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1.
Tumor iron homeostasis and immune regulation.
Zhang, YY, Han, Y, Li, WN, Xu, RH, Ju, HQ
Trends in pharmacological sciences. 2024;(2):145-156
Abstract
Abnormal iron metabolism has long been regarded as a key metabolic hallmark of cancer. As a critical cofactor, iron contributes to tumor progression by participating in various processes such as mitochondrial electron transport, gene regulation, and DNA synthesis or repair. Although the role of iron in tumor cells has been widely studied, recent studies have uncovered the interplay of iron metabolism between tumor cells and immune cells, which may affect both innate and adaptive immune responses. In this review, we discuss the current understanding of the regulatory networks of iron metabolism between cancer cells and immune cells and how they contribute to antitumor immunity, and we analyze potential therapeutics targeting iron metabolism. Also, we highlight several key challenges and describe potential therapeutic approaches for future investigations.
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2.
Research progress on the regulation of oxidative stress by phenolics: the role of gut microbiota and Nrf2 signaling pathway.
Liu, Y, Wang, X, Podio, NS, Wang, X, Xu, S, Jiang, S, Wei, X, Han, Y, Cai, Y, Chen, X, et al
Journal of the science of food and agriculture. 2024;(4):1861-1873
Abstract
In recent years, the increase in high-calorie diets and sedentary lifestyles has made obesity a global public health problem. An unbalanced diet promotes the production of proinflammatory cytokines and causes redox imbalance in the body. Phenolics have potent antioxidant activity and cytoprotective ability. They can scavenge free radicals and reactive oxygen species, and enhance the activity of antioxidant enzymes, thus combating the body's oxidative stress. They can also improve the body's inflammatory response, enhance the enzyme activity of lipid metabolism, and reduce the contents of cholesterol and triglyceride. Most phenolics are biotransformed and absorbed into the blood after the action by gut microbiota; these metabolites then undergo phase I and II metabolism and regulate oxidative stress by scavenging free radicals and increasing expression of antioxidant enzymes. Phenolics induce the expression of genes encoding antioxidant enzymes and phase II detoxification enzymes by stimulating Nrf2 to enter the nucleus and bind to the antioxidant response element after uncoupling from Keap1, thereby promoting the production of antioxidant enzymes and phase II detoxification enzymes. The absorption rate of phenolics in the small intestine is extremely low. Most phenolics reach the colon, where they interact with the microbiota and undergo a series of metabolism. Their metabolites will reach the liver via the portal vein and undergo conjugation reactions. Subsequently, the metabolites reach the whole body to exert biological activity by traveling with the systemic circulation. Phenolics can promote the growth of probiotics, reduce the ratio of Firmicutes/Bacteroidetes (F/B), and improve intestinal microecological imbalance. This paper reviews the nutritional value, bioactivity, and antioxidant mechanism of phenolics in the body, aiming to provide a scientific basis for the development and utilization of natural antioxidants and provide a reference for elucidating the mechanism of action of phenolics for regulating oxidative stress in the body. © 2023 Society of Chemical Industry.
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3.
Epidemiological and clinical features of malignant hyperthermia: A scoping review.
Cong, Z, Wan, T, Wang, J, Feng, L, Cao, C, Li, Z, Wang, X, Han, Y, Zhou, Y, Gao, Y, et al
Clinical genetics. 2024;(3):233-242
Abstract
Malignant hyperthermia (MH) is a potentially fatal inherited pharmacogenetic disorder related to pathogenic variants in the RYR1, CACNA1S, or STAC3 genes. Early recognition of the occurrence of MH and prompt medical treatment are indispensable to ensure a positive outcome. The purpose of this study was to provide valuable information for the early identification of MH by summarizing epidemiological and clinical features of MH. This scoping review followed the methodological framework recommended by Arksey and O'Malley. PubMed, Embase, and Web of science databases were searched for studies that evaluated the epidemical and clinical characteristics of MH. A total of 37 studies were included in this review, of which 26 were related to epidemiology and 24 were associated with clinical characteristics. The morbidity of MH varied from 0.18 per 100 000 to 3.9 per 100 000. The mortality was within the range of 0%-18.2%. Identified risk factors included sex, age, disorders associated with MH, and others. The most frequent initial clinical signs included hyperthermia, sinus tachycardia, and hypercarbia. The occurrence of certain signs, such as hypercapnia, delayed first temperature measurement, and peak temperature were associated with poor outcomes. The epidemiological and clinical features of MH varied considerably and some risk factors and typical clinical signs were identified. The main limitation of this review is that the treatment and management strategies were not assessed sufficiently due to limited information.
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4.
