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Curcumin, a compound in turmeric, shows promise for its anti-cancer properties. In this study, we successfully synthesised curcumin-reduced and capped gold nanoparticles. Most evaluations have been limited to in-vitro studies for these nanoparticles; our study takes a step further by highlighting the in-vivo assessment of these curcumin-reduced and capped gold nanoparticles (GNPCs) using non-invasive imaging (SPECT and optical) and possible therapeutic potential. The GNPCs showed an average hydrodynamic diameter of 58 nm and a PDI of 0.336. The synthesised and fully characterised GNPCs showed ex-vivo hemolysis value of ≤ 1.74 % and serum stability of ≥ 95 % over 24 h. Using in-vivo non-invasive (SPECT and optical Imaging), prolonged circulation and enhanced bioavailability of GNPCs were seen. The biodistribution studies after radiolabelling GNPCs with 99 m Tc complemented the optical imaging. The SPECT images showed higher uptake of the GNPCs at the tumour site, viz the contralateral muscle and the native Curcumin, resulting in a high target-to-non-target ratio that differentiated the tumour sufficiently and enhanced the diagnostics. Other organs also accumulate radiolabeled GNPCs in systemic circulation; bio dosimetry is performed. It was found that the dose received by the different organs was safe for use, and the in-vivo toxicity studies in rats indicated negligible toxicity over 30 days. The tumour growth was also reduced in mice models treated with GNPCs compared to the control. These significant findings demonstrate that GNPC shows synergistic activity in vivo, indicating its ability as a green diagnostic probe that has the potential for therapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Advanced methodologies, such as hyperthermia and modulation of reactive oxygen species (ROS), exhibit considerable promise in the therapeutic landscape of cancer. These strategies offer a targeted paradigm for combating malignant cells while mitigating damage to healthy tissue. Noteworthy among these approaches is the utilization of superparamagnetic iron oxide nanoparticles, which are renowned for their ability to enhance both hyperthermia and ROS generation specifically within tumor microenvironments. The objective of this investigation is to scrutinize the relationship between the reaction duration and the characteristics of carbon-doped silica core-shell iron oxide nanoparticles (CSIONPs). Specifically, we focus on CSIONP-12, CSIONP-24, and CSIONP-36, synthesized by using varying reaction periods. Through a comprehensive analysis, we primarily evaluate the impact of these formulations on T1 and T2 magnetic resonance imaging (MRI), aiming to elucidate their mechanisms and therapeutic potential in promoting hyperthermia and ROS-mediated cancer therapy. CSIONP-24 emerges as a compelling candidate due to its dual influence on magnetic hyperthermia and ROS generation, suggesting its promise in enhancing cancer treatment outcomes. Furthermore, the findings underscore the exceptional T1-T2 MRI capabilities of this technology, underscoring its versatility and efficacy in the nuanced realm of cancer theranostic.

Antibiotics are commonly used as antibacterial medications due to their extensive and potent therapeutic properties. However, the overconsumption of these chemicals leads to their accumulation in the human body via the food chain, amplifying drug resistance and compromising immunity, thus presenting a significant hazard to human health. Antibiotics are classified as organic pollutants. Therefore, it is crucial to conduct research on precise methodologies for detecting antibiotics in many substances, including food, pharmaceutical waste, and biological samples like serum and urine. The methodology described in this research paper introduces an innovative technique for producing nanoparticles using silica as the shell material, iron oxide as the core material, and carbon as the shell dopant. By integrating a carbon-doped silica shell, this substance acquires exceptional fluorescence characteristics and a substantial quantum yield value of 80%. By capitalising on this characteristic of the substance, we have effectively constructed a fluorescent sensor that enables accurate ofloxacin analysis, with a detection limit of 1.3 × 10 -6 M and a linear range of concentrations from 0 to 120 × 10 -6 M. We also evaluated the potential of CSIONPs for OLF detection in blood serum and tap water analysis. The obtained relative standard deviation values were below 3.5%. The percentage of ofloxacin recovery from blood serum ranged from 95.52% to 103.28%, and from 89.9% to 96.0% from tap water.

