MG53/TRIM72: multi-organ repair protein and beyond.

MG53, a member of the tripartite motif protein family, possesses multiple functionalities due to its classic membrane repair function, anti-inflammatory ability, and E3 ubiquitin ligase properties. Initially recognized for its crucial role in membrane repair, the therapeutic potential of MG53 has been extensively explored in various diseases including muscle injury, myocardial damage, acute lung injury, and acute kidney injury. However, further research has revealed that the E3 ubiquitin ligase characteristics of MG53 also contribute to the pathogenesis of certain conditions such as diabetic cardiomyopathy, insulin resistance, and metabolic syndrome. Moreover, recent studies have highlighted the anti-tumor effects of MG53 in different types of cancer, such as small cell lung cancer, liver cancer, and colorectal cancer; these effects are closely associated with their E3 ubiquitin ligase activities. In summary, MG53 is a multifunctional protein that participates in important physiological and pathological processes of multiple organs and is a promising therapeutic target for various human diseases. MG53 plays a multi-organ protective role due to its membrane repair function and its exertion of anti-tumor effects due to its E3 ubiquitin ligase properties. In addition, the controversial aspect of MG53's E3 ubiquitin ligase properties potentially causing insulin resistance and metabolic syndrome necessitates further cross-validation for clarity.

Cancer cachexia: Focus on cachexia factors and inter-organ communication.

ABSTRACT: Cancer cachexia is a multi-organ syndrome and closely related to changes in signal communication between organs, which is mediated by cancer cachexia factors. Cancer cachexia factors, being the general name of inflammatory factors, circulating proteins, metabolites, and microRNA secreted by tumor or host cells, play a role in secretory or other organs and mediate complex signal communication between organs during cancer cachexia. Cancer cachexia factors are also a potential target for the diagnosis and treatment. The pathogenesis of cachexia is unclear and no clear effective treatment is available. Thus, the treatment of cancer cachexia from the perspective of the tumor ecosystem rather than from the perspective of a single molecule and a single organ is urgently needed. From the point of signal communication between organs mediated by cancer cachexia factors, finding a deeper understanding of the pathogenesis, diagnosis, and treatment of cancer cachexia is of great significance to improve the level of diagnosis and treatment. This review begins with cancer cachexia factors released during the interaction between tumor and host cells, and provides a comprehensive summary of the pathogenesis, diagnosis, and treatment for cancer cachexia, along with a particular sight on multi-organ signal communication mediated by cancer cachexia factors. This summary aims to deepen medical community's understanding of cancer cachexia and may conduce to the discovery of new diagnostic and therapeutic targets for cancer cachexia.

Collagen code in tumor microenvironment: Functions, molecular mechanisms, and therapeutic implications.

The tumor microenvironment (TME) is crucial in cancer progression, and the extracellular matrix (ECM) is an important TME component. Collagen is a major ECM component that contributes to tumor cell infiltration, expansion, and distant metastasis during cancer progression. Recent studies reported that collagen is deposited in the TME to form a collagen wall along which tumor cells can infiltrate and prevent drugs from working on the tumor cells. Collagen-tumor cell interaction is complex and requires the activation of multiple signaling pathways for biochemical and mechanical signaling interventions. In this review, we examine the effect of collagen deposition in the TME on tumor progression and discuss the interaction between collagen and tumor cells. This review aims to illustrate the functions and mechanisms of collagen in tumor progression in the TME and its role in tumor therapy. The findings indicated collagen in the TME appears to be a better target for cancer therapy.

A research on the expression of Nucb2/ cAMP / PKA in the hippocampus of alcohol-dependent rats.

