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Targeting autophagy with natural products as a potential therapeutic approach for diabetic microangiopathy.
Liu, F, Zhao, L, Wu, T, Yu, W, Li, J, Wang, W, Huang, C, Diao, Z, Xu, Y
Frontiers in pharmacology. 2024;:1364616
Abstract
As the quality of life improves, the incidence of diabetes mellitus and its microvascular complications (DMC) continues to increase, posing a threat to people's health and wellbeing. Given the limitations of existing treatment, there is an urgent need for novel approaches to prevent and treat DMC. Autophagy, a pivotal mechanism governing metabolic regulation in organisms, facilitates the removal of dysfunctional proteins and organelles, thereby sustaining cellular homeostasis and energy generation. Anomalous states in pancreatic β-cells, podocytes, Müller cells, cardiomyocytes, and Schwann cells in DMC are closely linked to autophagic dysregulation. Natural products have the property of being multi-targeted and can affect autophagy and hence DMC progression in terms of nutrient perception, oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis. This review consolidates recent advancements in understanding DMC pathogenesis via autophagy and proposes novel perspectives on treating DMC by either stimulating or inhibiting autophagy using natural products.
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Curcumae Radix: A Review of Traditional Use, Phytochemistry, Pharmacology, Toxicology and Quality Control.
Niu, YT, Xu, HN, Zhang, YY, Li, XZ, Li, YZ, Song, XM, Zhang, DD, Wang, W
Chemistry & biodiversity. 2024;:e202400098
Abstract
Curcumae Radix (CuR) is a traditional Chinese medicine that has been used in China for more than 1,000 years. It has the traditional efficacy of activating blood and relieving pain, promoting qi and relieving depression, clearing heart and cooling blood, and promoting gallbladder and removing jaundice. Based on this, many domestic and foreign scholars have conducted systematic studies on its chemical composition, pharmacological effects, toxicity and quality control. Currently, 250 compounds, mainly including terpenoids and curcuminoids, have been isolated and identified from CuR, which has pharmacological activities, including antitumor, anti-inflammatory and analgesic, antidepressant, hepatoprotective, hemostatic, hematopoietic, and treatment of diabetes mellitus. In modern clinical practice, CuR is widely used in the treatment of tumors, breast hyperplasia, hepatitis, and stroke. However, the generation of toxicity and clinical application of CuR and Caryophylli Flos, the determination of the concoction process of artifacts, the determination of specific Quality Marker, and the establishment of the quality control system of CuR, are problems that need to be solved urgently at present.
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Targeted intervention of natural medicinal active ingredients and traditional Chinese medicine on epigenetic modification: Possible strategies for prevention and treatment of atherosclerosis.
Wang, W, Li, H, Shi, Y, Zhou, J, Khan, GJ, Zhu, J, Liu, F, Duan, H, Li, L, Zhai, K
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2024;:155139
Abstract
BACKGROUND Atherosclerosis is a deadly consequence of cardiovascular disease and has very high mortality rate worldwide. The epigenetic modifications can regulate the pervasiveness and progression of atherosclerosis through its involvement in regulation of inflammation, oxidative stress, lipid metabolism and several other factors. Specific non-coding RNAs, DNA methylation, and histone modifications are key regulatory factors of atherosclerosis. Natural products from traditional Chinese medicine have shown promising therapeutic potential against atherosclerosis by means of regulating the expression of specific genes, stabilizing arterial plaques and protecting vascular endothelial cells. OBJECTIVE Our study is focusing to explore the pathophysiology and probability of traditional Chinese medicine and natural medicinal active ingredients to treat atherosclerosis. METHODS Comprehensive literature review was conducted using PubMed, Web of Science, Google Scholar and China National Knowledge Infrastructure with a core focus on natural medicinal active ingredients and traditional Chinese medicine prying in epigenetic modification related to atherosclerosis. RESULTS Accumulated evidence demonstrated that natural medicinal active ingredients and traditional Chinese medicine have been widely studied as substances that can regulate epigenetic modification. They can participate in the occurrence and development of atherosclerosis through inflammation, oxidative stress, lipid metabolism, cell proliferation and migration, macrophage polarization and autophagy respectively. CONCLUSION The function of natural medicinal active ingredients and traditional Chinese medicine in regulating epigenetic modification may provide a new potential strategy for the prevention and treatment of atherosclerosis. However, more extensive research is essential to determine the potential of these natural medicinal active ingredients to treat atherosclerosis because of least clinical data.
