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1.
Scutellarin activates IDH1 to exert antitumor effects in hepatocellular carcinoma progression.
Cui, Z, Li, C, Liu, W, Sun, M, Deng, S, Cao, J, Yang, H, Chen, P
Cell death & disease. 2024;(4):267
Abstract
Isochlorate dehydrogenase 1 (IDH1) is an important metabolic enzyme for the production of α-ketoglutarate (α-KG), which has antitumor effects and is considered to have potential antitumor effects. The activation of IDH1 as a pathway for the development of anticancer drugs has not been attempted. We demonstrated that IDH1 can limit glycolysis in hepatocellular carcinoma (HCC) cells to activate the tumor immune microenvironment. In addition, through proteomic microarray analysis, we identified a natural small molecule, scutellarin (Scu), which activates IDH1 and inhibits the growth of HCC cells. By selectively modifying Cys297, Scu promotes IDH1 active dimer formation and increases α-KG production, leading to ubiquitination and degradation of HIF1a. The loss of HIF1a further leads to the inhibition of glycolysis in HCC cells. The activation of IDH1 by Scu can significantly increase the level of α-KG in tumor tissue, downregulate the HIF1a signaling pathway, and activate the tumor immune microenvironment in vivo. This study demonstrated the inhibitory effect of IDH1-α-KG-HIF1a on the growth of HCC cells and evaluated the inhibitory effect of Scu, the first IDH1 small molecule agonist, which provides a reference for cancer immunotherapy involving activated IDH1.
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2.
Recent insights into the physicochemical properties, bioactivities and their relationship of tea polysaccharides.
Zhang, Z, Sun, L, Chen, R, Li, Q, Lai, X, Wen, S, Cao, J, Lai, Z, Li, Z, Sun, S
Food chemistry. 2024;:137223
Abstract
Tea polysaccharides (TPS) is receiving global concern in past years due to their therapeutic effects in many diseases such as obesity and diabetes. Many publications imply that the unique physicochemical properties and bioactivities of TPS are prerequisites for its use as a biofilm, drug carrier and emulsifier. Despite numerous healthy benefits, studies on the in-deep structure-activity relationship of TPS still not well explored and explained yet. The main reasons for the research limitation are attributed mainly to the unbreakable advanced structural research technology and the formation of TPS conjugates. The present review also summarizes some similar parameters in primary structure of TPS with better bioactivities, discusses the relationships between their physicochemical properties and bioactivities, and suggests that function-specific TPS would be obtained in the future if the links between preparation methods, physicochemical properties and bioactivities of TPS could be well understood and established.
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3.
Revealing the clinical effect and biological mechanism of acupuncture in COPD: A review.
Shi, F, Cao, J, Zhou, D, Wang, X, Yang, H, Liu, T, Chen, Z, Zeng, J, Du, S, Yang, L, et al
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2024;:115926
Abstract
BACKGROUND To provide new ideas for the clinical and mechanism research of acupuncture in the treatment of chronic obstructive pulmonary disease (COPD), this study systematically reviews clinical research and the progress of basic research of acupuncture in the treatment of COPD. METHODS PubMed and Web of Science databases were searched using acupuncture and COPD as keywords in the last 10 years, and the included literature was determined according to exclusion criteria. FINDINGS Acupuncture can relieve clinical symptoms, improve exercise tolerance, anxiety, and nutritional status, as well as hemorheological changes (blood viscosity), reduce the inflammatory response, and reduce the duration and frequency of COPD in patients with COPD. Mechanistically, acupuncture inhibits M1 macrophage activity, reduces neutrophil infiltration, reduces inflammatory factor production in alveolar type II epithelial cells, inhibits mucus hypersecretion of airway epithelial cells, inhibits the development of chronic inflammation in COPD, and slows tissue structure destruction. Acupuncture may control pulmonary COPD inflammation through the vagal-cholinergic anti-inflammatory, vagal-adrenomedullary-dopamine, vagal-dual-sensory nerve fiber-pulmonary, and CNS-hypothalamus-orexin pathways. Furthermore, acupuncture can increase endogenous cortisol levels by inhibiting the HPA axis, thus improving airway antioxidant capacity and reducing airway inflammation in COPD. In conclusion, the inhibition of the chronic inflammatory response is the key mechanism of acupuncture treatment for COPD.
