Effect of High Magnesium and Astragaloside IV on Vascular Endothelial Cells.

Percutaneous coronary intervention (PCI) is the main treatment for patients with severe coronary vascular stenosis. However, In-stent neo-atherosclerosis (ISNA) is an important clinical complication in patients after PCI, which is mainly caused by a persistent inflammatory response and endothelial insufficiency. In the cardiovascular field, magnesium-based scaffolds stand out due to their properties. Magnesium plays a key role in regulating cardiovascular physiology. Magnesium deficiency can promote endothelial cell dysfunction, which contributes to the formation of atherosclerosis. Since astragaloside IV (AS­IV) has been proven to have potent cardioprotective effects, we asked whether high levels of magnesium cooperate with AS­IV might have effects on endothelial function and ISNA. We performed in vitro experiments on endothelial cells. Being treated with different concentrations of magnesium or/and AS-IV, the cell growth and migration were detected by CCK-8 and wound healing assay, respectively. The pro-inflammatory factors tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), adhesion molecule vascular cell adhesion molecule-1 (VCAM-1), and NF-kB were determined by qRT-PCR, ELISA kits or western blot. Results showed that high magnesium and AS-IV improved endothelial function, including promoting cell migration and decreasing the content of TNF-α, IL-6, VCAM-1, and NF-kB. With the supplement of AS-IV, additive magnesium maintains cell proliferation, migration, and function of endothelial cells. In conclusion, these findings suggest that high magnesium and AS­IV could improve vascular endothelial dysfunction. Early detection and treatment for neo-atherosclerosis may be of great clinical significance for improving stent implantation efficacy and long-term prognosis.

Polyvalent Aptamer-Functionalized NIR-II Quantum Dots for Targeted Theranostics in High PD-L1-Expressing Tumors.

Ag2S quantum dots (QDs) show superior optical properties in the NIR-II region and display significant clinical potential with favorable biocompatibility. However, inherent defects of low targeting and poor solubility necessitate practical modification methods to achieve the theranostics of Ag2S QDs. Herein, we used rolling circle amplification (RCA) techniques to obtain long single-stranded DNA containing the PD-L1 aptamer and C-rich DNA palindromic sequence. The C-rich DNA palindromic sequences can specifically chelate Ag2+ and thus serve as a template to result in biomimetic mineralization and formation of pApt-Ag2S QDs. These QDs enable specific targeting and illuminate hot tumors with high PD-L1 expression effectively, serving as excellent molecular targeted probes. In addition, due to the high NIR-II absorption of Ag2S QDs, pApt-Ag2S QDs exhibit remarkable photothermal properties. And besides, polyvalent PD-L1 aptamers can recognize PD-L1 protein and effectively block the inhibitory signal of PD-L1 on T cells, enabling efficient theranostics through the synergistic effect of photothermal therapy and immune checkpoint blocking therapy. Summary, we enhance the biological stability and antibleaching ability of Ag2S QDs using long single-stranded DNA as a template, thereby establishing a theranostic platform that specifically targets PD-L1 high-expressing inflamed tumors and demonstrates excellent performance both in vitro and in vivo.

Effect of respiratory training on swallowing function in swallowing disorders: a systematic review and meta-analysis.

PURPOSE: To determine the clinical efficacy of different respiratory training interventions on swallowing function in patients with swallowing disorders through the systematic review. METHODS: We reviewed the literature regarding the application of respiratory training therapy in patients with swallowing disorders, followed by a PRISMA search of published literature in five databases (PubMed, Web of Science, The Cochrane Library, CINAHL and EMBASE) in December 2022. Two reviewers performed study selection, quality evaluation, and risk of bias, followed by data extraction and detailed analysis. RESULTS: A total of six randomized controlled studies with a total sample size of 193 cases were included. Respiratory training improved swallowing safety (PAS (n = 151, SMD = 0.69, 95% CI - 1.11 to - 0.26, I2 = 36, p < 0.001)) and swallowing efficiency [residual (n = 63, SMD = 1.67, 95% CI - 2.26 to - 1.09, I2 = 23%, p < 0.001)] compared to control groups. The results of the qualitative analysis conducted in this study revealed that respiratory training enhanced hyoid bone movement but had no effect on swallowing quality of life. CONCLUSIONS: Respiratory training interventions may improve swallowing safety and efficiency in patients with dysphagia. However, the level of evidence is low, and there is a limited amount of research on the effectiveness and physiology of this intervention to improve swallowing function. In the future, there is a need to expand clinical studies, standardize measurement tools, and improve study protocols.

