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1.
ER: a critical hub for STING signaling regulation.
Luo, Y, Chang, L, Ji, Y, Liang, T
Trends in cell biology. 2024
Abstract
The Stimulator of Interferon Genes (STING) has a crucial role in mediating the immune response against cytosolic double-stranded DNA (dsDNA) and its activation is critically involved in various diseases. STING is synthesized, modified, and resides in the endoplasmic reticulum (ER), and its ER exit is intimately connected with its signaling. The ER, primarily known for its roles in protein folding, lipid synthesis, and calcium storage, has been identified as a pivotal platform for the regulation of a wide range of STING functions. In this review, we discuss the emerging factors that regulate STING in the ER and examine the interplay between STING signaling and ER pathways, highlighting the impacts of such regulations on immune responses and their potential implications in STING-related disorders.
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AMPK role in epilepsy: a promising therapeutic target?
Qi, Y, Zhang, YM, Gao, YN, Chen, WG, Zhou, T, Chang, L, Zang, Y, Li, J
Journal of neurology. 2024;(2):748-771
Abstract
Epilepsy is a complex and multifaceted neurological disorder characterized by spontaneous and recurring seizures. It poses significant therapeutic challenges due to its diverse etiology and often-refractory nature. This comprehensive review highlights the pivotal role of AMP-activated protein kinase (AMPK), a key metabolic regulator involved in cellular energy homeostasis, which may be a promising therapeutic target for epilepsy. Current therapeutic strategies such as antiseizure medication (ASMs) can alleviate seizures (up to 70%). However, 30% of epileptic patients may develop refractory epilepsy. Due to the complicated nature of refractory epilepsy, other treatment options such as ketogenic dieting, adjunctive therapy, and in limited cases, surgical interventions are employed. These therapy options are only suitable for a select group of patients and have limitations of their own. Current treatment options for epilepsy need to be improved. Emerging evidence underscores a potential association between impaired AMPK functionality in the brain and the onset of epilepsy, prompting an in-depth examination of AMPK's influence on neural excitability and ion channel regulation, both critical factors implicated in epileptic seizures. AMPK activation through agents such as metformin has shown promising antiepileptic effects in various preclinical and clinical settings. These effects are primarily mediated through the inhibition of the mTOR signaling pathway, activation of the AMPK-PI3K-c-Jun pathway, and stimulation of the PGC-1α pathway. Despite the potential of AMPK-targeted therapies, several aspects warrant further exploration, including the detailed mechanisms of AMPK's role in different brain regions, the impact of AMPK under various conditional circumstances such as neural injury and zinc toxicity, the long-term safety and efficacy of chronic metformin use in epilepsy treatment, and the potential benefits of combination therapy involving AMPK activators. Moreover, the efficacy of AMPK activators in refractory epilepsy remains an open question. This review sets the stage for further research with the aim of enhancing our understanding of the role of AMPK in epilepsy, potentially leading to the development of more effective, AMPK-targeted therapeutic strategies for this challenging and debilitating disorder.
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Comprehensive review: Effects of climate change and greenhouse gases emission relevance to environmental stress on horticultural crops and management.
Shah, IH, Manzoor, MA, Jinhui, W, Li, X, Hameed, MK, Rehaman, A, Li, P, Zhang, Y, Niu, Q, Chang, L
Journal of environmental management. 2024;:119978
Abstract
Global climate change exerts a significant impact on sustainable horticultural crop production and quality. Rising Global temperatures have compelled the agricultural community to adjust planting and harvesting schedules, often necessitating earlier crop cultivation. Notably, climate change introduces a suite of ominous factors, such as greenhouse gas emissions (CGHs), including elevated temperature, increased carbon dioxide (CO2) concentrations, nitrous oxide (N2O) and methane (CH4) ozone depletion (O3), and deforestation, all of which intensify environmental stresses on crops. Consequently, climate change stands poised to adversely affect crop yields and livestock production. Therefore, the primary objective of the review article is to furnish a comprehensive overview of the multifaceted factors influencing horticulture production, encompassing fruits, vegetables, and plantation crops with a particular emphasis on greenhouse gas emissions and environmental stressors such as high temperature, drought, salinity, and emission of CO2. Additionally, this review will explore the implementation of novel horticultural crop varieties and greenhouse technology that can contribute to mitigating the adverse impact of climate change on agricultural crops.
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Advances and future research in ecological stoichiometry under saline-alkali stress.
