Glucose-modified BSA/procyanidin C1 NPs penetrate the blood-brain barrier and alleviate neuroinflammation in Alzheimer's disease models.

Alzheimer's disease (AD) is a chronic neurodegenerative disease with high prevalence, long duration and poor prognosis. The blood-brain barrier (BBB) is a physiologic barrier in the central nervous system, which hinders the entry of most drugs into the brain from the blood, thus affecting the efficacy of drugs for AD. Natural products are recognized as one of the promising and unique therapeutic approaches to treat AD. To improve the efficiency and therapeutic effect of the drug across the BBB, a natural polyphenolic compound, procyanidin C-1 (C1) was encapsulated in glucose-functionalized bovine serum albumin (BSA) nanoparticles to construct Glu-BSA/C1 NPs in our study. Glu-BSA/C1 NPs exhibited good stability, slow release, biocompatibility and antioxidant properties. In addition, Glu-BSA/C1 NPs penetrated the BBB, accumulated in the brain by targeting Glut1, and maintained the BBB integrity both in vitro and in vivo. Moreover, Glu-BSA/C1 NPs alleviated memory impairment of 5 × FAD mice by reducing Aß deposition and Tau phosphorylation and promoting neurogenesis. Mechanistically, Glu-BSA/C1 NPs significantly activated the PI3K/AKT pathway and inhibited the NLRP3/Caspase-1/IL-1ß pathway thereby suppressing neuroinflammation. Taken together, Glu-BSA/C1 NPs could penetrate the BBB and mitigate neuroinflammation in AD, which provides a new therapeutic approach targeting AD.

Network pharmacology, molecular docking, and molecular dynamics simulation analysis reveal the molecular mechanism of halociline against gastric cancer.

Halociline, a derivative of alkaloids, was isolated from the marine fungus Penicillium griseofulvum by our group. This remarkable compound exhibits promising antineoplastic activity, yet the precise molecular mechanisms underlying its anticancer properties remain enigmatic. To unravel these mechanisms, we employed an integrated approach of network pharmacology analysis, molecular docking simulations, and molecular dynamics simulations to explore halociline therapeutic targets for gastric cancer. The data from network pharmacology indicate that halociline targets MAPK1, MMP-9, and PIK3CA in gastric cancer cells, potentially mediated by diverse pathways including cancer, lipid metabolism, atherosclerosis, and EGFR tyrosine kinase inhibitor resistance. Notably, molecular docking and dynamics simulations revealed a high affinity between halociline and these targets, with free binding energies (ΔEtotal) of - 20.28, - 27.94, and - 25.97 kcal/mol for MAPK1, MMP-9, and PIK3CA, respectively. This study offers valuable insights into the potential molecular mechanism of halociline's inhibition of gastric cancer cells and serves as a valuable reference for future basic research efforts.

Proteomic analysis of mitochondria associated membranes in renal ischemic reperfusion injury.