Alleviative effect of melatonin against the nephrotoxicity induced by cadmium exposure through regulating renal oxidative stress, inflammatory reaction, and fibrosis in a mouse model.

Chronic cadmium (Cd) exposure causes severe adverse health effects on the human body, especially the kidney tissue. Studies have demonstrated oxidative stress to be involved in renal pathological variations after exposure to Cd, but few effective treatments are available for the disease yet. Therefore, the present study was carried out to investigate the potential therapeutic intervention and its underlying molecular mechanisms of melatonin (MT), a natural antioxidant with multiple biological activities, against renal injury caused by Cd exposure in mice. C57BL/6 male mice (eight-week-old) were intragastrically administered with CdCl2, MT, or both for 30 days. Biochemical analysis showed that MT intervention significantly improved the SOD, GSH, and CAT activities while markedly decreasing the kidney MDA content of the mice exposed to Cd. Histological examination indicated that Cd exposure resulted in the atrophy of the renal glomerular, the degeneration and dilation of tubules, and the accumulation of fibrocytes. By contrast, MT administration effectively ameliorated the histological outcome of the injured kidney tissue. Moreover, administrating MT significantly inhibited proinflammatory cytokines TNF-α and iNOS expression in Cd-treated mice. Further, MT treatment markedly suppressed the expressions of renal fibrosis-related factors TGF-ß1, α-SMA, and collagen Ⅰ in the injured renal tissue and the accumulation and development of renal fibrosis. In addition, the administration of MT significantly reduced the expression of caspase-3 and cell apoptotic death in the kidney tissue of Cd-exposed mice. In all, the data showed that MT has a compelling therapeutic potential in alleviating the pathological variations of renal injury caused by Cd exposure.

Association Between Estradiol and Human Aggression: A Systematic Review and Meta-Analysis.

OBJECTIVE: Although several studies have examined the association between estradiol and human aggression, a consistent understanding of their correlation has yet to be established. This study aimed to investigate this relationship comprehensively. METHODS: We systematically searched five English databases (PubMed, Web of Science, EMBASE, Cochrane Library, and CINAHL) from their inception to June 5, 2023. Two authors independently screened publications and extracted data based on predefined inclusion and exclusion criteria. Statistical analyses were performed using Review Manager 5.4, and a random-effects model was used to pool the data. RESULTS: We identified 14 eligible studies comprising data from 1820 participants that met the inclusion criteria. This meta-analysis indicated a positive correlation between estradiol and human aggression, albeit a weak one. The pooled Fisher z value was 0.16 (95% confidence interval = 0.05-0.26; I2 = 73%, p <.00001). Furthermore, we found that participants' sex and age, the measures of aggression, and the literature quality might be sources of heterogeneity. CONCLUSIONS: Human aggression exhibited a weak positive correlation with estradiol concentration, whereas this relationship was influenced by participants' sex and age, the measure of aggression used, and the quality assessment of the literature. Gaining a better understanding of the association between estradiol and aggression could aid in the identification of populations prone to aggression.

E7 as a Promising Biomarker for Monitoring the Progression of Cervical Lesions in Patients with HPV 16/18 Infections.

