Astaxanthin targets IL-6 and alleviates the LPS-induced adverse inflammatory response of macrophages.

Numerous natural compounds are recognized for their anti-inflammatory properties attributed to antioxidant effects and the modulation of key inflammatory factors. Among them, astaxanthin (AST), a potent carotenoid antioxidant, remains relatively underexplored regarding its anti-inflammatory mechanisms and specific molecular targets. In this study, human monocytic leukemia cell-derived macrophages (THP-1) were selected as experimental cells, and lipopolysaccharides (LPS) served as inflammatory stimuli. Upon LPS treatment, the oxidative stress was significantly increased, accompanied by remarkable cellular damage. Moreover, LPSs escalated the expression of inflammation-related molecules. Our results demonstrate that AST intervention could effectively alleviate LPS-induced oxidative stress, facilitate cellular repair, and significantly attenuate inflammation. Further exploration of the anti-inflammatory mechanism revealed AST could substantially inhibit NF-κB translocation and activation, and mitigate inflammatory factor production by hindering NF-κB through the antioxidant mechanism. We further confirmed that AST exhibited protective effects against cell damage and reduced the injury from inflammatory cytokines by activating p53 and inhibiting STAT3. In addition, utilizing network pharmacology and in silico calculations based on molecular docking, molecular dynamics simulation, we identified interleukin-6 (IL-6) as a prominent core target of AST anti-inflammation, which was further validated by the RNA interference experiment. This IL-6 binding capacity actually enabled AST to curb the positive feedback loop of inflammatory factors, averting the onset of possible inflammatory storms. Therefore, this study offers a new possibility for the application and development of astaxanthin as a popular dietary supplement of anti-inflammatory or immunomodulatory function.

Spatial amine metabolomics and histopathology reveal localized brain alterations in subacute traumatic brain injury and the underlying mechanism of herbal treatment.

INTRODUCTION: Spatial changes of amine metabolites and histopathology of the whole brain help to reveal the mechanism of traumatic brain injury (TBI) and treatment. METHODS: A newly developed liquid microjunction surface sampling-tandem mass tag-ultra performance liquid chromatography-mass spectrometry technique is applied to profile brain amine metabolites in five brain regions after impact-induced TBI at the subacute stage. H&E, Nissl, and immunofluorescence staining are performed to spatially correlate microscopical changes to metabolic alterations. Then, bioinformatics, molecular docking, ELISA, western blot, and immunofluorescence are integrated to uncover the mechanism of Xuefu Zhuyu decoction (XFZYD) against TBI. RESULTS: Besides the hippocampus and cortex, the thalamus, caudate-putamen, and fiber tracts also show differentiated metabolic changes between the Sham and TBI groups. Fourteen amine metabolites (including isomers such as L-leucine and L-isoleucine) are significantly altered in specific regions. The metabolic changes are well matched with the degree of neuronal damage, glia activation, and neurorestoration. XFZYD reverses the dysregulation of several amine metabolites, such as hippocampal Lys-Phe/Phe-Lys and dopamine. Also, XFZYD enhances post-TBI angiogenesis in the hippocampus and the thalamus. CONCLUSION: This study reveals the local amine-metabolite and histological changes in the subacute stage of TBI. XFZYD may promote TBI recovery by normalizing amine metabolites and spatially promoting dopamine production and angiogenesis.

Comparative effectiveness of nonpharmacological interventions in reducing psychological symptoms among patients with chronic low back pain.

