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1.
Role of sodium taurocholate cotransporting polypeptide (NTCP) in HBV-induced hepatitis: Opportunities for developing novel therapeutics.
Zhang, Z, Zhang, Q, Zhang, Y, Lou, Y, Ge, L, Zhang, W, Zhang, W, Song, F, Huang, P
Biochemical pharmacology. 2024;:115956
Abstract
Hepatitis B is an infectious disease caused by the HBV virus. It presents a significant challenge for treatment due to its chronic nature and the potential for developing severe complications, including hepatocirrhosis and hepatocellular carcinoma. These complications not only cause physical and psychological distress to patients but also impose substantial economic and social burdens on both individuals and society as a whole. The internalization of HBV relies on endocytosis and necessitates the involvement of various proteins, including heparin sulfate proteoglycans, epidermal growth factor receptors, and NTCP. Among these proteins, NTCP is pivotal in HBV internalization and is primarily located in the liver's basement membrane. As a transporter of bile acids, NTCP also serves as a receptor facilitating HBV entry into cells. Numerous molecules have been identified to thwart HBV infection by stifling NTCP activity, although only a handful exhibit low IC50 values. In this systematic review, our primary focus dwells on the structure and regulation of NTCP, as well as the mechanism involved in HBV internalization. We underscore recent drug breakthroughs that specifically target NTCP to combat HBV infection. By shedding light on these advances, this review contributes novel insights into developing effective anti-HBV medications.
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Inflammatory stress response after transanal vs laparoscopic total mesorectal excision: a cohort study based on the TaLaR trial.
Chen, M, Ye, F, Huang, P, Liang, Z, Liu, H, Zheng, X, Li, W, Luo, S, Kang, L, Huang, L
International journal of surgery (London, England). 2024;(1):151-158
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Abstract
BACKGROUND Transanal total mesorectal excision (taTME) is a novel approach to radical surgery for low rectal cancer; however, it is not clear whether taTME causes a more severe inflammatory stress response than laparoscopic total mesorectal excision (laTME). Therefore, the authors conducted this study to address this question, with the secondary objective of analyzing the predictive effect of inflammatory indexes on postoperative infective complications between laTME and taTME. METHODS A total of 545 cases of laTME and 544 cases of taTME from the TaLaR randomized controlled trial were included. Inflammatory stress response was assessed via C-reactive protein (CRP), white blood cell count, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio, and prognostic nutritional index. Inflammatory indexes were measured and calculated preoperatively (t1) and on postoperative days one (t2) and seven (t3). The accuracy of inflammatory indexes as predictor of infective complications was evaluated by areas under the receiver operating characteristic curve. RESULTS Preoperative blood parameters were comparable between the two surgical methods. There were no significant differences in CRP, white blood cell count, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, lymphocyte-monocyte ratio, or prognostic nutritional index between the two surgical methods at any time point ( P >0.05). Among the inflammatory indexes at three time points, CRP on the first postoperative day was the most accurate predictor of infective complications, which is suitable for two surgical methods. The AUC was 0.7671 ( P <0.0001) with a cutoff of 39.84 mg/l, yielding 94% sensitivity and 47% specificity. CONCLUSIONS Compared with laTME, taTME surgery has no obvious disadvantage with respect to the postoperative inflammatory stress response. In addition, inflammatory indexes were favorable in predicting infective complications, with the best results for CRP on the first postoperative day. Defining the specific predictors for laTME and taTME is unnecessary.
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Comprehensive effect of Naoxintong capsule combined with Western medicine on coronary heart disease after percutaneous coronary intervention: a meta-analysis.