To probe into the expression of Nucb2/cAMP/PKA signaling in the hippocampus of alcohol-dependent rats. Male SD rats were first divided into control (n = 8) and model groups (n = 8) at random. Subsequently, alcohol dependence model was prepared by double bottles of intermittent drinking 20% alcohol. Apart from that, the changes of body weight, alcohol intake and alcohol preference were recorded during the modeling period; the behavioral changes of rats were recorded by elevated plus maze and water maze; Followed by model establishment, qRT-PCR was being applied to detect mRNA levels and protein expression levels of nucleobindin-2 (Nucb2), adenylate cyclase (AC), cAMP-dependent protein kinase A (PKA) and cAMP-responsive element binding protein (CREB) etc. There was no remarkable distinction between the weight of rats in both control and model groups throughout the experiment (P＞0.05); after the alcohol consumption of rats in the drinking group exceeded 28d, the alcohol intake finally reached the plateau (16.65 ± 1.31) g/(kg.24 h). What's more, the alcohol preference (61.77 ± 2.81) % reached the stable baseline, which means that the rat alcohol dependence model was established; in comparison with those of the control group (P < 0.01), the number of open arm entries and the retention time of open arm in the model group were remarkably decreased in the elevated plus maze assay; in the water maze assay, the memory ability of the model group was reduced in comparison with the control group (P < 0.05); In comparison with the control group, the relative expression levels of Nucb2, AC, PKA and CREB were noticeably decreased in the model group. Nucb2 is not only bound up with alcohol dependence,but also may conduct a pivotal role in alcohol dependence by regulating the cAMP/PKA signaling pathway.

Targeting cancer cachexia: Molecular mechanisms and clinical study.

Cancer cachexia is a complex systemic catabolism syndrome characterized by muscle wasting. It affects multiple distant organs and their crosstalk with cancer constitute cancer cachexia environment. During the occurrence and progression of cancer cachexia, interactions of aberrant organs with cancer cells or other organs in a cancer cachexia environment initiate a cascade of stress reactions and destroy multiple organs including the liver, heart, pancreas, intestine, brain, bone, and spleen in metabolism, neural, and immune homeostasis. The role of involved organs turned from inhibiting tumor growth into promoting cancer cachexia in cancer progression. In this review, we depicted the complicated relationship of cancer cachexia with the metabolism, neural, and immune homeostasis imbalance in multiple organs in a cancer cachexia environment and summarized the treatment progress in recent years. And we discussed the molecular mechanism and clinical study of cancer cachexia from the perspective of multiple organs metabolic, neurological, and immunological abnormalities. Updated understanding of cancer cachexia might facilitate the exploration of biomarkers and novel therapeutic targets of cancer cachexia.

Brain Magnetic Resonance Imaging Features of Nicotine-Dependent Individuals and Its Correlation with Polymorphisms of Dopamine D Receptor Gene.

The aim of this research was developed to provide a scientific basis for individualized prevention, clinical diagnosis, and corrective treatment of nicotine addiction. The objects were 214 cases in the smoke group and 43 cases in the control group. According to the Fagerstrom Nicotine Dependence Test (FTND), the smokers were divided into mild nicotine dependence group (FTND < 6 points, 138 cases) and nicotine severe dependence group (≥6 points, 76 cases). The brain structure in long-term smokers was evaluated by using magnetic resonance imaging (MRI). The nicotine dependence was further analyzed by grouping the included individuals, and some candidate genes related to nicotine addiction were screened by combining with bioinformatics analysis. The family research strategy was adopted to detect nicotine addiction susceptibility genes and their polymorphisms. The MRI imaging results showed that the bilateral thalamus, right parietal, and left lens gram-molecule volume (GMV) were negatively correlated with smoking index and smoking years in the smoking group. The GMV of the posterior cingulate cortex in the severe nicotine dependence group was lower than that of the control group, and the GMVs of bilateral thalamus and bilateral superior limbic gyrus in the mild nicotine dependence group were lower than those of the control group. The gene polymorphism detection showed that rs6275 was highly polymorphic in the target population and the frequency of rs6275-C allele was 53.26%. Therefore, the MRI imaging characteristics suggested that the affected brain regions of smokers and people with varying degrees of nicotine dependence were mainly concentrated in response-related pathways and the limbic system and had cumulative effects on the central nervous system. In addition, the M6275 polymorphism of DRD2 gene was associated with susceptibility to nicotine addiction in Chinese population, and the M6275-C allele had a protective effect on susceptibility to nicotine addiction and smoking initiation.