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4.
Technical note: High-efficient and wireless transcranial ultrasound excitation based on electromagnetic acoustic transducer.
Huang, L, Qiao, S, Ling, W, Wang, W, Feng, Q, Cao, J, Luo, Y
Medical physics. 2024;(1):662-669
Abstract
BACKGROUND The generation of transcranial ultrasound is usually based on the piezoelectric effect, so it is necessary to attach transducers around the skull. However, the skull will cause serious attenuation and scattering of ultrasound, which makes it particularly difficult for transcranial ultrasound imaging and modulation. PURPOSE In transcranial ultrasound imaging, there is significant attenuation and scattering of ultrasound waves by the skull bone. To mitigate this influence and enable precise imaging and high-efficient transcranial ultrasound for specific patients (such as stroke patients who already require craniotomy as part of their surgical care), this paper proposes to use EMAT to excite metal plates placed inside the skull based on the excellent penetration characteristics of EM waves into the skull, generating ultrasound signals, which can completely avoid the influence of skull on ultrasound transmission. METHODS Based on an efficient wireless transcranial ultrasound experimental platform, we first verified that the skull would not affect the propagation of electromagnetic waves generated by EMAT. In addition, the distribution of the transcranial sound field generated by EMAT was measured. RESULTS EMAT can generate 1.0 MHz ultrasound by wireless excitation of a 0.1 mm thick copper plate through an adult skull with a thickness of ∼1 cm, and the frequency and amplitude of the generated ultrasound are not affected by the skull. The results indicated that the electromagnetic waves successfully penetrated the skull, with a recorded strength of approximately 2 mV. We also found that the ultrasound signals generated by the EMAT probe through the skull remained unaffected, measuring around 2 mV. In addition, the measurement of the transcranial sound field distribution (80*50 mm2 ) generated by EMAT shows that compared with the traditional extracranial ultrasound generation method, the sound field distribution generated by the wireless excitation of the intracranial copper plate based on EAMT is no longer affected by the uneven and irregular skull. CONCLUSION Our experiments involved validating the penetration capabilities of electromagnetic waves utilizing the EMAT probe through a 7 (5+2) mm thick organic glass plate and a real human skull ranging from 8 to 15 mm in thickness. The efficient and wireless transcranial ultrasound excitation proposed in this paper may be possible for transcranial ultrasound imaging and therapy.
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5.
The Regulation Role of the Gut-Islets Axis in Diabetes.
Yang, S, Cao, J, Sun, C, Yuan, L
Diabetes, metabolic syndrome and obesity : targets and therapy. 2024;:1415-1423
Abstract
The gut-islets axis is an important endocrine signaling axis that regulates the function of islets by modulating the gut micro-environment and its endocrine metabolism. The discovery of intestinal hormones, such as GLP-1 and GIP, has established a preliminary link between the gut and the islet, paving the way for the development of GLP-1 receptor agonists based on the regulation theory of the gut-islets axis for diabetes treatment. This discovery has created a new paradigm for diabetes management and rapidly made the regulation theory of the gut-islets axis a focal point of research attention. Recent years, with in-depth study on gut microbiota and the discovery of intestinal-derived extracellular vesicles, the concept of gut endocrine and the regulation theory of the gut-islets axis have been further expanded and updated, offering tremendous research opportunities. The gut-islets axis refers to the complex interplay between the gut and the islet, which plays a crucial role in regulating glucose homeostasis and maintaining metabolic health. The axis involves various components, including gut microbiota, intestinal hormones, amino acids and ACE2, which contribute to the communication and coordination between the gut and the islet.
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6.
Identification and validation of serum metabolite biomarkers for endometrial cancer diagnosis.
