRACT FROM AUTHOR]

Turmeric is widely used worldwide, and there are many examples of its use in treating hepatobiliary diseases. The gut–liver axis is a bidirectional relationship between gut microorganisms and the liver that is closely related to the pathogenesis of hepatobiliary diseases. This review systematically summarizes the components of turmeric. It links the studies on turmeric affecting gut microorganisms to its effects on liver and biliary diseases to explain the potential mechanism of turmeric's regulation of the gut–liver axis. Besides, ethnopharmacology, phytochemicals, and clinical adverse events associated with turmeric have been researched. Furthermore, turmeric is a safe agent with good clinical efficacy and without apparent toxicity at a certain amount. By summarizing the influence of turmeric on the liver by regulating the gut–liver axis, especially the gut microbiota, it provides a preclinical basis for using turmeric as a safe and effective therapeutic agent for the prevention and treatment of hepatobiliary diseases based on the gut–liver axis. However, more efforts should be made to exploit its clinical application further. [ABSTRACT FROM AUTHOR]

Liver injury, the main factor in the pathogenesis of most liver diseases, is a known contributor to acute liver failure, liver fibrosis, or liver cancer. Curcuma phaeocaulis Val. (PEZ) has been broadly used in treating liver injury with satisfying therapeutic effects; however, the mechanism is still unclear. This study aimed to explore the mechanism of PEZ in ameliorating thioacetamide (TAA)-induced zebrafish liver injury based on a comprehensive method integrating network-based computational prediction and experimental validations. Ultrahigh-performance liquid chromatography-quadrupole exactive mass spectrometry/mass spectrometry (UPLC-Q-Exactive MS/MS) analysis was used to analyze components in raw and vinegar-processed PEZ (VPEZ). Network pharmacology was used to construct a compound-target network for liver injury to predict the possible biological targets of PEZ along with potential signaling pathways. TAA-induced zebrafish larvae liver injury model was established, and the anti-liver injury effect of PEZ by a series of indexes was measured, including liver phenotype analysis, histopathological analysis of liver tissues, and biochemical indexes analysis. Remarkably, the predicted pathway by network pharmacology was further validated using RT-qPCR and Western blotting analyzes in animal experiments. 40 chemical constituents derived from PEZ were identified, while 45 chemical components derived from VPEZ were identified. Based on it, 565 genes related to these identified compounds in PEZ and 1023 genes linked to liver injury were collected by network pharmacology. Critically, KEGG analysis indicated that the TLR4/MyD88/NF-κB signaling pathway was recommended as one of the main pathways related to the anti-liver injury effect of PEZ. Experimentally, PEZ could alleviate TAA-induced liver injury. Compared to the liver injury model group without any treatment, the treatment of PEZ significantly reduced the expression of both mRNA and protein targets in the TLR4/MyD88/NF-κB signaling pathway. In addition, the effect of VPEZ was more significant than that of the raw one. The raw and vinegar-processed PEZ could ameliorate TAA-induced zebrafish liver injury through TLR4/MyD88/NF-κB signaling pathway. [Display omitted] • PEZ ameliorates thioacetamide-induced zebrafish liver injury. • KEGG analysis indicates that the TLR4/MyD88/NF-κB signaling pathway is related to the anti-liver injury effect of PEZ. • PEZ significantly reduces the expression of both mRNA and protein targets in the TLR4/MyD88/NF-κB signaling pathway. • Vinegar-processed PEZ has more significant efficacy of improving TAA -induced zebrafish liver injury than the raw PEZ. [ABSTRACT FROM AUTHOR]

Background/Aims: Ketamine has been reported to exert anti-inflammatory effects on astrocytes stimulated by lipopolysaccharide (LPS) in vitro and in vivo. However, the mechanism has not been elicited clearly. The aim of this study was to investigate the effects of ketamine on TLR4 expression and NF-κB-p65 phosphorylation, as well as the production of proinflammatory cytokines in LPS challenged astrocytes. Methods: Astrocytes were stimulated with LPS (1μg/ ml) in the absence and presence of various concentrations of ketamine (10, 100, 1000μM). The concentrations of IL-1β, IL-6 and TNF-α were measured by ELISA, the expression of glial fibrillary acidic protein (GFAP) in astrocytes was detected by immunofluorescence staining, the level of phosphorylated NF-κB p65 and the expression of TLR4 were detected by western blotting. Results: LPS increased TLR4 expression and the phosphorylation of NF-κB p65 subunit as well as GFAP expression and the production of IL-1β, IL-6 and TNF-α in cultured astrocytes. Ketamine (100 and 1000 μM) reduced the expression of GFAP and the production of these proinflammatory cytokines, inhibited the expression of TLR4 and attenuated the phosphorylation of NF-κB p65 in astrocytes challenged by LPS. Conclusion: The inhibitory effects of ketamine on LPS-induced astrocytes activation and inflammation response may be mediated by suppressing NF-κB activation through reducing the expression of TLR4. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