BACKGROUND: The mitochondria and endoplasmic reticulum (ER) communicate via contact sites known as mitochondria associated membranes (MAMs). Many important cellular functions such as bioenergetics, mitophagy, apoptosis, and calcium signaling are regulated by MAMs, which are thought to be closely related to ischemic reperfusion injury (IRI). However, there exists a gap in systematic proteomic research addressing the relationship between these cellular processes. METHODS: A 4D label free mass spectrometry-based proteomic analysis of mitochondria associated membranes (MAMs) from the human renal proximal tubular epithelial cell line (HK-2 cells) was conducted under both normal (N) and hypoxia/reperfusion (HR) conditions. Subsequent differential proteins analysis aimed to characterize disease-relevant signaling molecules. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was applied to total proteins and differentially expressed proteins, encompassing Biological Process (BP), Cell Component (CC), Molecular Function (MF), and KEGG pathways. Further, Protein-Protein Interaction Network (PPI) exploration was carried out, leading to the identification of hub genes from differentially expressed proteins. Notably, Mitofusion 2 (MFN2) and BCL2/Adenovirus E1B 19-kDa interacting protein 3(BNIP3) were identified and subsequently validated both in vitro and in vivo. Finally, the impact of MFN2 on MAMs during hypoxia/reoxygenation was explored through regulation of gene expression. Subsequently, a comparative proteomics analysis was conducted between OE-MFN2 and normal HK-2 cells, providing further insights into the underlying mechanisms. RESULTS: A total of 4489 proteins were identified, with 3531 successfully quantified. GO/KEGG analysis revealed that MAM proteins were primarily associated with mitochondrial function and energy metabolism. Differential analysis between the two groups showed that 688 proteins in HR HK-2 cells exhibited significant changes in expression level with P-value < 0.05 and HR/N > 1.5 or HR/N < 0.66 set as the threshold criteria. Enrichment analysis of differentially expressed proteins unveiled biological processes such as mRNA splicing, apoptosis regulation, and cell division, while molecular functions were predominantly associated with energy metabolic activity. These proteins play key roles in the cellular responses during HR, offering insights into the IRI mechanisms and potential therapeutic targets. The validation of hub genes MFN2 and BNIP3 both in vitro and vivo was consistent with the proteomic findings. MFN2 demonstrated a protective role in maintaining the integrity of mitochondria associated membranes (MAMs) and mitigating mitochondrial damage following hypoxia/reoxygenation injury, this protective effect may be associated with the activation of the PI3K/AKT pathway. CONCLUSIONS: The proteins located in mitochondria associated membranes (MAMs) are implicated in crucial roles during renal ischemic reperfusion injury (IRI), with MFN2 playing a pivotal regulatory role in this context.

Stimulated Raman Scattering Microscopy Reveals Bioaccumulation of Small Microplastics in Protozoa from Natural Waters.

Microplastics (MPs) are pollutants of global concern, and bioaccumulation determines their biological effects. Although microorganisms form a large fraction of our ecosystem's biomass and are important in biogeochemical cycling, their accumulation of MPs has never been confirmed in natural waters because current tools for field biological samples can detect only MPs > 10 µm. Here, we show that stimulated Raman scattering microscopy (SRS) can image and quantify the bioaccumulation of small MPs (<10 µm) in protozoa. Our label-free method, which differentiates MPs by their SRS spectra, detects individual and mixtures of different MPs (e.g., polyethylene, polypropylene, polyvinyl chloride, polyethylene terephthalate, polystyrene, and poly(methyl methacrylate)) in protozoa. The ability of SRS to quantify cellular MP accumulation is similar to that of flow cytometry, a fluorescence-based method commonly used to determine cellular MP accumulation. Moreover, we discovered that protozoa in water samples from Yangtze River, Xianlin Wastewater Treatment Plant, Lake Taihu and the Pearl River Estuary accumulated MPs < 10 µm, but the proportion of MP-containing cells was low (∼2-5%). Our findings suggest that small MPs could potentially enter the food chain and transfer to organisms at higher trophic levels, posing environmental and health risks that deserve closer scrutiny.

Lipid droplets' functional protein caveolin-2 is associated with lipid metabolism-related molecule FABP5 and EMT marker E-cadherin in oral epithelial dysplasia.