Optimization of Lithium Metaborate Fusion and Post-ultrasonic Extraction for Multi-element Determination in Graphite by ICP-AES.

Existing methods can not achieve rapid mass decomposition and multi-element analysis of graphite ore samples. In this study, it is found that molten lithium metaborate can destroy the structure of graphite, causing graphite C to be oxidized and decomposed in an oxygen environment. We have established a method for testing graphite ore samples with lithium metaborate at 950°C with melting-ultrasonic extraction-ICP-AES multi-element (Al, Ca, Fe, K, Mg, Mn, Na, P, Si, and Ti) testing. The verification results of the national first-level reference materials show that the detection limit of this method is low and the accuracy and precision are good. The results of the measured samples show no significant difference between this method and the classical chemical analysis method. This method has the following advantages over the existing ones: simple operation process, faster decomposition and testing, low reagent consumption, reduced possibility of sample contamination, and better results reproducibility.

The miR-203a Regulatory Network Affects the Proliferation of Chronic Myeloid Leukemia K562 Cells.

To study the molecular mechanism by which miR-203a affects the development of CML, bioinformatics software was used to predict the upstream transcription factors and downstream target genes of miR-203a. A 5'-rapid amplification of cDNA ends assay was performed to detect gene transcription initiation sites. A chromatin immunoprecipitation assay was used to verify the binding of transcription factors and promoter regions. A double luciferase reporter gene vector was constructed to demonstrate the regulatory effect of miR-203a on target genes. Real-time PCR and western blotting were used to detect the relative expression levels of genes and proteins, respectively. The results showed that there was a binding site for the transcription factor EGR1 in the upstream promoter region of miR-203a. WT1, BMI1, and XIAP were identified as target genes regulated by miR-203a. EGR1 and miR-203a were downregulated in human peripheral blood mononuclear cells and the CML K562 cell line, while WT1, BMI1, and XIAP were upregulated. The transcription initiation site of miR-203a was identified in the upstream promoter region (G nucleotide at -339 bp), and the transcription factor EGR1 could bind to the promoter region (at -268 bp) of miR-203a and increase its expression. Over expression of miR-203a inhibited the proliferation of K562 cells. A rescue assay showed that overexpression of WT1, BMI1, and XIAP offset the antitumor effect of miR-203a. Conclusion, EGR1 positively regulated the expression of miR-203a, thus relieving the inhibition of miR-203a on the translation of its target genes (WT1, BMI1, and XIAP) and affecting the proliferation of K562 cells.

Recognition of typical antibiotic residues in environmental media related to groundwater in China (2009-2019).

The potential adverse environmental and health-related impacts of antibiotics are becoming more and more concerning. China is globally the largest antibiotic producer and consumer, possibly resulting in the ubiquity and high detection levels of antibiotics in environmental compartments. Clear status on the concentration levels and spatial distribution of antibiotic contamination in China's environment is necessary to gain insight into the establishment of legal and regulatory frameworks. This study collects information from over 170 papers reporting the occurrence and distribution of antibiotics in China's environment. A total of 110 antibiotics were detected, and 28 priority antibiotics were ubiquitous in China in almost all compartments of the environment, excluding the atmosphere. Seven dominant antibiotics in all environment compartments were identified by cluster analysis, including tetracycline, oxytetracycline, chlortetracycline, ofloxacin, enrofloxacin, norfloxacin, and ciprofloxacin. Meanwhile, sulfamethoxazole, sulfadiazine, and sulfamethazine were also frequently found in aqueous phases. Among the main basins where antibiotics were detected, the Haihe River Basin had higher median antibiotic concentrations in surface water compared to other basins, while the Huaihe River Basin had higher median concentrations in sediment. The median values of antibiotic concentrations in the sources were as follows: animal manure, 39 µg/kg (microgram per kilogram); WWTP (wastewater treatment plant) sludge, 39 µg/kg; animal wastewater, 156 ng/L (nanogram per liter); WWTP effluent: 15 ng/L. These concentrations are 1 - 2 orders of magnitude higher than that of the receptors (soil, 2.1 µg/kg; sediment, 4.7 µg/kg; surface water, 8.1 ng/L; groundwater, 2.9 ng/L), whether in solid or aqueous phases. Based on the number of detected antibiotics in various environmental compartments, animal farms and WWTPs are the main sources of antibiotics, and surface water and sediment are the main receptors of antibiotics. Hierarchical clustering identified the two main pathways of antibiotic transfer in various environmental compartments, which are from animal wastewater/WWTP effluent to surface water/sediment and from animal manure/WWTP sludge to soil/groundwater.