A comprehensive review of ethnopharmacology, chemical constituents, pharmacological effects, pharmacokinetics, toxicology, and quality control of gardeniae fructus.
Wang, L, Chen, S, Liu, S, Biu, AM, Han, Y, Jin, X, Liang, C, Liu, Y, Li, J, Fang, S, et al
Journal of ethnopharmacology. 2024;:117397
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Gardeniae Fructus (GF), the desiccative mature fruitage of Gardenia jasminoides J. Ellis (G. jasminoides), belongs to the Rubiaceae family. It has abundant medicinal value, such as purging fire and eliminating annoyance, clearing heat and diuresis, cooling blood, and detoxifying. GF is usually used in combination with other drugs to treat diseases such as fever and jaundice in damp heat syndrome in traditional Chinese medicines (TCMs) clinical practice. THE AIM OF THE REVIEW This review comprehensively summarizes the research progress in botany, traditional medical use, processing method, phytochemistry, pharmacological activity, quality control, pharmacokinetics, and toxicology, which aims to provide a scientific basis for the rational application and future research of GF. MATERIALS AND METHODS ScienceDirect, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Embase, Scopus etc. databases were retrieved to gain the comprehensive information of GF. RESULTS At present, more than 215 compounds were isolated and identified from GF, including iridoids, diterpenes, triterpenoids, flavonoids, organic esters, and so on. The traditional application of GF mainly focused on clearing heat and detoxification. Pharmacological studies proved that GF had anti-inflammatory, antioxidation, antifatigue, antithrombotic, liver and gallbladder protection, and other pharmacological effects. In addition, many improved processing methods can alleviate the side effects and toxic reactions caused by long-term use of GF, so controlling its quality through multi-component content measurement has become an important means of research. CONCLUSION GF has a wide range of applications, the mechanisms by which some effective substances exert their pharmacological effects have not been clearly explained due to the complexity and diversity of its components. This review systematically elaborates on the traditional medical use, processing method, phytochemistry, pharmacological activity, quality control, and toxicology of GF, and it is expected to become a candidate drug for treating diseases, such as depression, pancreatitis, alcoholic or non-alcoholic fatty liver.
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5.
Efficacy and Safety of Inclisiran in Asian Patients: Results From ORION-18.
Huo, Y, Lesogor, A, Lee, CW, Chiang, CE, Mena-Madrazo, J, Poh, KK, Jeong, MH, Maheux, P, Zhang, M, Wei, S, et al
JACC. Asia. 2024;(2):123-134
Abstract
BACKGROUND Management of low-density lipoprotein cholesterol (LDL-C) in Asia remains suboptimal, with ∼50% of patients who are treated with lipid-lowering therapies (LLTs) unable to achieve their guideline-recommended LDL-C goals. Asian-representative studies of the use of inclisiran are needed. OBJECTIVES The authors sought to evaluate the efficacy and safety of inclisiran in Asian patients with atherosclerotic cardiovascular disease (ASCVD) or high risk of ASCVD, as an adjunct to diet and maximally tolerated statin dose, with or without additional LLTs. METHODS The ORION-18 was a phase 3 double-blind trial in which patients were randomized 1:1 to receive either 300 mg inclisiran sodium or matching placebo on days 1, 90, and 270. Percentage change in LDL-C from baseline to day 330 was the primary endpoint. RESULTS A total of 345 patients (mean age 59.5 years, mean baseline LDL-C 109 mg/dL, 74.7% male) were randomized to inclisiran or placebo. Baseline characteristics were similar in both groups. The percentage decrease in LDL-C from baseline to day 330 was 57.2% (P < 0.001); proprotein convertase subtilisin/kexin type 9 was reduced by 78.3% (P < 0.001). Time-adjusted percentage reduction in LDL-C from baseline after day 90 and up to day 360 was 56.3%. At day 330, 71.7% of participants with inclisiran achieved ≥50% reduction in LDL-C compared with 1.5% with placebo. Over the study period, total cholesterol, apolipoprotein B, and non-high-density lipoprotein cholesterol (HDL-C) levels were decreased significantly, and HDL-C levels increased. The incidence of adverse events with inclisiran was similar to that with placebo. CONCLUSIONS In Asian patients with ASCVD or high risk of ASCVD, inclisiran was effective and safe. (Study of Efficacy and Safety of Inclisiran in Asian Participants With Atherosclerotic Cardiovascular Disease [ASCVD] or ASCVD High Risk and Elevated Low-Density Lipoprotein Cholesterol [LDL-C] [ORION-18]; NCT04765657).
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6.
Genomic approaches to enhance adaptive plasticity to cope with soil constraints amidst climate change in wheat.
