Modulatory Effects of XIAOPI Formula on CXCL1 and Selected Outcomes in Triple-Negative Breast Cancer: A Randomized Controlled Clinical Trial.

Background: Triple-negative breast cancer (TNBC) is the most aggressive malignancy. Psychological distress and elevated CXCL1 level have been reported to be closely associated with the poor prognosis and quality of life of patients with TNBC. In preclinical studies using xenograft mouse models, XIAOPI formula, a nationally approved drug prescribed to patients at high risk for breast cancer, inhibited CXCL1 expression and improved survival. Traditional Chinese medicine has unique advantages in improving patients' emotional disorders and quality of life. However, the impact of XIAOPI formula on the serum level of CXCL1, psychological distress, and quality of life among patients with TNBC is currently unknown. Methods: In this study, we designed a randomized, double-blind, placebo-controlled trial. Patients with TNBC were randomly assigned to receive either the XIAOPI formula or a placebo for three months. The primary outcomes include serum CXCL1 expression, Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS). Secondary outcomes included the Pittsburgh Sleep Quality Index (PSQI) and the Functional Assessment of Cancer Therapy-Breast (FACT-B). Results: A total of 60 patients with TNBC were enrolled in the investigation. The results showed that the XIAOPI formula significantly decreased CXCL1 expression compared with the control group. Moreover, in comparison to the placebo, the XIAOPI formula increased FACT-B scores while decreasing SDS, SAS, and PSQI scores. Conclusion: In patients with TNBC, XIAOPI formula may be effective in reducing CXCL1 levels, enhancing psychological well-being, and quality of life. While our research offers a natural alternative therapy that may enhance the prognosis of TNBC, future validation of its therapeutic effects will require large-scale, long-term clinical trials. Clinical Registration Number: Registration website: www.chictr.org.cn, Registration date: 2018-1-19, Registration number: ChiCTR1800014535.

Oxytocin attenuates neuroinflammation-induced anxiety through restoration of excitation and inhibition balance in the anterior cingulate cortex in mice.

BACKGROUND: Accumulative evidence suggested that the oxytocin system plays a role in socio-emotional disorders, although its role in neuroinflammation-induced anxiety remains unclear. METHOD: In the present study, anxiety-like behavior was induced in cohorts of animals through repeated lipopolysaccharide (LPS, 0.5 mg/kg, daily, Escherichia coli O55:B5) i.p. injections for seven consecutive days. These different cohorts were subsequently used for anxiety-like behavior assessment with open field test, elevated plus maze, and novelty-suppressed feeding test or for electrophysiology (EEG) recordings of miniature excitatory postsynaptic currents (mEPSCs), miniature inhibitory postsynaptic currents (mIPSCs), or local field potential (LFP) in vivo or ex vivo settings. Samples of the anterior cingulate cortex (ACC) from some cohorts were harvested to conduct immunostaining or western blotting analysis of oxytocin, oxytocin receptor, CamkII, GABA, vGAT, vGLUT2, and c-fos. The dendritic spine density was assessed by Golgi-Cox staining. RESULTS: Repeated LPS injections induced anxiety-like behavior with concurrent decreases of oxytocin, vGLUT2, mEPSC, dendritic spine, c-fos, membrane excitability, and EEG beta and gamma oscillations, but increased oxytocin receptor and vGAT expressions in the ACC; all these changes were ameliorated by oxytocin intranasal or local brain (via cannula) administration. CONCLUSION: Taken together, our data suggested that oxytocin system may be a therapeutic target for developing treatment to tackle neuroinflammation-induced anxiety.

Spatial distribution characteristics of perfluoroalkyl substances in bulk and grain size fractionated sediments in Shenzhen Bay.