Recent advances in fluorescent carbon dots have shown great potential for the sensing of biological molecules. In this study, one-step hydrothermally synthesised carbon dots (CD) and nitrogen doped carbon dots (NCD) with high quantum yields of 54.29% and 89.82%, respectively, were investigated and demonstrated to be a reliable, cost-effective, and naked-eye fluorescent probe for the detection of dopamine, a neurotransmitter, in human serum fluids. The current study is well supported by a comprehensive synthesis approach and has been described utilizing a variety of microscopic and spectroscopic techniques. The discovered approach is time and pH dependent, and it provides a robust platform for specifically detecting aberrant dopamine levels using a fluorescence quenching mechanism. Dopamine detection limits for CD were calculated to be 5.54 μM for CD and 5.12 μM for NCD, respectively. The fluorescence quenching shows a linear continuous trend with a range within 3.3-500 μM and 3.3-400 μM of dopamine concentration for CD and NCD respectively. To further verify the sensitivity of CD and NCD as fluorescent probes, interference studies in the presence of different biological components were also studied and validated. This work shows that carbon-based nanomaterials and their doped nanostructures, due to their high fluorescence, have significant potential as fluorescent probes in neurological disease diagnosis as they display high selectivity, sensitivity and fast responses in the real time spectroscopic detection of dopamine in human fluid samples.

The protective effects of breastfeeding on various childhood malignancies have been established but an association has not yet been determined for retinoblastoma (RB). We aimed to further investigate the role of breastfeeding in the severity of nonhereditary RB development, assessing relationship to (1) age at diagnosis, (2) ocular prognosis, measured by International Intraocular RB Classification (IIRC) or Intraocular Classification of RB (ICRB) group and success of eye salvage, and (3) extraocular involvement. Analyses were performed on a global dataset subgroup of 344 RB patients whose legal guardian(s) consented to answer a neonatal questionnaire. Patients with undetermined or mixed feeding history, family history of RB, or sporadic bilateral RB were excluded. There was no statistically significant difference between breastfed and formula-fed groups in (1) age at diagnosis ( p = 0.20), (2) ocular prognosis measures of IIRC/ICRB group ( p = 0.62) and success of eye salvage ( p = 0.16), or (3) extraocular involvement shown by International Retinoblastoma Staging System (IRSS) at presentation ( p = 0.74), lymph node involvement ( p = 0.20), and distant metastases ( p = 0.37). This study suggests that breastfeeding neither impacts the sporadic development nor is associated with a decrease in the severity of nonhereditary RB as measured by age at diagnosis, stage of disease, ocular prognosis, and extraocular spread. A further exploration into the impact of diet on children who develop RB is warranted., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Magneto-fluorescent nanoparticles have attracted great attention because of their dual nature as multimodal imaging probes in various biomedical applications. Particulary, it is desirable to understand how these nanoparticles interact with human serum proteins before they are used in biological systems. In this work, the physiological interactions between magneto-fluorescent nanoparticles (MFNPs) and bovine serum albumin (BSA) were systematically investigated. The present observations identified that the collision of MFNPs and BSA caused fluorescence quenching of BSA. Steady state fluorescence, lifetime and anisotropy measurements in the presence of MFNPs supported dynamic quenching of the BSA emission. Furthermore, in the presence of MFNPs, the conformation changes in the BSA structure indicate merely the secondary structural changes. The findings demonstrated that random interactions and hydrophobic forces play a major role in the dynamic quenching. Further, subsequent coating of BSA over MFNPs result in protein corona formation, as is evident through spectroscopic measurements. In light of the present work, MFNPs could serve a purpose in magnetic separation and optical detection of serum proteins from blood plasma in real-time disease diagnosis.

