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Imbalance of gut microbiota in gestational diabetes.
Shen, W, Chen, Q, Lin, R, Hu, Z, Luo, M, Ren, Y, Huang, K, Wang, L, Chen, S, Wang, L, et al
BMC pregnancy and childbirth. 2024;(1):226
Abstract
AIM: To investigate the differences in gut microbiota composition among nonpregnant women of reproductive age, healthy pregnant women, and gestational diabetes (GD) patients. METHODS A total of 45 outpatients were enrolled and divided into three groups: nonpregnant women of reproductive age (control group, n = 23), healthy pregnant women (normal group, n = 10), and GD patients (GD group, n = 12). Faecal samples were collected and sequenced using 16S rRNA gene sequencing to analyse the microbial composition. RESULTS (1) Pregnant patients exhibited an increase in the abundance of Streptococcus (Pnormal = 0.01286, PGD = 0.002965) and Blautia (Pnormal = 0.0003924, PGD = 0.000246) but a decrease in the abundance of Roseburia (Pnormal = 0.0361, PGD = 0.007075), Phascolarctobacterium (Pnormal = 0.0003906, PGD = 0.02499) and Lachnoclostridium (Pnormal = 0.0003906, PGD = 0.03866). (2) Compared with healthy pregnant women, GD patients had an excessive increase in Streptococcus abundance and decrease in Roseburia abundance. The increase in Blautia abundance and the decrease in Phascolarctobacterium and Lachnoclostridium abundance in GD patients were less than those in healthy pregnant women. (3) The abundance of Faecalibacterium prausnitzii decreased significantly in GD patients (PGD = 0.02985) but not in healthy pregnant patients (Pnormal = 0.1643). CONCLUSIONS Abnormal increases and decreases in the abundances of gut microbiota components, especially Faecalibacterium prausnitzii, were observed in GD patients. TRIAL REGISTRATION The cross-sectional research was conducted in accordance with the Declaration of Helsinki, and approved by Sir Run Run Shaw Hospital Clinical Trials and Biomedical Ethics Committee. The study has been registered in the Chinese Clinical Trial Registry (ChiCTR1900026164, 24/09/2019, http://www.chictr.org.cn/showproj.aspx?proj=43,455 ).
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Dual role of PRDX1 in redox-regulation and tumorigenesis: Past and future.
Guan, X, Ruan, Y, Che, X, Feng, W
Free radical biology & medicine. 2024;:120-129
Abstract
Tumour cells often display an active metabolic profile, leading to the intracellular accumulation of reactive oxygen species. As a member of the peroxidase family, peroxiredoxin 1 (PRDX1) functions generally in protecting against cell damage caused by H2O2. Additionally, PRDX1 plays a role as a molecular chaperone in various malignant tumours, exhibiting either tumour-promoting or tumour-suppressing effects. Currently, PRDX1-targeting drugs have demonstrated in vitro anticancer effects, indicating the potential of PRDX1 as a molecular target. Here we discussed the diverse functions of PRDX1 in tumour biology and provided a comprehensive analysis of the therapeutic potential of targeting PRDX1 signalling across various types of cancer.
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Exploring Novel Antidepressants Targeting G Protein-Coupled Receptors and Key Membrane Receptors Based on Molecular Structures.
