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Background: Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of 25% and is one of the main causes of cirrhosis and hepatocellular carcinoma. Recently, the stress response protein mesencephalon-astrocyte-derived neurotrophic factor (MANF) has been shown to regulate hepatic and systemic metabolic homeostasis. Objectives: The main purpose of this study is to investigate the relationship between mesencephalon-astrocyte-derived neurotrophic factor levels with other anthropometric indicators, and its function in the pathogenesis of non-alcoholic fatty liver disease. Materials and Methods: A total of 120 patients with ages ranging between 40 to 73 years were included in this study and their serum samples were collected and kept at -2°C. The liver function test, lipid profile, and albumin were determined using the automated biochemistry analyzer, while the mesencephalic astrocyte-derived neurotrophic factor biomarker was determined by the ELIZA technique. Results: Our study showed that MANF levels decrease with age, and decreased MANF levels are associated with inflammatory phenotypes. The mean levels of ALT, ALP, AST, TSB, and the ALT/AST ratio in the non-alcoholic fatty liver patients were significantly higher than that for the non-fatty liver patients. As well, the mean level of MANF in the non-fatty liver patients was 305.25 ± 110.49 mg/dl which was significantly higher in the non-alcoholic fatty liver group (157.52). (P ≤ 0.001). Conclusion: A novel finding of our study is that the reduction of serum MANF levels is strongly associated with the pathogenesis of nonalcoholic fatty liver disorders and could be used as a potential therapeutic target in the treatment of hepatic disorders. [ABSTRACT FROM AUTHOR]

Objectives: The main aim of this subject is to determine the oxidative status of Iraqi sickle cell anemic patients and then correlated with various biomarkers. Methods: In this study, blood samples from 100 sickle cell anemic subjects were analyzed, and then compared with control group which consisting of 50 individuals without sickle cell anemia was established. Various biochemical techniques were employed to measure different oxidative stress markers and inflammatory mediators. Serum samples were collected from blood to determine the levels of antioxidants such as catalase (CAT), glutathione peroxidase (G-Px), reduced glutathione (GSH), and lipid-peroxidation product malondialdehyde (MDA). Results: The results revealed that the levels of serum antioxidant activity (CAT), GSH, and G-Px were significantly reduced with (P < 0.05) in sickle cell anemic patients as compared with apparently control group. In contrast, the MDA level was significantly higher in sickle cell anemic patients than that found in the apparently control group. Conclusion: In this work, there is an increased oxidative stress in sickle cell anemic patients, which is accompanied by a decrease in antioxidant activity and a rise in lipid peroxidation, leading to the intensification of sickle cell anemic symptoms in patients. [ABSTRACT FROM AUTHOR]

Exploration of versatile nanoplatforms within one single nanostructure for multidisciplinary treatment modalities, especially achieving a synergistic therapeutic efficacy of combinational gene/photothermal cancer therapy is still a great challenge in biomedicine and nanotechnology. In this study, a unique photothermal nanocarrier has successfully been designed and developed for a combination of gene therapy (GT) and photothermal therapy (PTT) of cancer cells. Surface-engineered iron oxides (α-Fe2O3) nanoparticles (NPs) with poly(3,4-ethylenedioxythiophene) (PEDOT) polymer coatings are synthesized using a one-pot in situ oxidative polymerization method. The results show that the as-prepared α-Fe2O3@PEDOT core–shell NPs with a uniform particle size exhibit positively charged surfaces, facilitating efficient siRNA Bcl-2 (B-cell lymphoma-2) uptake for delivery to breast cancer cells. More importantly, α-Fe2O3@PEDOT core–shell NPs not only display good biocompatibility and water dispersibility but also strong optical absorption enhancement in the Vis-NIR region as compared to α-Fe2O3 NPs. The obtained α-Fe2O3@PEDOT core–shell NPs show an efficient photothermal conversion efficacy (η = 54.3%) and photostability under NIR laser irradiation. As a result, both in vitro and in vivo biological studies on two types of breast cancer cells/tumors treated with α-Fe2O3@PEDOT-siRNA nanocomplexes demonstrate high cancer cell apoptosis and tumor inhibition induced by synergistic GT/PTT therapy under mild conditions compared to an individual GT or PTT alone. Taken together, this is the first example of the use of an α-Fe2O3@PEDOT core–shell nanoagent as a siRNA delivery nanocarrier for highly effective gene/photothermal combination anticancer therapy. [ABSTRACT FROM AUTHOR]

Development of near infrared (NIR) light-responsive nanomaterials for high performance multimodal phototherapy within a single nanoplatform is still challenging in technology and biomedicine. Herein, a new phototherapeutic nanoagent based on FDA-approved Prussian blue (PB) functionalized oxygen-deficient molybdenum oxide nanoparticles (MoO3−x NPs) is strategically designed and synthesized by a facile one-pot size/morphology-controlled process. The as-prepared PB-MoO3−x nanocomposites (NCs) with a uniform particle size of ∼90 nm and high water dispersibility exhibited strong optical absorption in the first biological window, which is induced by plasmon resonance in an oxygen-deficient MoO3−x semiconductor. More importantly, PB-MoO3−x NCs not only exhibited a high photothermal conversion efficiency of ∼63.7% and photostability but also offered a further approach for the generation of reactive oxygen species (ROS) upon singular NIR light irradiation which significantly improved the therapeutic efficiency of the PB agent. Furthermore, PB-MoO3−x NCs showed a negligible cytotoxic effect in the dark, but an excellent therapeutic effect toward two triple-negative breast cancer (TNBC) cell lines at a low concentration (20 μg mL−1) of NCs and a moderate NIR laser power density. Additionally, efficient tumor ablation and metastasis inhibition in a 4T1 TNBC mouse tumor model can also be realized by synergistic photothermal/photodynamic therapy (PTT/PDT) under a single continuous NIR wave laser. Taken together, this study paved the way for the use of a single nanosystem for multifunctional therapy. [ABSTRACT FROM AUTHOR]

