Protective role of curcumin in disease progression from non-alcoholic fatty liver disease to hepatocellular carcinoma: a meta-analysis

Background: Pathological progression from non-alcoholic fatty liver disease (NAFLD) to liver fibrosis (LF) to hepatocellular carcinoma (HCC) is a common dynamic state in many patients. Curcumin, a dietary supplement derived from the turmeric family, is expected to specifically inhibit the development of this progression. However, there is a lack of convincing evidence.Methods: The studies published until June 2023 were searched in PubMed, Web of Science, Embase, and the Cochrane Library databases. The SYstematic Review Center for Laboratory animal Experimentation (SYRCLE) approach was used to evaluate the certainty of evidence. StataSE (version 15.1) and Origin 2021 software programs were used to analyze the critical indicators.Results: Fifty-two studies involving 792 animals were included, and three disease models were reported. Curcumin demonstrates a significant improvement in key indicators across the stages of NAFLD, liver fibrosis, and HCC. We conducted a detailed analysis of common inflammatory markers IL-1β, IL-6, and TNF-α, which traverse the entire disease process. The research results reveal that curcumin effectively hinders disease progression at each stage by suppressing inflammation. Curcumin exerted hepatoprotective effects in the dose range from 100 to 400 mg/kg and treatment duration from 4 to 10 weeks. The mechanistic analysis reveals that curcumin primarily exerts its hepatoprotective effects by modulating multiple signaling pathways, including TLR4/NF-κB, Keap1/Nrf2, Bax/Bcl-2/Caspase 3, and TGF-β/Smad3.Conclusion: In summary, curcumin has shown promising therapeutic effects during the overall progression of NAFLD–LF–HCC. It inhibited the pathological progression by synergistic mechanisms related to multiple pathways, including anti-inflammatory, antioxidant, and apoptosis regulation

Gradient differences of immunotherapy efficacy in metastatic melanoma related to sunlight exposure pattern: A population-based study

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionized metastatic melanoma (MM) treatment in just a few years. Ultraviolet (UV) in sunlight is the most significant environmental cause of melanoma, which is considered to be the main reason for tumor mutation burden (TMB) increase in melanoma. High TMB usually predicts that PD-1 inhibitors are effective. The sunlight exposure pattern of MM might be a clinical feature that matches TMB. The relationship between sunlight exposure patterns and immunotherapy response in MM is unclear. This study aims to investigate the correlation between sunlight exposure patterns and immunotherapy response in MM and establish nomograms that predict 3- and 5-year overall survival (OS) rate.MethodsWe searched the Surveillance, Epidemiology, and End Results (SEER) database and enrolled MM cases from 2005-2016. According to the advent of ICIs in 2011, the era was divided into the non-ICIs era (2005-2010) and the ICIs era (2011-2016). Patients were divided into three cohorts according to the primary site sunlight exposure patterns: head and neck in the first cohort, trunk arms and legs in the second cohort, and acral sites in the third cohort. We compared survival differences for each cohort between the two eras, performed stratified analysis, established nomograms for predicting 3- and 5-year OS rate, and performed internal validation.ResultsComparing the survival difference between the ICIs and non-ICIs era, head and neck melanoma showed the greatest improvement in survival, with 3- and 5-year OS rate increasing by 10.2% and 9.1%, respectively (P=0.00011). In trunk arms and legs melanoma, the 3- and 5-year OS rate increased by 4.6% and 3.9%, respectively (P<0.0001). There is no improvement in survival in acral melanoma (AM) between the two eras (P=0.78). The receiver operating characteristic (ROC) curve, area under the ROC curve (AUC) and calibration graphs show good discrimination and accuracy of nomograms. Decision curve analysis (DCA) suggests good clinical utility of nomograms.ConclusionsBased on the classification of sunlight exposure patterns, there is a gradient difference in immunotherapy efficacy for MM. The degree of sunlight exposure is positively correlated with immunotherapy response. The nomograms are sufficiently accurate to predict 3- and 5-year OS rate for MM, allowing for individualized clinical decisions for future clinical work