Yao, H, Wang, X, Chi, J, Chen, H, Liu, Y, Yang, J, Yu, J, Ruan, Y, Xiang, X, Pi, J, et al
Molecules (Basel, Switzerland). 2024;(5)
Abstract
Major Depressive Disorder (MDD) is a complex mental disorder that involves alterations in signal transmission across multiple scales and structural abnormalities. The development of effective antidepressants (ADs) has been hindered by the dominance of monoamine hypothesis, resulting in slow progress. Traditional ADs have undesirable traits like delayed onset of action, limited efficacy, and severe side effects. Recently, two categories of fast-acting antidepressant compounds have surfaced, dissociative anesthetics S-ketamine and its metabolites, as well as psychedelics such as lysergic acid diethylamide (LSD). This has led to structural research and drug development of the receptors that they target. This review provides breakthroughs and achievements in the structure of depression-related receptors and novel ADs based on these. Cryo-electron microscopy (cryo-EM) has enabled researchers to identify the structures of membrane receptors, including the N-methyl-D-aspartate receptor (NMDAR) and the 5-hydroxytryptamine 2A (5-HT2A) receptor. These high-resolution structures can be used for the development of novel ADs using virtual drug screening (VDS). Moreover, the unique antidepressant effects of 5-HT1A receptors in various brain regions, and the pivotal roles of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and tyrosine kinase receptor 2 (TrkB) in regulating synaptic plasticity, emphasize their potential as therapeutic targets. Using structural information, a series of highly selective ADs were designed based on the different role of receptors in MDD. These molecules have the favorable characteristics of rapid onset and low adverse drug reactions. This review offers researchers guidance and a methodological framework for the structure-based design of ADs.
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Associations of microvascular complications with all-cause death in patients with diabetes and COVID-19: The CORONADO, ABCD COVID-19 UK national audit and AMERICADO study groups.
Hadjadj, S, Saulnier, PJ, Ruan, Y, Zhu, X, Pekmezaris, R, Marre, M, Halimi, JM, Wargny, M, Rea, R, Gourdy, P, et al
Diabetes, obesity & metabolism. 2023;(1):78-88
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Abstract
AIM: To provide a detailled analysis of the microvascular burden in patients with diabetes hopitalized for COVD-19. MATERIALS AND METHODS We analysed data from the French CORONADO initiative and the UK Association of British Clinical Diabetologists (ABCD) COVID-19 audit, two nationwide multicentre studies, and the AMERICADO, a multicentre study conducted in New York area. We assessed the association between risk of all-cause death during hospital stay and the following microvascular complications in patients with diabetes hospitalized for COVID-19: diabetic retinopathy and/or diabetic kidney disease and/or history of diabetic foot ulcer. RESULTS Among 2951 CORONADO, 3387 ABCD COVID-19 audit and 9327 AMERICADO participants, microvascular diabetic complications status was ascertained for 1314 (44.5%), 1809 (53.4%) and 7367 (79.0%) patients, respectively: 1010, 1059 and 1800, respectively, had ≥1 severe microvascular complication(s) and 304, 750 and 5567, respectively, were free of any complications. The patients with isolated diabetic kidney disease had an increased risk of all-cause death during hospital stay: odds ratio [OR] 2.53 (95% confidence interval [CI] 1.66-3.83), OR 1.24 (95% CI 1.00-1.56) and OR 1.66 (95% CI 1.40-1.95) in the CORONADO, the ABCD COVID-19 national audit and the AMERICADO studies, respectively. After adjustment for age, sex, hypertension and cardiovascular disease (CVD), compared to those without microvascular complications, patients with microvascular complications had an increased risk of all-cause death during hospital stay in the CORONADO, the ABCD COVID-19 diabetes national audit and the AMERICADO studies: adjusted OR (adj OR) 2.57 (95% CI 1.69-3.92), adj OR 1.22 (95% CI 1.00-1.52) and adj OR 1.33 (95% CI 1.15-1.53), respectively. In meta-analysis of the three studies, compared to patients free of complications, those with microvascular complications had an unadjusted OR for all-cause death during hospital stay of 2.05 (95% CI 1.42-2.97), which decreased to 1.62 (95% CI 1.19-2.119) after adjustment for age and sex, and to 1.50 (1.12-2.02) after hypertension and CVD were further added to the model. CONCLUSION Microvascular burden is associated with an increased risk of death in patients hospitalized for COVID-19.
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American Society for Gastrointestinal Endoscopy guideline on endoscopic submucosal dissection for the management of early esophageal and gastric cancers: methodology and review of evidence.
