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Gut microbiota and its therapeutic implications in tumor microenvironment interactions.
Feng, P, Xue, X, Bukhari, I, Qiu, C, Li, Y, Zheng, P, Mi, Y
Frontiers in microbiology. 2024;:1287077
Abstract
The development of cancer is not just the growth and proliferation of a single transformed cell, but its tumor microenvironment (TME) also coevolves with it, which is primarily involved in tumor initiation, development, metastasis, and therapeutic responses. Recent years, TME has been emerged as a potential target for cancer diagnosis and treatment. However, the clinical efficacy of treatments targeting the TME, especially its specific components, remains insufficient. In parallel, the gut microbiome is an essential TME component that is crucial in cancer immunotherapy. Thus, assessing and constructing frameworks between the gut microbiota and the TME can significantly enhance the exploration of effective treatment strategies for various tumors. In this review the role of the gut microbiota in human cancers, including its function and relationship with various tumors was summarized. In addition, the interaction between the gut microbiota and the TME as well as its potential applications in cancer therapeutics was described. Furthermore, it was summarized that fecal microbiota transplantation, dietary adjustments, and synthetic biology to introduce gut microbiota-based medical technologies for cancer treatment. This review provides a comprehensive summary for uncovering the mechanism underlying the effects of the gut microbiota on the TME and lays a foundation for the development of personalized medicine in further studies.
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Sirt3 Protects Retinal Pigment Epithelial Cells From High Glucose-Induced Injury by Promoting Mitophagy Through the AMPK/mTOR/ULK1 Pathway.
Yang, W, Qiu, C, Lv, H, Zhang, Z, Yao, T, Huang, L, Wu, G, Zhang, X, Chen, J, He, Y
Translational vision science & technology. 2024;(3):19
Abstract
PURPOSE The regulation of mitophagy by Sirt3 has rarely been studied in ocular diseases. In the present study, we determined the effects of Sirt3 on AMPK/mTOR/ULK1 signaling pathway-mediated mitophagy in retinal pigment epithelial (RPE) cells in a high glucose environment. METHODS The mRNA expression levels of Sirt3, AMPK, mTOR, ULK1, and LC3B in RPE cells under varying glucose conditions were measured by real-time polymerase chain reaction (RT-PCR). The expressions of Sirt3, mitophagy protein, and AMPK/mTOR/ULK1 signaling pathway-related proteins were detected by Western blotting. Lentivirus (LV) transfection mediated the stable overexpression of Sirt3 in cell lines. The experimental groups were NG (5.5 mM glucose), hypertonic, HG (30 mM glucose), HG + LV-GFP, and HG + LV-Sirt3. Western blotting was performed to detect the expressions of mitophagy proteins and AMPK/mTOR/ULK1-related proteins in a high glucose environment during the overexpression of Sirt3. Reactive oxygen species (ROS) production in a high glucose environment was measured by DCFH-DA staining. Mitophagy was detected by labeling mitochondria and lysosomes with MitoTracker and LysoTracker probes, respectively. Apoptosis was detected by flow cytometry. RESULTS Sirt3 expression was reduced in the high glucose group, inhibiting the AMPK/mTOR/ULK1 pathway, with diminished mitophagy and increased intracellular ROS production. The overexpression of Sirt3, increased expression of p-AMPK/AMPK and p-ULK1/ULK1, and decreased expression of p-mTOR/mTOR inhibited cell apoptosis and enhanced mitophagy. CONCLUSIONS Sirt3 protected RPE cells from high glucose-induced injury by activating the AMPK/mTOR/ULK1 signaling pathway. TRANSLATIONAL RELEVANCE By identifying new targets of action, we aimed to establish effective therapeutic targets for diabetic retinopathy treatment.
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Revolutionizing breast cancer treatment: Harnessing the related mechanisms and drugs for regulated cell death (Review).