Understanding Perfluoroalkyl substances (PFASs) spatial distribution in natural environments is crucial due to their environmental persistence and potential bioaccumulation. However, limited research has investigated PFASs spatial distribution at a high resolution, especially in the Guangdong-Hong Kong-Macao Greater Bay Area. Here, we examined the composition and concentration of PFASs in 36 bulk surface sediments and grain-size fractionated sediments from 9 representative sites to determine the spatial distribution characteristics in Shenzhen Bay. We found that ΣPFASs decreased gradually from nearshore area to offshore area (0.680 and 0.297 ng g-1 dw, respectively). Furthermore, PFASs are easily adsorbed on fine-grained sediments, likely due to their chain length and hydrophobicity. We argue that the lateral movement of sediments may transport fine-grained sediments associated with ΣPFASs out of the bay, resulting in the spatial difference in ΣPFASs in Shenzhen Bay. Our findings provide important insights into explore the mechanisms associated with preservation and transport of PFASs.

Evaluation of the ovarian reserve in women and adolescent girls with Hashimoto's thyroiditis by serum anti-Müllerian hormone level: A systematic review and meta-analysis.

Objectives: Several researchers performed case-control studies to explore the relationship between Hashimoto's thyroiditis(HT) and ovarian reserve using anti-Müllerian hormone(AMH) in adolescent girls and women. But the results among these studies are inconsistent and the relationship between HT and ovarian reserve is still controversial. The study aimed to conduct the meta analysis of case-control studies to confirm the relationship between HT and ovarian reserve using AMH. Methods: 6 electronic databases including PubMed, EMBASE, the Cochrane Library, China National Knowledge Internet(CNKI), SinoMed and Wanfang were searched from inception to December 2021. Endnote X7.0 software was applied to managing all the relevant records. Then data extraction and evaluation of methodological quality of included studies were conducted after two-step selection.Review manager 5.4 version software and Stata 12.0 version software were used to perform all statistical analyses. Results: 10 case-control studies involving 1202 individuals were included in the present study. The preliminary results revealed AMH values were significantly higher in adolescent girls with euthyroid HT compared with healthy adolescent girls(MD = 1.97; 95%CI, 1.43-2.51; P < 0.001; I2 = 0%). The pooled results in the subgroup of female adults with euthyroid HT showed AMH values were not significantly different between patients with HT and healthy women(MD = -0.21; 95%CI, -0.51-0.09; P = 0.18; I2 = 38%). The pooled results in the two subgroups of female adults with subclinical hypothyroidism and overt hypothyroidism both showed AMH values were significantly lower in the HT group compared with healthy women [(MD = -0.60; 95%CI, -0.86 to -0.34; P < 0.001; I2 = 0%), (MD = -1.34; 95%CI, -1.94 to -0.74; P < 0.001; I2 = 65%)]. Conclusions: Ovarian reserve evaluated by serum AMH concentration is affected by female adults with subclinical hypothyroidism and overt hypothyroidism. The AMH level was significantly higher in euthyroid adolescent girls.

Acute and long-term cognitive impairment following sepsis: mechanism and prevention.

INTRODUCTION: Sepsis is a severe host response to infection, which induces both acute and long-term cognitive impairment. Despite its high incidence following sepsis, the underlying mechanisms remain elusive and effective treatments are not available clinically. AREA COVERED: This review focuses on elucidating the pathological mechanisms underlying cognitive impairment following sepsis. Specifically, the authors discuss the role of systemic inflammation response, blood-brain barrier disruption, neuroinflammation, mitochondrial dysfunction, neuronal dysfunction, and Aß accumulation and tau phosphorylation in cognitive impairment after sepsis. Additionally, they review current strategies to ameliorate cognitive impairment. EXPERT OPINION: Potential interventions to reduce cognitive impairment after sepsis include earlier diagnosis and effective infection control, hemodynamic homeostasis, and adequate brain perfusion. Furthermore, interventions to reduce inflammatory response, reactive oxygen species, blood-brain barrier disruption, mitochondrial dysfunction, neuronal injury or death could be beneficial. Implementing strategies to minimize delirium, sleep disturbance, stress factors, and immobility are also recommended. Furthermore, avoiding neurotoxins and implementing early rehabilitation may also be important for preventing cognitive impairment after sepsis.