AIMS: To explore the accumulation of lipid droplets (LDs) and its relationship with lipid metabolism, and epithelial-mesenchymal transition (EMT) in the carcinogenesis processes in the oral cavity. METHODS: LDs were stained by oil red O. Forty-eight oral squamous cell carcinomas (OSCC), 78 oral potentially malignant disorders (OPMDs) and 25 normal tissue sections were included to explore the LDs surface protein caveolin-2 and perilipin-3, lipid metabolism-related molecule FABP5 and EMT biomarker E-cadherin expression by immunohistochemical staining. RESULTS: The accumulation of LDs was observed in OPMDs and OSCCs compared with normal tissues (p<0.05). In general, an increasing trend of caveolin-2, perilipin-3 and FABP5 expression was detected from the normal to OPMDs to OSCC groups (p<0.05). Additionally, caveolin-2, perilipin-3 and FABP5 expression were positively correlated with epithelial dysplasia in OPMDs, whereas E-cadherin positivity was negatively correlated with histopathological grade in both OPMDs and OSCC, respectively. A negative correlation of caveolin-2 (p<0.01, r =-0.1739), and FABP5 (p<0.01, r =-0.1880) with E-cadherin expression was detected. The caveolin-2 (p<0.0001, r=0.2641) and perilipin-3 (p<0.05, r=0.1408) staining was positively correlated with FABP5. Increased caveolin-2 expression was related to local recurrence and worse disease-free survival (p<0.05). CONCLUSION: In the oral epithelial carcinogenesis process, LDs begin to accumulate early in the precancerous stage. LDs may be the regulator of FABP5-associated lipid metabolism and may closely related to the process of EMT; caveolin-2 could be the main functional protein.

The Potential of Lipid Droplet-associated Genes as Diagnostic and Prognostic Biomarkers in Head and Neck Squamous Cell Carcinoma.

OBJECTIVE: The role of lipid droplets (LDs) and lipid droplet-associated genes (LD-AGs) remains unclear in head and neck squamous cell carcinoma (HNSCC). This study aimed to investigate LDs in HNSCC and identify LD-AGs essential for the diagnosis and prognosis of HNSCC patients. METHODS: The LDs in the HNSCC and normal cell lines were stained with oil red O. Bioinformatic analysis was used to find LD-AGs in HNSCC that had diagnostic and prognostic significance. RESULTS: LDs accumulation was increased in HNSCC cell lines compared with normal cell lines (P<0.05). Fifty-three differentially expressed genes, including 34 upregulated and 19 downregulated, were found in HNSCC based on the TCGA platform (P<0.05). Then, 53 genes were proved to be functionally enriched in lipid metabolism and LDs. Among them, with an AUC value > 0.7, 34 genes demonstrated a high predictive power. Six genes (AUP1, CAV1, CAV2, CAVIN1, HILPDA, and SQLE) out of 34 diagnostic genes were linked to overall survival in patients with HNSCC (P<0.05). The significant prognostic factors AUP1, CAV1, CAV2, and SQLE were further identified using the univariate and multivariate cox proportional hazard models (P<0.05). The protein expression of CAV2 and SQLE was significantly increased in the HNSCC tissue compared to normal tissues (P<0.05). Finally, the knockdown of the four LD-AGs decreased LDs accumulation, respectively. CONCLUSIONS: Increased LDs accumulation was a hallmark of HNSCC, and AUP1, CAV1, CAV2, and SQLE were discovered as differentially expressed LD-AGs with diagnostic and prognostic potential in HNSCC.

Genome-Centric Metatranscriptomic Characterization of a Humin-Facilitated Anaerobic Tetrabromobisphenol A-Dehalogenating Consortium.

Tetrabromobisphenol A (TBBPA), a widely used brominated flame retardant in electronics manufacturing, has caused global contamination due to improper e-waste disposal. Its persistence, bioaccumulation, and potential carcinogenicity drive studies of its transformation and underlying (a)biotic interactions. This study achieved an anaerobic enrichment culture capable of reductively dehalogenating TBBPA to the more bioavailable bisphenol A. 16S rRNA gene amplicon sequencing and quantitative PCR confirmed that successive dehalogenation of four bromide ions from TBBPA was coupled with the growth of both Dehalobacter sp. and Dehalococcoides sp. with growth yields of 5.0 ± 0.4 × 108 and 8.6 ± 4.6 × 108 cells per µmol Br- released (N = 3), respectively. TBBPA dehalogenation was facilitated by solid humin and reduced humin, which possessed the highest organic radical signal intensity and reducing groups -NH2, and maintained the highest dehalogenation rate and dehalogenator copies. Genome-centric metatranscriptomic analyses revealed upregulated putative TBBPA-dehalogenating rdhA (reductive dehalogenase) genes with humin amendment, cprA-like Dhb_rdhA1 gene in Dehalobacter species, and Dhc_rdhA1/Dhc_rdhA2 genes in Dehalococcoides species. The upregulated genes of lactate fermentation, de novo corrinoid biosynthesis, and extracellular electron transport in the humin amended treatment also stimulated TBBPA dehalogenation. This study provided a comprehensive understanding of humin-facilitated organohalide respiration.