Objective: To investigate the expression of E7 protein and its relationship with the progression and prognosis of cervical pre-cancerous lesions in patients with human papillomavirus (HPV) 16/18 infections. Methods: A total of 211 patients with positive HPV 16/18 were included in this study. Patients were categorized into three groups based on colposcopy results: NILM (Negative for Intraepithelial Lesion or Malignancy), LSIL (Low-Grade Squamous Intraepithelial Lesion), and HSIL (High-Grade Squamous Intraepithelial Lesion). E7 protein levels were quantified using Immunochromatographic Assay and compared using ANOVA. Cervical E7 protein levels were assessed before and one year after cervical cone biopsy in the HSIL group. Results: Among HPV 16/18-positive patients with normal Cervical Thinprep Cytologic Test (TCT) results, E7 protein content exhibited abnormal and significant values (P = .001). Mean E7 protein levels for the NILM, LSIL, and HSIL groups were 44.52 ng/mL, 114.60 ng/mL, and 389.20 ng/mL, respectively, and showed statistical significance (P = .000). In the HSIL group, E7 protein levels in HPV-negative patients were significantly lower one year after cervical cone biopsy compared to before (P = .001). However, HPV-positive patients displayed no significant alteration in E7 protein levels before and after biopsy (P = .08). Conclusions: E7 protein levels in detached cervical cells are closely associated with the severity and prognosis of cervical pre-cancerous lesions, suggesting their potential role as a biomarker for monitoring cervical lesion development.

LncRNA RP4-639F20.1 interacts with THRAP3 to attenuate atherosclerosis by regulating c-FOS in vascular smooth muscle cells proliferation and migration.

BACKGROUND AND AIMS: The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) play an essential role in the pathogenesis of atherosclerosis (AS). Long noncoding RNAs (lncRNAs) have been reported as important regulators in a number of diseases. However, very little is known regarding the functional role of lncRNAs in governing proliferation and migration of VSMCs and AS development. METHODS: Both in vitro and in vivo assays were performed to investigate the role of lncRNA in the pathophysiology of AS. Our previous lncRNA arrays revealed that lncRNA RP4-639F20.1 was significantly decreased in atherosclerotic plaques. Lentivirus overexpressing RP4-639F20.1 and lncRNA RP4-639F20.1 silencing vectors (Si-lnc-RP4-639F20.1) were constructed and transfected in VSMCs. The in vitro functions of lncRNA were analyzed by CCK-8 assays, EdU assays, scratch wound assays, transwell assays, qRT-PCR and Western blot analyses. RNA fluorescence in situ hybridization, immunoprecipitation and mRNA microarrays were used to explore the underlying mechanism. Adeno-associated-virus-9 (AAV9) overexpressing RP4-639F20.1 was constructed and injected intravenously into ApoE-/- mice to explore the role of lncRNA in vivo. RESULTS: In vitro experiments showed that lncRNA RP4-639F20.1 interacted with THRAP3 and downregulated c-FOS expression. Both increase of lncRNA RP4-639F20.1 expression and knockdown of c-FOS inhibited the expression of MMP10 and VEGF-α in VSMCs and suppressed VSMCs proliferation and migration. In vivo experiments using ApoE-/- mice fed a high-fat diet demonstrated that lncRNA RP4-639F20.1 overexpression deterred atherosclerosis and decreased lipid levels in atherosclerotic lesions. Patients with coronary artery disease were found to have higher c-FOS levels than healthy individuals and c-FOS expression was positively correlated with the SYNTAX score of patients. CONCLUSIONS: Overall, these data indicated that lncRNA RP4-639F20.1/THRAP3/c-FOS pathway protects against the development of atherosclerosis by suppressing VSMCs proliferation and migration. LncRNA RP4-639F20.1 and c-FOS could represent potential therapeutic targets to ameliorate atherosclerosis-related diseases.

[Effects of pre-electroacupuncture on blood pressure and cardiac function in high-salt-induced hypertension rats].

