The resistance of tumor cells to apoptosis often leads to chemoresistance and treatment failure in clinic. In this study, we have developed a Cu²⁺-coordinated lignosulfonate (CLS) /doxorubicin (DOX) biological complex (referred to as LCD) with the aim of overcoming cellular resistance to apoptosis for combined lung cancer therapy. The copper complexes modified by CLS exhibit significant water solubility and excellent in vivo biocompatibility. The proportion of copper in the composite is simultaneously increased. Due to the coordination and π-π stacking effects, the self-assembled LCD exhibits nanometer-scale particle size, a narrow and homogeneous grain distribution, as well as excellent dispersion stability. Furthermore, LCD has the potential to disassemble in the presence of high levels of glutathione (GSH) and low pH, leading to effective drug release. Cu²⁺-mediated cuproptosis can lead to the down-regulation of FDX1 and DLAT protein expression by reducing mitochondrial membrane potential, resulting in non-apoptotic programmed cell death (PCD) regardless of cellular resistance to apoptosis. Moreover, the released DOX not only exhibits a preference for localizing in the cell nucleus to induce apoptosis for combined chemotherapy, but also generates a substantial amount of H₂O₂. This H₂O₂ further produces ROS to induce apoptosis through Fenton reaction with Cu²⁺. LCD demonstrates significant superiority over monotherapy in inhibiting tumor growth while minimizing systemic toxicity through the combined action of cuproptosis and apoptosis. This study may provide a potential avenue for the advancement of self-delivery nanomedicine to overcome resistance to apoptosis in tumor therapy.

2024-10-01·Clinical Nutrition

Effects of time-restricted eating and low-carbohydrate diet on psychosocial health and appetite in individuals with metabolic syndrome: A secondary analysis of a randomized controlled trial

Article

作者: Wang, Xin ; Li, Qian ; He, Mingqian ; Guo, Hui ; Sui, Jing ; Wang, Yanan ; Wang, Ting ; Yang, Jing ; Shi, Bingyin ; Zhu, Wenzhi ; Zheng, Yixuan ; Wang, Yue ; Wang, Jingya ; Qiang, Wei

BACKGROUND & AIMSTime-restricted eating (TRE) and low-carbohydrate diet (LCD) can improve multiple cardiometabolic parameters in patients with metabolic syndrome (MetS), but their effects on psychosocial health and satiety are unclear. In this study, we aimed to evaluate the effects of TRE, LCD, and their combination (TRE + LCD) on quality of life (QoL), sleep, mood, appetite, and metabolic hormones in patients with MetS.METHODSThis is a secondary analysis of a single-center, 3-month, open-label, randomized clinical trial investigating the effects of TRE, LCD, and TRE + LCD on weight and cardiometabolic parameters in individuals with MetS. This secondary analysis examined QoL, sleep, mood, and appetite using the Rand 36-Item Short Form (SF-36); Pittsburgh Sleep Quality Index (PSQI); Depression, Anxiety, and Stress Scale; and Eating Behavior Rating Scale, respectively, as well as measured levels of metabolic hormones including leptin, amylin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP), and peptide YY. Between-group comparisons were conducted via one-way ANOVAs and post hoc LSD tests for normally distributed variables or Kruskal‒Wallis H tests and the Nemenyi test for abnormally distributed variables. P < 0.017 was considered significant in multiple comparisons following Bonferroni adjustment.RESULTSA total of 162 participants (mean [SD] age, 41.2 [9.9] years; mean [SD] body mass index, 29.3 [3.4] kg/m²; 102 [63%] men) who started the intervention were analyzed. After 3 months, only the TRE group decreased GLP-1 levels (-0.9 [IQR, -1.9 to -0.3] pg/mL; P = 0.002), increased PP levels (8.9 [IQR, -7.6 to 71.8] pg/mL; P = 0.011), physical functioning in the SF-36 (5.2 [95% CI, 1.9 to 8.5]; P = 0.001), social functioning in the SF-36 (9.1 [95% CI, 2.5 to 15.6]; P = 0.005), role-physical in the SF-36 (24.1 [95% CI, 11.8 to 36.4]; P < 0.001), role-emotional in the SF-36 (22.4 [95% CI, 12.6 to 32.2]; P < 0.001), and sleep efficiency in the PSQI (0.29 [95% CI, 0.03 to 0.55]; P = 0.021). Compared with changes in LCD, TRE further increased general health in the SF-36 (9.7 [95% CI, 3.3 to 16.0]; P = 0.006). Relative to the changes of TRE + LCD, TRE significantly increased role-emotional in the SF-36 (19.9 [95% CI 4.9 to 34.8]; P = 0.006). Changes in sleep quality, mood status, appetite, and metabolic hormones did not differ among three groups. Greater weight loss was associated with decreased leptin levels (r = 0.538), decreased amylin levels (r = 0.294), reduced total appetite scores (r = 0.220), and improved general health (r = -0.253) (all P ≤ 0.01).CONCLUSIONSTRE, LCD, and TRE + LCD all could improve psychosocial health and reduce appetite. Notably, TRE yielded greater benefits in QoL compared with LCD or TRE + LCD in individuals with MetS.TRIAL REGISTRATIONClinicalTrials.gov Identifier: NCT04475822.