Nuciferine Inhibits Oral Squamous Cell Carcinoma Partially through Suppressing the STAT3 Signaling Pathway.

Oral squamous cell carcinoma (OSCC) poses a significant obstacle to the worldwide healthcare system. Discovering efficient and non-toxic medications is crucial for managing OSCC. Nuciferine, an alkaloid with an aromatic ring, is present in the leaves of Nelumbo nucifera. It has been proven to play a role in multiple biological processes, including the inhibition of inflammation, regulation of the immune system, formation of osteoclasts, and suppression of tumors. Despite the demonstrated inhibitory effects of nuciferine on different types of cancer, there is still a need for further investigation into the therapeutic effects and potential mechanisms of nuciferine in OSCC. Through a series of in vitro experiments, it was confirmed that nuciferine hindered the growth, movement, and infiltration, while enhancing the programmed cell death of OSCC cells. Furthermore, the administration of nuciferine significantly suppressed the signal transducer and activator of transcription 3 (STAT3) signaling pathway in comparison to other signaling pathways. Moreover, the activation of the STAT3 signaling pathway by colivelin resulted in the reversal of nuciferine-suppressed OSCC behaviors. In vivo, we also showed the anti-OSCC impact of nuciferine using the cell-based xenograft (CDX) model in nude mice. Nonetheless, colivelin diminished the tumor-inhibiting impact of nuciferine, suggesting that nuciferine might partially impede the advancement of OSCC by suppressing the STAT3 signaling pathway. Overall, this research could offer a fresh alternative for the pharmaceutical management of OSCC.

Marine Fungi: A Prosperous Source of Novel Bioactive Natural Products.

As the number of viruses, bacteria, and tumors that are resistant to drugs continues to rise, there is a growing need for novel lead compounds to treat them. Marine fungi, due to their unique secondary metabolic pathways and vast biodiversity, have become a crucial source for lead compounds in drug development. This review utilizes bibliometric methods to analyze the research status of natural products from marine fungi in the past decade, revealing the hotspots and trends in this field from Web of Science database. Furthermore, this review summarizes the biological activities and effects on molecular mechanisms of novel natural compounds isolated from marine fungi in the past five years. These novel compounds belong to six different structural classes, such as alkaloids, terpenoids, anthraquinones, polyketones, etc. They also exhibited highly potent biological properties, including antiviral, antitumor, antibacterial, antiinflammatory, and other properties. This review demonstrates the hotspots and trends of marine fungi research in recent years, as well as the variety of chemical structure and biological activities of their natural products, and it may provide guidance for those interested in discovering new drugs from marine fungi and specific targeting mechanisms.

Developmental toxicity in Daphnia magna induced by environmentally relevant concentrations of carbon black: From the perspective of metabolomics and symbiotic bacteria composition.