Neuroinflammation-induced parvalbumin interneuron and oscillation deficits might contribute to neurobehavioral abnormities in a two-hit model of depression.

Depression is a common neuropsychiatric disorder that causes profound disability worldwide, yet the underlying mechanism remains unclear. Thus, the present study aimed to evaluate the effects of a two-hit model of depression on glial activation, parvalbumin (PV) interneuron, oscillation activity, and behavior alternations, and whether chronic fluoxetine treatment can reverse these abnormalities. Male mice were submitted to lipopolysaccharide (LPS) injection, followed by a modified chronic unpredictable stress (CUS) protocol. In our study, we showed that mice exposed to LPS and CUS exhibited reduced body weight, anhedonic-like behavior as well as cognitive and anxiety symptoms. These behavioral alternations were related to enhanced neuroinflammation, as reflected by significantly increased IL-1ß and IL-6 levels and microglia activation in the prefrontal cortex (PFC). In addition, mice exposed to LPS and CUS displayed significantly decreased PV expression and disturbance of theta and gamma oscillations in the PFC. However, chronic fluoxetine treatment reversed most of these abnormalities. In conclusion, our study suggests that neuroinflammation-induced PV interneuron and oscillation deficits might contribute to neurobehavioral abnormalities in a two-hit model of depression.

Clinical nutrition service capacity of 445 secondary or above hospitals in Sichuan, China: the 2021 annual survey.

BACKGROUND AND OBJECTIVES: To investigate the capacity of clinical nutrition services in secondary and tertiary hospitals in the Sichuan Province, China. METHODS AND STUDY DESIGN: Convenience sampling was used. E-questionnaires were distributed to all eligible medical institutions in Sichuan through the official network of provincial and municipal clinical nutrition quality control centers. The data obtained were sorted in Microsoft Excel and analyzed by SPSS. RESULTS: A total of 519 questionnaires were returned, of which 455 were valid. Only 228 hospitals were accessible to clinical nutrition services, of which 127 hospitals had independently set up clinical nutrition departments (CNDs). The ratio of clinical nutritionists to beds was 1:214. During the last decade, the rate of constructing new CNDs was maintained at approximately 5 units/year. A total of 72.4% of hospitals managed their clinical nutrition units as part of their medical technology departments. The specialist number ratio of senior, associate, intermediate and junior is approximately 1:4:8:10. There were 5 common charges for clinical nutrition. CONCLUSIONS: The sample representation was limited, and the capacity of clinical nutrition services may have been overestimated. Secondary and tertiary hospitals in Sichuan are currently in the second high tide of department establishment, with a positive trend of departmental affiliation standardization and a basic formation of a talent echelon.

Piperlongumine inhibits proliferation and oncogenic MYCN expression in chemoresistant metastatic retinoblastoma cells directly and through extracellular vesicles.