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Identifying Potential Causal Effects of Telomere Length on Health Outcomes: A Phenome-Wide Investigation and Mendelian Randomization Study.
Wang, W, Huang, N, Zhuang, Z, Song, Z, Li, Y, Dong, X, Xiao, W, Zhao, Y, Jia, J, Liu, Z, et al
The journals of gerontology. Series A, Biological sciences and medical sciences. 2024;(1)
Abstract
BACKGROUND Telomere length has been linked to various health outcomes. To comprehensively investigate the causal effects of telomere length throughout the human disease spectrum, we conducted a phenome-wide Mendelian randomization study (MR-PheWAS) and a systematic review of MR studies. METHODS We conducted a PheWAS to screen for associations between telomere length and 1 035 phenotypes in the UK Biobank (n = 408 354). The exposure of interest was the genetic risk score (GRS) of telomere length. Observed associations passing multiple testing corrections were assessed for causality by 2-sample MR analysis. A systematic review of MR studies on telomere length was performed to harmonize the published evidence and complement our findings. RESULTS Of the 1 035 phenotypes tested, PheWAS identified 29 and 78 associations of telomere length GRS at a Bonferroni- and false discovery rate-corrected threshold; 24 and 66 distinct health outcomes were causal in the following principal MR analysis. The replication MR using data from the FinnGen study provided evidence of causal effects of genetically instrumented telomere length on 28 out of 66 outcomes, including decreased risks of 5 diseases in respiratory diseases, digestive diseases, and myocardial infarction, and increased risks of 23 diseases, mainly comprised neoplasms, diseases of the genitourinary system, and essential hypertension. A systematic review of 53 MR studies found evidence to support 16 out of the 66 outcomes. CONCLUSIONS This large-scale MR-PheWAS identified a wide range of health outcomes that were possibly affected by telomere length, and suggested that susceptibility to telomere length may vary across disease categories.
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SIRT1 is a regulator of autophagy: Implications for the progression and treatment of myocardial ischemia-reperfusion.
Ding, X, Zhu, C, Wang, W, Li, M, Ma, C, Gao, B
Pharmacological research. 2024;:106957
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Abstract
SIRT1 is a highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase. It is involved in the regulation of various pathophysiological processes, including cell proliferation, survival, differentiation, autophagy, and oxidative stress. Therapeutic activation of SIRT1 protects the heart and cardiomyocytes from pathology-related stress, particularly myocardial ischemia/reperfusion (I/R). Autophagy is an important metabolic pathway for cell survival during energy or nutrient deficiency, hypoxia, or oxidative stress. Autophagy is a double-edged sword in myocardial I/R injury. The activation of autophagy during the ischemic phase removes excess metabolic waste and helps ensure cardiomyocyte survival, whereas excessive autophagy during reperfusion depletes the cellular components and leads to autophagic cell death. Increasing research on I/R injury has indicated that SIRT1 is involved in the process of autophagy and regulates myocardial I/R. SIRT1 regulates autophagy through various pathways, such as the deacetylation of FOXOs, ATGs, and LC3. Recent studies have confirmed that SIRT1-mediated autophagy plays different roles at different stages of myocardial I/R injury. By targeting the mechanism of SIRT1-mediated autophagy at different stages of I/R injury, new small-molecule drugs, miRNA activators, or blockers can be developed. For example, resveratrol, sevoflurane, quercetin, and melatonin in the ischemic stage, coptisine, curcumin, berberine, and some miRNAs during reperfusion, were involved in regulating the SIRT1-autophagy axis, exerting a cardioprotective effect. Here, we summarize the possible mechanisms of autophagy regulation by SIRT1 in myocardial I/R injury and the related molecular drug applications to identify strategies for treating myocardial I/R injury.
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Mood and microbes: a comprehensive review of intestinal microbiota's impact on depression.