An herbal pair is a classic form of clinical dispensing in Traditional Chinese Medicine (TCM), often used in prescriptions to enhance the effect or reduce potential side effects. It is the smallest component unit of Chinese medicine prescription and an essential bridge between Chinese medicine and prescription. Curcumae Rhizoma (called Ezhu in Chinese) is a representative TCM herb that promotes blood circulation and removes blood stasis. It has been used in Chinese medicine for thousands of years. Ezhu is generally used in clinical applications as a part of a "drug pair" to treat heartburn, stomach pain, tumour, amenorrhea and abdominal pain caused by blood stasis, qi stagnation and injury. This review aims to summarize the latest and comprehensive situation of the biological activity and clinical application of drug pairs containing Ezhu, find the law of Ezhu compatibility application, and discuss the rationalization of Ezhu drug compatibility. For Ezhu, herb pairs to provide a theoretical basis for clinical research in TCM and serve as a research foundation for developing new drugs. Using a self-built prescription database and Apriori algorithm for association rule mining. A systematic search for studies on herb pairs containing Ezhu was carried out by using the internet databases of PubMed, CNKI, Baidu Scholar, Google Scholar and Web of Science, as well as other relevant textbooks, reviews and documents (e.g. Chinese Pharmacopoeia , 2020 edition, Chinese herbal classic books and PhD and MSc theses, etc.). Among them with keywords including "Curcumae Rhizoma", "Ezhu", "herb pairs", "clinical application", etc. and their combinations. Moreover, the t-copula function was used to analyse the dose-coupling effect of five drug pairs, including Ezhu. The preliminary statistical analysis retrieved Ezhu prescriptions from self-built prescription database and internet databases. The results showed that the compatibility frequency of Ezhu with the other five Chinese medicines was high. Most of these selected herbal combinations are used to treat internal diseases. In this paper, the progress of the ethnopharmacology of Ezhu was reviewed, emphasizing the changes in bioactive components and compatibility of Chinese traditional medicine combinations such as Ezhu and Astragalus Curcuma (Sparganium stoloniferum Buch. -Ham; called Sanleng in Chinese), Ezhu and Astragali Radix (Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, Astragalus membranaceus (Fisch.) Bge.; called Huangqi in Chinese). Some other varieties, such as Ezhu and Rhizoma Chuanxiong (Ligusticum chuanxiong Hort.; called Chuanxiong in Chinese), Trionycis Carapax (Trionyx sinensis Wiegmann; called Biejia in Chinese), and Coptidis Rhizoma (Coptis chinensis Franch., Coptis deltoidea C. Y. Cheng et Hsiao, Coptis teeta Wall.; called Huanglian in Chinese), are also recorded in ancient books but rarely researched. The dose of Ezhu is strongly correlated with the amount of Sanleng, Huangqi, Biejia, Chuanxiong and Huanglian, respectively. Furthermore, there was a positive correlation between them. The bioactive components and compatibility effects of Ezhu herb pairs were studied in detail using data mining and t-copula function analysis. Ezhu and Astragalus Curcuma (Sanleng) mainly treat gynecological disorders by activating blood circulation and relieving congestion. Ezhu and Astragali Radix (Huangqi) drug pair and Ezhu and Trionycis Carapax (Biejia) drug pair are all commonly used in the clinical treatment of tumors, the former is mainly used clinically for the treatment of digestive tract-related inflammation and tumors, liver cancer and gynecological tumors, and the latter is commonly used for the treatment of malignant tumors, such as liver cancer and mammary cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Aim: Fluoroquinolones (FQs) are the cornerstone in treating drug-resistant tuberculosis (TB); the prevalence of TB among the population is diverse in different regions, understanding the relationship between resistance pattern and molecular characteristic of FQs in preextensive drug-resistant (pre-XDR) clinical isolates is limited in China. Methods: A total of 141 pre-XDR clinical isolates from different individuals stored at the National Clinical Centre were collected from the Beijing Chest Hospital, minimal inhibitory concentrations of levofloxacin (Lfx) and moxifloxacin (Mfx) as well as sequences of quinolone-resistant determining regions in gyrA and gyrB genes were examined. Results: One hundred twelve pre-XDR clinical isolates were resistant to both Lfx and Mfx, molecular analyses showed that 87.50%, 0.89%, and 6.25% of the pre-XDR clinical isolates harbored FQ resistance mutations in gyrA, gyrB, and in both. We found five amino acid mutation positions in gyrA and four in gyrB, The mutation position in gyrA included codons 94, 91, 90, 88, and 74, and in gyrB included codons 504, 500, 512, and 501. Codon 94 of gyrA was the most prevalent mutation (83.04%), containing the Asp amino acid substitution with Gly (50.89%), Asn (15.17%), Ala (8.93%), Tyr (6.25%), and His (1.79%). Conclusions: The mutations of gyrA were most common and the frequency of Asp94Gly was the highest in pre-XDR clinical isolates in Beijing, China. The mutations at codon 94 significantly contributed to the resistance to both Lfx and Mfx in pre-XDR clinical isolates and may cause a high resistance level. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this study was to observe the effect of N-acetylcysteine (NAC) on oxidative stress (OS), intracellular Mycobacterium tuberculosis (MTB) load, apoptosis, and autophagy of macrophages infected with H37Rv MTB. In addition, we explored the possible mechanism of action, to provide a rationale for the use of NAC in the treatment of tuberculosis., Methodology: We divided THP-1 macrophages into four groups: control, control + NAC, H37Rv, and H37Rv + NAC. OS, apoptosis, autophagy and intracellular MTB colony-forming unit (CFU) indexes were measured at 0, 4, 24, and 48 hours, respectively. Then, various indicator changes were systematically compared., Results: The levels of reactive oxygen species (ROS), malondialdehyde (MDA), apoptosis rate, and LC3II/ β-actin ratio in the H37Rv group increased at 4 hours and reached their peak at 48 hours. The ROS and MDA in the H37Rv + NAC group were lower than those in the H37Rv group. CFU in the H37Rv + NAC group increased at 24 hours and decreased at 48 hours after treatment with NAC, relative to the H37Rv group. In addition, the H37Rv + NAC group showed a decrease in LC3II/β-actin ratio 48 hours after NAC treatment, compared to the H37Rv group., Conclusions: MTB infection can lead to an increase in macrophage OS, apoptosis, and autophagy levels. However, after treatment with NAC, the growth of MTB in macrophages is inhibited, and OS and autophagy levels are reduced. The antioxidant effect and inhibitory effect of NAC on MTB are related to MTB-mediated macrophage OS and autophagy., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2024 Renchun Su, Min Qiao, Tianhui Gao, Jingtao Gao, Lihui Nie, Shanshan Li, Yufeng Wang, Yu Pang, Qi Li.)