OBJECTIVE: To observe the effects of pre-electroacupuncture at "Taichong"(LR3), "Neiguan"(PC6) and "Waiguan"(TE5) on blood pressure and cardiac function of high-salt-induced hypertension rats, so as to explore the possible mechanism of pre-electroacupuncture in improving hypertension. METHODS: Twenty-four SD rats were randomly divided into control group, high-salt group and pre-electroacupuncture group, with 8 rats in each group. The hypertension model was established by feeding high-salt diet for 7 weeks. In the pre-electroacupuncture group, rats received electroacupuncture intervention at bilate-ral LR3, PC6 and TE5 (2 Hz/15 Hz, 2 mA) for 30 min, once a day, from the first day of modeling, for a total of 7 weeks. The blood pressure of rats was monitored by caudal artery noninvasive blood pressure measurement technique before and at the 1st, 3rd, 5th and 7th week of modeling. At the 8th week of the experiment, left ventricular catheterization was performed and biological signal acquisition system was used to detect left ventricular hemodynamics indexes and analyze left ventricular function, the car-diac mass ratio was measured to evaluate the degree of myocardial hypertrophy. The mRNA expressions of atrial natriuretic peptide(ANP), myosin heavy chain 7(MYH7), α-smooth muscle actin(α-SMA), interleukin(IL)-1ß, and IL-6 of myocardial tissues were detected by quantitative real-time PCR. Sirius red staining was used to observe the degree of myocardial fibrosis. RESULTS: Compared with the control group, systolic blood pressure, diastolic blood pressure, mean arterial pressure, left ventricular end-diastolic pressure (LVEDP), cardiac mass ratio，and the mRNA expressions of ANP, MYH7, α-SMA, IL-1ß, and IL-6, and sirius red staining area of myocardium were all significantly increased(P<0.01,P<0.05)，maximal rate of rise and descent of left ventricular pressure(LVP±dP/dtmax) were decreased (P<0.05,P<0.01) in the high-salt group. Compared with the high-salt group, rats in the pre-electroacupuncture group had lower systolic blood pressure, diastolic blood pressure, mean arterial pressure, LVEDP，cardiac mass ratio，higher LVP±dP/dtmax,down-regulated mRNA expressions of ANP, MYH7, α-SMA, IL-1ß, IL-6, and smaller area of sirius red staining(P<0.05, P<0.01). CONCLUSION: Pre-electroacupuncture tends to lower blood pressure, improve cardiac function and reduce myocardial fibrosis in high-salt-induced hypertension rats, which may be associated with inhibiting inflammatory response.

Poliovirus receptor (PVR) mediates carboplatin-induced PD-L1 expression in non-small-cell lung cancer cells.

Programmed death-ligand-1 (PD-L1) is an immune suppressor that inhibits T cell based immunity. Anti-PD-L1/PD-1 immunotherapy benefits those patients receiving platinum-based combinational chemotherapy. However, the underlying mechanism is still largely unknown. In this study, we found that carboplatin could induce PD-L1 expression in NSCLC H292, A549 and H1299 cells in a dose-dependent manner. mRNA sequencing and the subsequent validation assays found that carboplatin significantly induced PVR expression, which is considered as an immuno-adhesion molecule. Mechanistically, PVR knockdown significantly abrogated carboplatin-induced PD-L1 expression. Functionally, knockdown of PVR significantly reversed the CD3+ T cells proliferation inhibition caused by carboplatin increased PD-L1. Moreover, the carboplatin-induced PVR and subsequent up-regulation of PD-L1 might be mediated via the EGFR, PI3K/AKT, and ERK signaling pathways. Immunohistochemical staining results showed that the PD-L1 expression was positively associated with PVR expression in clinical NSCLC samples. Our study reveals a novel regulatory mechanism of PD-L1 expression, provides evidence that carboplatin inhibits tumor immune response by up-regulating PD-L1 expression and explains the rationale for combining platinum-based chemotherapy with PD-L1/PD-1 inhibitors.

Analysis of metal(loid) pollution and possibilities of electrokinetic phytoremediation of abandoned coking plant soil.