The level of carbon black (CB) pollution in the environment is rapidly increasing, owing to the increase in natural and industrial emissions. The water environment has become an important sink for CB. However, studies on CB mainly focused on its impact on air pollution and phytoremediation applications, and the toxicity mechanism of CB in aquatic organisms is relatively limited. Thus, Daphnia magna was used as a model organism to explore the developmental toxicity of environmentally relevant concentrations of CB under a full life-cycle exposure. The toxicity mechanism of CB in aquatic organisms was investigated based on metabolomic and symbiotic microbial analyses. It was found that compared with the control group, the body length of exposed D. magna decreased, while the mortality and intestinal inflammation increased with increasing concentration of CB. The normal reproductive regularity of D. magna was disturbed, and the deformity and body length of the offspring increased and decreased, respectively, after CB exposure. Metabolomic analysis showed that the urea cycle metabolic pathway of exposed D. magna was increased significantly, suggesting a perturbation of N metabolism. In addition, two eicosanoids were increased, suggesting possible inflammation in D. magna. The levels of seven phospholipid metabolites decreased that might be responsible for offspring malformations. Microbiological analysis showed that the composition of the symbiotic microbial community of D. magna was disturbed, including microorganisms involved in carbon cycling, nitrogen cycling, and biodegradation of pollutants, as well as pathogenic microorganisms. Overall, this study found that the inflammatory related metabolites and symbiotic bacterial, as well as reproductive related metabolites, were disrupted after D. magna exposed to different concentrations of CB, which revealed a possible developmental toxicity mechanism of CB in D. magna. These findings provide a scientific basis for analyzing the risks of CB in aquatic environments.

Z-scheme cobalt-iron oxide/perylene diimide supermolecule heterojunction for high-efficiency ciprofloxacin removal in a photocatalysis-self-Fenton system.

Fenton technology has been famous on antibiotics removal, but seriously restricted by the extra addition of H2O2 and low mineralization efficiency. Herein, we develop a novel cobalt-iron oxide/perylene diimide organic supermolecule (CoFeO/PDIsm) Z-scheme heterojunction under photocatalysis-self-Fenton system, in which the holes (h+) of photocatalyst can mineralize organic pollutants and the photo-generated electrons (e-) are used to in-situ H2O2 production with high efficiency. The CoFeO/PDIsm exhibits superior in-situ H2O2 production at a rate of 281.7 µmol g-1 h-1 in contaminating solution, correspondingly of total organic carbon (TOC) removal rate of ciprofloxacin (CIP) is 63.7 %, far exceeding current photocatalysts. The high H2O2 production rate and remarkable mineralization ability are ascribed to great charge separation in Z-scheme heterojunction. This work provides a novel Z-scheme heterojunction with photocatalysis-self-Fenton system for environmental-friendly removing the organic containment.

Scopolamine causes delirium-like brain network dysfunction and reversible cognitive impairment without neuronal loss.

Delirium is a severe acute neuropsychiatric syndrome that commonly occurs in the elderly and is considered an independent risk factor for later dementia. However, given its inherent complexity, few animal models of delirium have been established and the mechanism underlying the onset of delirium remains elusive. Here, we conducted a comparison of three mouse models of delirium induced by clinically relevant risk factors, including anesthesia with surgery (AS), systemic inflammation, and neurotransmission modulation. We found that both bacterial lipopolysaccharide (LPS) and cholinergic receptor antagonist scopolamine (Scop) induction reduced neuronal activities in the delirium-related brain network, with the latter presenting a similar pattern of reduction as found in delirium patients. Consistently, Scop injection resulted in reversible cognitive impairment with hyperactive behavior. No loss of cholinergic neurons was found with treatment, but hippocampal synaptic functions were affected. These findings provide further clues regarding the mechanism underlying delirium onset and demonstrate the successful application of the Scop injection model in mimicking delirium-like phenotypes in mice.

Effect of iron-loaded sludge biochar amendments on phytoremediation potential of Cr-contaminated soils by Leersia hexandra swartz.