Exploration of versatile nanoplatforms within one single nanostructure for multidisciplinary treatment modalities, especially achieving a synergistic therapeutic efficacy of combinational gene/photothermal cancer therapy is still a great challenge in biomedicine and nanotechnology. In this study, a unique photothermal nanocarrier has successfully been designed and developed for a combination of gene therapy (GT) and photothermal therapy (PTT) of cancer cells. Surface-engineered iron oxides (α-Fe 2 O 3 ) nanoparticles (NPs) with poly(3,4-ethylenedioxythiophene) (PEDOT) polymer coatings are synthesized using a one-pot in situ oxidative polymerization method. The results show that the as-prepared α-Fe 2 O 3 @PEDOT core-shell NPs with a uniform particle size exhibit positively charged surfaces, facilitating efficient siRNA Bcl-2 (B-cell lymphoma-2) uptake for delivery to breast cancer cells. More importantly, α-Fe 2 O 3 @PEDOT core-shell NPs not only display good biocompatibility and water dispersibility but also strong optical absorption enhancement in the Vis-NIR region as compared to α-Fe 2 O 3 NPs. The obtained α-Fe 2 O 3 @PEDOT core-shell NPs show an efficient photothermal conversion efficacy ( η = 54.3%) and photostability under NIR laser irradiation. As a result, both in vitro and in vivo biological studies on two types of breast cancer cells/tumors treated with α-Fe 2 O 3 @PEDOT-siRNA nanocomplexes demonstrate high cancer cell apoptosis and tumor inhibition induced by synergistic GT/PTT therapy under mild conditions compared to an individual GT or PTT alone. Taken together, this is the first example of the use of an α-Fe 2 O 3 @PEDOT core-shell nanoagent as a siRNA delivery nanocarrier for highly effective gene/photothermal combination anticancer therapy.

Exploring a combined phototherapeutic strategy to overcome the limitations of a single mode therapy and inducing high anticancer efficiency is highly promising for precision cancer nanomedicine. However, a single-wavelength laser activates dual photothermal/photodynamic therapy (PTT/PDT) treatment is still a formidable challenge. Herein, we strategically design and fabricate a multifunctional theranostic nanosystem based on chlorin e6-functionalized polydopamine (PDA) coated prussian blue/manganese dioxide nanoparticles (PB-MnO 2 @PDA-Ce6 NPs). Interestingly, the obtained PB-MnO 2 @PDA NPs not only offer an effective delivery system for Ce6 but also provide strong optical absorption in the near-infrared range, endowing high antitumor efficacy of PTT. More importantly, the as-prepared PB-MnO 2 @PDA-Ce6 nanoagents exhibit an effective oxygen generation, superior reactive oxygen species (ROS), and outstanding photothermal conversion ability to greatly improve PTT and PDT treatments. As a result, both in vitro and in vivo treatments guided by MR imaging on liver cancer cells reveal the complete cell/tumor eradication under a single wavelength of 660 nm laser irradiation, implying the simultaneous synergistic PDT/PTT effects triggered by PB-MnO 2 @PDA-Ce6 nanoplatform, which are much higher than individual treatment. Taken together, our phototherapeutic nanoagents exhibit an excellent therapeutic performance, which may act as a nanoplatform to find safe and clinically translatable routes to accelerate cancer therapeutics.

Development of near infrared (NIR) light-responsive nanomaterials for high performance multimodal phototherapy within a single nanoplatform is still challenging in technology and biomedicine. Herein, a new phototherapeutic nanoagent based on FDA-approved Prussian blue (PB) functionalized oxygen-deficient molybdenum oxide nanoparticles (MoO 3-x NPs) is strategically designed and synthesized by a facile one-pot size/morphology-controlled process. The as-prepared PB-MoO 3-x nanocomposites (NCs) with a uniform particle size of ∼90 nm and high water dispersibility exhibited strong optical absorption in the first biological window, which is induced by plasmon resonance in an oxygen-deficient MoO 3-x semiconductor. More importantly, PB-MoO 3-x NCs not only exhibited a high photothermal conversion efficiency of ∼63.7% and photostability but also offered a further approach for the generation of reactive oxygen species (ROS) upon singular NIR light irradiation which significantly improved the therapeutic efficiency of the PB agent. Furthermore, PB-MoO 3-x NCs showed a negligible cytotoxic effect in the dark, but an excellent therapeutic effect toward two triple-negative breast cancer (TNBC) cell lines at a low concentration (20 μg mL -1 ) of NCs and a moderate NIR laser power density. Additionally, efficient tumor ablation and metastasis inhibition in a 4T1 TNBC mouse tumor model can also be realized by synergistic photothermal/photodynamic therapy (PTT/PDT) under a single continuous NIR wave laser. Taken together, this study paved the way for the use of a single nanosystem for multifunctional therapy.