Ai, L, Yi, N, Qiu, C, Huang, W, Zhang, K, Hou, Q, Jia, L, Li, H, Liu, L
International journal of oncology. 2024;(5)
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Abstract
Breast cancer arises from the malignant transformation of mammary epithelial cells under the influence of various carcinogenic factors, leading to a gradual increase in its prevalence. This disease has become the leading cause of mortality among female malignancies, posing a significant threat to the health of women. The timely identification of breast cancer remains challenging, often resulting in diagnosis at the advanced stages of the disease. Conventional therapeutic approaches, such as surgical excision, chemotherapy and radiotherapy, exhibit limited efficacy in controlling the progression and metastasis of the disease. Regulated cell death (RCD), a process essential for physiological tissue cell renewal, occurs within the body independently of external influences. In the context of cancer, research on RCD primarily focuses on cuproptosis, ferroptosis and pyroptosis. Mounting evidence suggests a marked association between these specific forms of RCD, and the onset and progression of breast cancer. For example, a cuproptosis vector can effectively bind copper ions to induce cuproptosis in breast cancer cells, thereby hindering their proliferation. Additionally, the expression of ferroptosis‑related genes can enhance the sensitivity of breast cancer cells to chemotherapy. Likewise, pyroptosis‑related proteins not only participate in pyroptosis, but also regulate the tumor microenvironment, ultimately leading to the death of breast cancer cells. The present review discusses the unique regulatory mechanisms of cuproptosis, ferroptosis and pyroptosis in breast cancer, and the mechanisms through which they are affected by conventional cancer drugs. Furthermore, it provides a comprehensive overview of the significance of these forms of RCD in modulating the efficacy of chemotherapy and highlights their shared characteristics. This knowledge may provide novel avenues for both clinical interventions and fundamental research in the context of breast cancer.
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Thiolutin has complex effects in vivo but is a direct inhibitor of RNA polymerase II in vitro.
Qiu, C, Arora, P, Malik, I, Laperuta, AJ, Pavlovic, EM, Ugochukwu, S, Naik, M, Kaplan, CD
Nucleic acids research. 2024;(5):2546-2564
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Abstract
Thiolutin is a natural product transcription inhibitor with an unresolved mode of action. Thiolutin and the related dithiolopyrrolone holomycin chelate Zn2+ and previous studies have concluded that RNA Polymerase II (Pol II) inhibition in vivo is indirect. Here, we present chemicogenetic and biochemical approaches to investigate thiolutin's mode of action in Saccharomyces cerevisiae. We identify mutants that alter sensitivity to thiolutin. We provide genetic evidence that thiolutin causes oxidation of thioredoxins in vivo and that thiolutin both induces oxidative stress and interacts functionally with multiple metals including Mn2+ and Cu2+, and not just Zn2+. Finally, we show direct inhibition of RNA polymerase II (Pol II) transcription initiation by thiolutin in vitro in support of classical studies that thiolutin can directly inhibit transcription in vitro. Inhibition requires both Mn2+ and appropriate reduction of thiolutin as excess DTT abrogates its effects. Pause prone, defective elongation can be observed in vitro if inhibition is bypassed. Thiolutin effects on Pol II occupancy in vivo are widespread but major effects are consistent with prior observations for Tor pathway inhibition and stress induction, suggesting that thiolutin use in vivo should be restricted to studies on its modes of action and not as an experimental tool.
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Multimorbidity, cognitive phenotypes, and Alzheimer's disease plasma biomarkers in older adults: A population-based study.
Ren, Y, Li, Y, Tian, N, Liu, R, Dong, Y, Hou, T, Liu, C, Han, X, Han, X, Wang, L, et al
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2024;(3):1550-1561
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Abstract
INTRODUCTION To examine the burden and clusters of multimorbidity in association with mild cognitive impairment (MCI), dementia, and Alzheimer's disease (AD)-related plasma biomarkers among older adults. METHODS This population-based study included 5432 participants (age ≥60 years); of these, plasma amyloid beta (Aβ), total tau, and neurofilament light chain (NfL) were measured in a subsample (n = 1412). We used hierarchical clustering to generate five multimorbidity clusters from 23 chronic diseases. We diagnosed dementia and MCI following international criteria. Data were analyzed using logistic and linear regression models. RESULTS The number of chronic diseases was associated with dementia (multivariable-adjusted odds ratio = 1.22; 95% confidence interval [CI] = 1.11 to 1.33), AD (1.13; 1.01 to 1.26), vascular dementia (VaD) (1.44; 1.25 to 1.64), and non-amnestic MCI (1.25; 1.13 to 1.37). Metabolic cluster was associated with VaD and non-amnestic MCI, whereas degenerative ocular cluster was associated with AD (p < 0.05). The number of chronic diseases was associated with increased plasma Aβ and NfL (p < 0.05). DISCUSSION Multimorbidity burden and clusters are differentially associated with subtypes of dementia and MCI and AD-related plasma biomarkers in older adults. HIGHLIGHTS We used hierarchical clustering to generate five clusters of multimorbidity. The presence and load of multimorbidity were associated with dementia and mild cognitive impairment. Multimorbidity clusters were differentially associated with subtypes of dementia and Alzheimer's disease plasma biomarkers.