Yu, L, Huang, P, Wang, M, Li, Z, Cai, H, Feng, Y, Wu, L, Peng, W, Zeng, J, Chen, B
Frontiers in pharmacology. 2024;:1274000
Abstract
AIMS: To systematically evaluate the comprehensive effect of combining Naoxintong capsule (NXT) with Western medicine (WM) on coronary heart disease post-percutaneous coronary intervention (PCI). METHODS Randomized controlled trials (RCTs) of NXT for patients with CHD after PCI were systematically searched across multiple databases, including the Cochrane Library, PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Database (VIP), and Wan Fang, from inception until 31 January 2023. Study selection, data extraction, and quality assessment were performed by two independent reviewers. The quality of the included studies was evaluated using version 2 of the Cochrane risk-of-bias tool (RoB 2), and data analysis was performed using R4.2.2. RESULTS Fifteen RCTs conducted between 2011 and 2022 and involving 1,551 patients were identified, with 774 and 777 patients in the experimental and control groups respectively. It was found that the NXT and WM combination was superior to the WM therapy alone in terms of the effective clinical rate (odds ratio [OR] = 4.69, 95% confidence interval [CI] = 2.13-10.30), effective rate in electrocardiogram (OR = 6.92, 95% CI = 3.44-13.92), effective rate in angina (OR = 5.90, 95% CI = 3.04-11.46), left ventricular ejection fraction (mean difference [MD] = 4.94, 95% CI = 2.89-6.99), brain natriuretic peptide (MD = -294.00, 95% CI = -584.60 to -3.39), creatine kinase-MB (MD = -7.82, 95% CI = -13.26 to -2.37), major adverse cardiovascular events (OR = 0.24, 95% CI = 0.14-0.43), maximum platelet aggregation rate (MD = -8.33, 95% CI = -11.64 to -5.01), and Chinese medicine evidence score (OR = 9.79, 95% CI = 3.57-26.85). However, there was no significant difference in cardiac troponin I level reduction (MD = -0.13, 95% CI = 0.35-0.09) or the occurrence of adverse medicine events (OR = 0.92, 95% CI = 0.41-2.05). Meta-regression and subgroup analyses indicated that NXT capsule dosage, treatment duration, and patient baseline characteristics contributed to the heterogeneity. CONCLUSION A combination of NXT and WM can improve clinical outcomes in patients undergoing PCI. However, further studies are needed to confirm the reliability and safety of this combined treatment approach. SYSTEMATIC REVIEW REGISTRATION PROSPERO, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=369174, Identifier CRD42022369174.
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Effect of multicomponent intervention on malnutrition in older adults: A multicenter randomized clinical trial.
Chen, B, Zhao, H, Li, M, Zhao, T, Liao, R, Lu, J, Zou, Y, Tu, J, Teng, X, Huang, Y, et al
Clinical nutrition ESPEN. 2024;:31-40
Abstract
BACKGROUND & AIMS Malnutrition is a significant geriatric syndrome (GS) prevalent in older adults and seriously affects patient prognosis and quality of life. We assessed the impact of the multicomponent intervention of health education, dietary advice, and exercise with oral nutritional supplementation (ONS) on nutritional status, body composition, physical functions, and quality of life. METHODS This multicenter randomized clinical trial (RCT) was performed from April 2021 to April 2022. The intervention lasted for 12 weeks, and 99 older adults with malnutrition or at risk of malnutrition were enrolled in six nursing homes. All participants were randomly assigned to the control (health education plus standard diet plus exercise) or research (health education plus standard diet plus exercise plus ONS) group. The research group consumed ONS (244 kcal, 9.8g protein, and 9.6g fat per time) twice a day between meals. The primary outcomes were changes in the nutritional status and body composition from baseline to 12 weeks. The secondary outcomes were changes in physical function, quality of life and nutritional associated other blood markers. RESULTS For primary outcomes, after 12 weeks, body weight increased similarly in both treatment arms (time × treatment effect, P > 0.05). There were no between-group differences in body mass index (BMI) or mini nutritional assessment tool-short form (MNA-SF) scores (time × treatment effects, P > 0.05). The MNA-SF score from 11.0 (10.5, 12.0) to 13.0 (11.0, 13.0) in the research group and from 11.0 (10.0, 12.0) to 12.0 (11.0, 13.0) in the control group (both P < 0.05). There were no between-group differences in the skeletal muscle mass index (SMI), fat-free mass index (FFMI), appendicular skeletal muscle mass (ASMM), fat mass (FAT), or leg muscle mass (LMM) (time × treatment effects, P > 0.05). Both groups showed similar and highly significant increases in SMI, FFMI, and LMM after (P < 0.05). The research group showed an increase in fat-free mass (FFM) and ASMM and a decrease in the percent of body fat (PBF) and waist circumference (WC) (P < 0.05). For secondary outcomes, There were no between-group differences in grip strength, short physical performance battery (SPPB), 6-min walking distance (6MWD), activities of daily living (ADL), instrumental activities of daily living (IADL), frailty status (FRAIL), mini-mental state examination (MMSE), Tinetti, geriatric depression scale-15 (GDS-15), or 12-item short form survey (SF-12) (time × treatment effects, P > 0.05). Although there was no significant difference, the 6MWD changed differentially between the two treatment arms during the study period in favor of the research group. Although not significant, SF-12 scores improved after 12 weeks in both groups. No between-group differences were observed in prealbumin (PRE), c-reactive protein (CRP), vitamin D (VIT-D), insulin-like growth factor 1 (IGF-1), alanine transaminase (ALT), aspartate aminotransferase (AST), serum creatinine (Scr), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), insulin, and adiponectin levels (time × treatment effects, P > 0.05). Insulin and adiponectin levels were significantly higher in the control group (P < 0.05). CONCLUSION The twelve-week multicomponent intervention improved the nutritional status of older people in China at risk of malnutrition. ONS may enhance the effects of exercise on muscle mass. This clinical trial was registered (https://www. CLINICALTRIALS gov). The trial number is ChiCTR2000040343.