Gadolinium embedded iron oxide nanoclusters as T-1-T-2 dual-modal MRI-visible vectors for safe and efficient siRNA delivery

Major State Basic Research Development Program of China (973 Program) [2013CB733802]; National Science Foundation of China (NSFC) [81101101, 51273165, 81201086, 81201190]; Key Project of Chinese Ministry of Education [212149]; Fundamental Research Funds for the Central Universities [2013121039]; National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH)This report illustrates a new strategy of designing a T-1-T-2 dual-modal magnetic resonance imaging (MRI)-visible vector for siRNA delivery and MRI. Hydrophobic gadolinium embedded iron oxide (GdIO) nanocrystals are self-assembled into nanoclusters in the water phase with the help of stearic acid modified low molecular weight polyethylenimine (stPEI). The resulting water-dispersible GdIO-stPEI nanoclusters possess good stability, monodispersity with narrow size distribution and competitive T-1-T-2 dual-modal MR imaging properties. The nanocomposite system is capable of binding and delivering siRNA for knockdown of a gene of interest while maintaining its magnetic properties and biocompatibility. This new gadolinium embedded iron oxide nanocluster provides an important platform for safe and efficient gene delivery with non-invasive T-1-T-2 dual-modal MRI monitoring capability

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure

A novel phosphorus-nitrogen-based hyperbranched polysiloxane for improving the fire safety of PA6 with suppressed melt droplets and good mechanical properties

The combustible defects of polyamide 6 (PA6), especially the flammable melt-dripping behavior, have greatly limited its application in some particular fields. In this work, a halogen-free hyperbranched polysiloxane (PBDSi) containing DOPO and Schiff base was designed via Michael's addition reaction and dehydration-condensation reaction. Results showed that the char yield (Yc) of PBDSi attained 37.9 wt%, confirming the satisfactory charring behavior of PBDSi for preparing flame-retardant PA6. Just by adding 3 wt% of PBDSi, the serious melt droplets of PA6 were suppressed effectively. The prepared PA6/PBDSi-3 with 5 wt% of PBDSi could achieve the highest value of limited oxygen index (LOI) of 27.2 %, while that of PA6 is 21.0 %. Meanwhile, PA6/PBDSi-3 obtained an apparent reduction in the peak heat release rate (PHRR) value of 31.1 % compared with pure PA6. The cooperated effect of DOPO, Schiff base, and polysiloxane that contributed to generating a silicon-phosphorous-rich char layer and releasing incombustible volatiles that were determined to be the essential factor for the improved fire safety of PA6/PBDSi were explored intensively. Inspiringly, PA6/PBDSi composites exhibited a slight mechanical loss concerning PA6, overcoming the great challenge of developing additive flame-retardant materials to balance mechanical properties and fire safety

Menthol: An underestimated anticancer agent

Menthol, a widely used natural, active compound, has recently been shown to have anticancer activity. Moreover, it has been found to have a promising future in the treatment of various solid tumors. Therefore, using literature from PubMed, EMBASE, Web of Science, Ovid, ScienceDirect, and China National Knowledge Infrastructure databases, the present study reviewed the anticancer activity of menthol and the underlying mechanism. Menthol has a good safety profile and exerts its anticancer activity via multiple pathways and targets. As a result, it has gained popularity for significantly inhibiting different types of cancer cells by various mechanisms such as induction of apoptosis, cell cycle arrest, disruption of tubulin polymerization, and inhibition of tumor angiogenesis. Owing to the excellent anticancer activity menthol has demonstrated, further research is warranted for developing it as a novel anticancer agent. However, there are limitations and gaps in the current research on menthol, and its antitumor mechanism has not been completely elucidated. It is expected that more basic experimental and clinical studies focusing on menthol and its derivatives will eventually help in its clinical application as a novel anticancer agent

Integrative evidence construction for resveratrol treatment of nonalcoholic fatty liver disease: preclinical and clinical meta-analyses