Lung cancer remains the tumor with the highest global incidence and mortality rates. Current primary treatment modalities encompass targeted therapy, immunotherapy, and chemotherapy; however, a subset of patients derives no benefit from these interventions. Recently, the HER2-targeting antibody drug Disitamab vedotin (RC48) was approved and introduced primarily for gastric and bladder cancers, with minimal investigation in the field of lung cancer. This study demonstrates that FOXA1 directly binds to the promoter region of HER2, influencing the HER2/PI3K/AKT signaling pathway, which consequently modulates factors that foster lung cancer proliferation and impede apoptosis. Unlike FOXA1, HER2 does not influence the expression of FOXA1. Intriguingly, in lung cancer cells, RC48 not only impacts the HER2/PI3K/AKT pathway but also affects the FOXA1/HER2/PI3K/AKT pathway, thereby exerting a robust antitumor effect. In clinical specimens, heightened expressions of FOXA1 and HER2 correlate positively with clinical progression and poorer prognosis. These findings suggest that FOXA1 may serve as a potential biomarker or therapeutic target in future non-small cell lung cancer (NSCLC) treatments, and ongoing research may position RC48 as a transformative agent in lung cancer therapy., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Esophageal cancer-related gene 4 (ECRG4) is a tumor suppressor gene associated with the prognosis of esophageal squamous-cell carcinoma (ESCC). Studies have reported that ECRG4 effectively inhibits the proliferation, migration and invasion of ESCC cells. In the current study, ectopic expression of ECRG4 significantly induced ESCC cell apoptosis. To further understand the molecular profile of ECRG4 overexpression in ESCC cells, tandem mass tag (TMT) labeling followed by LC-MS/MS analysis was applied on samples from ECRG4 overexpressed cells and control cells. Among the identified differentially expressed proteins, four up-regulated proteins (PLK1, CDK4, PLOD1 and PLOD2) associated with cell apoptosis, cell cycle and metastasis were chosen for the further investigation. The effects of ECRG4 protein levels on the expression of these four proteins were validated by manipulating the expression of ECRG4 in ESCC cells followed by Western blotting analysis. The immunohistochemical staining results showed a significant decrease in ECRG4 levels and a notable increase in the four proteins in ESCC samples as compared to matched esophageal tissues (n=75). More importantly, the protein levels of ECRG4 had a negative association with those of PLK1, CDK4, PLOD1 and PLOD2. Thus, our data suggested that the tumor-repressor functions of ECRG4 may be associated with PLK1, CDK4, PLOD1 and PLOD2, providing important insights into the molecular mechanisms of esophageal carcinogenesis., Competing Interests: None.