Ocular retinoblastoma malignancies, which develop into metastatic phenotypes, result in poor prognosis and survival for infant and child patients. To improve the prognosis of metastatic retinoblastoma, it is important to identify novel compounds with less toxic side effects and higher therapeutic efficacy compared to existing chemotherapeutics. Piperlongumine (PL), a neuroprotective, plant-derived compound has been explored for its anticancer activities both in vitro and in vivo. Here, we analyze the potential efficacy of PL for metastatic retinoblastoma cell treatment. Our data reveal that PL treatment significantly inhibits cell proliferation in metastatic retinoblastoma Y79 cells compared to the commonly used retinoblastoma chemotherapeutic drugs carboplatin, etoposide, and vincristine. PL treatment also significantly increases cell death compared to treatment with other chemotherapeutic drugs. PL-induced cell-death signaling was associated with significantly higher caspase 3/7 activities and greater loss of mitochondrial membrane potential. PL was also internalized into Y79 cells with an estimated concentration of 0.310pM and expression analysis revealed reduced MYCN oncogene levels. We next examined extracellular vesicles derived from PL-treated Y79 cells. Extracellular vesicles in other cancers are pro-oncogenic, mediating systemic toxicities via the encapsulation of chemotherapeutic drugs. Within metastatic Y79 EV samples, an estimated PL concentration of 0.026pM was detected. PL treatment significantly downregulated Y79 EV cargo of the oncogene MYCN transcript. Interestingly, non-PL-treated Y79 cells incubated with EVs from PL-treated cells exhibited significantly reduced cell growth. These findings indicate that in metastatic Y79 cells, PL exhibits potent anti-proliferation effects and oncogene downregulation. Importantly, PL is also incorporated into extracellular vesicles released from treated metastatic cells with measurable anti-cancer effects on target cells at a distance from the site of primary treatment. The use of PL in the treatment of metastatic retinoblastoma may reduce primary tumor proliferation and inhibit metastatic cancer activity systemically via extracellular vesicle circulation.

Development of a Pt-graphene nanocomposite-based solid-phase extraction coupled with ultra-performance liquid chromatography-tandem mass spectrometry for the determination of carbamate pesticides in fish.

In the present work, a potential solid-phase extraction (SPE) material based on graphene anchored with platinum nanoparticles (Pt-Graphene) was prepared and characterized by scanning electron micrographs and transmission electron micrograph. The carbamates residues in fish were enriched by SPE filled with Pt-Graphene and detected by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The proposed extraction protocol exhibited satisfactory recoveries (76.5-115.6%), low limit of quantitation values in µg kg-1 level, and good precision for the studied ten carbamates. These results demonstrated the feasibility of the proposed protocol. The developed Pt-Graphene nanoparticles showed excellent performance for extracting analytes at trace levels, indicating that it could be used as a potential SPE sorbent in food residue analysis.

Application of Marine Natural Products against Alzheimer's Disease: Past, Present and Future.

Alzheimer's disease (AD), a neurodegenerative disease, is one of the most intractable illnesses which affects the elderly. Clinically manifested as various impairments in memory, language, cognition, visuospatial skills, executive function, etc., the symptoms gradually aggravated over time. The drugs currently used clinically can slow down the deterioration of AD and relieve symptoms but cannot completely cure them. The drugs are mainly acetylcholinesterase inhibitors (AChEI) and non-competitive N-methyl-D-aspartate receptor (NDMAR) antagonists. The pathogenesis of AD is inconclusive, but it is often associated with the expression of beta-amyloid. Abnormal deposition of amyloid and hyperphosphorylation of tau protein in the brain have been key targets for past, current, and future drug development for the disease. At present, researchers are paying more and more attention to excavate natural compounds which can be effective against Alzheimer's disease and other neurodegenerative pathologies. Marine natural products have been demonstrated to be the most prospective candidates of these compounds, and some have presented significant neuroprotection functions. Consequently, we intend to describe the potential effect of bioactive compounds derived from marine organisms, including polysaccharides, carotenoids, polyphenols, sterols and alkaloids as drug candidates, to further discover novel and efficacious drug compounds which are effective against AD.

The exhaustion of lymphocytes is the main factor that decreases the sensitivity of QFT-GIT detection in silicosis.