Al-Haddad, MA, Elhanafi, SE, Forbes, N, Thosani, NC, Draganov, PV, Othman, MO, Ceppa, EP, Kaul, V, Feely, MM, Sahin, I, et al
Gastrointestinal endoscopy. 2023;(3):285-305.e38
Abstract
This document from the American Society for Gastrointestinal Endoscopy (ASGE) provides a full description of the methodology used in the review of the evidence used to inform the final guidance outlined in the accompanying Summary and Recommendations document regarding the role of endoscopic submucosal dissection (ESD) in the management of early esophageal and gastric cancers. This guideline used the Grading of Recommendations, Assessment, Development and Evaluation framework and specifically addresses the role of ESD versus EMR and/or surgery, where applicable, for the management of early esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric adenocarcinoma (GAC) and their corresponding precursor lesions. For ESCC, the ASGE suggests ESD over EMR for patients with early-stage, well-differentiated, nonulcerated cancer >15 mm, whereas in patients with similar lesions ≤15 mm, the ASGE suggests either ESD or EMR. The ASGE suggests against surgery for such patients with ESCC, whenever possible. For EAC, the ASGE suggests ESD over EMR for patients with early-stage, well-differentiated, nonulcerated cancer >20 mm, whereas in patients with similar lesions measuring ≤20 mm, the ASGE suggests either ESD or EMR. For GAC, the ASGE suggests ESD over EMR for patients with early-stage, well or moderately differentiated, nonulcerated intestinal type cancer measuring 20 to 30 mm, whereas for patients with similar lesions <20 mm, the ASGE suggests either ESD or EMR. The ASGE suggests against surgery for patients with such lesions measuring ≤30 mm, whereas for lesions that are poorly differentiated, regardless of size, the ASGE suggests surgical evaluation over endosic approaches.
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Insight into the binding model of per- and polyfluoroalkyl substances to proteins and membranes.
Zhao, L, Teng, M, Zhao, X, Li, Y, Sun, J, Zhao, W, Ruan, Y, Leung, KMY, Wu, F
Environment international. 2023;:107951
Abstract
Legacy per- and polyfluoroalkyl substances (PFASs) have elicited much concern because of their ubiquitous distribution in the environment and the potential hazards they pose to wildlife and human health. Although an increasing number of effective PFAS alternatives are available in the market, these alternatives bring new challenges. This paper comprehensively reviews how PFASs bind to transport proteins (e.g., serum albumin, liver fatty acid transport proteins and organic acid transporters), nuclear receptors (e.g., peroxisome proliferator activated receptors, thyroid hormone receptors and reproductive hormone receptors) and membranes (e.g., cell membrane and mitochondrial membrane). Briefly, the hydrophobic fluorinated carbon chains of PFASs occupy the binding cavities of the target proteins, and the acid groups of PFASs form hydrogen bonds with amino acid residues. Various structural features of PFAS alternatives such as chlorine atom substitution, oxygen atom insertion and a branched structure, introduce variations in their chain length and hydrophobicity, which potentially change the affinity of PFAS alternatives for endogenous proteins. The toxic effects and mechanisms of action of legacy PFASs can be demonstrated and compared with their alternatives using binding models. In future studies, in vitro experiments and in silico quantitative structure-activity relationship modeling should be better integrated to allow more reliable toxicity predictions for both legacy and alternative PFASs.
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Retrospective study of the combination of TP and PF regimens with or without immune checkpoint inhibitors for the first-line treatment of locally advanced or advanced esophageal squamous cell carcinoma.