OBJECTIVES: Chronic low back pain (CLBP) can seriously impair the quality of life of patients and has a remarkable comorbidity with psychological symptoms, which, in turn, can further exacerbate the symptoms of CLBP. Psychological treatments are critical and nonnegligent for the management of CLBP, and thus, should attract sufficient attention. However, current evidence does not suggest the superiority and effectiveness of nonpharmacological interventions in reducing psychological symptoms among patients with CLBP.Thus, this study was designed to compare the effectiveness of nonpharmacological interventions for depression, anxiety, and mental health among patients with CLBP and to recommend preferred strategies for attenuating psychological symptoms in clinical practice. METHODS: In this systematic review and network meta-analysis (NMA), PubMed, Embase Database, Web of Science, and Cochrane Library were searched from database inception until March 2022. Randomized clinical trials (RCTs) that compare different nonpharmacological interventions for depression, anxiety, and mental health among patients with CLBP were eligible. The Preferred Reporting Items for Systematic Reviews and Meta-analyses statement was used. Four reviewers in pairs and divided into two groups independently performed literature selection, data extraction, and risk of bias, and certainty of evidence assessments. This NMA was conducted with a random effects model under a frequentist framework. The major outcomes were depression, anxiety, and mental health presented as the standardized mean difference (SMD) with the corresponding 95% CI. RESULTS: A total of 66 RCTs that randomized 4806 patients with CLBP met the inclusion criteria. The quality of evidence was typically low or some risks of bias (47 out of 66 trials, 71.3%), and the precision of summary estimates for effectiveness varied substantially. In addition, 7 categories of interventions with 26 specific treatments were evaluated. For depression, mind body therapy (pooled SMD = -1.20, 95% CI: -1.63 to -0.78), biopsychosocial approach (pooled SMD = -0.41, 95% CI: -0.70 to -0.12), and physical therapy (pooled SMD = -0.26, 95% CI: -0.50 to -0.02) exhibited remarkable effectiveness in reducing depression compared with the control group. For managing anxiety, mind body therapy (pooled SMD = -1.35, 95% CI: -1.90 to -0.80), multicomponent intervention (pooled SMD = -0.47, 95% CI: -0.88 to -0.06), and a biopsychosocial approach (pooled SMD = -0.46, 95% CI: -0.79 to -0.14) were substantially superior to the control group. For improving mental health, multicomponent intervention (pooled SMD = 0.77, 95% CI: 0.14 to 1.39), exercise (pooled SMD = 0.60, 95% CI: 0.08 to 1.11), and physical therapy (pooled SMD = 0.47, 95% CI: 0.02-0.92) demonstrated statistically substantial effectiveness compared with the control group. The rank probability indicated that mind body therapy achieved the highest effectiveness in reducing depression and anxiety among patients with CLBP. Besides, the combined results should be interpreted cautiously based on the results of analyses evaluating the inconsistency and certainty of the evidence. CONCLUSION: This systemic review and NMA suggested that nonpharmacological interventions show promise for reducing psychological symptoms among patients with CLBP. In particular, mind body therapy and a biopsychosocial approach show considerable promise, and mind body therapy can be considered a priority choice in reducing depression and anxiety. These findings can aid clinicians in assessing the potential risks and benefits of available treatments for CLBP comorbidity with psychological symptoms and provide evidence for selecting interventions in clinical practice. More RCTs involving different interventions with rigorous methodology and an adequate sample size should be conducted in future research.

[Expression and Clinical Significance of Exosome Component 4 in Newly Diagnosed Patients with Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To explore the expression of Exosome Component 4（EXOSC4） in the tissues of newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) and its clinical significance. METHODS: The expression of EXOSC4 protein in the tissues of 181 newly diagnosed DLBCL patients was analyzed by immunohistochemical staining. Clinical data were collected. The correlation between EXOSC4 protein expression in the tissues of newly diagnosed DLBCL patients and clinical features were analyzed and its prognostic significance. RESULTS: The positive rate of EXOSC4 protein expression was 68.51% in the tissues of 181 newly diagnosed DLBCL patients. These patients were divided into two groups, with 44 cases in high expression group and 137 cases in low expression group. There were no significant differences in age, gender, B symptoms, serum lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group (ECOG) score, Ann Arbor stage, extranodal disease, International Prognostic Index (IPI) score, National Comprehensive Cancer Network IPI (NCCN-IPI) score, and cell origin between the two groups (P>0.05). Cox multivariate regression analysis showed that high EXOSC4 protein expression in tissues was an independent poor prognostic factor for OS and PFS in newly diagnosed DLBCL patients (all P<0.05). K-M survival analysis showed that newly diagnosed DLBCL patients with high EXOSC4 protein expression had significantly shorter overall survival (OS) and progression free survival (PFS) than those patients with low EXOSC4 protein expression (all P<0.05). CONCLUSION: High EXOSC4 protein expression in tissues of newly diagnosed DLBCL patients is an independent poor prognostic factor for survival.

Ginsenoside Rh2 and its octyl ester derivative inhibited invasion and metastasis of hepatocellular carcinoma via the c-Jun/COX2/PGE2 pathway.