BACKGROUND: Tuberculosis infection is a major complication of silicosis, but there is no study on whether silicosis can affect the sensitivity of QuantiFERON-TB Gold In-Tube (QFT-GIT) assays. This study will analyze the relationship between silicosis and QFT-GIT, determine the main factor of the QFT-GIT sensitivity decrease in silicosis and explore the methods to increase the sensitivity. METHODS: Silicosis patients with positive tubercle bacillus cultures were collected. The QFT-GIT, flow cytometry and blocking antibodies were used. RESULTS: The sensitivity of QFT-GIT in silicosis patients (58.46%) was significantly decreased and the expression of PD-1 on T cells and CD56+NK cells in pulmonary tuberculosis combined with silicosis were higher than normal tuberculosis patients and silicosis only patients. Further analysis found that the ratio of PD-1+CD4+T and IFN-γwere negatively correlated and blockaded the PD-1 pathway with antibodies can restore the sensitivity of QFT-GIT in silicosis. CONCLUSIONS: This is the first study to analyze the relationship between immune exhaustion and QFT-GIT in silicosis and found that the sensitivity of QFT-GIT was decreased by the expression of PD-1 on lymphocytes. Antibody blocking experiments increased the expression of IFN-γ and provided a new method to improve the sensitivity of QFT in silicosis. The study also found that silicosis can increase PD-1 expression. As PD-1 functions in infectious diseases, it will promote immune exhaustion in silicosis and lead to tuberculosis from latent to active infection. The study provided theoretical evidence for the diagnosis and immunotherapy of silicosis complications, and it has great value in clinical diagnostics and treatment.

Amino-Acid-Induced Circular Polarized Luminescence in One-Dimensional Manganese(II) Halide Hybrid.

Circular polarized luminescence (CPL)-active materials attract great attentions owing to their widely applications in 3D optical displays and encrypted transmission. Inspired by the strategies adopted in perovskite based CPL materials, herein, CPL-active hybrids (D)- and (L)-(tert-butyl prolinate)MnCl3 were successfully prepared by assembling chiral D/L tert-butyl prolinate with manganese (II) chloride. Single crystal structures show the as-formed hybrids possess one-dimensional (1D) structure containing linear chains of face-sharing MnCl6 octahedral surrounded by prolinate cations. The 1D Mn(II) hybrids display strong red emission peaked at 646 nm with PLQY of 67.1 % and 57.2 % for d-type and l-type, respectively, representing the highest PLQY for 1D MnII hybrids. Interestingly, the 1D Mn(II) hybrids exhibit prominent circular dichroism (CD) signals and remarkable CPL activity with the dissymmetry factor g of 6.1*10-3 and -6.3*10-3 from 550 to 800 nm for (D)- and (L)-(tert-butyl prolinate)MnCl3 , respectively, owing to the existence of chiral cations. It is worthy noted the obtained g represents the highest value for non-lead organic-inorganic hybrids.

Heavy metals and Pb isotopes in a marine sediment core record environmental changes and anthropogenic activities in the Pearl River Delta over a century.

Heavy metal accumulation in marine sediments is associated with changes in both the natural environment and human activities. This study used heavy metals and Pb isotopes in a precisely dated (by 210Pb and 137Cs) sediment core from the Macao Sea to reconstruct the historical changes in anthropogenic activities and the environment in the western Pearl River Estuary (PRE). The distribution of heavy metals in the sediment core could be divided into four stages (pre-1950, 1950-1976, 1976-2000, and post-2000), which corresponded to the changes in anthropogenic activities and environment of the Pearl River Delta during the past 100 years. The contribution of anthropogenic metals (Pb and Zn) in the sediments increased gradually over time. However, the concentrations, enrichment factors, and fluxes of heavy metals in the sediments all displayed a downward trend since 2010, revealing a decline in metal pollutant input due to strict emission reduction policies implemented in the last decade. The Pb isotopes in the sediments showed a similar trajectory to the heavy metals, reflecting the changes in Pb sources in the sediments at different stages. Based on a binary Pb isotope mixing model, the calculated proportions of anthropogenic and natural Pb in the sediments were 0-50.9% (mean 15.9%) and 49.1-100% (mean 84.1%), respectively, suggesting that the Pb in the PRE sediments is mainly controlled by natural sources.

Histone deacetylase inhibitor givinostat attenuates nonalcoholic steatohepatitis and liver fibrosis.