In this study, the effect of iron-loaded sludge biochar (ISBC) with different amendment dosages (mass ratio of biochar to soil equal to 0, 0.01, 0.025 and 0.05) on the phytoremediation potential of Leersia hexandra swartz (L. hexandra) to Cr-contaminated soil was investigated. With increasing ISBC dosage from 0 to 0.05, plant height, aerial tissue biomass and root biomass increased from 15.70 cm, 0.152 g pot-1 and 0.058 g pot-1 to 24.33 cm, 0.304 g pot-1 and 0.125 g pot-1, respectively. Simultaneously, the Cr contents in aerial tissues and roots increased from 1039.68 mg kg-1 to 2427.87 mg kg-1 to 1526.57 mg kg-1 and 3242.62 mg kg-1, respectively. Thus, the corresponding bioenrichment factor (BCF), bioaccumulation factor (BAF), total phytoextraction (TPE) and translocation factor (TF) values were also increased from 10.52, 6.20, 0.158 mg pot-1 (aerial tissue)/0.140 mg pot-1 (roots) and 0.428 to 15.15, 9.42, 0.464 mg pot-1 (aerial tissue)/0.405 mg pot-1 (roots) and 0.471, respectively. The significant positive effect of ISBC amendment was primarily attributed to the following three aspects: 1) the root resistance index (RRI), tolerance index (TI) and growth toxicity index (GTI) of L. hexandra to Cr were increased from 100%, 100% and 0%-216.88%, 155.02% and 42.18%, respectively; 2) the bio-available Cr content in the soil was decreased from 1.89 mg L-1 to 1.48 mg L-1, while the corresponding TU (toxicity units) value was declined from 0.303 to 0.217; 3) the activities of urease, sucrase and alkaline phosphatase in soil were increased from 0.186 mg g-1, 1.40 mg g-1 and 0.156 mg g-1 to 0.242 mg g-1, 1.86 mg g-1 and 0.287 mg g-1, respectively. In summary, ISBC amendment was able to significantly improve the phytoremediation of Cr-contaminated soils by L. hexandra.

Transcriptomics reveals key regulatory pathways and genes associated with skin diseases induced by face paint usage.

The use of face paint cosmetics can cause skin diseases in opera performers due to the presence of heavy metals and other toxic ingredients in the cosmetics. However, the underlying molecular mechanism for these diseases remains unknown. Here we examined the transcriptome gene profile of human skin keratinocytes exposed to artificial sweat extracts of face paints, and identified the key regulatory pathways and genes, using RNA sequencing technique. Bioinformatics analyses suggested that the face paint exposure induced the differentially expression of 1531 genes and enriched inflammation-relevant TNF and IL-17 signaling pathways after just 4 h of exposure. Inflammation-relevant genes CREB3L3, FOS, FOSB, JUN, TNF, and NFKBIA were identified as the potential regulatory genes, and SOCS3 capable to prevent inflammation-induced carcinogenesis as the hub-bottleneck gene. Long-term exposure (24 h) could exacerbate inflammation, accompanied by interference in cellular metabolism pathways, and the potential regulatory genes (ATP1A1, ATP1B1, ATP1B2, FXYD2, IL6, and TNF) and hub-bottleneck genes (JUNB and TNFAIP3) were all related to inflammation induction and other adverse responses. We proposed that the exposure to face paint might cause the inflammatory factors TNF and IL-17, which are encoded by the genes TNF and IL17, to bind to receptors and activate TNF and IL-17 signaling pathways, leading to the expression of cell proliferation factors (CREB and AP-1) and proinflammatory mediators including transcription factors (FOS, JUN, and JUNB), inflammatory factors (TNF-α and IL6), and intracellular signaling factors (TNFAIP3). This finally resulted in cell inflammation, apoptosis, and other skin diseases. TNF was identified as the key regulator and connector in all the enriched signaling pathways. Our study provides the first insights into the cytotoxicity mechanism of face paints to skin cells and highlights the need for stricter regulations in face paint safety.

[Effect of apigenin in combination with oxymatrine on non-small cell lung cancer and mechanism].