Zhang, Z, Yang, L, Wang, D, Ruan, Y, Zhang, J, Zhao, L, Yang, L, Lou, C
Therapeutic advances in medical oncology. 2023;:17588359231169981
Abstract
OBJECTIVE To investigate the efficacy and safety differences between the cisplatin + paclitaxel (TP) and cisplatin + fluorouracil (PF) regimens in combination with or without immune checkpoint inhibitors (ICIs) in advanced esophageal squamous cell carcinoma (ESCC) first-line treatment and prognostic factors. METHODS We selected the medical records of patients with late stage ESCC admitted to the hospital between 2019 and 2021. Based on the first-line treatment regimen, control groups were divided into chemotherapy plus ICIs (n = 243) and non-ICIs (n = 171), 119 (49%) in the TP + ICIs group, 124 (51%) in the PF + ICIs group, 83 (48.5%) in the TP group, and 88 (51.5%) in the PF group in the control group. We analyzed and compared factors related to efficacy, safety, or response to toxicity and prognosis across four subgroups. RESULTS The overall objective response rate (ORR) and disease control rate (DCR) of the TP plus ICIs group were 42.1% (50/119) and 97.5% (116/119), respectively, which were 6.6% and 7.2% higher than those of the PF plus ICIs group. Patients in the TP combined with ICIs group had higher overall survival (OS) and progression-free survival (PFS) than those in the PF combined with ICIs group [hazard ratio (HR) = 1.702, 95% confidence interval (CI): 0.767-1.499, p = 0.0167 and HR = 1.158, 95% CI: 0.828-1.619, p = 0.0055] ORR and DCR were 15.7% (13/83) and 85.5% (71/83) in the TP chemotherapy alone group, significantly higher than the PF group [13.6% (12/88) and 72.2% (64/88)] (p < 0.05), OS and PFS were also better in patients treated with TP regimen chemotherapy than PF (HR = 1.173, 95% CI: 0.748-1.839, p = 0.0014 and HR = 0.1.245, 95% CI: 0.711-2.183, p = 0.0061). Furthermore, following the combination of TP and PF diets with ICIs, the OS of the patients was higher than that of the group treated with chemotherapy alone (HR = 0.526, 95% CI: 0.348-0.796, p = 0.0023 and HR = 0.781, 95% CI: 0.0.491-1.244, p < 0.001). Regression analysis showed that the neutrophil-to-lymphocyte ratio (NLR), the control nuclear status score (CONUT), and the systematic immune inflammation index (SII) were independent prognostic factors for the efficacy of immunotherapy (p < 0.05). The overall incidence of treatment-associated adverse events (TRAEs) was 79.4% (193/243) and 60.8% (104/171) in the experimental and control groups, respectively, and there was no statistically significant difference in TRAEs between TP + ICIs (80.6%) and PF + ICIs (78.2%) (61.4%) and PF groups (60.2%) (p > 0.05). Overall, 21.0% (51/243) of patients in the experimental group experienced immune-related adverse events (irAEs), and all of these adverse effects were tolerated or remitted following drug treatment without affecting follow-up. CONCLUSION The TP regimen was associated with better PFS and OS with or without ICIs. Furthermore, high CONUT scores, high NLR ratios, and high SII were found to be associated with poor prognosis in combination immunotherapy.
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Extraction, Purification, Structural Characteristics, Health Benefits, and Application of the Polysaccharides from Lonicera japonica Thunb.: A Review.
Yang, X, Yu, A, Hu, W, Zhang, Z, Ruan, Y, Kuang, H, Wang, M
Molecules (Basel, Switzerland). 2023;(12)
Abstract
Lonicera japonica Thunb. is a widely distributed plant with ornamental, economic, edible, and medicinal values. L. japonica is a phytoantibiotic with broad-spectrum antibacterial activity and a potent therapeutic effect on various infectious diseases. The anti-diabetic, anti-Alzheimer's disease, anti-depression, antioxidative, immunoregulatory, anti-tumor, anti-inflammatory, anti-allergic, anti-gout, and anti-alcohol-addiction effects of L. japonica can also be explained by bioactive polysaccharides isolated from this plant. Several researchers have determined the molecular weight, chemical structure, and monosaccharide composition and ratio of L. japonica polysaccharides by water extraction and alcohol precipitation, enzyme-assisted extraction (EAE) and chromatography. This article searched in the Chinese Pharmacopoeia, Flora of China, Web of Science, PubMed, and CNKI databases within the last 12 years, using "Lonicera. japonica polysaccharides", "Lonicera. japonica Thunb. polysaccharides", and "Honeysuckle polysaccharides" as the key word, systematically reviewed the extraction and purification methods, structural characteristics, structure-activity relationship, and health benefits of L. japonica polysaccharides to provide insights for future studies. Further, we elaborated on the potential applications of L. japonica polysaccharides in the food, medicine, and daily chemical industry, such as using L. japonica as raw material to make lozenges, soy sauce and toothpaste, etc. This review will be a useful reference for the further optimization of functional products developed from L. japonica polysaccharides.