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The Method and Study of Detecting Phenanthrene in Seawater Based on a Carbon Nanotube-Chitosan Oligosaccharide Modified Electrode Immunosensor.
Wu, Y, Qu, W, Qiu, C, Chen, K, Zhuang, Y, Zeng, Z, Yan, Y, Gu, Y, Tao, W, Gao, J, et al
Molecules (Basel, Switzerland). 2023;(15)
Abstract
Phenanthrene (PHE), as a structurally simple, tricyclic, polycyclic aromatic hydrocarbon (PAHs), is widely present in marine environments and organisms, with serious ecological and health impacts. It is crucial to study fast and simple high-sensitivity detection methods for phenanthrene in seawater for the environment and the human body. In this paper, a immunosensor was prepared by using a multi-wall carbon nanotube (MWCNTs)-chitosan oligosaccharide (COS) nanocomposite membrane loaded with phenanthrene antibody. The principle was based on the antibody-antigen reaction in the immune reaction, using the strong electron transfer ability of multi-walled carbon nanotubes, coupled with chitosan oligosaccharides with an excellent film formation and biocompatibility, to amplify the detection signal. The content of the phenanthrene in seawater was studied via differential pulse voltammetry (DPV) using a potassium ferricyanide system as a redox probe. The antibody concentration, pH value, and probe concentration were optimized. Under the optimal experimental conditions, the response peak current of the phenanthrene was inversely proportional to the concentration of phenanthrene, in the range from 0.5 ng·mL-1 to 80 ng·mL-1, and the detection limit was 0.30 ng·mL-1. The immune sensor was successfully applied to the detection of phenanthrene in marine water, with a recovery rate of 96.1~101.5%, and provided a stable, sensitive, and accurate method for the real-time monitoring of marine environments.
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Cognitive Benefit of a Multidomain Intervention for Older Adults at Risk of Cognitive Decline: A Cluster-Randomized Controlled Trial.
Liu, X, Ma, Z, Zhu, X, Zheng, Z, Li, J, Fu, J, Shao, Q, Han, X, Wang, X, Wang, Z, et al
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. 2023;(3):197-209
Abstract
OBJECTIVE We sought to assess cognitive benefits of a community-based multidomain intervention for improving cognition among older adults at risk of cognitive decline (COMBAT). DESIGN A two-armed cluster-randomized controlled trial. SETTING AND PARTICIPANTS Community-dwelling older adults aged 60 years or older and were at risk of cognitive decline (n = 209). INTERVENTION In this 9-month intervention study, 10 community hospitals in Beijing, China, were randomized (1:1) to receive either a multidomain intervention of meditation, cognitive training, exercise, and nutrition counseling or usual care. The intervention was delivered with weekly 1-hour group training sessions and weekly home homework. MEASUREMENTS Primary outcome was change in cognition as measured by a composite Z score of seven cognitive tests. Secondary outcomes included subjective cognitive abilities, positive and negative affective experiences, physical activity, and dietary habits. Assessments were administered at baseline, end of the intervention, and 1 year after completing the intervention (1-year follow-up). RESULTS Immediately after the intervention, the intervention group showed significant enhancement in cognitive performance (p = 0.026). The between-group difference in the Z score of change of cognition was 0.20 (95% CI: 0.053, 0.35), with a Hedges' g of 0.40 (95% CI: 0.29, 0.50). However, this cognitive benefit was not significant at 1-year follow-up. CONCLUSION This multidomain intervention was effective to improve cognition for at-risk individuals. Long-term effects on cognitive function and individual differences in response to the intervention deserve further investigation.
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Can dementia risk be reduced by following the American Heart Association's Life's Simple 7? A systematic review and dose-response meta-analysis.
Wu, J, Xiong, Y, Xia, X, Orsini, N, Qiu, C, Kivipelto, M, Rizzuto, D, Wang, R
Ageing research reviews. 2023;83:101788
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The American Heart Association (AHA) has defined ideal levels of seven modifiable cardiovascular health (CVH) factors, known as Life's Simple 7, that consist of smoking, physical activity, diet, body mass index, fasting blood glucose, total cholesterol, and blood pressure. Maintaining ideal levels of these factors has been recommended as a prevention strategy against not only cardiovascular diseases but also neurodegenerative disorders, e.g., cognitive decline and dementia. However, studies exploring the beneficial effects of the AHA’s CVH metrics on cognitive outcomes, especially among older populations, have been uncertain, and solid evidence is lacking in this field. This systematic review and meta-analysis aimed to quantify the relationship between the AHA’s CVH metrics and cognitive outcomes. 14 longitudinal studies were included in the meta-analysis. The results showed a considerable effect of a favourable total CVH score on reduced risk of incident dementia in adults aged 70 years or older. When looking at the individual factors, dementia risk can be reduced significantly if older adults achieved the recommended level of physical activity, blood glucose, or total cholesterol. The association with smoking appeared to be borderline, and there was no association between diet, body mass index hazard ratio or blood pressure and dementia risk. The authors concluded that their findings provide evidence that maintaining a favourable level of CVH score, either in mid- or late- life, would substantially reduce the risk of dementia among older adults. Preserving cardiovascular health by quitting smoking, engaging in physical exercise, controlling blood glucose and total cholesterol might be especially effective for forestalling cognitive decline and dementia.