Nonalcoholic steatohepatitis (NASH) is a common chronic liver disease that is increasingly prevalent worldwide. Liver inflammation is an important contributor to disease progression from nonalcoholic fatty liver (NAFL) to NASH, but there is a lack of efficient therapies. In the current study we evaluated the therapeutic potential of givinostat, a histone deacetylase (HDAC) inhibitor, in the treatment of NASH in vivo and in vitro. Liver inflammation was induced in mice by feeding a methionine- and choline-deficient diet (MCD) or a fructose, palmitate, cholesterol diet (FPC). The mice were treated with givoinostat (10 mg·kg-1·d-1, ip) for 8 or 10 weeks. At the end of the experiment, the livers were harvested for analysis. We showed that givoinostat administration significantly alleviated inflammation and attenuated hepatic fibrosis in MCD-induced NASH mice. RNA-seq analysis of liver tissues form MCD-fed mice revealed that givinostat potently blocked expression of inflammation-related genes and regulated a broad set of lipid metabolism-related genes. In human hepatocellular carcinoma cell line HepG2 and human derived fetal hepatocyte cell line L02, givinostat significantly decreased palmitic acid-induced intracellular lipid accumulation. The benefit of givinostat was further confirmed in FPC-induced NASH mice. Givinostat administration significantly attenuated hepatic steatosis, inflammation as well as liver injury in this mouse model. In conclusion, givinostat is efficacious in reversing diet-induced NASH, and may serve as a therapeutic agent for the treatment of human NASH.

Extracellular vesicles of human diabetic retinopathy retinal tissue and urine of diabetic retinopathy patients are enriched for the junction plakoglo bin protein.

Introduction: Diabetic Retinopathy (DR) is a potentially blinding retinal disorder that develops through the pathogenesis of diabetes. The lack of disease predictors implies a poor prognosis with frequent irreversible retinal damage and vision loss. Extracellular Vesicles (EVs) present a novel opportunity for pre-symptomatic disease diagnosis and prognosis, both severely limited in DR. All biological fluids contain EVs, which are currently being studied as disease biomarkers. EV proteins derived from urine have emerged as potential noninvasive biomarkers. Methods: In this study, we isolated EVs from DR retinal tissue explants and from DR patients' urine, and characterized the vesicles, finding differences in particle number and size. Next, we performed proteomic analysis on human explanted DR retinal tissue conditioned media, DR retinal EVs and DR urinary EVs and compared to normal human retinal tissue, retinal EVs, and urinary EVs, respectively. Results: Our system biology analysis of DR tissue and EV expression profiles revealed biological pathways related to cell-to-cell junctions, vesicle biology, and degranulation processes. Junction Plakoglobin (JUP), detected in DR tissue-derived EVs and DR urinary EVs, but not in controls, was revealed to be a central node in many identified pathogenic pathways. Proteomic results were validated by western blot. Urinary EVs obtained from healthy donors and diabetic patient without DR did not contain JUP. Conclusion: The absence of JUP in healthy urinary EVs provide the basis for development of a novel Diabetic Retinopathy biomarker, potentially facilitating diagnosis.

Extracellular vesicles released by human retinal pigment epithelium mediate increased polarised secretion of drusen proteins in response to AMD stressors.

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Drusen are key contributors to the etiology of AMD and the ability to modulate drusen biogenesis could lead to therapeutic strategies to slow or halt AMD progression. The mechanisms underlying drusen biogenesis, however, remain mostly unknown. Here we demonstrate that under homeostatic conditions extracellular vesicles (EVs) secreted by retinal pigment epithelium (RPE) cells are enriched in proteins associated with mechanisms involved in AMD pathophysiology, including oxidative stress, immune response, inflammation, complement system and drusen composition. Furthermore, we provide first evidence that drusen-associated proteins are released as cargo of extracellular vesicles secreted by RPE cells in a polarised apical:basal mode. Notably, drusen-associated proteins exhibited distinctive directional secretion modes in homeostatic conditions and, differential modulation of this directional secretion in response to AMD stressors. These observations underpin the existence of a finely-tuned mechanism regulating directional apical:basal sorting and secretion of drusen-associated proteins via EVs, and its modulation in response to mechanisms involved in AMD pathophysiology. Collectively, our results strongly support an active role of RPE-derived EVs as a key source of drusen proteins and important contributors to drusen development and growth.