This study explores the effect of apigenin(APG), oxymatrine(OMT), and APG+OMT on the proliferation of non-small cell lung cancer cell lines and the underlying mechanisms. Cell counting kit-8(CCK-8) assay was used to detect the vitality of A549 and NCI-H1975 cells, and colony formation assay to evaluate the colony formation ability of the cells. EdU assay was employed to examine the proliferation of NCI-H1975 cells. RT-qPCR and Western blot were performed to detect the mRNA and protein expression of PLOD2. Molecular docking was carried out to explore the direct action ability and action sites between APG/OMT and PLOD2/EGFR. Western blot was used to study the expression of related proteins in EGFR pathway. The viability of A549 and NCI-H1975 cells was inhibited by APG and APG+OMT at 20, 40, and 80 µmol·L~(-1) in a dose-dependent manner. The colony formation ability of NCI-H1975 cells was significantly suppressed by APG and APG+OMT. The mRNA and protein expression of PLOD2 was significantly inhibited by APG and APG+OMT. In addition, APG and OMT had strong binding activity with PLOD2 and EGFR. In APG and APG+OMT groups, the expression of EGFR and proteins in its downstream signaling pathways was significantly down-regulated. It is concluded that APG in combination with OMT could inhibit non-small lung cancer, and the mechanism may be related to EGFR and its downstream signaling pathways. This study lays a new theoretical basis for the clinical treatment of non-small cell lung cancer with APG in combination with OMT and provides a reference for further research on the anti-tumor mechanism of APG in combination with OMT.

Characterization and Antioxidant Evaluation of Four Kinds of Marine Oils in vitro.

The objective of this study was to characterize the lipid class and fatty acid composition of four kinds of marine oils including Phaeodactylum tricornutum oil (PO), Laminaria japonica oil (LO), krill oil (KO) and fish oil (FO), and evaluate their antioxidant capacities in vitro. The results indicated that compared to other three oils, PO showed the highest contents of total lipids and fucoxanthin (194.70 and 7.48 mg/g dry weight, respectively), the relatively higher content of long-chain polyunsaturated fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (30.94 % in total fatty acids), and total phenolic content (675.88 mg gallic acid equivalent /100 g lipids), thereby contribute to great advantages in scavenging free radicals such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2-azino-bis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS), peroxyl radical, as well as reducing FRAP value. In conclusion, PO should be considered as a potential ingredient for dietary supplement with antioxidant capacity.

PDK1 regulates the progression of esophageal squamous cell carcinoma through metabolic reprogramming.

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest human malignancies characterized by late-stage diagnosis, drug resistance, and poor prognosis. Pyruvate dehydrogenase kinase 1 (PDK1) plays an important role in regulating the metabolic reprogramming of cancer cells. However, its expression, function, and regulatory mechanisms of PDK1 in ESCC have not been reported. In this study, we found that PDK1 silence and dichloroacetic acid (DCA) significantly inhibited the growth of ESCC cells and induced cell apoptosis. Interestingly, PDK1 is a direct target of miR-6516-5p, and miR-6516-5p/PDK1 axis suppressed the growth of ESCC cell by inhibiting glycolysis. Moreover, DCA and cisplatin (cis-diammine-dichloroplatinum, DDP) synergistically inhibited the progression and glycolysis ability of ESCC cells both in vitro and in vivo by increasing oxidative stress via the inhibition of the Keap1/Nrf2 signaling pathway. And, Tert-butylhydroquinone (TBHQ), a specific activator of the Keap1/Nrf2 signaling, could diminish the synergic antitumor effects of DCA and DDP on ESCC cells. Collectively, our findings indicate that PDK1 may regulate the progression of ESCC by metabolic reprogramming, which provides new strategy for the treatment of ESCC.

Insights into Health Risks of Face Paint Application to Opera Performers: The Release of Heavy Metals and Stage-Light-Induced Production of Reactive Oxygen Species.

