Oroxylin A ameliorates ultraviolet radiation-induced premature skin aging by regulating oxidative stress via the Sirt1 pathway.

Skin is susceptible to premature aging in response to ultraviolet (UV) radiation-induced oxidative stress, which can ultimately result in aberrant aging or age-related disorders. Accordingly, strategies that can be adopted to mitigate oxidative stress may contribute to protecting skin from induced aging-related damage, thereby offering promising approaches for the treatment of skin diseases and disorders. In this regard, oroxylin A (OA), a natural flavonoid isolated from certain plants used in traditional Chinese medicine, is considered to have notable antioxidant, anti-inflammatory, and anti-apoptotic properties, and is often used to treat certain inflammatory diseases. To date, however, there has been comparatively little research on the effects of OA with respect skin aging. In this study, we utilized UV radiation-induced mouse and cellular models of aging to assess the efficacy of OA in protecting against skin aging. Subsequently, to elucidate the potential mechanisms underlying the protective effect of OA on skin aging, we performed molecular docking analysis to investigate the involvement of the anti-aging gene Sirt1, which was further confirmed on the basis of Sirt1 gene silencing. We accordingly demonstrated that by promoting an increase in the expression of Sirt1, OA can contribute to suppressing UV-induced skin photo-aging in cells/mice by reducing oxidative stress. Furthermore, we established that by activating Sirt1, OA can also promote the dissociation of Nrf2 from Keap1 and its subsequent nuclear translocation. Collectively, our findings in this study reveal OA to be an effective natural compound that can be administered to delay the aging of skin triggered by UV, both in vivo and in vitro, by binding to Sirt1 to promote the deacetylation and nuclear translocation of Nrf2, thereby contributing to a reduction in oxidative stress. These findings may this provide a therapeutic target for the prevention of skin aging or aging-induced skin diseases.

Economic burden of adult patients with ß-thalassaemia major in mainland China.

BACKGROUND: ß-thalassaemia major poses a substantial economic burden, especially in adults. We aimed to estimate the economic burden of adult patients with ß-thalassaemia major from a societal perspective using the real-world data. According to the clinical guideline, we also estimated the annual medical costs for patients with the same body weight and calculated the lifetime medical costs over 50 years in mainland China. METHODS: This was a retrospective cross-sectional study. An online survey with snowball sampling covering seven provinces was conducted. We extracted patient demographics, caregiver demographics, disease and therapy information, caring burden, and costs for adult patients diagnosed with ß-thalassaemia major and their primary caregivers. In the real world, we estimated the annual direct medical cost, direct nonmedical cost, and indirect cost. In addition, we calculated the annual direct medical cost and lifetime direct medical cost by weight with discounted and undiscounted rates according to the clinical guideline. RESULTS: Direct medical costs was the main driver of total cost, with blood transfusion and iron chelation therapy as the most expensive components of direct medical cost. In addition, adult patients with ß-thalassaemia major weighing 56 kg were associated with an increase of $2,764 in the annual direct medical cost using the real-world data. The undiscounted and discounted (5% discount rate) total lifetime treatment costs were $518,871 and $163,441, respectively. CONCLUSIONS: Patients with ß-thalassaemia major often encounter a substantial economic burden in mainland China. Efforts must be made to help policymakers develop effective strategies to reduce the burden and pevalence of thalassaemia.

ErZhiFormula prevents UV-induced skin photoaging by Nrf2/HO-1/NQO1 signaling: An in vitro and in vivo studies.