Human retinal organoids release extracellular vesicles that regulate gene expression in target human retinal progenitor cells.

The mechanisms underlying retinal development have not been completely elucidated. Extracellular vesicles (EVs) are novel essential mediators of cell-to-cell communication with emerging roles in developmental processes. Nevertheless, the identification of EVs in human retinal tissue, characterization of their cargo, and analysis of their potential role in retina development has not been accomplished. Three-dimensional retinal tissue derived from human induced pluripotent stem cells (hiPSC) provide an ideal developmental system to achieve this goal. Here we report that hiPSC-derived retinal organoids release exosomes and microvesicles with small noncoding RNA cargo. EV miRNA cargo-predicted targetome correlates with Gene Ontology (GO) pathways involved in mechanisms of retinogenesis relevant to specific developmental stages corresponding to hallmarks of native human retina development. Furthermore, uptake of EVs by human retinal progenitor cells leads to changes in gene expression correlated with EV miRNA cargo predicted gene targets, and mechanisms involved in retinal development, ganglion cell and photoreceptor differentiation and function.

Plumbagin Induces Cytotoxicity via Loss of Mitochondrial Membrane Potential and Caspase Activation in Metastatic Retinoblastoma.

BACKGROUND/AIM: We investigated the cytotoxic effects of plumbagin on metastatic retinoblastoma, using the highly metastatic cell line Y79. MATERIALS AND METHODS: Effect of plumbagin on cell growth was assessed with water-soluble tetrazolium 1 (WST-1) cell proliferation assay and automated hemocytometry with trypan blue-exclusion assay. Cell death was studied with acridine orange/ethidium bromide live-dead assay and annexin-V-fluorescein isothiocyanate/propidium iodide microscopy. Loss of mitochondrial membrane potential was studied with JC-10 dye and caspase activation was investigated using CellEvent Caspase-3/7 Green detection reagent. RESULTS: Plumbagin highly significantly reduced the growth of Y79 cells treated for 24 h with 2.5 µM or more. Plumbagin also induced significantly high levels of cell death which was associated with loss of mitochondrial membrane potential and caspase activation. CONCLUSION: At very low concentration (2.5 µM), plumbagin potently induced cytotoxicity in metastatic retinoblastoma cells via loss of mitochondrial membrane potential and caspase activation.

Distribution, Risk Assessment, and Sources of Trace Metals in Surface Sediments from the Sea Area of Macao, South China.

Due to rapid economic development in the Pearl River Delta, South China, trace metals pose a significant threat to the coastal ecosystems. In this study, we investigated the spatial distribution, contamination status, ecological risk, and possible sources of trace metals in 150 surface sediment samples from the Macao sea area. The results showed that concentrations of Ag, Pb, Cu, Zn, and Cd were highest in the Inner Harbour, whereas Cr, Co, As, and Ni were mainly accumulated in the downstream area of the Maliuzhou Waterway and the eastern area of Macao International Airport. Sediment grain composition, organic matter, total phosphorus, and hydrological regime were key factors influencing the spatial distribution patterns of trace metals. According to the environmental contamination indices of the enrichment factor, geo-accumulation index, and contamination factor, moderate contamination of trace metals occurs in the study area, while Ag and Pb contribute significantly to the contamination. Based on the potential ecological risk index, trace metals in surface sediments pose a low ecological risk. Correlation analysis and principal component analysis indicated that Cr, Co, Ni, and As were mainly derived from natural sources, whereas Ag, Pb, Cu, Zn, and Cd were mainly associated with anthropogenic sources.