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The effect of dietary carbohydrate and calorie restriction on weight and metabolic health in overweight/obese individuals: a multi-center randomized controlled trial.
Sun, J, Ruan, Y, Xu, N, Wu, P, Lin, N, Yuan, K, An, S, Kang, P, Li, S, Huang, Q, et al
BMC medicine. 2023;(1):192
Abstract
BACKGROUND Both low-carbohydrate (LC) and calorie-restricted (CR) diets have been shown to have metabolic benefits. However, the two regimens have yet to be thoroughly compared. We conducted a 12-week randomized trial to compare the effects of these diets separately and in combination on both weight loss and metabolic risk factors in overweight/obese individuals. METHODS A total of 302 participants were randomized to LC diet (n = 76), CR diet (n = 75), LC + CR diet (n = 76), or normal control (NC) diet (n = 75) using a computer-based random number generator. The primary outcome was the change in body mass index (BMI). The secondary outcomes included body weight, waist circumference, waist-to-hip ratio, body fat, and metabolic risk factors. All participants attended health education sessions during the trial. RESULTS A total of 298 participants were analyzed. BMI change over 12 weeks was - 0.6 (95% CI, - 0.8 to - 0.3) kg/m2 in NC, - 1.3 (95% CI, - 1.5 to - 1.1) kg/m2 in CR, - 2.3 (95% CI, - 2.6 to - 2.1) kg/m2 in LC, and - 2.9 (95% CI, - 3.2 to - 2.6) kg/m2 in LC + CR. LC + CR diet was more effective than LC or CR diet alone at reducing BMI (P = 0.001 and P < 0.001, respectively). Furthermore, compared with the CR diet, the LC + CR diet and LC diet further reduced body weight, waist circumference, and body fat. Serum triglycerides were significantly reduced in the LC + CR diet group compared with the LC or CR diet alone. Plasma glucose, homeostasis model assessment of insulin resistance, and cholesterol concentrations (total, LDL, and HDL) did not change significantly between the groups during the 12-week intervention. CONCLUSIONS The reduction of carbohydrate intake without restricting caloric intake is more potent to achieve weight loss over 12 weeks when compared to a calorie-restricted diet in overweight/obese adults. The combination of restricting carbohydrate and total calorie intake may augment the beneficial effects of reducing BMI, body weight, and metabolic risk factors among overweight/obese individuals. TRIAL REGISTRATION The study was approved by the institutional review board of Zhujiang Hospital of Southern Medical University and registered at the China Clinical Trial Registration Center (registration number: ChiCTR1800015156).
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A UK nationwide study of adults admitted to hospital with diabetic ketoacidosis or hyperosmolar hyperglycaemic state and COVID-19.
Field, BCT, Ruan, Y, Várnai, KA, Davies, J, Ryder, REJ, Gandhi, R, Harris, S, Nagi, D, Patel, D, Kempegowda, P, et al
Diabetes, obesity & metabolism. 2023;(7):2012-2022
Abstract
AIMS: To investigate characteristics of people hospitalized with coronavirus-disease-2019 (COVID-19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission. MATERIALS AND METHODS Retrospective cohort study with anonymized data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID-19 and diabetes, from start of pandemic to November 2021. The primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age-adjusted odds ratios were calculated using logistic regression. RESULTS In total, 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalized with COVID-19. Mean (SD) age was 60 (18.2) years in DKA and 74 (11.8) years in HHS (p < .001). A higher proportion of patients with HHS than with DKA were of non-White ethnicity (71.4% vs 39.0% p = .038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared with non-users [21.4% vs. 52.2%; age-adjusted odds ratio 0.13 (95% CI 0.03-0.60)]. Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, p = .001) and in statin users versus non-users (36.4% vs. 100%; p = .035) but these were not statistically significant after age adjustment. CONCLUSIONS Hospitalization with COVID-19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes-associated DKA.