Liu, W, Ma, J, Zhang, J, Cao, J, Hu, X, Huang, Y, Wang, R, Wu, J, Di, W, Qian, K, et al
EMBO molecular medicine. 2024;(4):988-1003
Abstract
Endometrial cancer (EC) stands as the most prevalent gynecological tumor in women worldwide. Notably, differentiation diagnosis of abnormity detected by ultrasound findings (e.g., thickened endometrium or mass in the uterine cavity) is essential and remains challenging in clinical practice. Herein, we identified a metabolic biomarker panel for differentiation diagnosis of EC using machine learning of high-performance serum metabolic fingerprints (SMFs) and validated the biological function. We first recorded the high-performance SMFs of 191 EC and 204 Non-EC subjects via particle-enhanced laser desorption/ionization mass spectrometry (PELDI-MS). Then, we achieved an area-under-the-curve (AUC) of 0.957-0.968 for EC diagnosis through machine learning of high-performance SMFs, outperforming the clinical biomarker of cancer antigen 125 (CA-125, AUC of 0.610-0.684, p < 0.05). Finally, we identified a metabolic biomarker panel of glutamine, glucose, and cholesterol linoleate with an AUC of 0.901-0.902 and validated the biological function in vitro. Therefore, our work would facilitate the development of novel diagnostic biomarkers for EC in clinics.
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7.
Lateral root primordium: Formation, influencing factors and regulation.
Hu, F, Fang, D, Zhang, W, Dong, K, Ye, Z, Cao, J
Plant physiology and biochemistry : PPB. 2024;:108429
Abstract
Roots are the primary determinants of water and nutrient uptake by plants. The structure of roots is largely determined by the repeated formation of new lateral roots (LR). A new lateral root primordium (LRP) is formed between the beginning and appearance of LR, which defines the organization and function of LR. Therefore, proper LRP morphogenesis is a crucial process for lateral root formation. The development of LRP is regulated by multiple factors, including hormone and environmental signals. Roots integrate signals and regulate growth and development. At the molecular level, many genes regulate the growth and development of root organs to ensure stable development plans, while also being influenced by various environmental factors. To gain a better understanding of the LRP formation and its influencing factors, this study summarizes previous research. The cell cycle involved in LRP formation, as well as the roles of ROS, auxin, other auxin-related plant hormones, and genetic regulation, are discussed in detail. Additionally, the effects of gravity, mechanical stress, and cell death on LRP formation are explored. Throughout the text unanswered or poorly understood questions are identified to guide future research in this area.
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8.
Structural Determination of Glucosyltransferase C by Cryo-Electron Microscopy.
Xie, Q, Cao, J, Zhang, H, Wu, H
Methods in molecular biology (Clifton, N.J.). 2024;:227-237
Abstract
Biofilm formation is a critical factor in the development of cariogenic virulence of Streptococcus mutans. S. mutans has evolved a concerted mechanism to synthesize a biofilm matrix from dietary sugars by a family of glucosyltransferases (Gtfs). Three Gtfs, GtfB, C, and D utilize sucrose to form a sticky polymer consisting of insoluble and soluble glucans, a biofilm foundation. Each Gtf possesses two distinct domains, an N-terminal enzyme catalytic domain and a C-terminal glucan binding domain. X-ray crystallographic studies have determined a three-dimensional structure of the catalytic domain of GtfC, however, the structure of the C-terminal domain and the overall structure of Gtfs are unknown. Here, we provided a protocol that will guide us to solve Gtf structures using cryo-electron microscopy (cryo-EM). Cryo-EM and X-ray crystallography are two widely used techniques for determining protein structures, and both methods have their own advantages and limitations. Additionally, we also predicted the full-length GtfC structural using AlphaFold2. Overall, the combination of AlphaFold 2 with experimental approaches offers a powerful and synergistic strategy for protein structure determination, accelerating the pace of scientific discovery and enabling new insights into the molecular basis that govern the biosynthetic activities of Gtfs, which may inform the design of more effective treatments for cariogenic biofilms and associated diseases.
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9.
Establishment and validation of a heart failure risk prediction model for elderly patients after coronary rotational atherectomy based on machine learning.