Abstract
This study aimed to quantify the relationships between the American Heart Association (AHA) Cardiovascular Health (CVH) metrics, namely AHA Life's Simple 7, and cognitive outcomes. We searched PubMed and Embase (January 1, 2010-August 24, 2022) and finally included 14 longitudinal studies (311654 participants with 8006 incident dementia cases). Random-effects meta-analysis and one-stage linear mixed-effects models were performed. Increased CVH score seemed to associate with decreased risk of incident dementia in a linear manner, but this relationship varied by the measurement age of CVH metrics. That is, midlife CVH tended to have a linear association with late-life dementia risk, whereas a J-shaped association was observed between the late-life CVH score and dementia. In addition, late-life dementia risk was reduced significantly if individuals maintained an ideal level of AHA's CVH guidelines of physical activity, fasting plasma glucose, total cholesterol, and smoking. However, our meta-analysis did not show a significant association between CVH score and global cognitive decline rate. Following AHA's CVH guidelines and maintaining CVH at an optimal level would substantially reduce the late-life dementia risk. More research is required to explore the link between a favorable CVH score and cognitive trajectories among cognitively asymptomatic older populations.
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Application of starch-based nanoparticles and cyclodextrin for prebiotics delivery and controlled glucose release in the human gut: a review.
Liu, Y, Qiu, C, Li, X, McClements, DJ, Wang, C, Zhang, Z, Jiao, A, Long, J, Zhu, K, Wang, J, et al
Critical reviews in food science and nutrition. 2023;(23):6126-6137
Abstract
Starches are a major constituent of staple foods and are the main source of energy in the human diet (55-70%). In the gastrointestinal tract, starches are hydrolyzed into glucose by α-amylase and α-glucosidase, which leads to a postprandial glucose elevation. High levels of blood glucose levels over sustained periods may promote type 2 diabetes mellitus (T2DM) and obesity. Increasing consumption of starchy foods with a lower glycemic index may therefore contribute to improved health. In this paper, the preparation and properties of several starch-based nanoparticles (SNPs) and cyclodextrins (CDs) derivatives are reviewed. In particular, we focus on the various mechanisms responsible for the ability of these edible nanomaterials to modulate glucose release and the gut microbiome in the gastrointestinal tract. The probiotic functions are achieved through encapsulation and protection of prebiotics or bioactive components in foods or the human gut. This review therefore provides valuable information that could be used to design functional foods for improving human health and wellbeing.
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Chronic kidney disease-induced muscle atrophy: Molecular mechanisms and promising therapies.
Wang, K, Liu, Q, Tang, M, Qi, G, Qiu, C, Huang, Y, Yu, W, Wang, W, Sun, H, Ni, X, et al
Biochemical pharmacology. 2023;:115407
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Abstract
Chronic kidney disease (CKD) is a high-risk chronic catabolic disease due to its high morbidity and mortality. CKD is accompanied by many complications, leading to a poor quality of life, and serious complications may even threaten the life of CKD patients. Muscle atrophy is a common complication of CKD. Muscle atrophy and sarcopenia in CKD patients have complex pathways that are related to multiple mechanisms and related factors. This review not only discusses the mechanisms by which inflammation, oxidative stress, mitochondrial dysfunction promote CKD-induced muscle atrophy but also explores other CKD-related complications, such as metabolic acidosis, vitamin D deficiency, anorexia, and excess angiotensin II, as well as other related factors that play a role in CKD muscle atrophy, such as insulin resistance, hormones, hemodialysis, uremic toxins, intestinal flora imbalance, and miRNA. We highlight potential treatments and drugs that can effectively treat CKD-induced muscle atrophy in terms of complication treatment, nutritional supplementation, physical exercise, and drug intervention, thereby helping to improve the prognosis and quality of life of CKD patients.