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1.
Gut microbial metabolites SCFAs and chronic kidney disease.
He, M, Wei, W, Zhang, Y, Xiang, Z, Peng, D, Kasimumali, A, Rong, S
Journal of translational medicine. 2024;(1):172
Abstract
The global incidence of Chronic Kidney Disease (CKD) is steadily escalating, with discernible linkage to the intricate terrain of intestinal microecology. The intestinal microbiota orchestrates a dynamic equilibrium in the organism, metabolizing dietary-derived compounds, a process which profoundly impacts human health. Among these compounds, short-chain fatty acids (SCFAs), which result from microbial metabolic processes, play a versatile role in influencing host energy homeostasis, immune function, and intermicrobial signaling, etc. SCFAs emerge as pivotal risk factors influencing CKD's development and prognosis. This paper review elucidates the impact of gut microbial metabolites, specifically SCFAs, on CKD, highlighting their role in modulating host inflammatory responses, oxidative stress, cellular autophagy, the immune milieu, and signaling cascades. An in-depth comprehension of the interplay between SCFAs and kidney disease pathogenesis may pave the way for their utilization as biomarkers for CKD progression and prognosis or as novel adjunctive therapeutic strategies.
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2.
Exogenous Chemicals Used to Alleviate or Salvage Plants under Flooding/Waterlogging Stress: Their Biochemical Effects and Perspectives.
Feng, D, Wang, L, Ning, S, Peng, D, Xu, H, Sun, C, Sun, X
Journal of agricultural and food chemistry. 2024;(1):65-79
Abstract
Plant flooding/waterlogging stress (FWS) can be a threat to food security worldwide due to climate change. To mitigate its potential devastation, numerous exogenous chemicals (ECs) have been used to demonstrate their effectiveness on alleviating FWS for the last 20 years. This review has summarized the most recent findings on use of various ECs as either nutrients or regulatory substances on crop plants under FWS and their roles involved in improving root respiration of seedlings, optimizing nutritional status, synthesizing osmotic regulators, enhancing the activity of antioxidant enzymes, adjusting phytohormone levels, maintaining photosynthetic systems, and activating flood-tolerance related gene expressions. The effect of ESs on alleviating plants under FWS proves to be beneficial and useful but rather limited unless they are applied on appropriate crops, at the right time, and with optimized methods. Further research should be focused on use of ESs in field settings and on their potential synergetic effect for more FWS tolerance.
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3.
Short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer: A pooling up analysis.
Kang, B, Liu, XR, Peng, D
Open medicine (Warsaw, Poland). 2023;(1):20220605
Abstract
The purpose of this study was to evaluate the short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer patients. PUBMED, EMBASE, and the Cochrane Library were searched from inception to Apr 15, 2021. Short-term surgical outcomes were compared between the simultaneous gastrectomy plus cholecystectomy group and the gastrectomy only group. Five retrospective studies with 3,315 patients and 1 randomized controlled trial with 130 patients were included. There was no significant difference in age, sex, surgical methods, or reconstruction. In terms of short-term outcomes, no significance was found in postoperative complications (odds ratio, OR = 1.08, I 2 = 24%, 95% CI = 0.78-1.50, P = 0.65), postoperative biliary complications (OR = 0.98, I 2 = 0%, 95% CI = 0.43-2.25, P = 0.96), mortality (OR = 1.28, I 2 = 0%, 95% CI = 0.49-3.37, P = 0.61), and postoperative hospital stay (MD = -0.10, I 2 = 0%, 95% CI = -0.73-0.54, P = 0.77) between the two groups. Simultaneous gastrectomy plus cholecystectomy in gastric cancer patients is safe and does not increase the short-term outcomes.
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4.
Caged Polyprenylated Xanthones in Garcinia hanburyi and the Biological Activities of Them.
He, R, Jia, B, Peng, D, Chen, W
Drug design, development and therapy. 2023;:3625-3660
Abstract
The previous phytochemical analyses of Garcinia hanburyi revealed that the main structural characteristic associated with its biological activity is the caged polyprenylated xanthones with a unique 4-oxatricyclo [4.3.1.03,7] dec-2-one scaffold, which contains a highly substituted tetrahydrofuran ring with three quaternary carbons. Based on the progress in research of the chemical constituents, pharmacological effects and modification methods of the caged polyprenylated xanthones, this paper presents a preliminary predictive analysis of their drug-like properties based on the absorption, distribution, metabolism, excretion and toxicity (ADME/T) properties. It was found out that these compounds have very similar pharmacokinetic properties because they possess the same caged xanthone structure, the 9,10-double bond in a,b-unsaturated ketones are critical for the antitumor activity. The author believes that there is an urgent need to seek new breakthroughs in the study of these caged polyprenylated xanthones. Thus, the research on the route of administration, therapeutic effect, structural modification and development of such active ingredients is of great interest. It is hoped that this paper will provide ideas for researchers to develop and utilize the active ingredients derived from natural products.
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5.
Mechanisms of unusual response to lipid-lowering therapy: PCSK9 inhibition.