Objective: To evaluate the prognosis and predictive values of preoperative Glasgow prognostic score (GPS) for adenocarcinoma of esophagogastric junction(AEG) patients., Methods: A retrospective study of 322 AEG patients who received operation between January 2007 and March 2010 in Henan Provincial People's Hospital was performed. Clinical data, pathological characteristics, laboratory parameters and survival data were collected. The GPS was calculated based on C-reactive protein(CRP) and serum albumin(ALB) levels. Univariate and multivariate analysis were used to evaluate the prognostic value of GPS., Results: Among 322 patients, 0, 1, 2 of GPS were 192, 104 and 26 patients respectively. The median follow-up was 37 (4-73) months. In Kaplan-Meier analysis, median diseases-free survival (DFS) of GPS 0, 1, 2 was 47.0 (95% CI: 31.6-62.4), 15.0 (95% CI: 11.8-8.2) and 4.7 (95% CI: 3.8-5.6) months (P<0.01), and median overall survival (OS) was out of reach, 20.6 (95% CI: 15.8-25.4) and 7.0 (95% CI: 5.8-8.2) months (P<0.01). Univariate and multivariate analysis revealed that GPS was an independent predictor of DFS (P<0.01) and OS (P<0.01) of AEG., Conclusion: GPS is an effective predictor of survival in AEG.

Background/aims: Ketamine has been reported to exert anti-inflammatory effects on astrocytes stimulated by lipopolysaccharide (LPS) in vitro and in vivo. However, the mechanism has not been elicited clearly. The aim of this study was to investigate the effects of ketamine on TLR4 expression and NF-ĸB-p65 phosphorylation, as well as the production of proinflammatory cytokines in LPS challenged astrocytes., Methods: Astrocytes were stimulated with LPS (1µg/ ml) in the absence and presence of various concentrations of ketamine (10, 100, 1000µM). The concentrations of IL-1β, IL-6 and TNF-α were measured by ELISA, the expression of glial fibrillary acidic protein (GFAP) in astrocytes was detected by immunofluorescence staining, the level of phosphorylated NF-ĸB p65 and the expression of TLR4 were detected by western blotting., Results: LPS increased TLR4 expression and the phosphorylation of NF-ĸB p65 subunit as well as GFAP expression and the production of IL-1β, IL-6 and TNF-α in cultured astrocytes. Ketamine (100 and 1000 µM) reduced the expression of GFAP and the production of these proinflammatory cytokines, inhibited the expression of TLR4 and attenuated the phosphorylation of NF-ĸB p65 in astrocytes challenged by LPS., Conclusion: The inhibitory effects of ketamine on LPS-induced astrocytes activation and inflammation response may be mediated by suppressing NF-ĸB activation through reducing the expression of TLR4., (Copyright © 2012 S. Karger AG, Basel.)