[Pollution characteristics and ecological risk assessment of heavy metals in the surface sediments of the Yangtze River].

The concentrations of Cr, Co, Ni, Cu, Zn, Pb, Cd, As and Hg in surface sediment samples of Yangtze River collected in 2007 were analyzed and evaluated. The results indicated that the concentrations of Cu, Zn, Pb, Cd, As and Hg were significantly higher than those measured in 1990s. Principal component analysis showed that the cumulative proportion of the first three components accounted for 86.75% of the total variable, indicating the three major sources of heavy metals were industrial and mining wastewater, weathering and erosion of rocks, and urban electroplating industry wastewater and natural sources. Geoaccumulation index (Igeo) and enrichment factors (EF) also showed that the surface sediments of the Yangtze River were not contaminated with Cr, Co and Ni, lightly contaminated with Cu, Zn, As and Hg, and majorly contaminated with Ph and Cd. The ecological hazards for the heavy metals in the sediments were evaluated with the Hakanson ecological risk index. It was concluded the ecological hazards for each metal in a descending order were Cd > Hg > As > Zn > Pb > Cu > Co > Ni > Cr. The comprehensive index of potential ecological risks for metals indicated that 36% of the 61 sites had moderate potential ecological risks. Three sites had a high potential ecological risk, namely, Chongqing site of the main Yangtze River, Zishui Dongting Lake and Xinjiang site, whereas Xiangjiang Hengyang section, Xiangjiang Zhuzhou section, Xiangjiang Dongting Lake entrance, Dongting Lake and Shunan River belonged to the areas with extremely high potential ecological risk.

Analysis and evaluation of the source of heavy metals in water of the River Changjiang.

In order to analyze and evaluate different trace metals on surface water of the Changjiang River, concentrations of dissolved trace metals (Cu, Ni, Fe, Co, Sc, Al, Zn, Pb, Cd, Se, As, Cr, and Hg), major elements (Ca and Mg), and nutrient (NO3- were measured. Samples were taken at 76 positions along Changjiang River in flood and dry seasons during 2007-2008. Spatial distributions identified two main large zones mainly influenced by mineral erosion (sites 1-22) and anthropogenic action (sites 23-76), respectively. Principal component analysis (PCA) and hierarchical cluster analysis were used to identify the variance distinguishing the origin of water. Four significant components were extracted by PCA, explaining 74.91% of total variable. Cu, Ni, Fe, Co, Sc, Al, Ca, and Mg were mainly associated with the weathering and erosion of various rocks and minerals, while an anthropogenic source was identified for Cd and As. Although erosion was one source of Pb and Zn, they were also input by atmospheric deposition and industrial pollutions. NO3- and Se were mainly associated with agriculture activities. However, Hg and Cr showed different sources. CA confirmed and completed the results obtained by PCA, classifying the data into two large groups representing different areas. Group 1 referred to the upper reaches which represented samples mainly corresponding to natural background areas. Group 2 referred to the middle and lower reaches including samples under anthropogenic influence. Meanwhile, group 2 was subdivided into three new groups, representing agricultural, industrial, and various artificial pollution sources, respectively.