Zhang, L, Zhou, X, Cao, J
PeerJ. 2024;:e16867
Abstract
OBJECTIVE To develop and validate a heart failure risk prediction model for elderly patients after coronary rotational atherectomy based on machine learning methods. METHODS A retrospective cohort study was conducted to select 303 elderly patients with severe coronary calcification as the study subjects. According to the occurrence of postoperative heart failure, the study subjects were divided into the heart failure group (n = 53) and the non-heart failure group (n = 250). Retrospective collection of clinical data from the study subjects during hospitalization. After processing the missing values in the original data and addressing sample imbalance using Adaptive Synthetic Sampling (ADASYN) method, the final dataset consists of 502 samples: 250 negative samples (i.e., patients not suffering from heart failure) and 252 positive samples (i.e., patients with heart failure). According to a 7:3 ratio, the datasets of 502 patients were randomly divided into a training set (n = 351) and a validation set (n = 151). On the training set, logistic regression (LR), extreme gradient boosting (XGBoost), support vector machine (SVM), and lightweight gradient boosting machine (LightGBM) algorithms were used to construct heart failure risk prediction models; Evaluate model performance on the validation set by calculating the area under the receiver operating characteristic curve (ROC) curve (AUC), sensitivity, specificity, positive predictive value, negative predictive value, F1-score, and prediction accuracy. RESULT A total of 17.49% of 303 patients occured postoperative heart failure. The AUC of LR, XGBoost, SVM, and LightGBM models in the training set were 0.872, 1.000, 0.699, and 1.000, respectively. After 10 fold cross validation, the AUC was 0.863, 0.972, 0.696, and 0.963 in the training set, respectively. Among them, XGBoost had the highest AUC and better predictive performance, while SVM models had the worst performance. The XGBoost model also showed good predictive performance in the validation set (AUC = 0.972, 95% CI [0.951-0.994]). The Shapley additive explanation (SHAP) method suggested that the six characteristic variables of blood cholesterol, serum creatinine, fasting blood glucose, age, triglyceride and NT-proBNP were important positive factors for the occurrence of heart failure, and LVEF was important negative factors for the occurrence of heart failure. CONCLUSION The seven characteristic variables of blood cholesterol, blood creatinine, fasting blood glucose, NT-proBNP, age, triglyceride and LVEF are all important factors affecting the occurrence of heart failure. The prediction model of heart failure risk for elderly patients after CRA based on the XGBoost algorithm is superior to SVM, LightGBM and the traditional LR model. This model could be used to assist clinical decision-making and improve the adverse outcomes of patients after CRA.
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10.
Role of low molecular additives in the myofibrillar protein gelation: underlying mechanisms and recent applications.
Zhang, Y, Bai, G, Jin, G, Wang, Y, Wang, J, Puolanne, E, Cao, J
Critical reviews in food science and nutrition. 2024;(11):3604-3622
Abstract
Understanding mechanisms of myofibrillar protein gelation is important for development of gel-type muscle foods. The protein-protein interactions are largely responsible for the heat-induced gelation. Exogenous additives have been extensively applied to improve gelling properties of myofibrillar proteins. Research has been carried out to investigate effects of different additives on protein gelation, among which low molecular substances as one of the most abundant additives have been recently implicated in the modifications of intermolecular interactions. In this review, the processes of myosin dissociation under salt and the subsequent interaction via intermolecular forces are elaborated. The underlying mechanisms focusing on the role of low molecular additives in myofibrillar protein interactions during gelation particularly in relation to modifications of the intermolecular forces are comprehensively discussed, and six different additives i.e. metal ions, phosphates, amino acids, hydrolysates, phenols and edible oils are involved. The promoting effect of low molecular additives on protein interactions is highly attributed to the strengthened hydrophobic interactions providing explanations for improved gelation. Other intermolecular forces i.e. covalent bonds, ionic and hydrogen bonds could also be influenced depending on varieties of additives. This review can hopefully be used as a reference for the development of gel-type muscle foods in the future.