Superparamagnetic iron oxide nanoparticles (SPIONs) have been used for a variety of biomedical applications, from multimodal imaging to the mechanical activity of cells and tissues. Herein, we present fluorescently mantled carbon coated core-shell superparamagnetic iron oxide nanoparticles (FC-SPIONs) as an excellent material to promote the neuronal differentiation and neuronal network outgrowth in neural tissue engineering applications. Morphological, structural, and functional group characterizations were systematically investigated. FC-SPIONs showed superior magnetic and inherent fluorescence characteristic properties. Furthermore, FC-SPIONs interactions against neuronal PC12 cells showed promising results and deliberate their potential for significant applications in neuroengineering. Interestingly, FC-SPIONs were assessed as biocompatible and promoted the neuronal PC12 cell differentiation process. Accompanied by these results, network outgrowth and branching patterns of neuronal processes can be regulated using FC-SPIONs. Importantly, FC-SPIONs are promising due to their biocompatibility and selective affinity toward neuronal cells, paving the way for neuronal differentiation and outgrowth and neuronal therapeutics in neuroengineering applications.

A new bimetallic MOF (BMOF) has been synthesized using iron and zinc as inorganic metal nodes and 1,4-benzenedicarboxylic acid (BDC) as the organic linker molecule. BMOF was confirmed by single-crystal X-ray diffraction (SCXRD), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy high-angle annular dark-field imaging (TEM-HAADF), field emission scanning electron microscopy energy-dispersive X-ray analysis (FESEM-EDX), vibrating sample magnetometry (VSM) and inductively coupled plasma mass spectrometry (ICP-MS) analysis. The synthesized BMOF shows excellent optical and magnetic properties. BMOF acts as a heterogeneous catalyst and shows high catalytic activity towards bis(indolyl)methane synthesis and photocatalytic degradation of methylene blue (MB) under visible-light illumination., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Due to their unique magnetic properties, multiple surface functionality and biocompatibility, superparamagnetic iron oxide nanoparticles (SPIONs) show very promising characteristics as magnetic resonance (MR) contrast agents in biomedical applications. However, a lack of fluorescence makes SPIONs inappropriate for multimodal bioimaging. SPIONs surface functionalized by either organic fluorescent molecules or semiconductor quantum dots (QDs) have been reported as bioimaging probes but subsequent deterioration of the fluorescent dyes due to low photostability and quick photobleaching limits their long term practical application. In addition, QDs are found to be toxic in nature. Here, we present a novel one step method to synthesize non-toxic carbon coated highly photostable core-shell magnetic and fluorescent SPIONs with long-lasting fluorescence alongside a superior magnetic resonance (MR) imaging ability. Apart from the highly comparable superparamagnetic properties of the SPIONs, the optical response of the material is much better than commonly used Rhodamine or cyanine dyes.

Metal organic frameworks (MOFs) exhibit unique features of finely tunable pore structures, excellent chemical stability and flexible surface structural functionality, making them advantageous for a wide range of applications including energy storage, compound separation, catalysis, and drug delivery. The present work enlightens a novel approach of single step fabrication of CCM-ZIF-8 as a drug carrier and its application as stimuli responsive drug delivery systems via external stimuli involving change in pH and in presence of biomimetic cell membrane like environment using liposomes and SDS micelles. The methodology is devoid of any post synthesis drug loading steps. The synthesized curcumin encapsulated ZIF-8 frameworks demonstrate ultrahigh drug encapsulation efficiency (ca. 83.33%) and good chemical stability. In vitro drug release of curcumin was three times higher in acidic medium than in physiological pH. Cytotoxicity results demonstrated enhanced therapeutic effect of CCM-ZIF-8 than free curcumin. Confocal microscopy results confirmed the easy cellular internalization of CCM-ZIF-8 in HeLa cells. Intracellular distribution studies at various incubation times confirmed the clathrin-mediated endocytosis to lysosomal pathway of CCM-ZIF-8, but without mitochondria being an intracellular fate. The results signify that CCM-ZIF-8 is an efficient drug carrier for passive tumor therapy in future for cancer treatments.