In this study, the spatial distribution of eight metal(loid)s in the soil of an abandoned coking plant in Shanxi, China, was mapped, and the ecological and health risks of the coking plant were assessed. The results showed that the soil Pb content of the coking plant greatly exceeded the background value, and Hg, Cd and Pb were the most polluting factors contributing to the considerable ecological risk level. There was also a non-carcinogenic risk in the coking plant, in which oral intake was the main pathway, and As, Pb and Cr were the main contributors. As the main contributor to ecological risk and non-carcinogenic risks and the most polluting metal, Pb was selected as a priority pollutant in the coking plant. Based on the detected concentration of Pb in the coking plant soil and in consideration of phytostabilization, ryegrass, alfalfa and castor were employed to study the phytoremediation and electrokinetic-enhanced phytoremediation effect in a series of Pb-contaminated soils (0, 100, 200, 300 and 400 mg/kg). It was found that the underground parts of alfalfa and castor had stronger Pb enrichment ability, and their biomass and Pb absorption capacity were improved in electrokinetic remediation methods. The Pb absorption capacities of the tested plants and the promotion efficiencies of electrokinetic-enhanced phytoremediation followed the order castor > ryegrass > alfalfa. Under the optimal electrical conditions, the remediation efficiency of castor was increased by 106 %, 83 %, 51 % and 48 % in 100, 200, 300, and 400 mg/kg Pb-contaminated soils, respectively.

The effect of voice training interventions on patients with oropharyngeal dysphagia: a systematic review.

BACKGROUND: Voice training has been proposed as an intervention to improve swallowing function in patients with dysphagia. However, little is known about the effects of voice training on swallowing physiology. OBJECTIVES: This systematic review investigates the effect of voice training on the swallowing function of patients with oropharyngeal dysphagia and provides the theoretical basis for improving the swallowing function and life quality of patients with oropharyngeal dysphagia. DATA SOURCES: A systematic review using a narrative synthesis approach of all published studies was sought with no date restrictions. Five electronic databases (EMBASE, PubMed, CINAHL, Web of Science, and The Cochrane Library) were searched from inception to April 2022. STUDY SELECTION: Eight studies were included. Two researchers screened the literature according to inclusion and exclusion criteria, extracted data, and carried out quality control according to the Cochrane handbook5.1.0. Data were analyzed narratively and descriptively. CONCLUSIONS: In general, statistically significant positive therapy effects were found. Voice training improves the oral and pharyngeal stages of swallowing in patients with neurological causes of dysphagia, such as stroke, and in patients with non-neurological causes of dysphagia, such as head and neck cancer. However, the current literature is limited and further primary research is required to provide more evidence to support voice training intervention in dysphagia.  Future studies could  further refine the content of voice training interventions, increase the number of patients enrolled, assess the long-term effects of voice training interventions and add associated assessments of the quality of life after treatment.

Copper peroxide coated upconversion nanoparticle modified with glucose oxidase for H2O2 self-supplying starvation-enhanced chemodynamic therapy in vitro.

Chemodynamic therapy (CDT) can convert endogenous hydrogen peroxide (H2O2) to highly reactive hydroxyl radical (˙OH) through Fenton or Fenton-like reaction to kill tumor cells, which is a promising anticancer strategy. However, the limited H2O2 and overexpressed glutathione (GSH) in tumor cells make CDT ineffective. Here, an efficient nanocomposite, UCN@CuO2-GOx (UCCuG), was synthesized, realizing both starvation therapy and H2O2 self-supplying CDT in vitro. In this case, the glucose oxidase (GOx) of the nanocomposite could consume glucose for starvation therapy after the UCCuG nanocomposite entered tumor cells. In addition, the acidic environment of the lysosome triggered the release of Cu2+ and H2O2 by the decomposition of UCCu; then, Cu2+ was reduced to Cu+ by GSH in tumor cells; and finally, Cu+ catalyzed the released H2O2 to generate ˙OH for CDT. The in vitro experiments demonstrated starvation-enhanced CDT with remarkable results. Meanwhile, under 980 nm laser irradiation, the upconversion luminescence signal of UCN in the UCCuG nanocomposite was reduced due to the CuO2-GOx coating, while it gradually recovered after the UCCuG nanocomposite reacted with glucose and GSH under the tumor microenvironment (TME). Such a luminescent intensity recovery process is expected to monitor the TME-activated therapeutic effect in real time. This strategy may solve the problem of insufficient CDT efficacy caused by limited endogenous H2O2 and overexpressed GSH in tumor cells. This multifunctional nanocomposite demonstrates the promising application of starvation-enhanced CDT in tumor treatment.