Face paints used by opera performers have been shown to contain high levels of heavy metals. However, whether frequent exposure, via dermal contact and inadvertent oral ingestion, results in occupational diseases is unknown, as is the potential exacerbation of toxicity by high-intensity irradiation from stage lights. In this study, we examined the release of Cr, Cu, Pb, and Zn from 40 face paints and the consequent health risks posed by different practical scenarios involving their use. The results showed that the in vitro bioaccessibility (IVBA) of Cr, Cu, Pb, and Zn in the tested products was, on average, 7.0, 5.5, 19.9, and 7.9% through oral ingestion and 1.1, 2.2, 1.6, and 1.2% through dermal contact, respectively. Stage light irradiation significantly increased the IVBA associated with dermal contact, to the average of 4.8, 34.9, 5.7, and 1.9% for Cr, Cu, Pb, and Zn, respectively. The increase was mainly due to the light-induced generation of reactive oxygen species, particularly hydroxyl free radicals. The vitality and transcriptional response of 3D skin models as well as a quantitative risk assessment of skin sensitization indicated that dermal contact with face paints may induce predictable skin damage and potentially other skin diseases. Long-term exposure to face paints on stage may also pose a non-carcinogenic health risk. The demonstrated health risks to opera performers of face paint exposure should lead to strict regulations regarding the content of theatrical face paints.

Acupoint massage at Shenque (CV 8) for chronic fatigue syndrome: a randomized controlled trial. / ç¥žé˜™ç©´ä½æŒ‰æ‘©æ²»ç–—æ ¢æ€§ç–²åŠ³ç»¼åˆå¾ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To observe the clinical efficacy of acupoint massage at Shenque (CV 8) for chronic fatigue syndrome (CFS). METHODS: A total of 71 patients with CFS were randomized into an observation group (36 cases, 2 cases were eliminated, 3 cases dropped out) and a control group (35 cases). Using a specially made massage instrument, acupoint massage was adopted at the the five points of Shenque (CV 8), i.e. the center and the upper, lower, left, and right parts of the inner wall. The manipulation was given 10 min a time, once every 2 days, 3 times a week for 4 weeks continuously. No intervention was delivered in the control group. Before and after treatment, the scores of fatigue scale-14 (FS-14) and Pittsburgh sleep quality index (PSQI) were observed, and the clinical efficacy was evaluated in the both groups. RESULTS: After treatment, the physical fatigue and mental fatigue scores, as well as the total score of FS-14 were decreased compared with those before treatment in the observation group (P<0.001); the above scores in the observation group were lower than those in the control group (P<0.001). After treatment, excepted for the sleep time and hypnotic scores, the remaining item scores and the total score of PSQI were decreased compared with those before treatment in the observation group (P<0.05); the each item score and the total score of PSQI were lower than those in the control group (P<0.05). The total effective rate in the observation group was superior to that in the control group (P<0.01). CONCLUSIONS: Acupoint massage at Shenque (CV 8) can effectively improve the fatigue state and sleep quality in patients with chronic fatigue syndrome.

Investigation of the bactericidal mechanism of Penicilazaphilone C on Escherichia coli based on 4D label-free quantitative proteomic analysis.

There is an urgent need to find new antibiotics to fight against the increasing drug resistance of microorganisms. A novel natural compound, Penicilazaphilone C (PAC), was isolated from a marine-derived fungus. It has displayed broad bactericidal activities against Gram-negative and Gram-positive bacteria. However, its bactericidal mechanism is still unknown. Herein, time-kill assays verified that PAC is a fast and efficient bactericidal agent. Furthermore, data from 4D label-free quantitative proteome assays revealed that PAC significantly influences over 898 proteins in Escherichia coli. Combining the results of biofilm formation, ß-galactosidase measurement, TEM observation, soft agar plate swimming, reactive oxygen species measurement, qRT-PCR, and west-blotting, the mode of PAC action against E. coli was to block respiration, inhibit assimilatory nitrate reduction and dissimilar sulfur reduction, facilitate assimilatory sulfate reduction, suppress cysteine and methionine biosynthesis, down-regulate antioxidant protein expression and induced intracellular ROS accumulation, weaken bacterial chemotaxis, destroy flagellar assembly, etc., and finally cause the bacteria's death. Our findings suggest that PAC could have a multi-target regulatory effect on E. coli and could be used as a new antibiotic in medicine.