Luqman, A, He, M, Hassan, A, Ullah, M, Zhang, L, Rashid Khan, M, Din, AU, Ullah, K, Wang, W, Wang, G
Frontiers in psychiatry. 2024;:1295766
Abstract
Depression is considered a multifaceted and intricate mental disorder of growing concern due to its significant impact on global health issues. The human gut microbiota, also known as the "second brain," has an important role in the CNS by regulating it through chemical, immunological, hormonal, and neurological processes. Various studies have found a significant bidirectional link between the brain and the gut, emphasizing the onset of depression therapies. The biological and molecular processes underlying depression and microbiota are required, as the bidirectional association may represent a novel study. However, profound insights into the stratification and diversity of the gut microbiota are still uncommon. This article investigates the emerging evidence of a bacterial relationship between the gut and the brain's neurological system and its potential pathogenicity and relevance. The interplay of microbiota, immune system, nervous system neurotransmitter synthesis, and neuroplasticity transitions is also widely studied. The consequences of stress, dietary fibers, probiotics, prebiotics, and antibiotics on the GB axis are being studied. Multiple studies revealed the processes underlying this axis and led to the development of effective microbiota-based drugs for both prevention and treatment. Therefore, the results support the hypothesis that gut microbiota influences depression and provide a promising area of research for an improved knowledge of the etiology of the disease and future therapies.
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Phellinus linteus polysaccharides: A review on their preparation, structure-activity relationships, and drug delivery systems.
Kou, F, Mei, Y, Wang, W, Wei, X, Xiao, H, Wu, X
International journal of biological macromolecules. 2024;(Pt 1):128702
Abstract
Phellinus linteus polysaccharides exhibit antitumor, immunomodulatory, anti-inflammatory, and antioxidant properties, mitigate insulin resistance, and enhance the diversity and abundance of gut microbiota. However, the bioactivities of P. linteus polysaccharides vary owing to the complex structure, thereby, limiting their application. Various processing strategies have been employed to modify them for improving the functional properties and yield. Herein, we compare the primary modes of extraction and purification employed to improve the yield and purity, review the structure-activity relationships, and discuss the application of P. linteus polysaccharides using nano-carriers for the encapsulation and delivery of various drugs to improve bioactivity. The limitations and future perspectives are also discussed. Exploring the bioactivity, structure-activity relationship, processing methods, and delivery routes of P. linteus polysaccharides will facilitate the development of functional foods and dietary supplements rich in P. linteus polysaccharides.
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Machine learning identifies the risk of complications after laparoscopic radical gastrectomy for gastric cancer.
Hong, QQ, Yan, S, Zhao, YL, Fan, L, Yang, L, Zhang, WB, Liu, H, Lin, HX, Zhang, J, Ye, ZJ, et al
World journal of gastroenterology. 2024;(1):79-90
Abstract
BACKGROUND Laparoscopic radical gastrectomy is widely used, and perioperative complications have become a highly concerned issue. AIM: To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery, guide perioperative treatment strategies for gastric cancer patients, and prevent serious complications. METHODS In total, 998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model, and 398 patients were included in the validation group. The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected. Three machine learning methods, lasso regression, random forest, and artificial neural networks, were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy, and their prediction efficacy and accuracy were evaluated. RESULTS The constructed complication model, particularly the random forest model, could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy. It exhibited stable performance in external validation and is worthy of further promotion in more centers. CONCLUSION Using the risk factors identified in multicenter datasets, highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established. We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.
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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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Genus Helleborus: a comprehensive review of phytochemistry, pharmacology and clinical applications.
Li, S, Chen, X, Tang, J, Zhang, D, Jiang, Y, Zhang, H, Song, X, Wang, W, Li, Y
Natural product research. 2024;:1-17
Abstract
The genus Helleborus belongs to the Ranunculaceae family, distributed in southeastern Europe and western Asia. In folk medicine, it is commonly used as an anti-inflammatory and analgesic medicine for rheumatoid arthritis and bruises. Through reviewing recent articles, it was found that two hundred and twenty-six compounds have been isolated and identified from the genus Helleborus. These compounds include steroids, flavonoids, phenylpropanoids, lignans, anthraquinones, phenolics and others. Among them, the main chemical constituents are steroids. Pharmacological studies show Helleborus has anti-cancer, immunomodulatory, anti-inflammatory, analgesic, anti-hyperglycaemic, antioxidant and antibacterial properties. This article reviews the botany, phytochemistry, pharmacological effects and clinical applications of the genus Helleborus. Hopefully, it will provide a reference for in-depth research and exploitation of the genus Helleborus.