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Targeting one-carbon metabolism for cancer immunotherapy.
Ren, X, Wang, X, Zheng, G, Wang, S, Wang, Q, Yuan, M, Xu, T, Xu, J, Huang, P, Ge, M
Clinical and translational medicine. 2024;(1):e1521
Abstract
BACKGROUND One-carbon (1C) metabolism is a metabolic network that plays essential roles in biological reactions. In 1C metabolism, a series of nutrients are used to fuel metabolic pathways, including nucleotide metabolism, amino acid metabolism, cellular redox defence and epigenetic maintenance. At present, 1C metabolism is considered the hallmark of cancer. The 1C units obtained from the metabolic pathways increase the proliferation rate of cancer cells. In addition, anticancer drugs, such as methotrexate, which target 1C metabolism, have long been used in the clinic. In terms of immunotherapy, 1C metabolism has been used to explore biomarkers connected with immunotherapy response and immune-related adverse events in patients. METHODS We collected numerous literatures to explain the roles of one-carbon metabolism in cancer immunotherapy. RESULTS In this review, we focus on the important pathways in 1C metabolism and the function of 1C metabolism enzymes in cancer immunotherapy. Then, we summarise the inhibitors acting on 1C metabolism and their potential application on cancer immunotherapy. Finally, we provide a viewpoint and conclusion regarding the opportunities and challenges of targeting 1C metabolism for cancer immunotherapy in clinical practicability in the future. CONCLUSION Targeting one-carbon metabolism is useful for cancer immunotherapy.
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Glucose transport, transporters and metabolism in diabetic retinopathy.
Zhang, C, Gu, L, Xie, H, Liu, Y, Huang, P, Zhang, J, Luo, D, Zhang, J
Biochimica et biophysica acta. Molecular basis of disease. 2024;(3):166995
Abstract
Diabetic retinopathy (DR) is the most common reason for blindness in working-age individuals globally. Prolonged high blood glucose is a main causative factor for DR development, and glucose transport is prerequisite for the disturbances in DR caused by hyperglycemia. Glucose transport is mediated by its transporters, including the facilitated transporters (glucose transporter, GLUTs), the "active" glucose transporters (sodium-dependent glucose transporters, SGLTs), and the SLC50 family of uniporters (sugars will eventually be exported transporters, SWEETs). Glucose transport across the blood-retinal barrier (BRB) is crucial for nourishing the neuronal retina in the context of retinal physiology. This physiological process primarily relies on GLUTs and SGLTs, which mediate the glucose transportation across both the cell membrane of retinal capillary endothelial cells and the retinal pigment epithelium (RPE). Under diabetic conditions, increased accumulation of extracellular glucose enhances the retinal cellular glucose uptake and metabolism via both glycolysis and glycolytic side branches, which activates several biochemical pathways, including the protein kinase C (PKC), advanced glycation end-products (AGEs), polyol pathway and hexosamine biosynthetic pathway (HBP). These activated biochemical pathways further increase the production of reactive oxygen species (ROS), leading to oxidative stress and activation of Poly (ADP-ribose) polymerase (PARP). The activated PARP further affects all the cellular components in the retina, and finally resulting in microangiopathy, neurodegeneration and low-to-moderate grade inflammation in DR. This review aims to discuss the changes of glucose transport, glucose transporters, as well as its metabolism in DR, which influences the retinal neurovascular unit (NVU) and implies the possible therapeutic strategies for treating DR.