ETHNOPHARMACOLOGICAL RELEVANCE: ErZhiFormula (EZF) is a classical traditional Chinese medicinal formulation. It can be used to treat liver and kidney yin deficiency, dizziness, lumbar debility, insomnia, nocturnal emission, lower extremity weakness, and other aging-related diseases. However, the protective effect of EZF in skin photoaging and its potential mechanism has not been clarified. AIM OF THE STUDY: This study aims to explore the role of EZF in the skin photoaging mechanism induced by UV radiation. MATERIALS AND METHODS: Ultra Performance Liquid Chromatography (UPLC) was used to identify the fingerprint of EZF. The mice were irradiated with UVA and UVB to establish the photoaging model in vivo. Human immortalized keratinocytes (HaCaT) were irradiated with UVB to establish the photoaging model in vitro. The activity of cells was detected by CCK-8 and LDH kits, the level of reactive oxygen species was detected by DCF fluorescent probe, and the apoptosis was detected by PE annexin V and 7-Amino-Actinomycin (7-AAD) staining. Comet assay was used to detect cell DNA damage. The antioxidant enzyme levels in cell and mouse serum were detected by antioxidant kit, and Western blot was used to detect protein expression. RESULTS: We found that EZF contain many active ingredients, including salidroside, specnuezhenide, isoquercitrin, etc. EZF can improve the photoaging of HaCaT cells and mouse skin caused by UV radiation. The results of animal experiments are consistent with those of cell experiments. Combined with Western blot analysis, we found that EZF finally played an anti-skin photoaging role by regulating the Nrf2/HO-1/NQO1 pathway. CONCLUSIONS: EZF can protect skin from UV-induced photoaging by regulating the Nrf2/HO-1/NQO1 signal pathway. EZF may become a traditional Chinese medicine with the potential to prevent skin photoaging.

Normalization of the H3K9me2/H3K14ac-ΔFosB pathway in the nucleus accumbens underlying the reversal of morphine-induced behavioural and synaptic plasticity by Compound 511.

BACKGROUND: Although opioid agonist-based treatments are considered the first-line treatment for opioid use disorders, nonopioid alternatives are urgently needed to combat the inevitable high relapse rates. Compound 511 is a formula derived from ancient traditional Chinese medical literature on opiate rehabilitation. Previously, we observed that Compound 511 could effectively prevent the acquisition of conditioned place preference (CPP) during early morphine exposure. However, its effects on drug-induced reinstatement remain unclear. PURPOSE: This study aims to estimate the potential of Compound 511 for the therapeutic intervention of opioid relapse in rodent models and explore the potential mechanisms underlying the observed actions. STUDY DESIGN/METHODS: The CPP and locomotor sensitization paradigm were established to evaluate the therapeutic effect of Compound 511 treatment on morphine-induced neuroadaptations, followed by immunofluorescence and western blot (WB) analysis of the synaptic markers PSD-95 and Syn-1. Furthermore, several addiction-associated transcription factors and epigenetic marks were examined by qPCR and WB, respectively. Furthermore, the key active ingredients and targets of Compound 511 were further excavated by network pharmacology approach and experimental validation. RESULTS: The results proved that Compound 511 treatment during abstinence blunted both the reinstatement of morphine-evoked CPP and locomotor sensitization, accompanied by the normalization of morphine-induced postsynaptic plasticity in the nucleus accumbens (NAc). Additionally, Compound 511 was shown to exert a selectively repressive influence on morphine-induced hyperacetylation at H3K14 and a reduction in H3K9 dimethylation as well as ΔFosB activation and accumulation in the NAc. Finally, two herbal ingredients of Compound 511 and six putative targets involved in the regulation of histone modification were identified. CONCLUSION: Our findings indicated that Compound 511 could block CPP reinstatement and locomotor sensitization predominantly via the reversal of morphine-induced postsynaptic plasticity through epigenetic mechanisms. Additionally, 1-methoxy-2,3-methylenedioxyxanthone and 1,7-dimethoxyxanthone may serve as key ingredients of Compound 511 by targeting specific epigenetic enzymes. This study provided an efficient nonopioid treatment against opioid addiction.

Uncovering the effect and mechanism of Panax notoginseng saponins on metabolic syndrome by network pharmacology strategy.

ETHNOPHARMACOLOGICAL RELEVANCE: Metabolic syndrome (MetS) is a cluster of disease centered on obesity, which is the result of stagnation of liver qi according to traditional Chinese medicine. Panax notoginseng is a traditional Chinese herbal medicine, entering liver and stomach meridians and dissipating blood stasis, in which panax notoginseng saponins (PNS) are the main active components. However, its effects and mechanism on metabolic syndrome has not been revealed yet. AIM OF STUDY: To evaluate the anti-MetS effect of PNS, including body weight and adiposity, glucose metabolism and non-alcoholic fatty liver disease (NAFLD), as well as to explore the mechanism and signaling pathway of PNS on MetS effect. MATERIALS AND METHODS: HPLC was utilized to affirm the percentages of saponins in PNS. In vivo, normal C57BL/6J mice and high-fat diet (HFD)-induced MetS mice were used to evaluate anti-MetS effect of PNS. Body weight, food and water intake were recorded. NMR imager was used for NMR imaging and lipid-water analysis. Blood glucose detection, glucose and insulin tolerance test were performed to evaluate glucose metabolism. Biochemical indexes analysis and histopathological staining were used to evaluate the effect on NAFLD. The expressions of mRNA and proteins related to thermogenesis in adipose tissue were determined using real-time PCR and Western blot. In silico, network pharmacology was utilized to predict potential mechanism. In vitro, matured 3T3-L1 adipocyte was used as subject to confirm the signaling pathway by Western blot. RESULTS: We determined the content of PNS component by HPLC. In vivo, PNS could improve metabolic syndrome with weight loss, reduction of adiposity, improvement of adipose distribution, correction of glucose metabolism disorder and attenuation of NAFLD. Mechanismly, PNS boosted energy exhaustion and dramatically enhanced thermogenesis in brown adipose tissue (BAT), induced white adipose tissue (WAT) browning. In silico, utilizing network pharmacology strategy, we identified 307 candidate targets which were enriched in MAPK signaling pathway specifically in liver tissue and adipocyte. In vitro validation confirmed ERK and p38MAPK mediated anti-MetS effects of PNS, not JNK signaling pathway. CONCLUSION: PNS exerted protective effect on metabolic syndrome through MAPK-mediated adipose thermogenic activation, which may serve as a prospective therapeutic drug for metabolic syndrome.

Risk assessment of Artemia egg shell-Mg-P composites as a slow-release phosphorus fertilizer during its formation and application in typical heavy metals contaminated environment.

Artemia egg shell loaded with nano-magnesium (shell-Mg) can be used to recover phosphorus from wastewater. The exhausted Artemia egg shell-Mg (denoted as shell-Mg-P) can be used as a slow-release fertilizer for phosphorus reuse. However, due to the coexistence of heavy metal ions in the environment, the application of slow-release fertilizer for phosphorus removal and reuse may have potential risks. In this paper, the potential risks of Pb2+, Cd2+, Zn2+ and Cu2+ in phosphorus wastewater and soil were studied from the formation and application process of shell-Mg-P. The result showed that shell-Mg adsorbed Pb2+, Cd2+, Zn2+ and Cu2+ in phosphate wastewater during the formation of shell-Mg-P and became shell-Mg-P-metal hybrid biomaterial. Although the experiment proved that the existence of heavy metal ions did not affect the phosphorus slow-release behavior of slow-release fertilizer, but the heavy metal ions in the shell-Mg-P-metal were also slow released. The pot experiment results confirmed that the slow-release phosphorus fertilizers (shell-Mg-P and shell-Mg-P-metal) in the soil polluted in low concentration of heavy metals can reduce the amount of heavy metals in whole wheat seedlings and promote wheat seedling growth. However, the application of slow-release fertilizers increased the translocation efficiency (TFR to SL) of metal from root (R) to aboveground part (stem and leaves, SL), promoted the transportation of heavy metals from roots to the stems and leaves, and increased the safety risk of the wheat seedling edible. Therefore, besides the positive role of slow-release fertilizers in retaining heavy metals and reducing the amount of heavy metals in whole seedlings, the risk that it may aggravate the translocation of heavy metals to stems and leaves should be paid more attention, so as to ensure the safe and reliable application of slow-release fertilizers.

Modified Qing'e Formula protects against UV-induced skin oxidative damage via the activation of Nrf2/ARE defensive pathway.

Exposure to ultraviolet (UV) light triggers the rapid generation and accumulation of reactive oxygen species (ROS) in skin cells, which increases oxidative stress damage and leads to photoaging. Nuclear factor E2-related factor 2 (Nrf2) modulates the antioxidant defense of skin cells against environmental factors, especially ultraviolet radiation. Natural products that target Nrf2-regulated antioxidant reactions are promising candidates for anti-photoaging. The aim of this study was to investigate the protective effect of Modified Qing'e Formula (MQEF) on UV-induced skin oxidative damage and its molecular mechanisms. In this study, the photoaging models of human keratinocytes (HaCaT) and ICR mice were established by UV irradiation. In vitro models showed that MQEF displayed potent antioxidant activity, significantly increased cell viability and reduced apoptosis and excess ROS levels. Meanwhile, the knockdown of Nrf2 reversed the antioxidant and anti-apoptotic effects of MQEF. In vivo experiments indicated that MQEF could protect the skin against UV-exposed injury which manifested by water loss, sensitivity, tanning, wrinkling, and breakage of collagen and elastic fibers. The application of MQEF effectively increased the activity of antioxidant enzymes and reduced the content of malondialdehyde (MDA) in mice. In addition, MQEF was able to activate Nrf2 nuclear translocation in mouse skin tissue. In summary, MQEF may attenuate UV-induced photoaging by upregulating Nrf2 expression and enhancing antioxidant damage capacity. MQEF may be a potential candidate to prevent UV-induced photoaging by restoring redox homeostasis.

Corylin from Psoralea fructus (Psoralea corylifolia L.) protects against UV-induced skin aging by activating Nrf2 defense mechanisms.

Oxidative stress damage can lead to premature skin aging or age-related skin disorders. Therefore, strategies to improve oxidative stress-induced aging are needed to protect the skin and to treat skin diseases. This study aimed to determine whether the flavonoid corylin derived from Psoralea corylifolia can prevent UV-induced skin aging and if so, to explore the potential molecular mechanisms. We found that corylin potently blocked UV-induced skin photoaging in mice by reducing oxidative stress and increasing the nuclear expression of nuclear factor-erythroid factor 2-related factor 2 Nrf2. We also found that corylin stimulated Nrf2 translocation into the nucleus and increased the delivery of its target antioxidant genes together with Kelch-like ECH-associated protein 1 (Keap1) to dissociate Nrf2. These findings indicate that corylin could prevent skin aging by inhibiting oxidative stress via Keap1-Nrf2 in mouse cells. Thus, Nrf2 activation might be a therapeutic target for preventing skin aging or skin diseases caused by aging. Our findings also provided evidence that warrants the further investigation of plant ingredients to facilitate the discovery of novel therapies targeting skin aging.

Bioremediation of selenium-contaminated soil using earthworm Eisenia fetida: Effects of gut bacteria in feces on the soil microbiome.

Selenium (Se) contamination in the soil poses a food safety risk to humans. The present study was to investigate the role of earthworm Eisenia fetida in soil Se remediation. When exposed to selenite at 4 mg Se/kg, E. fetida efficiently concentrated Se in tissues (24.53 mg Se/kg dry weight), however, only accounting for a minor portion of the added Se. Microbial analysis shows 12 out of 15 functional genera became more abundant in the worm-inhabited soil when exposed to Se, suggesting E. fetida contributed to Se remediation mainly by introducing Se-reducing bacteria to the soil via feces, which were dominated by the genera Pseudomonas (∼62.65%) and Aeromonas (∼29.99%), whose abundance was also significantly boosted in the worm-inhabited soil. However, when isolated from worm feces at 200 mg Se/L, Pseudomonas strains only displayed a high tolerance to Se rather than removal capacity. In contrast, among 4 isolated Aeromonas strains, A. caviae rapidly removing 85.74% of the added selenite, mainly through accumulation (67.38%), while A. hydrophila and A. veronii were more effective at volatilizing Se (27.77% and 24.54%, respectively), and A. media performed best by reducing Se by ∼49.00% under anaerobic conditions. Overall, our findings have highlighted the importance of E. fetida as a key contributor of functional bacteria to the soil microbiome, building a strong foundation for the development of an earthworm-soil system for Se bioremediation.

Economic Evaluation of Sintilimab Plus Bevacizumab Versus Sorafenib as a First-line Treatment for Unresectable Hepatocellular Carcinoma.

INTRODUCTION: This study aimed to evaluate the cost-effectiveness of sintilimab plus bevacizumab versus sorafenib as a first-line treatment for unresectable hepatocellular carcinoma (HCC) in China to provide economic evidence to inform health decision making. METHODS: We performed an economic evaluation from the perspective of the Chinese healthcare system using a partitioned survival model with three mutually exclusive health states: progression free, post-progression, and death. Efficacy data were obtained from the ORIENT-32 clinical trial and extrapolated to the lifetime horizon. Cost and utility values were derived from published studies and online price databases. The primary outcomes of the model were quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were carried out to verify the robustness of the model results. RESULTS: Compared with sorafenib, sintilimab plus bevacizumab incurred a higher lifetime cost ($33,766 vs. $23,294) and yielded more QALYs (1.428 vs. 0.928 QALYs). The ICER for sintilimab plus bevacizumab was $20,968/QALY and lower than the willingness-to-pay threshold of $33,592. The results of sensitivity analysis showed that ICER values were most sensitive to the subsequent treatment cost of the sorafenib group after progression and the price of bevacizumab. In the scenario analysis, the ICER was $4191/QALY when a 7.5 mg/kg dose of bevacizumab was applied in the model. CONCLUSIONS: Compared with sorafenib, the sintilimab plus bevacizumab combination is likely to be a cost-effective option for patients with unresectable HCC in China.

Se transformation and removal by a cattail litter treatment system inoculated with sulfur-based denitrification sludge: Role of the microbial community composition under various temperature and aeration conditions.

With a narrow margin between deficiency and toxicity, rising levels of selenium (Se) are threatening aquatic ecosystems. To investigate the role of microorganisms in Se bioremediation, a cattail litter system inoculated with the sulfur-based denitrification sludge was conducted. The results show the litter, as a carrier and nutrient source for bacteria, efficiently removed Se by ~ 97.0% during a 12-d treatment with water circulating. As the major removal pathways, immobilization rates of selenite were ~ 2.9-fold higher than selenate, and the volatilization, contributing to ~ 87.7% of the total Se removal, was significantly correlated with temperature (positively) and oxidation-reduction potential (ORP; negatively). Using X-ray absorption spectroscopy to speciate litter-borne Se, more Se0 formed without aeration due to abundant Se-reducing bacteria, among which Azospira and Azospirillum were highly related to the removal of both Se oxyanions, while Desulfovibrio, Azoarcus, Sulfurospirillum, Thauera, Geobacter, Clostridium, and Pediococcus were the major contributors to selenate removal. Overall, our study suggests microbial Se metabolism in the litter system was significantly affected by temperature and ORP, which could be manipulated to enhance Se removal efficiency and the transformation of selenate/selenite into low toxic Se0 and volatile Se, reducing risks posed by the residual Se in the system.

The effects of CCRC on cognition and brain activity in aMCI patients: a pilot placebo controlled BOLD fMRI study.

OBJECTIVE: To investigate effects and functional mechanism of compound Congrongyizhi Capsule (CCRC), a Chinese medicine, on cognitive functions against amnestic mild cognitive impairment (aMCI) patients with functional magnetic resonance imaging (fMRI) based on n-back task. METHODS: Forty-one aMCI participants from hospital and local communities in Beijing and randomly divided into treatment (16 patients with CCRC capsule treatment), placebo (12 patients with placebo capsules) and control group (13 patients with no treatment). The duration of intervention lasted for 3 months. Neuropsychological tests and fMRI were applied to assess cognitive ability and brain activation changes after three months treatment. RESULTS: Drug group (n=16) presented increased significance in the MMSE (P=0.008) and digit span (P<0.001) tests, while other scores of neuropsychological tests showed no statistical significance. fMRI results showed an increased brain negative activation in drug group during performing the n-back working-memory task in posterior cingulate (PCC), inferior frontal gyrus and lingual gyrus regions after 3 months; placebo and control group did not show the same effect. Meanwhile, there were negative correlations between left PCC activation levels and changed values of MMSE and digit span separately since increased negative activation was associated with better performance on the scores of MMSE and Digit Span tests. CONCLUSIONS: CCRC can increase negative activation degree of PCC under performing working memory tasks while this modulation are associated with better performance on the MMSE and Digit Span.