Ouyang, M, Li, C, Hu, D, Peng, D, Yu, B
Clinica chimica acta; international journal of clinical chemistry. 2023;:113-123
Abstract
The efficacy of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition has broadened lipid-lowering therapy thus providing decreased risk in atherosclerotic cardiovascular disease. Unfortunately, the widespread use of PCSK9 inhibitors (PCSK9i), ie, monoclonal antibodies, has led to the findings of unusual responsiveness, ie, a phenomenon defined as an LDL-C reduction of <30% vs the average LDL-C reduction efficacy of 50-60%. This unusual responsiveness to PCSK9i is attributable to several factors, ie, lack of adherence, impaired absorption, poor distribution or early elimination as well as abnormal effects of PCSK9i in the presence of anti-antibodies or mutations in PCSK9 and LDLR. Unexpectedly increased lipoprotein (Lp)(a) also appear to contribute to the unusual responsiveness scenario. Identification of these responses and mechanisms underlying them are essential for effective management of LDL-C and cardiovascular risk. In this review, we describe plausible reasons underlying this phenomenon supported by findings of clinical trials. We also elaborate on the need for education and regular follow-up to improve adherence. Collectively, the review provides a summary of the past, present, and future of mechanisms and countermeasures revolving around unusual responses to PCSK9i therapy.
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6.
Rethinking glutamine metabolism and the regulation of glutamine addiction by oncogenes in cancer.
Ni, R, Li, Z, Li, L, Peng, D, Ming, Y, Li, L, Liu, Y
Frontiers in oncology. 2023;:1143798
Abstract
Glutamine, the most abundant non-essential amino acid in human blood, is crucial for cancer cell growth and cancer progression. Glutamine mainly functions as a carbon and nitrogen source for biosynthesis, energy metabolism, and redox homeostasis maintenance in cancer cells. Dysregulated glutamine metabolism is a notable metabolic characteristic of cancer cells. Some carcinogen-driven cancers exhibit a marked dependence on glutamine, also known as glutamine addiction, which has rendered the glutamine metabolic pathway a breakpoint in cancer therapeutics. However, some cancer cells can adapt to the glutamine unavailability by reprogramming metabolism, thus limiting the success of this therapeutic approach. Given the complexity of metabolic networks and the limited impact of inhibiting glutamine metabolism alone, the combination of glutamine metabolism inhibition and other therapeutic methods may outperform corresponding monotherapies in the treatment of cancers. This review summarizes the uptake, transport, and metabolic characteristics of glutamine, as well as the regulation of glutamine dependence by some important oncogenes in various cancers to emphasize the therapeutic potential of targeting glutamine metabolism. Furthermore, we discuss a glutamine metabolic pathway, the glutaminase II pathway, that has been substantially overlooked. Finally, we discuss the applicability of polytherapeutic strategies targeting glutamine metabolism to provide a new perspective on cancer therapeutics.
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7.
The advanced lung cancer inflammation index is a prognostic factor for gastrointestinal cancer patients undergoing surgery: a systematic review and meta-analysis.
Liu, XR, Wang, LL, Zhang, B, Liu, XY, Li, ZW, Kang, B, Yuan, C, Wei, ZQ, Peng, D
World journal of surgical oncology. 2023;(1):81
Abstract
BACKGROUND The advanced lung cancer inflammation index (ALI) is a comprehensive assessment indicator that can reflect inflammation and nutrition conditions. However, there are some controversies about whether ALI is an independent prognostic factor for gastrointestinal cancer patients undergoing surgical resection. Thus, we aimed to clarify its prognostic value and explore the potential mechanisms. METHODS Four databases including PubMed, Embase, the Cochrane Library, and CNKI were used for searching eligible studies from inception to June 28, 2022. All gastrointestinal cancers, including colorectal cancer (CRC), gastric cancer (GC), esophageal cancer (EC), liver cancer, cholangiocarcinoma, and pancreatic cancer were enrolled for analysis. We focused on prognosis most in the current meta-analysis. Survival indicators, including overall survival (OS), disease-free survival (DFS), and cancer-special survival (CSS) were compared between the high ALI group and the low ALI group. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was submitted as a supplementary document. RESULTS We finally included fourteen studies involving 5091 patients in this meta-analysis. After pooling the hazard ratios (HRs) and 95% confidence intervals (CIs), ALI was found to be an independent prognostic factor for both OS (HR = 2.09, I2 = 92%, 95% CI = 1.53 to 2.85, P < 0.01), DFS (HR = 1.48, I2 = 83%, 95% CI = 1.18 to 1.87, P < 0.01), and CSS (HR = 1.28, I2 = 1%, 95% CI = 1.02 to 1.60, P = 0.03) in gastrointestinal cancer. After subgroup analysis, we found that ALI was still closely related to OS for CRC (HR = 2.26, I2 = 93%, 95% CI = 1.53 to 3.32, P < 0.01) and GC (HR = 1.51, I2 = 40%, 95% CI = 1.13 to 2.04, P = 0.006) patients. As for DFS, ALI also has a predictive value on the prognosis of CRC (HR = 1.54, I2 = 85%, 95% CI = 1.14 to 2.07, P = 0.005) and GC (HR = 1.37, I2 = 0%, 95% CI = 1.09 to 1.73, P = 0.007) patients. CONCLUSION ALI affected gastrointestinal cancer patients in terms of OS, DFS, and CSS. Meanwhile, ALI was a prognostic factor both for CRC and GC patients after subgroup analysis. Patients with low ALI had poorer prognoses. We recommended that surgeons should perform aggressive interventions in patients with low ALI before the operation.