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Association of systemic immune-inflammation index and systemic inflammation response index with chronic kidney disease: observational study of 40,937 adults.
Huang, P, Mai, Y, Zhao, J, Yi, Y, Wen, Y
Inflammation research : official journal of the European Histamine Research Society ... [et al.]. 2024;(4):655-667
Abstract
BACKGROUND Chronic kidney disease (CKD) is linked to immunity and inflammation. Systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) are novel measures for gauging an individual's systemic inflammatory activity. We aim to investigate the potential associations between them. METHODS This study encompassed a cohort of 40,937 adults from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. SII and SIRI were log2-transformed before conducting regression analysis, considering that these inflammatory markers were right skewed distributed. Weighted logistic regression models assessed the association of log2-SII and log2-SIRI levels with CKD prevalence. Weighted Cox regression models were utilized to estimate the risk of death. Subgroup analyses were performed to further clarify the effects of other covariates on the associations. Sensitivity analyses were performed to assess the robustness of our results. RESULTS 6986 participants with CKD were recorded, and 2818 patients died during a mean follow-up time of 100 months. After adjusting for all covariates, the highest level of log2-SII increased the CKD incidence (odds ratio [OR]: 1.47, 95% confidence intervals [CI]: 1.32-1.65, P < 0.001), as well as log2-SIRI (OR: 1.79, 95% CI 1.60-2.01, P < 0.001) when compared with the lowest level reference group. The highest level of log2-SII significantly increased all-cause mortality (hazard risk [HR]: 1.29; 95% CI 1.13-1.48, P < 0.001), cardiovascular mortality (HR: 1.61, 95% CI 1.25-2.09, P < 0.001), and hypertension mortality (HR: 1.73, 95% CI 1.23-2.42, P = 0.001) in CKD patients. Additionally, the positive associations were also found between log2-SIRI and all cause (HR: 1.54, 95% CI 1.35-1.76, P < 0.001), cardiovascular (HR: 1.90, 95% CI 1.38-2.60, P < 0.001), and hypertension mortality (HR: 2.15, 95% CI 1.56-2.94, P < 0.001). Subgroup analyses unveiled variations in these effects among different populations. CONCLUSION There existed a substantial association of SII and SIRI levels with CKD prevalence, as well as mortality in patients with CKD in the U.S.
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Mechanisms of Ferritinophagy and Ferroptosis in Diseases.
Li, S, Huang, P, Lai, F, Zhang, T, Guan, J, Wan, H, He, Y
Molecular neurobiology. 2024;(3):1605-1626
Abstract
The discovery of the role of autophagy, particularly the selective form like ferritinophagy, in promoting cells to undergo ferroptosis has inspired us to investigate functional connections between diseases and cell death. Ferroptosis is a novel model of procedural cell death characterized by the accumulation of iron-dependent reactive oxygen species (ROS), mitochondrial dysfunction, and neuroinflammatory response. Based on ferroptosis, the study of ferritinophagy is particularly important. In recent years, extensive research has elucidated the role of ferroptosis and ferritinophagy in neurological diseases and anemia, suggesting their potential as therapeutic targets. Besides, the global emergence and rapid transmission of COVID-19, which is caused by SARS-CoV-2, represents a considerable risk to public health worldwide. The potential involvement of ferroptosis in the pathophysiology of brain injury associated with COVID-19 is still unclear. This review summarizes the pathophysiological changes of ferroptosis and ferritinophagy in neurological diseases, anemia, and COVID-19, and hypothesizes that ferritinophagy may be a potential mechanism of ferroptosis. Advancements in these fields will enhance our comprehension of methods to prevent and address neurological disorders, anemia, and COVID-19.
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Identification and experimental validation of Stearoyl-CoA desaturase is a new drug therapeutic target for osteosarcoma.