BACKGROUND: Liver cancer is a topical global health issue. The treatment of liver cancer meets significant challenges in the high recurrence rate and invasive incidence. Therefore, the treatment strategies that target epithelial-mesenchymal transition (EMT) induced by cyclooxygenase 2 (COX2)/ prostaglandin E2 (PGE2) pathway have become epidemic. Ginsenoside Rh2 has been proved to inhibit the EMT. However, the underlying mechanisms remain unclear. Moreover, the octyl ester derivative of Rh2 (Rh2-O) exhibited superior anti-proliferative and immunomodulatory effects than Rh2 in our previous researches, which indicated that Rh2-O might also exert inhibitory effects on invasion and metastasis. PURPOSE: The aim of current study is to explore the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis of hepatocellular carcinoma, and to investigate whether these effects are dependent on the c-Jun/COX2/PGE2 pathway. STUDY DESIGN: The Huh-7 liver cancer cells and the H22 tumor-bearing mice were treated with Rh2 and Rh2-O. METHOD: In this paper, the inhibitory effects of Rh2 and Rh2-O on invasion and metastasis were tested by wound healing, trans-well assay and tumor-bearing mice, and the involvement of c-Jun/COX2/PGE2 pathway were verified by exogenous PGE2, activation of COX2 and overexpression of c-Jun. RESULTS: The results showed that Rh2 and Rh2-O could efficiently inhibit the invasion and metastasis in a dose-dependent manner (p < 0.05). And the Rh2-O showed stronger effects than Rh2. Moreover, the exogenous PGE2, activation of COX2 by exogenous LPS and the overexpression of c-Jun by transfection all reversed the inhibitory effects of Rh2 and Rh2-O on metastasis or EMT (p < 0.05). CONCLUSION: Rh2 and Rh2-O could inhibit the invasion and metastasis of hepatocellular carcinoma via restraining the EMT, which was mediated by c-Jun/COX2/PGE2 pathway.

The effects of astragaloside IV on gut microbiota and serum metabolism in a mice model of intracerebral hemorrhage.

BACKGROUND: Astragaloside IV (AS-IV) is the main active component of "Astragalus membranaceus (Fisch.) Bunge, a synonym of Astragalus propinquus Schischkin (Fabaceae)", which demonstrated to be useful for the treatment of intracerebral hemorrhage (ICH). However, due to the low bioavailability and barrier permeability of AS-IV, the gut microbiota may be an important key regulator for AS-IV to work. OBJECTIVE: To explore the influences of gut microbiota on the effects of AS-IV on ICH. METHODS: Mice were randomly divided into five groups: sham, ICH, and AS-IV-treated groups (25 mg/kg, 50 mg/kg, and 100 mg/kg). Behavioral tests, brain histopathology, and immunohistochemistry analysis were used to evaluate the degree of brain injury. Western blot was employed to verify peri­hematoma inflammation. The plasma lipopolysaccharide (LPS) leakage, the fluorescein isothiocyanate-dextran permeability, the colonic histopathology, and immunohistochemistry were detected to evaluate the barrier function of intestinal mucosal. Moreover, 16S rDNA sequencing and metabolomic analysis was applied to screen differential bacteria and metabolites, respectively. The correlation analysis was adopted to determine the potential relationship between differential bacteria and critical metabolites or neurological deficits. RESULTS: AS-IV alleviated neurological deficits, neuronal injury and apoptosis, and blood-brain barrier disruption. This compound reduced tumor necrosis factor (TNF)-α expression, increased arginase (Arg)-1 and interleukin (IL)-33 levels around the hematoma. Next, 16S rRNA sequencing indicated that AS-IV altered the gut microbiota, and inhibited the production of conditional pathogenic bacteria. Metabolomic analysis demonstrated that AS-IV regulated the serum metabolic profiles, especially the aminoacid metabolism and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Additionally, AS-IV mitigated intestinal barrier damage and LPS leakage. CONCLUSION: This study provides a new perspective on the use of AS-IV for the treatment of ICH. Among them, gut microbiota and its metabolites may be the key regulator of AS-IV in treating ICH.

Ethnobotanical study on medicinal plants used by Bulang people in Yunnan, China.

BACKGROUND: Despite the popularity of modern medicine, medicinal plants remain a cornerstone of treatment for numerous diseases, particularly among ethnic groups and tribal communities around the globe. Ethnomedicine offers advantages such as ease of use, convenience, and economic benefits. Medicinal plant knowledge within Bulang ethnic community of southwest China is a valuable complement to Chinese ethnomedicine systems. Accumulated medical knowledge is due to the extensive length of occupation by Bulang People, considered the earliest inhabitants of Xishuangbanna; this has resulted in the development of various traditional treatment methods with local characteristics and unique curative effects. Therefore, there is exceeding value in exploring the medical knowledge of Bulang. METHODS: A total of 175 local informants participated in the interviews and distribution of questionnaires in 10 Bulang villages in Menghai County, Xishuangbanna Prefecture, Yunnan Province, China. We documented the community of Bulang's use of medicinal herbs, and we used both the informant consensus factor (ICF) and use value (UV) methodologies to analyze the data. Furthermore, we conducted a comparative study to explore the potential of Bulang traditional medicine by comparing it to traditional Dai medicine. RESULTS: The study recorded 60 medicinal plant species belonging to 41 families and 59 genera, including 22 species of herb, 22 species of shrub, nine species of trees, and seven species of liana. Araceae, Compositae, Lamiaceae and Leguminosae were found to have the highest number of species. The affordability and cultural heritage of Bulang medicine make it advantageous, Investigated Informants report that increased usage of Western medicine (88%), less availability of herbal medicine (95.43%), and the reduction in medicinal plant resources (80.57%) pose significant threats to Bulang medicine. All Bulang medicinal plants are naturally grown, with only 22 per cent being cultivated. Camellia sinensis (0.94) and Zingiber officinale (0.89) showed the highest UV values, while the function of Phyllanthus emblica L. and Houttuynia cordata Thunb. were also noted. The ICF revealed digestive system related diseases were the most commonly treated, with conditions of the motor system using the highest number of plant species. Finally, a comparison with traditional Dai medicine determined that 22 plants (36.67%) of the 60 surveyed had higher medicinal value in Bulang medicine. CONCLUSION: Bulang communities primarily source medicinal plants from the wild. Should environmental damage lead to the extinction of these medicinal plants, it could result in a shift toward modern Western medicine as a preferred medical treatment. Bulang ethnomedicine is a vital supplement to China's traditional medicine, particularly aspects of ethnic medicine relevant to daily life. Future research should emphasize inter-ethnic medical studies to reveal the untapped potential of medicinal plants.