Bhoite, R, Han, Y, Chaitanya, AK, Varshney, RK, Sharma, DL
The plant genome. 2024;(1):e20358
Abstract
Climate change is varying the availability of resources, soil physicochemical properties, and rainfall events, which collectively determines soil physical and chemical properties. Soil constraints-acidity (pH < 6), salinity (pH ≤ 8.5), sodicity, and dispersion (pH > 8.5)-are major causes of wheat yield loss in arid and semiarid cropping systems. To cope with changing environments, plants employ adaptive strategies such as phenotypic plasticity, a key multifaceted trait, to promote shifts in phenotypes. Adaptive strategies for constrained soils are complex, determined by key functional traits and genotype × environment × management interactions. The understanding of the molecular basis of stress tolerance is particularly challenging for plasticity traits. Advances in sequencing and high-throughput genomics technologies have identified functional alleles in gene-rich regions, haplotypes, candidate genes, mechanisms, and in silico gene expression profiles at various growth developmental stages. Our review focuses on favorable alleles for enhanced gene expression, quantitative trait loci, and epigenetic regulation of plant responses to soil constraints, including heavy metal stress and nutrient limitations. A strategy is then described for quantitative traits in wheat by investigating significant alleles and functional characterization of variants, followed by gene validation using advanced genomic tools, and marker development for molecular breeding and genome editing. Moreover, the review highlights the progress of gene editing in wheat, multiplex gene editing, and novel alleles for smart control of gene expression. Application of these advanced genomic technologies to enhance plasticity traits along with soil management practices will be an effective tool to build yield, stability, and sustainability on constrained soils in the face of climate change.
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7.
The Effect of Post-Activation Potentiation Enhancement Alone or in Combination with Caffeine on Anaerobic Performance in Boxers: A Double-Blind, Randomized Crossover Study.
Zhang, Y, Diao, P, Wang, J, Li, S, Fan, Q, Han, Y, Liang, Y, Wang, Z, Del Coso, J
Nutrients. 2024;(2)
Abstract
Post-activation performance enhancement (PAPE) is a physiological phenomenon that refers to an acute excitation of the neuromuscular system following intense exercise that ends in enhanced physical performance in a subsequent bout of exercise. The scientific literature has primarily examined the effectiveness of PAPE alone or combined with caffeine (CAF) intake in all-out tests lasting ≤10 s, as the effect of PAPE is transitory. The aim of the present study was to determine the effect of a protocol to induce PAPE alone or in combination with caffeine intake on the 30 s Wingate Anaerobic Test in highly trained boxers. Twenty-five male and highly trained boxers (mean age: 20 ± 1 years) participated in a double-blind, randomized crossover study consisting of three different experimental conditions: (i) control (CON), with no substance intake and no PAPE protocol before the Wingate Anaerobic Test; (ii) PAPE + PLA, involving the intake of a placebo 60 min before and a PAPE protocol comprising a 10 s cycling sprint overloaded with 8.5% of the participants' body weight 10 min before the Wingate Anaerobic Test; and (iii) PAPE + CAF, involving the intake of 3 mg/kg of caffeine 60 min before and the same PAPE protocol used in the (ii) protocol before the Wingate Anaerobic Test. In all conditions, the participants performed the 30 s version of the Wingate Anaerobic Test with a load equivalent to 7.5% of their body weight, while the cycle ergometer setting was replicated. Immediately following the Wingate test, heart rate (HR), the rating of perceived exertion (RPE), and blood lactate concentration (Bla) were measured. In comparison to CON, PAPE + PLA enhanced mean power (p = 0.024; Effect size [ES] = 0.37) and total work (p = 0.022; ES = 0.38) during the Wingate test, accompanied by an increase in post-test blood lactate concentration (p < 0.01; ES = 0.83). In comparison to CON, PAPE + CAF enhanced mean power (p = 0.001; ES = 0.57), peak power (p = 0.013; ES = 0.57), total work (p = 0.001; ES = 0.53), post-test blood lactate concentration (p < 0.001; ES = 1.43) and participants' subjective perception of power (p = 0.041). There were no differences in any variable between PAPE + PLA and PAPE + CAF. In summary, a PAPE protocol that involves a 10 s all-out sprint 10 min before the Wingate Anaerobic Test was effective in enhancing Wingate mean power in highly trained boxers. The addition of 3 mg/kg of caffeine to the PAPE protocol produced an effect on mean power of a higher magnitude than PAPE alone, and it enhanced peak power along with participants' subjective perception of power. From a practical point of view, PAPE before exercise seems to be an effective approach for increasing Wingate performance in highly trained boxers, while the addition of caffeine can increase some benefits, especially peak power.