Zhang, K, Chang, L, Li, G, Li, Y
Environmental science and pollution research international. 2023;(3):5475-5486
Abstract
Saline-alkali stress is a serious abiotic factor which negatively impacts agricultural production and the ecological environment. Thus, improving the development of saline-alkali soil and reducing the effects of saline-alkali stress is a key issue for sustainable agricultural development and environmental protection. As such, it is unsurprising that researchers have lately focused on how to improve saline-alkali soil, increase the agricultural yield of saline-alkali land, and promote the adaptive growth of plants in saline-alkali soil. This paper reviews the latest research concerning nutrient content changes in saline-alkali soil, along with the associated changes in key nutrients in plants, to summarize which methods are most effective for improving the plant growth under saline-alkali stress. Finally, the prospects for alleviating saline-alkali stress and improving saline-alkali soil are put forward as a theoretical foundation for the stabilization of plant growth in saline-alkali soil, expansion of arable land area, crop yield improvement, and effective environmental protection.
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Plecanatide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation: Post hoc analyses of placebo-controlled trials in adults with severe constipation.
Cash, BD, Sharma, A, Walker, A, Laitman, AP, Chang, L
Neurogastroenterology and motility. 2023;(9):e14632
Abstract
BACKGROUND Patients with chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation (IBS-C) often experience severe symptoms. The current aim was to evaluate plecanatide in adults with CIC or IBS-C with severe constipation. METHODS Data were analyzed post hoc from randomized, placebo-controlled trials (CIC [n = 2], IBS-C [n = 2]) of plecanatide 3 mg, 6 mg, or placebo administered for 12 weeks. Severe constipation was defined as no complete spontaneous bowel movements (CSBMs) and an average straining score ≥3.0 (CIC; 5-point scale) or ≥8.0 (IBS-C; 11-point scale) during a 2-week screening. Primary efficacy endpoints were durable overall CSBM responders (CIC: ≥3 CSBMs/week, plus increase from baseline of ≥1 CSBM/week, for ≥9 of 12 weeks, including ≥3 of the last 4 weeks) and overall responders (IBS-C: ≥30% reduction from baseline in abdominal pain and ≥1 CSBM/week increase for ≥6 of 12 weeks). KEY RESULTS Severe constipation was observed in 24.5% (646/2639) and 24.2% (527/2176) of CIC and IBS-C populations, respectively. The CIC durable overall CSBM response rate (plecanatide 3 mg, 20.9%; plecanatide 6 mg, 20.2%; placebo, 11.3%) and IBS-C overall response rate (plecanatide 3 mg, 33.0%; plecanatide 6 mg, 31.0%; placebo, 19.0%) were significantly greater with plecanatide versus placebo (p ≤ 0.01 for all). Median time to first CSBM in CIC and IBS-C populations were significantly shorter with plecanatide 3 mg versus placebo (p = 0.01 for both). CONCLUSIONS AND INFERENCES Plecanatide was effective in the treatment of severe constipation in adults with CIC or IBS-C.
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An investigation of long-term outcome of rabbit anti-thymocyte globulin and cyclosporine therapy for pediatric severe aplastic anemia.
Chang, L, Yan, M, Zhang, J, Liu, B, Zhang, L, Guo, Y, Sun, J, Wan, Y, Yi, M, Lan, Y, et al
Blood science (Baltimore, Md.). 2023;(3):180-186
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Abstract
Children with severe aplastic anemia (SAA) face heterogeneous prognoses after immunosuppressive therapy (IST). There are few models that can predict the long-term outcomes of IST for these patients. The objective of this paper is to develop a more effective prediction model for SAA prognosis based on clinical electronic medical records from 203 children with newly diagnosed SAA. In the early stage, a novel model for long-term outcomes of SAA patients with IST was developed using machine-learning techniques. Among the indicators related to long-term efficacy, white blood cell count, lymphocyte count, absolute reticulocyte count, lymphocyte ratio in bone-marrow smears, C-reactive protein, and the level of IL-6, IL-8 and vitamin B12 in the early stage are strongly correlated with long-term efficacy (P < .05). Taken together, we analyzed the long-term outcomes of rabbit anti-thymocyte globulin and cyclosporine therapy for children with SAA through machine-learning techniques, which may shorten the observation period of therapeutic effects and reduce treatment costs and time.
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Effect of probiotic supplementation on cognition and depressive symptoms in patients with depression: A systematic review and meta-analysis.
He, J, Chang, L, Zhang, L, Wu, W, Zhuo, D
Medicine. 2023;(47):e36005
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Abstract
BACKGROUND Depression affects millions globally and often coexists with cognitive deficits. This study explored the potential of probiotics in enhancing cognition and ameliorating depressive symptoms in major depressive disorder patients. METHODS Utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol and the Population, Intervention, Comparator, Outcome, and Study design framework, we systematically reviewed randomized controlled trials examining probiotic effects on cognition and depressive symptoms. Searches spanned 7 databases from January 2010 to May 2022. Risk of bias was assessed using Revised Cochrane Risk of Bias 2.0, and meta-analysis was conducted with RevMan 5.4.1. Publication bias was evaluated via Egger test. RESULTS In a systematic review on the effects of probiotic supplementation on cognition and depressive symptoms in depression patients, 635 records were initially identified, with 4 studies ultimately included. These randomized controlled trials were conducted across diverse regions, primarily involving females, with assessment periods ranging from 1 to 2 months. Concerning cognitive outcomes, a statistically significant moderate improvement was found with probiotic supplementation, based on the mean difference and its 95% confidence interval. However, for depressive symptoms, the overall effect was negligible and not statistically significant. A heterogeneity test indicated consistent findings across studies for both cognitive and depressive outcomes (I² = 0% for both). The potential for publication bias was evaluated using the Egger linear regression test, suggesting no significant bias, though caution is advised due to the limited number of studies. CONCLUSION Probiotics may enhance cognitive domains and mitigate depressive symptoms, emphasizing the gut-brain axis role. However, methodological variations and brief intervention durations call for more standardized, extensive research.