A novel method for age identification of mountain-cultivated ginseng.

Panax ginseng, a slow-growing perennial herb, is the most praised and popular traditional medicinal herb. Mountain-cultivated ginseng (MCG) and cultivated ginseng (CG) both belong to Panax ginseng C. A. Meyer. The market price and medical effects of this popular health product are closely related to its age. It is widely acknowledged that CG is typically harvested after 4-6 years of growth, but MCG is often collected after 10 years. Until now, the age identification of MCG or mountain wild ginseng (MWG) has remained a major challenge. In this study, we established a novel and rapid method for staining xylem vessels with phloroglucinol and identifying the "annual growth rings" of ginseng by utilizing a stereoscope, which serves as a reliable indicator of the age of MCG. Statistical analysis of the ring radius and the ring density of MCG aged from 1 to 20 years shows that the secondary xylem of MCG increases rapidly in the first 3 years but then gradually slows down from 4 to 10 years, and minor fluctuation is observed in the next 10 years. Meanwhile, the space between the growth rings (ring density) becomes increasingly small with age. This straightforward staining approach can reveal the age of MCG with remarkable clarity and can distinguish MCG from CG. RESEARCH HIGHLIGHTS: A novel rapid staining method for Panax ginseng was established. The age of mountain-cultivated ginseng (MCG) can be identified by microscopic techniques. MCG and cultivated ginseng (CG) can be discriminated by microstructure characteristics.

[Leonurine inhibits ferroptosis in renal tubular epithelial cells by activating p62/Nrf2/HO-1 signaling pathway].

To investigate the protective effect and the potential mechanism of leonurine(Leo) against erastin-induced ferroptosis in human renal tubular epithelial cells(HK-2 cells), an in vitro erastin-induced ferroptosis model was constructed to detect the cell viability as well as the expressions of ferroptosis-related indexes and signaling pathway-related proteins. HK-2 cells were cultured in vitro, and the effects of Leo on the viability of HK-2 cells at 10, 20, 40, 60, 80 and 100 µmol·L~(-1) were examined by CCK-8 assay to determine the safe dose range of Leo administration. A ferroptosis cell model was induced by erastin, a common ferroptosis inducer, and the appropriate concentrations were screened. CCK-8 assay was used to detect the effects of Leo(20, 40, 80 µmol·L~(-1)) and positive drug ferrostatin-1(Fer-1, 1, 2 µmol·L~(-1)) on the viability of ferroptosis model cells, and the changes of cell morphology were observed by phase contrast microscopy. Then, the optimal concentration of Leo was obtained by Western blot for nuclear factor erythroid 2-related factor 2(Nrf2) activation, and transmission electron microscope was further used to detect the characteristic microscopic morphological changes during ferroptosis. Flow cytometry was performed to detect reactive oxygen species(ROS), and the level of glutathione(GSH) was measured using a GSH assay kit. The expressions of glutathione peroxidase 4(GPX4), p62, and heme oxygenase 1(HO-1) in each group were quantified by Western blot. RESULTS:: showed that Leo had no side effects on the viability of normal HK-2 cells in the concentration range of 10-100 µmol·L~(-1). The viability of HK-2 cells decreased as the concentration of erastin increased, and 5 µmol·L~(-1) erastin significantly induced ferroptosis in the cells. Compared with the model group, Leo dose-dependently increased cell via-bility and improved cell morphology, and 80 µmol·L~(-1) Leo promoted the translocation of Nrf2 from the cytoplasm to the nucleus. Further studies revealed that Leo remarkably alleviated the characteristic microstructural damage of ferroptosis cells caused by erastin, inhibited the release of intracellular ROS, elevated GSH and GPX4, promoted the nuclear translocation of Nrf2, and significantly upregulated the expression of p62 and HO-1 proteins. In conclusion, Leo exerted a protective effect on erastin-induced ferroptosis in HK-2 cells, which might be associated with its anti-oxidative stress by activating p62/Nrf2/HO-1 signaling pathway.