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8.
Current progress in research focused on salt tolerance in Vitis vinifera L.
Han, Y, Li, X
Frontiers in plant science. 2024;:1353436
Abstract
Soil salinization represents an increasingly serious threat to agronomic productivity throughout the world, as rising ion concentrations can interfere with the growth and development of plants, ultimately reducing crop yields and quality. A combination of factors is driving this progressive soil salinization, including natural causes, global climate change, and irrigation practices that are increasing the global saline-alkali land footprint. Salt stress damages plants both by imposing osmotic stress that reduces water availability while also inducing direct sodium- and chlorine-mediated toxicity that harms plant cells. Vitis vinifera L. exhibits relatively high levels of resistance to soil salinization. However, as with other crops, grapevine growth, development, fruit yields, and fruit quality can all be adversely affected by salt stress. Many salt-tolerant grape germplasm resources have been screened in recent years, leading to the identification of many genes associated to salt stress and the characterization of the mechanistic basis for grapevine salt tolerance. These results have also been leveraged to improve grape yields through the growth of more tolerant cultivars and other appropriate cultivation measures. The present review was formulated to provide an overview of recent achievements in the field of research focused on grapevine salt tolerance from the perspectives of germplasm resource identification, the mining of functional genes, the cultivation of salt-tolerant grape varieties, and the selection of appropriate cultivation measures. Together, we hope that this systematic review will offer insight into promising approaches to enhancing grape salt tolerance in the future.
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9.
Classification and design strategies of polysaccharide-based nano-nutrient delivery systems for enhanced bioactivity and targeted delivery: A review.
Wang, Z, Fu, S, Guo, Y, Han, Y, Ma, C, Li, R, Yang, X
International journal of biological macromolecules. 2024;(Pt 2):128440
Abstract
Since many nutrients are highly sensitive, they cannot be absorbed and utilized efficiently by the body. Using nano-delivery systems to encapsulate nutrients is an effective method of solving the problems associated with the application of nutrients at this stage. Polysaccharides, as natural biomaterials, have a unique chemical structure, ideal biocompatibility, biodegradability and low immunogenicity. This makes polysaccharides powerful carriers that can enhance the biological activity of nutrients. However, the true role of polysaccharide-based delivery systems requires an in-depth understanding of the structural and physicochemical characteristics of polysaccharide-based nanodelivery systems, as well as effective modulation of the intestinal delivery mechanism and the latest advances in nano-encapsulation. This review provides an overview of polysaccharide-based nano-delivery systems dependent on different carrier types, emphasizing recent advances in the application of polysaccharides, a biocomposite material designed for nutrient delivery systems. Strategies for polysaccharide-based nano-delivery systems to enhance the bioavailability of orally administered nutrients from the perspective of the intestinal absorption barrier are presented. Characterization methods for polysaccharide-based nano-delivery systems are presented as well as an explanation of the formation mechanisms behind nano-delivery systems from the perspective of molecular forces. Finally, we discussed the challenges currently facing polysaccharide-based nano-delivery systems as well as possible future directions for the future.
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10.
Cellular metabolism: A key player in cancer ferroptosis.
Jiang, X, Peng, Q, Peng, M, Oyang, L, Wang, H, Liu, Q, Xu, X, Wu, N, Tan, S, Yang, W, et al
Cancer communications (London, England). 2024;(2):185-204
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Abstract
Cellular metabolism is the fundamental process by which cells maintain growth and self-renewal. It produces energy, furnishes raw materials, and intermediates for biomolecule synthesis, and modulates enzyme activity to sustain normal cellular functions. Cellular metabolism is the foundation of cellular life processes and plays a regulatory role in various biological functions, including programmed cell death. Ferroptosis is a recently discovered form of iron-dependent programmed cell death. The inhibition of ferroptosis plays a crucial role in tumorigenesis and tumor progression. However, the role of cellular metabolism, particularly glucose and amino acid metabolism, in cancer ferroptosis is not well understood. Here, we reviewed glucose, lipid, amino acid, iron and selenium metabolism involvement in cancer cell ferroptosis to elucidate the impact of different metabolic pathways on this process. Additionally, we provided a detailed overview of agents used to induce cancer ferroptosis. We explained that the metabolism of tumor cells plays a crucial role in maintaining intracellular redox homeostasis and that disrupting the normal metabolic processes in these cells renders them more susceptible to iron-induced cell death, resulting in enhanced tumor cell killing. The combination of ferroptosis inducers and cellular metabolism inhibitors may be a novel approach to future cancer therapy and an important strategy to advance the development of treatments.