Background: Resveratrol, a polyphenol found in various plants, is known for its diverse bioactivities and has been explored in relation to nonalcoholic fatty liver disease (NAFLD). However, no high-quality evidence exists regarding its efficacy.Objective: a meta-analysis was conducted to evaluate the potential efficacy of resveratrol in treating nonalcoholic fatty liver disease by analyzing both preclinical studies and clinical trials.Method: PubMed, Embase and Web of Science were searched for the included literature with the criteria for screening. Quantitative synthesis and meta-analyses were performed by STATA 16.0.Results: Twenty-seven studies were included, and the results indicated that resveratrol effectively improved liver function, reduced fatty liver indicators, and affected other indices in preclinical studies. The effective dosage ranged from 50 mg/kg-200 mg/kg, administered over a period of 4–8 weeks. While there were inconsistencies between clinical trials and preclinical research, both study types revealed that resveratrol significantly reduced tumor necrosis factor-α levels, further supporting its protective effect against nonalcoholic fatty liver disease. Additionally, resveratrol alleviated nonalcoholic fatty liver disease primarily via AMPK/Sirt1 and anti-inflammatory signaling pathways.Conclusion: Current meta-analysis could not consistently verify the efficacy of resveratrol in treating nonalcoholic fatty liver disease, but demonstrated the liver-protective effects on nonalcoholic fatty liver disease. The large-sample scale and single region RCTs were further needed to investigate the efficacy

Cryptotanshinone Ameliorates Radiation-Induced Lung Injury in Rats

Cryptotanshinone (CTS) was reported to repress a variety of systemic inflammation and alleviate cardiac fibrosis, but it is still unclear whether CTS could prevent radiation-induced lung injury (RILI). Here, we investigated the effects and underlying mechanisms of CTS on a RILI rat model. Our data revealed that CTS could efficiently preserve pulmonary function in RILI rats and reduce early pulmonary inflammation infiltration elicited, along with marked decreased levels of IL-6 and IL-10. Moreover, we found that CTS is superior to prednisone in attenuating collagen deposition and pulmonary fibrosis, in parallel with a marked drop of HYP (a collagen indicator) and α-SMA (a myofibroblast marker). Mechanistically, CTS inhibited profibrotic signals TGF-β1 and NOX-4 expressions, while enhancing the levels of antifibrotic enzyme MMP-1 in lung tissues. It is noteworthy that CTS treatment, in consistent with trichrome staining analysis, exhibited a clear advantage over PND in enhancing MMP-1 levels. However, CTS exhibited little effect on CTGF activation and on COX-2 suppression. Finally, CTS treatment significantly mitigated the radiation-induced activation of CCL3 and its receptor CCR1. In summary, CTS treatment could attenuate RILI, especially pulmonary fibrosis, in rats. The regulation on production and release of inflammatory or fibrotic factors IL-6, IL-10, TGF-β1, NOX-4, and MMP-1, especially MMP-1 and inhibition on CCL3/CCR1 activation, may partly attribute to its attenuating RILI effect

A comprehensive review of natural products against atopic dermatitis: Flavonoids, alkaloids, terpenes, glycosides and other compounds

Atopic dermatitis (AD) is considered a great challenge for human communities and imposes both physiological and mental burdens on patients. Natural products have widely been used to treat a wide range of diseases, including cancer, gastrointestinal diseases, asthma, neurological disorders, and infections. To seek potential natural products against AD, in the current review, we searched the terms “atopic dermatitis” and “natural product” in Pubmed, Medline, Web of Science，Science Direct, Embase, EBSCO, CINAHL, ACS. The results show that many natural products, especially puerarin, ferulic acid and ginsenosides, cound protect against AD. Meanwhile, we discussed the therapeutic mechanisms and showed that the natural products exert their anti-inflammatory effects by suppressing the quantity and activity of many inflammatory cell types and cytokines, including neutrophils, monocytes, lymphocytes, Langerhans cells, interleukins (ILs, including IL-1α, IL-1β, IL-4), TNF-α, and TSLP, IgE. via inhibition of JAK/STAT, MAPKs and NF-κB signaling pathways, thereby, halting the inflammatory cascade. Future investigations should focus on studies with more reflective of the clinical characteristics and demographics, so as to develop natural products that will be hopefully available for the treatment of human AD disease