Nie, J, He, C, Shu, Z, Liu, N, Zhong, Y, Long, X, Liu, J, Yang, F, Liu, Z, Huang, P
European journal of pharmacology. 2024;:176249
Abstract
Osteosarcoma (OS) is the most common malignant bone tumor. Fatty acid reprogramming plays an essential role in OS progression. However, new fatty acid related therapeutic targets of OS have not been completely elucidated. Therefore, we firstly identified 113 differentially expressed fatty acid metabolism genes using bioinformatic analysis, 19 of which were found to be associated with OS prognosis. Then, 7 hub genes were screened out and yielded a strong prediction accuracy (AUC value = 0.88, at 3 years) for predicting the survival status of OS patients. Furthermore, we confirmed that SCD was highly expressed in OS cells and patients. And Knock-down of SCD impaired proliferation and migration of OS cells. Moreover, SCD was transcriptionally activated by c-Myc to promote proliferation and migration of OS cells. Finally, SCD inhibitor could significantly induce OS ferroptosis in vitro and in vivo. In conclusion, we identified that SCD was a reliable risk factor for OS patients. And SCD was activated by c-Myc. The inhibitor of SCD could significantly impaired OS growth and induce OS ferroptosis, which indicated that SCD was a potential drug target for OS treatment.
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10.
Comparative Effectiveness of Team-Based Care With and Without a Clinical Decision Support System for Diabetes Management : A Cluster Randomized Trial.
Shi, X, He, J, Lin, M, Liu, C, Yan, B, Song, H, Wang, C, Xiao, F, Huang, P, Wang, L, et al
Annals of internal medicine. 2023;(1):49-58
Abstract
BACKGROUND Uncontrolled hyperglycemia, hypercholesterolemia, and hypertension are common in persons with diabetes. OBJECTIVE To compare the effectiveness of team-based care with and without a clinical decision support system (CDSS) in controlling glycemia, lipids, and blood pressure (BP) among patients with type 2 diabetes. DESIGN Cluster randomized trial. (ClinicalTrials.gov: NCT02835287). SETTING 38 community health centers in Xiamen, China. PATIENTS 11 132 persons aged 50 years or older with uncontrolled diabetes and comorbid conditions, 5475 receiving team-based care with a CDSS and 5657 receiving team-based care alone. INTERVENTION Team-based care was delivered by primary care physicians, health coaches, and diabetes specialists in all centers. In addition, a computerized CDSS, which generated individualized treatment recommendations based on clinical guidelines, was implemented in 19 centers delivering team-based care with a CDSS. MEASUREMENTS Coprimary outcomes were mean reductions in hemoglobin A1c (HbA1c) level, low-density lipoprotein cholesterol (LDL-C) level, and systolic BP over 18 months and the proportion of participants with all 3 risk factors controlled at 18 months. RESULTS During the 18-month intervention, HbA1c levels, LDL-C levels, and systolic BP significantly decreased by -0.9 percentage point (95% CI, -0.9 to -0.8 percentage point), -0.49 mmol/L (CI, -0.53 to -0.45 mmol/L) (-19.0 mg/dL [CI, -20.4 to -17.5 mg/dL]), and -9.1 mm Hg (CI, -9.9 to -8.3 mm Hg), respectively, in team-based care with a CDSS and by -0.6 percentage point (CI, -0.7 to -0.5 percentage point), -0.32 mmol/L (CI, -0.35 to -0.29 mmol/L) (-12.5 mg/dL [CI, -13.6 to -11.3 mg/dL]), and -7.5 mm Hg (CI, -8.4 to -6.6 mm Hg), respectively, in team-based care alone. Net differences were -0.2 percentage point (CI, -0.3 to -0.1 percentage point) for HbA1c level, -0.17 mmol/L (CI, -0.21 to -0.12 mmol/L) (-6.5 mg/dL [CI, -8.3 to -4.6 mg/dL]) for LDL-C level, and -1.5 mm Hg (CI, -2.8 to -0.3 mm Hg) for systolic BP. The proportion of patients with controlled HbA1c, LDL-C, and systolic BP was 16.9% (CI, 15.7% to 18.2%) in team-based care with a CDSS and 13.0% (CI, 11.7% to 14.3%) in team-based care alone. LIMITATION There was no usual care control, and clinical outcome assessors were unblinded; the analysis did not account for multiple comparisons. CONCLUSION Compared with team-based care alone, team-based care with a CDSS significantly reduced cardiovascular risk factors in patients with diabetes, but the effect was modest. PRIMARY FUNDING SOURCE Xiamen Municipal Health Commission.