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Randomized controlled pilot study assessing fructose tolerance during fructose reintroduction in non-constipated irritable bowel syndrome patients successfully treated with a low FODMAP diet.
Cuff, C, Lin, LD, Mahurkar-Joshi, S, Jacobs, JP, Lagishetty, V, Jaffe, N, Smith, J, Dong, T, Sohn, J, Chang, L
Neurogastroenterology and motility. 2023;(7):e14575
Abstract
BACKGROUND Limited data exist to guide FODMAP (fermentable oligo-, di-, monosaccharides, and polyols) reintroduction to assess tolerance following a low FODMAP diet (LFD). Fructose reintroduction is often stepwise up to 7.5 g fructose (e.g., three tsp of honey). We aimed to determine the fructose tolerance threshold in non-constipated, LFD-responsive patients with irritable bowel syndrome (IBS) and assess whether stool microbiome predicted LFD response or fructose tolerance. METHODS Thirty-nine non-constipated IBS patients (51% women, mean age 33.7 years) completed a 4-week LFD. LFD responders were defined as those who reported adequate relief of IBS symptoms following the LFD. Responders were randomized to one of the three solution groups (100% fructose, 56% fructose/44% glucose, or 100% glucose) and received four doses (2.5, 5, 10, 15 g) for 3 days each. Patients reached their tolerance dose if their mean daily IBS symptom severity (visual analog scale [VAS], 0-100 mm) was >20 mm higher than post-LFD VAS. Stool samples before and after LFD were analyzed using shotgun metagenomics. RESULTS Seventy-nine percent of patients were LFD responders. Most responders tolerated the 15 g sugar dose. There was no significant difference in mean dose tolerated between solution groups (p = 0.56). Compared to baseline, microbiome composition (beta diversity) significantly shifted and six bacterial genes in fructose and mannose metabolism pathways decreased after LFD, irrespective of LFD response or the solution group. CONCLUSIONS Non-constipated, LFD-responsive IBS patients should be reintroduced to fructose in higher doses than 15 g to assess tolerance. LFD is associated with significant changes in microbial composition and bacterial genes involved in FODMAP metabolism.
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Recent Advancements and Biotechnological Implications of Carotenoid Metabolism of Brassica.
Shi, L, Chang, L, Yu, Y, Zhang, D, Zhao, X, Wang, W, Li, P, Xin, X, Zhang, F, Yu, S, et al
Plants (Basel, Switzerland). 2023;(5)
Abstract
Carotenoids were synthesized in the plant cells involved in photosynthesis and photo-protection. In humans, carotenoids are essential as dietary antioxidants and vitamin A precursors. Brassica crops are the major sources of nutritionally important dietary carotenoids. Recent studies have unraveled the major genetic components in the carotenoid metabolic pathway in Brassica, including the identification of key factors that directly participate or regulate carotenoid biosynthesis. However, recent genetic advances and the complexity of the mechanism and regulation of Brassica carotenoid accumulation have not been reviewed. Herein, we reviewed the recent progress regarding Brassica carotenoids from the perspective of forward genetics, discussed biotechnological implications and provided new perspectives on how to transfer the knowledge of carotenoid research in Brassica to the crop breeding process.
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Research Progresses on the Function and Detection Methods of Insect Gut Microbes.
Li, Y, Chang, L, Xu, K, Zhang, S, Gao, F, Fan, Y
Microorganisms. 2023;(5)
Abstract
The insect gut is home to an extensive array of microbes that play a crucial role in the digestion and absorption of nutrients, as well as in the protection against pathogenic microorganisms. The variety of these gut microbes is impacted by factors such as age, diet, pesticides, antibiotics, sex, and caste. Increasing evidence indicates that disturbances in the gut microbiota can lead to compromised insect health, and that its diversity has a far-reaching impact on the host's health. In recent years, the use of molecular biology techniques to conduct rapid, qualitative, and quantitative research on the host intestinal microbial diversity has become a major focus, thanks to the advancement of metagenomics and bioinformatics technologies. This paper reviews the main functions, influencing factors, and detection methods of insect gut microbes, in order to provide a reference and theoretical basis for better research utilization of gut microbes and management of harmful insects.