ABSTRACT
Background: The work aimed to compare the pharmacokinetic (PK) profiles and other outcomes reported in observational studies in de novo kidney transplant recipients (KTRs) receiving novel once-daily extended-release tablet tacrolimus (LCPT; LCP-tacrolimus; Envarsus XR) or receiving standard-of-care capsule tacrolimus (PR-Tac; prolonged-release tacrolimus; Advagraf/IR-Tac; immediate-release tacrolimus; Prograf). Methods: A systematic review was conducted for all randomized controlled trials (RCTs) and cohort studies investigating the outcomes in KTRs receiving LCPT or PR-Tac/IR-Tac. We systematically searched PubMed, Web of Science, and EMBASE, with no language restriction. The registered trials and references listed in relevant studies were also searched. Data were extracted for the PK profile, tacrolimus trough level (TTL), and changes in the estimated glomerular filtration rate (eGFR) and serum creatinine (Scr), biopsy-proven acute rejection (BPAR) rate, delayed graft function (DGF) rate, post-transplant diabetes mellitus (PTDM) rate, tremor rate (TR), death rate (DR), and rate of infection by cytomegalovirus (CMV). This study was registered with PROSPERO (registration number: CRD42023403787). Results: A total of seven eligible articles including 1,428 patients with 712 in the LCPT group versus 716 in the PR-Tac/IR-Tac group were included in this study for evidence synthesis. The baseline characteristics of the LCPT, PR-Tac, and IR-Tac groups were similar. The pooled analysis showed a higher PK profile in the LCPT group, and this result was consistent with those of all the included studies. In addition, no significant difference was observed for other outcomes. Conclusion: Considering heterogeneity between studies and potential bias, care providers should select agents based on patient-specific factors and their clinical experience for the immunosuppressive treatment of de novo KTRs.
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PURPOSE: Adrenocortical carcinoma (ACC) is an endocrine malignant tumor with poor prognosis. The study aimed to construct ACC immune-related gene prognostic signature and verify the efficacy of prognostic signature. METHODS: ACC RNA-seq data and clinical information are downloaded from TCGA databases and GEO databases. We used single sample gene set enrichment analysis (ssGSEA) to assess immune cell infiltration in ACC patients and ACC patients were divided into high- and low-immune cell infiltration clusters. The validity of ssGSEA grouping was verified using the ESTIMATE algorithm. A total of 275 differentially expressed immune-related genes (IRGs) were obtained from the intersection of IRGs and differentially expressed genes (DEGs) in high and low immune cell infiltration clusters. LASSO analysis was used to identify 13 IRGs that regulate the prognosis of ACC patients through immune infiltration. Kaplan-Meier analysis, ROC curve, univariate and multivariate Cox regression further confirmed that these 13 immune-related gene signatures were innovative and significant prognostic factors, which were independent of clinical features. Finally, ACC prognostic nomogram was constructed, ROC curve and calibration curve were drawn to evaluate the accuracy of the prognostic nomogram. RESULTS: LASSO regression analysis was used to screen out ACC survival-related genes. Univariate and multivariate Cox proportional risk regression models were used to analyze and construct the ACC prognosis nomogram. The AUC for predicting 1-, 3- and 5-year overall survival rate of ACC patients was 0.799, 0.966 and 0.969, suggesting good prediction accuracy. The calibration curve shows that the predicted results of the prognostic nomogram are in good agreement with the actual situation. CONCLUSION: ssGSEA technique plays an important role in the construction of ACC prognostic model. Based on IRGs associated with survival independently predicted ACC prognosis, we identified thirteen immune-related genes as prognostic signature for ACC.
ABSTRACT
A number of research has shown that the plant polyphenol resveratrol, one of the most prominent small molecules, has beneficial protective effects in multiple organisms, including worms, flies, and killifish. To understand the effects of resveratrol on lifespan, we evaluated its effects in the silkworm Bombyx mori. In this study, we found that lifespan was significantly prolonged in both female and male silkworms treated with resveratrol. Silkworm larval weight was significantly increased from day 3 of the 5th larval instar (L5D3) to day 7 of the 5th larval instar (L5D7). However, the weight of the pupa, cocoon, and total cocoon was not significantly different in female silkworms with resveratrol treatment than that in controls. Meanwhile, resveratrol significantly improved the thermotolerance of the silkworms, which enhanced their survival rate. Moreover, antioxidant activity was increased by resveratrol in both female and male silkworms. Furthermore, an antioxidant-related signalling pathway, SIRT7-FoxO-GST, was activated in silkworms with resveratrol treatment. Collectively, these results help us to understand the molecular pathways underlying resveratrol induced pro-longevity effects and indicate that silkworm is a promising animal model for evaluating the effects of lifespan-extending drugs.
ABSTRACT
A number of research has shown that the plant polyphenol resveratrol,one of the most prominent small molecules,has beneficial protective effects in multiple organisms,including worms,flies,and killifish.To understand the effects of resveratrol on lifespan,we evaluated its effects in the silkworm Bombyx mori.In this study,we found that lifespan was significantly prolonged in both female and male silkworms treated with resveratrol.Silkworm larval weight was significantly increased from day 3 of the 5th larval instar(L5D3) to day 7 of the 5th larval instar (L5D7).However,the weight of the pupa,cocoon,and total cocoon was not significantly different in female silkworms with resveratrol treatment than that in controls.Meanwhile,resveratrol significantly improved the thermotolerance of the silkworms,which enhanced their survival rate.Moreover,antioxidant activity was increased by resveratrol in both female and male silkworms.Furthermore,an antioxidant-related signalling pathway,SIRT7-FoxO-GST,was activated in silkworms with resveratrol treatment.Collectively,these results help us to understand the molecular pathways underlying resveratrol induced pro-longevity effects and indicate that silkworm is a promising animal model for evaluating the effects of lifespan-extending drugs.
ABSTRACT
BACKGROUND: Fibroblast growth factor 21 (FGF21), an FGF family member, is an atypical hormone and pro-longevity factor. METHODS: To better understand of the effects of exogenous administration of FGF21 on lifespan and stress tolerance, and the underlying molecular basis, we used the silkworm, Bombyx mori, as an experimental animal model to evaluate FGF21's pharmaceutical effects. RESULTS: Lifespan was significantly prolonged in female silkworms with FGF21 replenishment, whereas no effect was observed in the male silkworms. FGF21 replenishment also significantly improved the activity of antioxidant systems such as glutathione-S-transferase (GST) and superoxide dismutase (SOD) and significantly decreased malondialdehyde (MDA) content. Moreover, FGF21 was found to play a critical role in enhancing stress resistance, including ultraviolet (UV) irradiation tolerance and thermotolerance. Furthermore, AMPK, FoxO, and sirtuins were activated by FGF21 and may be responsible for the prolonged lifespan and enhanced antioxidant activity observed in silkworms. CONCLUSIONS: Collectively, the results suggest the molecular pathways underlying of FGF21-induced longevity and stress tolerance, and support the use of silkworms as a promising experimental animal model for evaluating the pharmaceutical effects of small molecules.