The Effect of Nursing Management of Patients Undergoing Interventional Therapy for Liver Cancer Compared with Standard Care on Patient-Reported Outcomes.

BACKGROUND: To investigate the efficacy of individualized symptom management based on patients' self-reports during interventional therapy (IT) for liver cancer. METHODS: Patients with liver cancer who recieved IT from April to August 2019 were assigned to either the intervention (n=70) or control group (n=70). The control group received routine nursing care and the intervention group received a nursing management program. The severity of specific symptoms, as measured by the Karnofsky Performance Scale (KPS), and satisfaction with nursing care, were analyzed. RESULTS: Compared to the control group, patients given individualized management experienced significantly less severe pain, nausea, anxiety, and fatigue (p < .05). The scores for KPS and satisfaction with care were both significantly improved in the intervention group than in the control group (p < .05). CONCLUSION: This high-quality nursing management program predicated on patients' self-reports is worthy of clinical application and popular adoption.

TRIM72 exerts antitumor effects in breast cancer and modulates lactate production and MCT4 promoter activity by interacting with PPP3CA.

A hypoxic tumor microenvironment (TME) promotes cancer progression, yet its value as a therapeutic target remains underexploited. Tripartite motif-containing 72 (TRIM72) may protect cells against various stresses including hypoxia. Recently, low TRIM72 expression has been implicated in cancer progression. However, the biological role and molecular mechanism of TRIM72 in breast cancer (BC) remain unclear. Herein, we analyzed the TRIM72 expression in BC tissue and cell lines by western blot (WB) and quantitative reverse transcription-PCR. We established the overexpression of TRIM72 using plasmids and lentiviral-mediated upregulation, as well as downregulation of protein phosphatase 3 catalytic subunit alpha (PPP3CA) by siRNA. The tumor-suppressive roles of TRIM72 were assessed on BT549 and MDA-MB-231 cells by MTS, Transwell, and flow cytometry assays in vitro and in xenografted tumors in vivo. The molecular mechanism of TRIM72 was investigated by luciferase reporter and co-immunoprecipitation (Co-IP) assay. Lactate production was measured by ELISA under hypoxic environments induced by CoCl2. Moreover, the expression of PI3K/Akt/mTOR pathway-associated proteins was detected by WB in BC cells. Results showed that TRIM72 was downregulated in BC. Overexpression of TRIM72 inhibited tumor proliferation and invasion in vitro and in a xenograft tumor model. Mechanistically, PPP3CA altered the inhibitory effects of TRIM72 on hypoxia-induced lactate production and monocarboxylate transporter 4-promoter activity, as well as the effect of the PI3K/Akt/mTOR signaling pathway. Our study suggests that TRIM72 modulates the TME and plays tumor-suppressive roles in BC progression. Therefore, TRIM72 may serve as a potential therapeutic target in BC.

A Potential MDM2 Inhibitor Formed by Restoring the Native Conformation of the p53 α-Helical Peptide on Gold Nanoparticles.

Many efforts have been made to develop inhibitors of MDM2 as potential drugs for cancer therapy. In this work, we use our previous developed conformational engineering technique to stabilize the binding conformation of the p53 transcription activation domain (TAD) peptide on gold nanoparticles (AuNPs), and create an AuNP-based anti-MDM2 artificial antibody, denoted as anti-MDM2 Goldbody, that specifically binds MDM2. Though the free TAD peptide is unstructured, circular dichroism (CD) spectra confirm that its α-helical conformation in the original p53 protein is restored on the anti-MDM2 Goldbody, and surface plasmon resonance (SPR) experiments confirm that there is strong specific interaction between the anti-MDM2 Goldbody and MDM2, demonstrating the anti-MDM2 Goldbody as a potential inhibitor of MDM2. This work demonstrates that the conformational engineering technique is not limited to the antigen-antibody systems, but can also be applied more widely in other protein-protein interfaces to create increasingly more artificial proteins for various biomedical applications.