2024-10-01·Obesity Science & Practice

Optimizing muscle preservation during weight loss in patients with cirrhosis: A pilot study comparing continuous energy restriction to alternate‐day modified fasting for weight loss in patients with obesity and non‐alcoholic cirrhosis of the liver

Article

作者: Honas, Jeffery J. ; Rachman, Jessica ; Montgomery, Robert N. ; Herrmann, Stephen D. ; Steger, Felicia L. ; Donnelly, Joseph E. ; Hastert, Mary ; Dunn, Winston

AbstractIntroductionObesity is associated with increased morbidity in patients with advanced liver disease, but it is particularly challenging for these patients to preserve skeletal muscle mass during weight loss and accelerating sarcopenia is a concern. Alternate‐day modified fasting (ADMF) may be particularly effective for weight loss in patients with concomitant cirrhosis and obesity due to preservation of fat‐free mass (FFM).MethodsA weight loss program featuring either ADMF or a continuous low‐calorie diet (LCD) was evaluated in a 24‐week randomized clinical trial in 20 adult patients with Child‐Pugh Class A cirrhosis and obesity. Participants were randomized to either ADMF (n = 11) or LCD (n = 9). Both groups received a remotely delivered exercise program. Body composition, sarcopenia measures, and functional outcomes were assessed pre‐post.ResultsThirteen participants completed the intervention (Age = 57 ± 10; BMI = 37.7 ± 5.8 kg/m2). The median body weight lost in ADMF was 13.7 ± 4.8 kg (13.9% of initial body weight), while LCD lost 9.9 ± 6.9 kg (10.7% of initial body weight). Total body fat percentage decreased in both groups (ADMF: −4.1 ± 4.0%; LCD = −2.8 ± 1.4%). Fat‐free mass accounted for 34 ± 20% of total weight loss in ADMF and 38 ± 10% in LCD. Functional measures, such as timed chair stands, improved in both groups.ConclusionThis pilot study demonstrates the feasibility of the ADMF and LCD interventions to produce significant weight loss while improving body composition in patients with cirrhosis and obesity. Further research is needed to validate these findings in larger cohorts and to assess changes in muscle quality and visceral fat.Trial RegistrationClinicalTrials.gov Identifier: NCT05367596.

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适应症	最高研发状态	国家/地区	公司	日期
非酒精性脂肪性肝炎	临床前	中国台湾	Chang Gung Memorial Hospital	2024-07-01
非酒精性脂肪性肝炎	临床前	中国台湾	义守大学	2024-07-01
乳腺癌	临床前	中国	山东第一医科大学（山东省医学科学院）	2024-06-27