Myelodysplastic syndromes (MDSs) are characterized by ineffective hematopoiesis and an increased risk of transformation. Few effective therapies are available for lower risk MDS patients, especially after the failure of hypomethylating agents. MDS progenitor cells are dependent on the nuclear factor-κB (NF-κB) for survival, which makes it an attractive therapeutic target. As a proteosomal inhibitor, bortezomib is thought to have inhibitory activity against NF-κB. We designed a proof-of-principle study of subcutaneous (SC) bortezomib in lower risk MDS patients with evidence of NF-κB activation in their bone marrow. Fifteen patients were treated, their median age was 71 (range 56-87), 33% were low and 67% int-1 by IPSS, median number of prior therapies was 2, all patients were transfusion dependent. Baseline median pp65 percentage was 31% and 11 patients had evidence of ring sideroblasts (RS). SC bortezomib was safe, well tolerated with no excess toxicity. Three patients out of the 15 (20%) had evidence of response with hematologic improvement (HI-E). Bortezomib caused a decrease in pp65 levels in 7 out of 13 evaluable patients (54%, P = .025). Of interest, unexpectedly, we observed a significant decrease in RS in 7 out of 10 (70%) evaluable patients during treatment. In conclusion, this study suggests that NF-κB activation, measured by pp65 levels, may be a useful biomarker in MDS. Bortezomib is safe in this patient population but has modest clinical activity. The role of the proteasome in the genesis of RS needs further study., (© 2017 Wiley Periodicals, Inc.)

Chronic lymphocytic leukemia (CLL) is the most prevalent type of adult leukemia encountered in the western world. Patients with CLL are typically older, with a median age in the 70s, and are at risk for certain complications due to the disease itself and due to the therapies imparted for this. Patients with CLL are at a higher risk of infections, partly due to disease and partly due to the immune dysfunction induced by treatment, such as purine analogous-based chemoimmunotherapy, which leads to lymphocyte depletion. Infections are a leading cause of complications and death in CLL patients. Also, CLL patients have been shown to have a higher incidence of other malignancies. Despite this knowledge, there are no definite guidelines as to what is the best approach to manage or prevent these associated complications of CLL. In this review, the authors discuss the data available and outline recommendations as to the best way to approach this issue in daily practice.

Poor solubility of newly developed drug molecules is the main problem in recent drug discovery research, so novel drug delivery approaches are being used to deliver these molecular entities for pharmacological action. Colloidal carriers (emulsion, suspensions, liposomes, polymer nanoparticles and solid lipid nanoparticles) have been used to administer poorly soluble drugs, but solid lipid nanoparticles are found to be the most reliable carriers for this type of drugs due to its advantages over other carriers. Solid lipid nanoparticles have the potential to solve the drug delivery problems with safe excipients used in its formulation. In this review all the aspects of solid lipid nanoparticles production, stability, characterization, differentiation based on route, preservation and storage have been discussed., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Solid lipid nanoparticles were prepared and studied for the possibility of entrapment of Paliperidone (PPN) an antipsychotic drug that can be used for the treatment of schizophrenia. Here we report the preparation of Paliperidone loaded solid lipid particles (SLNs) with Capmul GMS 50 K as lipid vehicle. SLNs were stabilized by a surfactant namely sodium deoxycholate which can also act as permeability enhancer. Final size of SLNs produced were approximately 200 nm which was confirmed by dynamic light scattering (DLS), atomic force microscopy (AFM) and transmission electron microscopy (TEM). SLNs appeared spherical in TEM images while dough nut like shape was observed by AFM. The entrapment efficiency of this system was found to be 55% with 4.15% of drug loading in lipid matrix. Structural characterization of SLNs by Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD) and differential scanning calorimetric (DSC) analysis revealed that, there was no interaction of PPN with lipid and PPN was well dispersed in the lipid matrix without any crystallization., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Endotoxemia promotes adhesive interactions between platelets and microvascular endothelium in vivo. We sought to determine whether endotoxin (lipopolysaccharide, LPS) modified platelet thrombus formation in mouse cremaster venules and whether Toll-like receptor 4 (TLR4) and neutrophils were involved in the response. Intravital videomicroscopy was performed in the cremaster microcirculation of pentobarbital-anesthetized mice; venular platelet thrombi were induced with a light/dye endothelial injury model. C57BL/6 mice treated with Escherichia coli endotoxin had enhanced rates of venular platelet thrombus formation: the time to microvessel occlusion was reduced by approximately 50% (P < 0.005) compared with saline-treated animals. Enhanced microvascular thrombosis was evident as early as 2 h after LPS administration. LPS had no effect on thrombosis in either of two mouse strains with altered TLR4 signaling (C57BL/10ScNJ or C3H/HeJ), whereas it enhanced thrombosis in the control strains (C57BL/10J and C3H/HeN). LPS also enhanced platelet adhesion to endothelium in the absence of light/dye injury. Platelet adhesion, but not enhanced thrombosis, was inhibited by depletion of circulating neutrophils. LPS failed to enhance platelet aggregation ex vivo and did not influence platelet P-selectin expression, a marker of platelet activation. These findings support the notion that endotoxemia promotes platelet thrombus formation independent of neutrophils and without enhancement of platelet aggregation, via a TLR4-dependent mechanism.