Deciphering Nanoparticle Trafficking into Glioblastomas Uncovers an Augmented Antitumor Effect of Metronomic Chemotherapy.

Nanoparticles have been explored in glioblastomas as they can traverse the blood-brain barrier and target glioblastoma selectively. However, direct observation of nanoparticle trafficking into glioblastoma cells and their underlying intracellular fate after systemic administration remains uncharacterized. Here, based on high-resolution transmission electron microscopy experiments of an intracranial glioblastoma model, it is shown that ligand-modified nanoparticles can traverse the blood-brain barrier, endocytose into the lysosomes of glioblastoma cells, and undergo endolysosomal escape upon photochemical ionization. Moreover, an optimal dose of metronomic chemotherapy using dual-drug-loaded nanocarriers can induce an augmented antitumor effect directly on tumors, which has not been recognized in previous studies. Metronomic chemotherapy enhances antitumor effects 3.5-fold compared with the standard chemotherapy regimen using the same accumulative dose in vivo. This study provides a conceptual framework that can be used to develop metronomic nanoparticle regimens as a safe and viable therapeutic strategy for treating glioblastomas and other advanced-stage solid tumors.

Protective effect of melatonin against chronic cadmium-induced hepatotoxicity by suppressing oxidative stress, inflammation, and apoptosis in mice.

Cadmium (Cd) is a widespread environmental heavy metal pollutant that has high toxicity to human health. Cd accumulates in the liver and results in oxidative stress and inflammatory reactions. Melatonin (MT), a hormone exhibiting strong antioxidative properties, has been proved to have hepatoprotective effect against both acute and chronic liver injury. However, the molecular mechanism underlying MT's hepatoprotective effect against Cd-induced liver injury remain not fully understood. In this study, the potential protective effect of MT on Cd-induced hepatic injury was investigated. Adult male C57BL/6 mice were randomly divided into four groups: control, CdCl2, MT, and CdCl2 plus MT groups. Animals were daily treated with either CdCl2 (5 mg/kg) or MT (10 mg/kg) or both through intragastric administration for 30 consecutive days. Serum enzymatic analysis indicated that treatment mice with Cd significantly increased AST, ALT, LDH and ALP levels, by contrast, MT treatment resulted in significant decreases of AST, ALT, LDH and ALP levels in the serum of Cd treated mice. By biochemical analysis, it was found that MT treatment significantly increased the activities of SOD, GSH, GST, CAT and GR, while significantly decreased the contents of MDA in the liver tissue of Cd treated mice. Moreover, MT treatment also suppressed the Cd-induced inflammation by reducing the inflammatory mediators, including IL-1ß, IL-6, TNF-α and iNOS. Furthermore, MT treatment ameliorated the Cd-induced histopathological variations of liver tissue, which was confirmed by the biochemical and molecular data. It is clear from the results of this study that MT exerts hepatoprotective effect by improving the redox state, suppressing inflammatory reaction and cell apoptosis as well as ameliorating the performance of liver tissue histopathology, which is eventually reflected by the improvement of liver function in mice.

Enhanced Photothermal Performance by Carbon Dot-Chelated Polydopamine Nanoparticles.