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8.
Eat for better cognition in older adults at risk for Alzheimer's disease.
Wang, Y, Niu, X, Peng, D
Nutrition (Burbank, Los Angeles County, Calif.). 2023;:111969
Abstract
Alzheimer's disease is a worldwide public health problem. However, the treatment method and treatment effects are limited. The stages of preclinical Alzheimer's disease are thought to be a better intervention period. Thus, in this review, food is given focus and the intervention stage put forward. We summarized the role of diet, nutrient supplementation, and microbioecologics in cognitive decline and found that interventions such as modified Mediterranean-ketogenic diet, nuts, vitamin B, and Bifidobacterium breve A1 are beneficial to cognition protection. Eating, rather than just taking medicine, is suggested to be an effective treatment method for older adults at risk for Alzheimer's disease.
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9.
The Effect of Metabolic Syndrome on Colorectal Cancer Prognosis after Primary Surgery.
Tao, W, Yuan, C, Kang, B, Liu, XY, Cheng, YX, Zhang, B, Wei, ZQ, Peng, D
Nutrition and cancer. 2023;(1):331-338
Abstract
PURPOSE The purpose of this study was to explore whether metabolic syndrome (MetS) affects the prognosis of colorectal cancer (CRC) patients after primary surgery and to analyze the effect of the specific components of MetS on CRC prognosis. METHODS The PubMed, Embase and Cochrane Library databases were searched from inception to July 29, 2021. Overall survival (OS) and disease-free survival (DFS) were compared between the MetS group and the non-MetS group. RESULTS The studies included in the meta-analysis included 4773 patients. All seven studies compared OS between the two groups, and after pooling all hazard ratios (HRs), no significant difference was found between the MetS group and the non-MetS group (HR = 1.17, 95% CI = 0.91 to 1.49, P = 0.21). Four studies compared DFS between the MetS group and the non-MetS group after pooling all the HRs, and there was no difference between the MetS group and the non-MetS group (HR = 1.05, 95% CI = 0.74 to 1.49, P = 0.21). Among the specific components of MetS, high fasting plasma glucose levels (HR = 1.25, 95% CI = 1.00 to 1.58, P = 0.05) had a marginally significant association with poor OS. CONCLUSION MetS may not affect the prognosis of CRC after primary surgery. However, high fasting plasma glucose levels might contribute to poor OS.
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10.
Safety, tolerability, pharmacokinetics and effects of diet on AD16, a novel neuroinflammatory inhibitor for Alzheimer's disease: a randomized phase 1 study.
Peng, D, Xu, S, Zou, T, Wang, Y, Ouyang, W, Zhang, Y, Dong, C, Li, D, Guo, J, Shen, Q, et al
BMC medicine. 2023;(1):459
Abstract
BACKGROUND AD16 is a Class 1.1 new drug candidate for Alzheimer's disease (AD), which has demonstrated potential benefits in AD by reducing neuroinflammation in preclinical studies. Herein, the pharmacokinetics (PK), safety, and tolerability of single and multiple-dose AD16 and the effect of food were assessed in healthy Chinese adults. METHODS Single-center, randomized, placebo-controlled, double-blind studies were conducted for single and multiple ascending doses. A total of 62 subjects were enrolled in single-dose groups; 10 each in 5, 10, 20, 30, and 40 mg groups, and 6 each in 60 and 80 mg dose groups. Twenty subjects were divided equally into 30 and 40 mg groups for the multiple-dose study. To determine the effect of a high-fat diet on AD16, 16 subjects were administered a single 20 mg dose of AD16 under the fasted and fed condition in a single-center, randomized, open-label, two-cycle, two-crossover study. Moreover, safety and PK parameters were also assessed. RESULTS Plasma exposure to a single oral dose of AD16 increased at an approximate dose-increasing rate. The pharmacodynamic dose of the AD16 can be maintained through the accumulation effect of the drug within the safety window. Compared to fasting, ingesting a high-fat meal decelerated the rate of AD16 absorption, albeit without effect on its overall absorption. No dose-related toxicities were seen in any of the studies, all treatment-emergent adverse events were grade I/II, and no serious adverse event occurred. CONCLUSIONS The present study exhibited favorable safety, tolerability, and PK profile of AD16, supporting its further research as a potential drug treatment for AD. TRIAL REGISTRATION ClinicalTrials.gov; NCT05787028, NCT05787041, NCT05806177. The SAD and FE studies were retrospectively registered on 28 March 2023. The MAD study was retrospectively registered on 10 April 2023.