N6-methyladenosine profiling reveals that Xuefu Zhuyu decoction upregulates METTL14 and BDNF in a rat model of traumatic brain injury.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese herbal formula Xuefu Zhuyu decoction (XFZYD) is a classic formula in the category of invigorating blood circulation and resolving blood stasis. It has been proven to improve the neurological and ethological prognosis of traumatic brain injury. XFZYD promotes synaptic and axonal regeneration after traumatic brain injury, which is functionally modulated by the N6-methyladenosine (m6A) modification of RNA. However, the epigenetic effects of XFZYD on m6A modification remain unknown. AIM OF THE STUDY: To explore how XFZYD protects against traumatic brain injury induced by controlled cortical impact (CCI) injury by altering RNA m6A modification. MATERIALS AND METHODS: The modified neurological severity scoring and Morris water maze were performed to evaluate the neuroprotective effects of XFZYD for 14 days and screen the dose. Then, dot blot, western blotting, and methylated RNA immunoprecipitation sequencing (MeRIP-Seq) were used to explore changes in RNA m6A modification in the perilesional cortex. The Metascape platform was used to analyze the Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway of the differential m6A-tagged genes. Furthermore, MeRIP-qPCR was conducted to quantify differences in the hub differential m6A modification gene brain-derived neurotrophic factor (Bdnf). RESULTS: XFZYD significantly ameliorated the neurological deficits, spatial learning, and memory impairments in rats post-CCI on day 14. XFZYD enhanced the m6A level, and the expression of METTL14 and YTHDC2 in the perilesional cortex of CCI rats. In all three groups, the 3'-untranslated regions and coding sequence were primarily enriched for m6A peaks. XFZYD reversed the increased proportion of 3'-untranslated regions, and the decreased proportion of coding sequence and 5'-untranslated regions post-CCI. Moreover, XFZYD markedly downregulated 41 elevated m6A-tagged transcripts and upregulated 119 decreased m6A-tagged transcripts following CCI. Gene ontology and KEGG pathway analysis revealed that XFZYD-regulated m6A-tagged transcripts were predominantly enriched in synapse assembly, synaptic plasticity, learning or memory, and MAPK signaling pathway. Then, the hub-regulated m6A-tagged gene BDNF was identified. Both the m6A methylation level and the protein level of BDNF were ascended by XFZYD treatment. CONCLUSION: XFZYD improves neurological deficits, spatial learning and memory impairments in rats post-TBI probably through increasing the expression of METTL14 and BDNF in the cortex. Our study highlights a novel post-transcriptional regulation mechanism mediated by herbal medicine for traumatic brain injury treatment.

Explorating the mechanism of Huangqin Tang against skin lipid accumulation through network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Tang (HQT), a famous prescription with the effect of clearing pathogenic heat and detoxifying, was first recorded in "Treatise on Typhoid and Miscellaneous Diseases". It has proved that HQT has good anti-inflammatory and antioxidant effects and can improve acne symptoms clinically. However, the study on the regulation of HQT on sebum secretion which is one of the inducements of acne is not enough. AIM OF THE STUDY: This paper aimed to investigate the mechanisms of HQT in the treatment of skin lipid accumulation by network pharmacology and validating the results via in vitro experiments. MATERIALS AND METHODS: Network pharmacology was employed to predict the potential targets of HQT against sebum accumulation. Then, the palmitic acid (PA)-induced SZ95 cell model was established to evaluate the effect of HQT on lipid accumulation and anti-inflammation, and the core pathways predicted by network pharmacology were verified in cell studies. RESULTS: 336 chemical compounds and 368 targets in HQT were obtained by network pharmacology, of which 65 targets were related to sebum synthesis. 12 core genes were revealed by protein-protein interaction (PPI) network analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results suggested that AMP-activated protein kinase (AMPK) signaling pathway might play a crucial role in regulating lipogenesis. In vitro experiments, HQT suppressed lipid accumulation, downregulated the expressions of sterol-regulatory element binding protein-1 (SREBP-1) and fatty acid synthase (FAS), and upregulated AMPK phosphorylation. Furthermore, AMPK inhibitor reversed HQT-mediated sebosuppressive effect. CONCLUSION: The results disclosed that HQT ameliorates lipogenesis in PA-induced SZ95 sebocytes partially through the AMPK signaling pathway.