Polydopamine (PDA) has been widely used in biomedical applications including imaging contrast agents, antioxidants, UV protection, and photothermal therapy due to its biocompatibility, metal-ion chelation, free-radical scavenging, and wideband absorption, but its low photothermal efficiency still needs to be improved. In this study, we chelated near-infrared (NIR) sensitive carbon quantum dots on the surface of polydopamine (PDA-PEI@N,S-CQDs) to increase its near-infrared absorption. Surprisingly, although only 4% (w/w) of carbon quantum dots was conjugated on the PDA surface, it still increased the photothermal efficiency by 30%. Moreover, PDA-PEI@N,S-CQDs could also be used as the drug carrier for loading 60% (w/w) of the DOX and achieved stimuli-responsive drug release under lysosomal pH (pH 5.0) and 808 nm laser illumination. For in vitro therapeutic experiment, PDA-PEI@N,S-CQDs showed the remarkable therapeutic performance under 808 nm laser irradiation for killing 90% of cancer cells compared with 50% by pure PDA nanoparticles, and the efficacy was even higher after loading DOX owing to the synergistic effect by photothermal therapy and chemotherapy. This intelligent and effective therapeutic nanosystem based on PDA-PEI@N,S-CQDs showed enhanced photothermal behavior after chelating carbon dots and promoted the future development of a nanoplatform for stimuli-responsive photothermal/chemo therapy.

Pressure-Controlled Encapsulation of Graphene Quantum Dots into Liposomes by the Reverse-Phase Evaporation Method.

Ultrasmall nanoparticles (USNPs) with sizes below 10 nm have shown great potentials in medical applications owing to their outstanding physical, chemical, optical, and biological properties. However, they suffer from a rapid renal clearance and biodegradation rate in the biological environment due to the small size. Liposomes are one of the most promising delivery nanocarriers for loading USNPs because of their excellent biocompatibility and lipid bilayer structure. Encapsulation of USNPs into liposomes in an efficient and controllable manner remains a challenge. In this study, we achieved a high loading of graphene quantum dots (GQDs, ∼4 nm), a typical USNP, into the aqueous core of liposomes (45.68 ± 1.44%), which was controllable by the pressure. The GQDs-loaded liposomes (GQDs-LPs) exhibited a very good aqueous stability for over a month. Furthermore, indocyanine green (ICG), an efficient near-infrared (NIR) photothermal agent, was introduced in the GQDs-LP system that could convert NIR laser energy into thermal energy and break down the liposomes, causing the release of GQDs in 6 min. Moreover, this NIR light-controlled release system (GQDs-ICG-LPs) also exhibited a good photothermal therapeutic performance in vitro, and 75% of cancer cells were killed at a concentration of 200 µg/mL. Overall, the successful development of the NIR light-controlled release system has laid a solid foundation for the future biomedical application of USNPs-loaded liposomes.

A CORM loaded nanoplatform for single NIR light-activated bioimaging, gas therapy, and photothermal therapy in vitro.

Carbon monoxide (CO) can cause mitochondrial dysfunction, inducing apoptosis of cancer cells, which sheds light on a potential alternative for cancer treatment. However, the existing CO-based compounds are inherently limited by their chemical nature, such as high biological toxicity and uncontrolled CO release. Therefore, a nanoplatform - UmPF - that addresses such pain points is urgently in demand. In this study, we have proposed a nanoplatform irradiated by near-infrared (NIR) light to release CO. Iron pentacarbonyl (Fe(CO)5) was loaded in the mesoporous polydopamine layer that was coated on rare-earth upconverting nanoparticles (UCNPs). The absorption wavelength of Fe(CO)5 overlaps with the emission bands of the UCNPs in the UV-visible light range, and therefore the emissions from the UCNPs can be used to incite Fe(CO)5 to control the release of CO. Besides, the catechol groups, which are abundant in the polydopamine structure, serve as an ideal locating spot to chelate with Fe(CO)5; in the meantime, the mesoporous structure of the polydopamine layer improves the loading efficiency of Fe(CO)5 and reduces its biological toxicity. The photothermal effect (PTT) of the polydopamine layer is highly controllable by adjusting the external laser intensity, irradiation time and the thickness of the polydopamine layer. The results illustrate that the combination of CO gas therapy (GT) and polydopamine PTT brought by the final nanoplatform can be synergistic in killing cancer cells in vitro. More importantly, the possible toxic side effects can be effectively prevented from affecting the organism, since CO will not be released in this system without near-infrared light radiation.