Gold-Based Nanostructures for Antibacterial Application.

Bacterial infections have become a fatal threat because of the abuse of antibiotics in the world. Various gold (Au)-based nanostructures have been extensively explored as antibacterial agents to combat bacterial infections based on their remarkable chemical and physical characteristics. Many Au-based nanostructures have been designed and their antibacterial activities and mechanisms have been further examined and demonstrated. In this review, we collected and summarized current developments of antibacterial agents of Au-based nanostructures, including Au nanoparticles (AuNPs), Au nanoclusters (AuNCs), Au nanorods (AuNRs), Au nanobipyramids (AuNBPs), and Au nanostars (AuNSs) according to their shapes, sizes, and surface modifications. The rational designs and antibacterial mechanisms of these Au-based nanostructures are further discussed. With the developments of Au-based nanostructures as novel antibacterial agents, we also provide perspectives, challenges, and opportunities for future practical clinical applications.

Polymorphisms of haptoglobin modify the relationship between dietary iron and the risk of gestational iron-deficiency anemia.

PURPOSE: To assess whether polymorphisms of haptoglobin (Hp) modify the relationship between dietary iron and the risk of gestational iron-deficiency anemia (IDA). METHODS: This study analyzed 1430 singleton pregnant women aged 20 ~ ≤ 48 years from the 2017-2019 National Nutrition and Health Survey of Pregnant Women in Taiwan. Sociodemographic, blood biochemical, Hp phenotype, and 24-h dietary recall data were collected. Erythropoiesis-related total prenatal supplementation was defined as the reported use of multivitamins and minerals, vitamin B complex, folate, and iron. RESULTS: Distributions of the Hp 1-1, Hp 2-1, and Hp 2-2 phenotypes were 13.6, 39.8, and 46.5%, respectively. Women with the Hp 1-1 phenotype had the lowest mean levels of serum ferritin (p-trend = 0.017), the highest prevalence of gestational ID (p-trend = 0.033) as well as the highest prevalence of gestational IDA (did not reach statistical differences, p-trend = 0.086). A gene-diet interaction on serum ferritin was observed between the Hp 1 and Hp 2 (2-1/2-2) alleles (p < 0.001). An adjusted multivariate logistic regression showed that compared to those with a normal blood iron status and who reported using erythropoiesis-related total prenatal supplements, those who did not had a 4.05-fold [odds ratio (OR) = 4.05 (95% confidence interval (CI) 2.63-6.24), p < 0.001] increased risk of gestational IDA. The corresponding ORs for carriers of the Hp 1 and Hp 2 alleles were 4.78 (95% CI 1.43-15.99) and 3.79 (95% CI 2.37-6.06), respectively. CONCLUSION: Pregnant women who are Hp 1 carriers are at increased risk for developing IDA if they do not meet the recommended dietary allowance for iron or use erythropoiesis-related prenatal supplements.

Haptoglobin-Conjugated Gold Nanoclusters as a Nanoantibiotic to Combat Bacteremia.

Gold nanoclusters have revealed great potential as nanoantibiotics due to their superior chemical and physical characteristics. In this study, a peptide with 83 amino acids derived from haptoglobin was utilized as a surface ligand to synthesize gold nanoclusters via a facile hydrothermal approach. Characterization of the structural and optical properties demonstrated the successful synthesis of derived haptoglobin-conjugated gold nanoclusters. The spherical derived haptoglobin-conjugated gold nanoclusters exhibited a (111) plane of cubic gold and an ultra-small size of 3.6 ± 0.1 nm. The optical properties such as ultraviolet-visible absorption spectra, X-ray photoelectron spectroscopy spectra, fluorescence spectra, and Fourier transform infrared spectra also validated the successful conjugation between the derived haptoglobin peptide and the gold nanoclusters surface. The antibacterial activity, reactive oxygen species production, and antibacterial mechanisms of derived haptoglobin-conjugated gold nanoclusters were confirmed by culturing the bacterium Escherichia coli with hemoglobin to simulate bacteremia. The surface ligand of the derived haptoglobin peptide of derived haptoglobin-conjugated gold nanoclusters was able to conjugate with hemoglobin to inhibit the growth of Escherichia coli. The derived haptoglobin-conjugated gold nanoclusters with an ultra-small size also induced reactive oxygen species production, which resulted in the death of Escherichia coli. The superior antibacterial activity of derived haptoglobin-conjugated gold nanoclusters can be attributed to the synergistic effect of the surface ligand of the derived haptoglobin peptide and the ultra-small size. Our work demonstrated derived haptoglobin-conjugated gold nanoclusters as a promising nanoantibiotic for combating bacteremia.

Lipid-Based Nanomaterials for Drug Delivery Systems in Breast Cancer Therapy.

Globally, breast cancer is one of the most prevalent diseases, inducing critical intimidation to human health. Lipid-based nanomaterials have been successfully demonstrated as drug carriers for breast cancer treatment. To date, the development of a better drug delivery system based on lipid nanomaterials is still urgent to make the treatment and diagnosis easily accessible to breast cancer patients. In a drug delivery system, lipid nanomaterials have revealed distinctive features, including high biocompatibility and efficient drug delivery. Specifically, a targeted drug delivery system based on lipid nanomaterials has inherited the advantage of optimum dosage and low side effects. In this review, insights on currently used potential lipid-based nanomaterials are collected and introduced. The review sheds light on conjugation, targeting, diagnosis, treatment, and clinical significance of lipid-based nanomaterials to treat breast cancer. Furthermore, a brighter side of lipid-based nanomaterials as future potential drug delivery systems for breast cancer therapy is discussed.

Toxicologic Concerns with Current Medical Nanoparticles.

Nanotechnology is one of the scientific advances in technology. Nanoparticles (NPs) are small materials ranging from 1 to 100 nm. When the shape of the supplied nanoparticles changes, the physiological response of the cells can be very different. Several characteristics of NPs such as the composition, surface chemistry, surface charge, and shape are also important parameters affecting the toxicity of nanomaterials. This review covered specific topics that address the effects of NPs on nanomedicine. Furthermore, mechanisms of different types of nanomaterial-induced cytotoxicities were described. The distributions of different NPs in organs and their adverse effects were also emphasized. This review provides insight into the scientific community interested in nano(bio)technology, nanomedicine, and nanotoxicology. The content may also be of interest to a broad range of scientists.

Design of novel self-assembled MXene and ZIF67 derivative composites as efficient electroactive material of energy storage device.

High surface area and tunable pore size are beneficial for metal organic frameworks (MOFs) as electroactive material of energy storage devices. Novel ZIF67 derivative proposed in our previous work, nickel cobalt fluoride coupled with ammonia ions (NCNF), is synthesized using ammonia fluoride to solve poor electrical conductivity of MOFs. MXene is commonly incorporated in pseudo-capacitive materials to enhance electrical conductivity and energy storage ability. In this study, it is the first time to design MXene and NCNF composites (MXene/NCNF) with different MXene amounts via incorporating MXene in growing process of NCNF. MXene and NCNF are combined via self-assembly in a simple room temperature solution process. The optimized MXene/NCNF electrode shows a higher specific capacitance of 1020.0 F g-1 (170.0 mAh g-1) than that of NCNF electrode (574.2 F g-1 and 95.7 mAh g-1) at 20 mV s-1, due to excellent surface properties of MXene/NCNF with conductive network of MXene and high electrocapacitive performance of NCNF. A symmetric energy storage device composed of the optimized MXene/NCNF electrodes presents outstanding cycling stability with Coulombic efficiency of 100% during whole cycling process and a high capacitance retention of 99% after 6000 cycles. Excellent electrochemical performance and simple synthesis of MXene/NCNF open new blueprints for designing novel electrocapacitive materials for electrochemical applications.

Tissue-Engineered Vascular Graft with Co-Culture of Smooth Muscle Cells and Human Endothelial Vein Cells on an Electrospun Poly(lactic-co-glycolic acid) Microtube Array Membrane.

Coronary artery disease is one of the major diseases that plagues today's modern society. Conventional treatments utilize synthetic vascular grafts such as Dacron® and Teflon® in bypass graft surgery. Despite the wide adaptation, these synthetic grafts are often plagued with weaknesses such as low hemocompatibility, thrombosis, intimal hyperplasia, and risks of graft infection. More importantly, these synthetic grafts are not available at diameters of less than 6 mm. In view of these challenges, we strived to develop and adapt the electrospun Poly Lactic-co-Glycolic Acid (PLGA) Microtube Array Membrane (MTAM) vascular graft for applications smaller than 6 mm in diameter. Homogenously porous PLGA MTAMs were successfully electrospun at 5.5-8.5 kV under ambient conditions. Mechanically, the PLGA MTAMs registered a maximum tensile strength of 5.57 ± 0.85 MPa and Young's modulus value of 1.134 ± 0.01 MPa; while MTT assay revealed that seven-day Smooth Muscle Cells (SMCs) and Human Umbilical Vein Endothelial Cells (HUVECs) registered a 6 times and 2.4 times higher cell viability when cultured in a co-culture setting in medium containing α-1 haptaglobulin. When rolled into a vascular graft, the PLGA MTAMs registered an overall degradation of 82% after 60 days of cell co-culture. After eight weeks of culturing, immunohistochemistry staining revealed the formation of a monolayer of HUVECs with tight junctions on the surface of the PLGA MTAM, and as for the SMCs housed within the lumens of the PLGA MTAMs, a monolayer with high degree of orientation was observed. The PLGA MTAM registered a burst pressure of 1092.2 ± 175.3 mmHg, which was sufficient for applications such as small diameter blood vessels. Potentially, the PLGA MTAM could be used as a suitable substrate for vascular engineering.

Thrombus-specific theranostic nanocomposite for codelivery of thrombolytic drug, algae-derived anticoagulant and NIR fluorescent contrast agent.

Thrombolysis is a standard treatment for rapidly restoring blood flow. However, the application of urokinase-type plasminogen activator (Uk) in clinical therapy is limited due to its nonspecific distribution and inadequate therapeutic accumulation. Precise thrombus imaging and site-specific drug delivery can enhance the diagnostic and therapeutic efficacy for thrombosis. Accordingly, we developed a P-selectin-specific, photothermal theranostic nanocomposite for thrombus-targeted codelivery of Uk and indocyanine green (ICG, a contrast agent for near-infrared (NIR) fluorescence imaging). We evaluated its capabilities for thrombus imaging and enzyme/hyperthermia combined thrombolytic therapy. