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1.
Targeting dysregulated lipid metabolism for the treatment of Alzheimer's disease and Parkinson's disease: Current advancements and future prospects.
Tong, B, Ba, Y, Li, Z, Yang, C, Su, K, Qi, H, Zhang, D, Liu, X, Wu, Y, Chen, Y, et al
Neurobiology of disease. 2024;:106505
Abstract
Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features of AD are memory decline and cognitive dysfunction, while PD mainly manifests as motor dysfunction such as limb tremors, muscle rigidity abnormalities, and slow gait. Abnormalities in cholesterol, sphingolipid, and glycerophospholipid metabolism have been demonstrated to directly exacerbate the progression of AD by stimulating Aβ deposition and tau protein tangles. Indirectly, abnormal lipids can increase the burden on brain vasculature, induce insulin resistance, and affect the structure of neuronal cell membranes. Abnormal lipid metabolism leads to PD through inducing accumulation of α-syn, dysfunction of mitochondria and endoplasmic reticulum, and ferroptosis. Great progress has been made in targeting lipid metabolism abnormalities for the treatment of AD and PD in recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, and monoclonal antibodies targeting apolipoprotein E (ApoE). This review comprehensively summarizes the involvement of dysregulated lipid metabolism in the pathogenesis of AD and PD, the application of Lipid Monitoring, and emerging lipid regulatory drug targets. A better understanding of the lipidological bases of AD and PD may pave the way for developing effective prevention and treatment methods for neurodegenerative disorders.
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2.
Non-coding RNAs and leaf senescence: Small molecules with important roles.
Li, S, Zhao, Y, Tan, S, Li, Z
Plant physiology and biochemistry : PPB. 2024;:108399
Abstract
Non-coding RNAs (ncRNAs) are a special class of functional RNA molecules that are not translated into proteins. ncRNAs have emerged as pivotal regulators of diverse developmental processes in plants. Recent investigations have revealed the association of ncRNAs with the regulation of leaf senescence, a complex and tightly regulated developmental process. However, a comprehensive review of the involvement of ncRNAs in the regulation of leaf senescence is still lacking. This manuscript aims to summarize the molecular mechanisms underlying ncRNAs-mediated leaf senescence and the potential applications of ncRNAs to manipulate the onset and progression of leaf senescence. Various classes of ncRNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), are discussed in terms of their regulatory mechanisms in leaf senescence. Furthermore, we explore the interactions between ncRNA and the key regulators of senescence, including transcription factors as well as core components in phytohormone signaling pathways. We also discuss the possible challenges and approaches related to ncRNA-mediated leaf senescence. This review contributes to a further understanding of the intricate regulatory network involving ncRNAs in leaf senescence.
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3.
Osteoporosis and Primary Biliary Cholangitis: A Trans-ethnic Mendelian Randomization Analysis.
Wu, Y, Qian, Q, Liu, Q, Wang, R, Pu, X, Li, Y, Zhang, H, You, Z, Miao, Q, Xiao, X, et al
Clinical reviews in allergy & immunology. 2024
Abstract
Osteoporosis is a major clinical problem in many autoimmune diseases, including primary biliary cholangitis (PBC), the most common autoimmune liver disease. Osteoporosis is a major cause of fracture and related mortality. However, it remains unclear whether PBC confers a causally risk-increasing effect on osteoporosis. Herein, we aimed to investigate the causal relationship between PBC and osteoporosis and whether the relationship is independent of potential confounders. We performed bidirectional Mendelian randomization (MR) analyses to investigate the association between PBC (8021 cases and 16,489 controls) and osteoporosis in Europeans (the UK Biobank and FinnGen Consortium: 12,787 cases and 726,996 controls). The direct effect of PBC on osteoporosis was estimated using multivariable MR analyses. An independent replication was conducted in East Asians (PBC: 2495 cases and 4283 controls; osteoporosis: 9794 cases and 168,932 controls). Trans-ethnic meta-analysis was performed by pooling the MR estimates of Europeans and East Asians. Inverse-variance weighted analyses revealed that genetic liability to PBC was associated with a higher risk of osteoporosis in Europeans (OR, 1.040; 95% CI, 1.016-1.064; P = 0.001). Furthermore, the causal effect of PBC on osteoporosis persisted after adjusting for BMI, calcium, lipidemic traits, and sex hormones. The causal relationship was further validated in the East Asians (OR, 1.059; 95% CI, 1.023-1.096; P = 0.001). Trans-ethnic meta-analysis confirmed that PBC conferred increased risk on osteoporosis (OR, 1.045; 95% CI, 1.025-1.067; P = 8.17 × 10-6). Our data supports a causal effect of PBC on osteoporosis, and the causality is independent of BMI, calcium, triglycerides, and several sex hormones.
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4.
Reprogramming of glucose metabolism: Metabolic alterations in the progression of osteosarcoma.
An, F, Chang, W, Song, J, Zhang, J, Li, Z, Gao, P, Wang, Y, Xiao, Z, Yan, C
Journal of bone oncology. 2024;:100521
Abstract
Metabolic reprogramming is an adaptive response of tumour cells under hypoxia and low nutrition conditions. There is increasing evidence that glucose metabolism reprogramming can regulate the growth and metastasis of osteosarcoma (OS). Reprogramming in the progress of OS can bring opportunities for early diagnosis and treatment of OS. Previous research mainly focused on the glycolytic pathway of glucose metabolism, often neglecting the tricarboxylic acid cycle and pentose phosphate pathway. However, the tricarboxylic acid cycle and pentose phosphate pathway of glucose metabolism are also involved in the progression of OS and are closely related to this disease. The research on glucose metabolism in OS has not yet been summarized. In this review, we discuss the abnormal expression of key molecules related to glucose metabolism in OS and summarize the glucose metabolism related signaling pathways involved in the occurrence and development of OS. In addition, we discuss some of the targeted drugs that regulate glucose metabolism pathways, which can lead to effective strategies for targeted treatment of OS.
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5.
The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy.
Alam, MR, Rahman, MM, Li, Z
Genes & diseases. 2024;(1):321-334
Abstract
Exosomes are small membrane vesicles containing microRNA, RNA, DNA fragments, and proteins that are transferred from donor cells to recipient cells. Tumor cells release exosomes to reprogram the factors associated with the tumor microenvironment (TME) causing tumor metastasis and immune escape. Emerging evidence revealed that cancer cell-derived exosomes carry immune inhibitory molecule program death ligand 1 (PD-L1) that binds with receptor program death protein 1 (PD-1) and promote tumor progression by escaping immune response. Currently, some FDA-approved monoclonal antibodies are clinically used for cancer treatment by blocking PD-1/PD-L1 interaction. Despite notable treatment outcomes, some patients show poor drug response. Exosomal PD-L1 plays a vital role in lowering the treatment response, showing resistance to PD-1/PD-L1 blockage therapy through recapitulating the effect of cell surface PD-L1. To enhance therapeutic response, inhibition of exosomal PD-L1 is required. Calcium signaling is the central regulator of tumorigenesis and can regulate exosome biogenesis and secretion by modulating Rab GTPase family and membrane fusion factors. Immune checkpoints are also connected with calcium signaling and calcium channel blockers like amlodipine, nifedipine, lercanidipine, diltiazem, and verapamil were also reported to suppress cellular PD-L1 expression. Therefore, to enhance the PD-1/PD-L1 blockage therapy response, the reduction of exosomal PD-L1 secretion from cancer cells is in our therapeutic consideration. In this review, we proposed a therapeutic strategy by targeting calcium signaling to inhibit the expression of PD-L1-containing exosome levels that could reduce the anti-PD-1/PD-L1 therapy resistance and increase the patient's drug response rate.
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6.
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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7.
The role of Keap1-Nrf2 signaling pathway during the progress and therapy of diabetic retinopathy.
Chen, J, Wang, Q, Li, R, Li, Z, Jiang, Q, Yan, F, Ye, J
Life sciences. 2024;:122386
Abstract
Diabetic retinopathy is a complex and progressive ocular complication of diabetes mellitus and is a leading cause of blindness in people of working age worldwide. The pathophysiology of diabetic retinopathy involves multifactorial processes, including oxidative stress, inflammation and vascular abnormalities. Understanding the underlying molecular mechanisms involved in its pathogenesis is essential for the development of effective therapeutic interventions. One of the pathways receiving increasing attention is the Keap1-Nrf2 signaling pathway, which regulates the cellular response to oxidative stress by activating Nrf2. In this review, we analyze the current evidence linking Keap1-Nrf2 signaling pathway dysregulation to diabetic retinopathy. In addition, we explore the potential therapeutic implications and the challenges of targeting this pathway for disease management. A comprehensive understanding of the molecular mechanisms of diabetic retinopathy and the therapeutic potential of the Keap1-Nrf2 pathway may pave the way for innovative and effective interventions to combat this vision-threatening disease.
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8.
The crosstalk between exosomes and ferroptosis: a review.
Wu, J, Li, Z, Wu, Y, Cui, N
Cell death discovery. 2024;(1):170
Abstract
Exosomes are a subtype of extracellular vesicles composed of bioactive molecules, including nucleic acids, proteins, and lipids. Exosomes are generated by the fusion of intracellular multivesicular bodies (MVBs) with the cell membrane and subsequently released into the extracellular space to participate in intercellular communication and diverse biological processes within target cells. As a crucial mediator, exosomes have been implicated in regulating ferroptosis-an iron-dependent programmed cell death characterized by lipid peroxide accumulation induced by reactive oxygen species. The involvement of exosomes in iron, lipid, and amino acid metabolism contributes to their regulatory role in specific mechanisms underlying how exosomes modulate ferroptosis, which remains incompletely understood, and some related studies are still preliminary. Therefore, targeting the regulation of ferroptosis by exosomes holds promise for future clinical treatment strategies across various diseases. This review aims to provide insights into the pathophysiology and mechanisms governing the interaction between exosomes and ferroptosis and their implications in disease development and treatment to serve as a reference for further research.
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9.
Metal-based nanoparticles in antibacterial application in biomedical field: Current development and potential mechanisms.
Jiang, H, Li, L, Li, Z, Chu, X
Biomedical microdevices. 2024;(1):12
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Abstract
The rise in drug resistance in pathogenic bacteria greatly endangers public health in the post-antibiotic era, and drug-resistant bacteria currently pose a great challenge not only to the community but also to clinical procedures, including surgery, stent implantation, organ transplantation, and other medical procedures involving any open wound and compromised human immunity. Biofilm-associated drug failure, as well as rapid resistance to last-resort antibiotics, necessitates the search for novel treatments against bacterial infection. In recent years, the flourishing development of nanotechnology has provided new insights for exploiting promising alternative therapeutics for drug-resistant bacteria. Metallic agents have been applied in antibacterial usage for several centuries, and the functional modification of metal-based biomaterials using nanotechnology has now attracted great interest in the antibacterial field, not only for their intrinsic antibacterial nature but also for their ready on-demand functionalization and enhanced interaction with bacteria, rendering them with good potential in further translation. However, the possible toxicity of MNPs to the host cells and tissue still hinders its application, and current knowledge on their interaction with cellular pathways is not enough. This review will focus on recent advances in developing metallic nanoparticles (MNPs), including silver, gold, copper, and other metallic nanoparticles, for antibacterial applications, and their potential mechanisms of interaction with pathogenic bacteria as well as hosts.
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Exploiting the Achilles' heel of cancer: disrupting glutamine metabolism for effective cancer treatment.
Fan, Y, Xue, H, Li, Z, Huo, M, Gao, H, Guan, X
Frontiers in pharmacology. 2024;:1345522
Abstract
Cancer cells have adapted to rapid tumor growth and evade immune attack by reprogramming their metabolic pathways. Glutamine is an important nitrogen resource for synthesizing amino acids and nucleotides and an important carbon source in the tricarboxylic acid (TCA) cycle and lipid biosynthesis pathway. In this review, we summarize the significant role of glutamine metabolism in tumor development and highlight the vulnerabilities of targeting glutamine metabolism for effective therapy. In particular, we review the reported drugs targeting glutaminase and glutamine uptake for efficient cancer treatment. Moreover, we discuss the current clinical test about targeting glutamine metabolism and the prospective direction of drug development.