Objective: A risk factor for cardiovascular disease, hyperhomocystinemia (HHcy), is associated with endothelial dysfunction. In this study, we examined the mechanistic role of HHcy in endothelial dysfunction., Methods and Results: Through the use of 2 functional models, aortic rings and intravital video microscopy of the cremaster, we found that arterial relaxation in response to the endothelium-dependent vessel relaxant, acetylcholine or the nitric oxide synthase (NOS) activator (A23187), was significantly impaired in cystathionine beta-synthase null (CBS(-/-)) mice. However, the vascular smooth muscle cell (VSMC) response to the nitric oxide (NO) donor (SNAP) was preserved in CBS(-/-) mice. In addition, superoxide dismutase and catalase failed to restore endothelium-dependent vasodilatation. Endothelial nitric oxide synthase (eNOS) activity was significantly reduced in mouse aortic endothelial cells (MAECs) of CBS(-/-) mice, as well as in Hcy-treated mouse and human aortic endothelial cells (HAECs). Hcy-mediated eNOS inhibition--which was not rescued by adenoviral transduction of superoxide dismutase and glutathione peroxidase, or by tetrahydrobiopterin, sepiapterin, and arginine supplementations in MAEC--was associated with decreased protein expression and increased threonine 495 phosphorylation of eNOS in HAECs. Ultimately, a protein kinase C (PKC) inhibitor, GF109203X (GFX), reversed Hcy-mediated eNOS inactivation and threonine 495 phosphorylation in HAECs., Conclusions: These data suggest that HHcy impairs endothelial function and eNOS activity, primarily through PKC activation.

Objective: Microvascular adhesion of platelets to endothelium occurs in response to various inflammatory stimuli, and in venules is often accompanied by adherent leukocytes. In a light/dye injury model, platelet adhesion and thrombi occur preferentially in venules, though the reasons for this predisposition are unknown. The authors sought to determine whether lower wall shear rates or leukocyte-endothelial interactions accounted for preferential platelet thrombi formation in venules relative to arterioles., Methods: A light/dye injury model of microvascular thrombosis was used in the mouse cremaster microcirculation., Results: In wild-type mice (n = 17), the time to form microvascular platelet aggregates was delayed in arterioles by 3.1-fold relative to venules (p <.0001). However, arterioles with spontaneously low wall shear rates, as well as arterioles manipulated to reduce wall shear rate to venous levels, still had delayed thrombosis as compared to venules. Similarly, in animals deficient in CD18, P-selectin, or ICAM-1, the time to form platelet thrombi in arterioles was >3.0-fold higher than in venules., Conclusions: Mouse cremaster venules are predisposed to light/dye-induced microvascular thrombosis. The data suggest that functional differences between arteriolar and venular endothelial cells (independent of wall shear rate and of CD18, P-selectin, and ICAM-1) account for the venular predisposition to thrombosis.