Hydrolyzed Conchiolin Protein (HCP) Extracted from Pearls Antagonizes both ET-1 and α-MSH for Skin Whitening.

Pearl powder is a famous traditional Chinese medicine that has a long history in treating palpitations, insomnia, convulsions, epilepsy, ulcers, and skin lightining. Recently, several studies have demonstrated the effects of pearl extracts on protection of ultraviolet A (UVA) induced irritation on human skin fibroblasts and inhibition of melanin genesis on B16F10 mouse melanoma cells. To further explore the effect we focused on the whitening efficacy of pearl hydrolyzed conchiolin protein (HCP) on human melanoma MNT-1 cells under the irritation of alpha-melanocyte-stimulating hormone (α-MSH) or endothelin 1 (ET-1) to evaluate the intracellular tyrosinase and melanin contents, as well as the expression levels of tyrosinase (TYR), tyrosinase related protein 1 (TRP-1), and dopachrome tautomerase (DCT) genes and related proteins. We found that HCP could decrease the intracellular melanin content by reducing the activity of intracellular tyrosinase and inhibiting the expression of TYR, TRP-1, DCT genes and proteins. At the same time, the effect of HCP on melanosome transfer effect was also investigated in the co-culture system of immortalized human keratinocyte HaCaT cells with MNT-1. The result indicated that HCP could promote the transfer of melanosomes in MNT-1 melanocytes to HaCaT cells, which might accelerate the skin whitening process by quickly transferring and metabolizing melanosomes during keratinocyte differentiation. Further study is needed to explore the mechanism of melanosome transfer with depigmentation.

Application of life cycle assessment and machine learning for the production and environmental sustainability assessment of hydrothermal bio-oil.

The hydrothermal bio-oil (HBO) production from biomass conversion can achieve sustainable and low-carbon development. It is always time-consuming and labor-intensive to quantitative relationship between influential variables and bio-oil yield and environmental sustainability impact in the hydrothermal conditions. Machine learning was used to predict bio-oil yield. Life cycle assessment (LCA) is further conducted to assess its environmental sustainability effect. The results demonstrated that gradient boosting decision tree regression (GBDT) have the most optimal prediction performance for the HBO yield (Training R2 = 0.97, Testing R2 = 0.92, RMSE = 0.05, MAE = 0.03). Lipid content is the most significant influential factor for HBO yield. LCA result further suggested that 1 kg of bio-oil production can cause 0.02 kg ep of SO2, 2.05 kg ep of CO2, and 0.01 kg ep of NOx emission, and environmental sustainability assessment of HBO is exhibited. This study provides meaningful insights to ML model prediction performance improvement and carbon footprint of HBO.

Evaluation of Polysaccharide Content in Shiitake Culinary-Medicinal Mushroom, Lentinula edodes (Agaricomycetes), via Near-Infrared Spectroscopy Integrated with Deep Learning.

Polysaccharide is one of the bioactive ingredients extracted from the fruiting body of Lentinula edodes (=L. edodes), which has many medicinal functions. While the content of polysaccharide can be measured by near-infrared (NIR) spectroscopy, the NIR analytical models established previously only covered L. edodes from very limited sources, and thus could not achieve high accuracy for large samples from more varied sources. Strictly, there is a nonlinear relationship between NIR spectral data and chemical label values, and traditional modeling methods for NIR data analysis have problems such as insufficient feature learning ability and difficulty in training. The deep learning model has excellent nonlinear modeling ability and generalization capacity, which is very suitable for analyzing larger samples. In this study, we constructed a novel framework with deep learning techniques on the NIR analysis of the content of polysaccharide in L. edodes. The siPLS model was established based on the combination of the bands 4797-3995 cm-1 and 6401-5600 cm-1, while the one-dimensional convolutional neural network (1D-CNN) model was established with improved feature in the treatment of the spectral data. The comparative experimental results showed that the 1D-CNN model (R2pre = 95.50%; RMSEP =0.1875) outperformed the siPLS model (R2pre = 87.89%, RMSEP = 0.6221). As such, this work has demonstrated that NIR spectroscopy with the integration of deep learning can provide more accurate quantification of polysaccharide in L. edodes. Such method can be very useful for nutritional grading and quality control of diverse L. edodes in the market.

Therapeutic potential and nutritional significance of Ganoderma lucidum - a comprehensive review from 2010 to 2022.

With a long history in traditional Asian medicine, Ganoderma lucidum (G. lucidum) is a mushroom species suggested to improve health and extend life. Its medicinal reputation has merited it with numerous attributes and titles, and it is evidenced to be effective in the prevention and treatment of various metabolic disorders owing to its unique source of bioactive metabolites, primarily polysaccharides, triterpenoids, and polyphenols, attributed with antioxidant, anti-inflammatory, anticancer, hepatoprotective, antidiabetic activities, etc. These unique potential pharmaceutical properties have led to its demand as an important resource of nutrient supplements in the food industry. It is reported that the variety of therapeutic/pharmacological properties was mainly due to its extensive prebiotic and immunomodulatory functions. All literature summarized in this study was collated based on a systematic review of electronic libraries (PubMed, Scopus databases, Web of Science Core Collection, and Google Scholar) from 2010-2022. This review presents an updated and comprehensive summary of the studies on the immunomodulatory therapies and nutritional significance of G. lucidum, with the focus on recent advances in defining its immunobiological mechanisms and the possible applications in the food and pharmaceutical industries for the prevention and management of chronic diseases. In addition, toxicological evidence and the adoption of standard pharmaceutical methods for the safety assessment, quality assurance, and efficacy testing of G. lucidum-derived compounds will be the gateway to bringing them into health establishments.

Exploring the mechanism of anti-fatigue of resveratrol based on network pharmacology and molecular docking, and in vitro studies.

To investigate the potential mechanism of resveratrol in anti-fatigue by network pharmacology and molecular docking, and to investigate the anti-fatigue efficacy of resveratrol through in vitro animal experiments. Resveratrol action targets and fatigue-related targets were obtained using various databases. The anti-fatigue targets of resveratrol were obtained using the Venn diagram, uploaded to the String database, imported into Cytoscape 3.7.1, and constructed into a Protein-protein interaction network. The target genes were then subjected to Gene ontology and Kyoto encyclopedia of gene and genome enrichment analysis. Molecular docking verification was performed on the binding ability of the core target to resveratrol. Using swimming-trained mice as exercise models, exhaustive swimming time and fatigue-related biochemical parameters were used as indicators to investigate the effects of resveratrol on exercise endurance and energy metabolism. 104 anti-fatigue targets and 10 core target genes of resveratrol were obtained. KEGG analysis enrichment included AGE-RAGE signaling pathway in diabetic complications, Human cytomegalovirus infection, and Pathways in cancer. Molecular docking showed that the core target genes TP53, PIK3R1, AKT1, PIK3CA, and MAPK1 had good binding activity to resveratrol. Animal experiments showed that resveratrol could prolong the exhaustive swimming time of endurance-trained mice (P < 0.01), decrease aspartate aminotransferase, alanine aminotransferase, uric acid, blood lactate (P < 0.01), decrease blood urea nitrogen (P < 0.05), increase the liver glycogen, muscle glycogen (P < 0.01). Conclusion: Resveratrol has the characteristics of multiple targets and multiple pathways in anti-fatigue; resveratrol can enhance exercise endurance in mice.

Alantolactone Inhibits Melanoma Cell Culture Viability and Migration and Promotes Apoptosis by Inhibiting Wnt/ß-Catenin Signaling.

BACKGROUND: Melanoma is a highly invasive and metastatic malignant tumor originating from melanocytes and is associated with a poor prognosis. Surgical resection and chemotherapy are currently the main therapeutic options for malignant melanoma; however, their efficacy is poor, highlighting the need for the development of new, safe, and effective drugs for the treatment of this cancer. OBJECTIVE: To investigate the effects of alantolactone (ALT) on the proliferative, migratory, invasive, and apoptotic ability of malignant melanoma cells and explore its potential anticancer mechanism. METHODS: Melanoma cells (A375 and B16) were treated with different concentrations (4, 6, 8, and 10 µmol/L) of ALT, with DMSO and no treatment serving as controls. The effects of the different concentrations of the drug on cell proliferation were assessed by crystal violet staining and CCK-8 assay. The effects on cell migration and invasion were detected by wound healing and Transwell assays, respectively. Flow cytometry was used to evaluate the effects of the drug on apoptosis and the cell cycle. ALT target genes in melanoma were screened using network pharmacology. Western blotting was used to measure the expression levels of the proliferation-related protein PCNA; the apoptosisrelated proteins Bax, Bcl-2, and caspase-3; the invasion and metastasis-related proteins MMP-2, MMP-7, MMP-9, vimentin, E-cadherin, and N-cadherin; and the canonical Wnt signaling pathway-related proteins ß-catenin, c-Myc, and p-GSK3ß. In addition, an l model of melanoma was established by the subcutaneous injection of A375 melanoma cells into nude mice, following which the effects of ALT treatment on malignant melanoma were determined in vivo. RESULTS: Compared with the controls, the proliferative, migratory, and invasive capacity of ALT-treated melanoma cells was significantly inhibited, whereas apoptosis was enhanced (P<0.01), showing effects that were exerted in a dose-dependent manner. The expression levels of the pro-apoptotic proteins Bax and caspase-3, as well as those of the interstitial marker E-cadherin, were upregulated in melanoma cells irrespective of the ALT concentration (P<0.05). In contrast, the expression levels of the anti-apoptotic protein Bcl-2, the proliferation-related protein PCNA, and the invasion and metastasis-related proteins MMP-2, MMP-7, MMP-9, N-cadherin, and vimentin were downregulated (P<0.05). The network pharmacology results indicated that GSK3ß may be a key ALT target in melanoma. Meanwhile, western blotting assays showed that ALT treatment markedly suppressed the expression of ß-catenin as well as that of its downstream effector c-Myc, and could also inhibit GSK3ß phosphorylation. CONCLUSION: ALT can effectively inhibit the culture viability, migration, and invasion of A375 and B16 melanoma cells while also promoting their apoptosis. ALT may exert its anti-melanoma effects by inhibiting the Wnt/ß-catenin signaling pathway. Combined, our data indicate that ALT has the potential as an effective and safe therapeutic drug for the treatment of melanoma.

Habitual fish oil supplementation and incident chronic obstructive pulmonary disease: Data from a prospective cohort study.

BACKGROUND: Fish oil is one of the most popular supplements in the UK and other developed countries. However, the relationship between fish oil use and chronic obstructive pulmonary disease (COPD) is unclear. OBJECTIVE: To prospectively examine the association of habitual fish oil supplementation with incident COPD risk and to evaluate potential effect modification by genetic predisposition. METHODS: This study included 484,414 participants (mean and standard deviation [SD] age: 56.5 [8.1] years) from the UK Biobank who completed a touchscreen questionnaire on habitual fish oil supplement use between 2006 and 2010 and were followed up through 2018. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for sociodemographic and lifestyle behaviours, health conditions, and other potential confounding factors. A weighted genetic risk score (GRS) for COPD was derived from 112 validated single nucleotide polymorphisms. RESULTS: During a median follow-up of 9.0 years, 8860 incident COPD events were recorded. A total of 31.4% (152,230) of the study participants reported habitual fish oil supplementation at baseline. Habitual fish oil supplementation was significantly associated with a lower risk of incident COPD (adjusted HR: 0.88; 95% CI: 0.84-0.93). The association with COPD did not differ by GRS strata (P for interaction = 0.880). The results from subgroup and sensitivity analyses supported the robustness of our findings. CONCLUSIONS: Our findings suggest that habitual fish oil supplementation is associated with a lower risk of incident COPD, irrespective of genetic predisposition.

Network Pharmacology Analyses of the Pharmacological Targets and Therapeutic Mechanisms of Salvianolic Acid A in Myocardial Infarction.

Objective: Salvianolic acid A, a natural polyphenolic ingredient extracted from traditional Chinese medicine, possesses an excellent pharmacological activity against cardiovascular diseases. Herein, therapeutic mechanisms of salvianolic acid A in myocardial infarction were explored through systematic and comprehensive network pharmacology analyses. Methods: The chemical structure of salvianolic acid A was retrieved from PubChem database. Targets of salvianolic acid A were estimated through SwissTargetPrediction, HERB, and TargetNet databases. Additionally, by GeneCards, OMIM, DisGeNET, and TTD online tools, myocardial infarction-relevant targets were predicted. Following intersection, therapeutic targets were determined. The interaction of their products was evaluated with STRING database, and hub therapeutic targets were selected. GO and KEGG enrichment analyses of therapeutic targets were then implemented. H9C2 cells were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic myocardial infarction and administrated with salvianolic acid A. Cellular proliferation was assayed via CCK-8 assay, and hub therapeutic targets were verified with RT-qPCR. Results: In total, 120 therapeutic targets of salvianolic acid A in myocardial infarction were identified. There were close interactions between their products. Ten hub therapeutic targets were determined, covering SRC, CTNNB1, PIK3CA, AKT1, RELA, EGFR, FYN, ITGB1, MAPK8, and NFKB1. Therapeutic targets were significantly correlated to myocardial infarction-relevant pathways, especially PI3K-Akt signaling pathway. Salvianolic acid A administration remarkably ameliorated the viability of OGD/R-induced H9C2 cells, and altered the expression of hub therapeutic targets. Conclusion: Our work uncovers therapeutic mechanisms of salvianolic acid A for the treatment of myocardial infarction, providing a new insight into further research on salvianolic acid A.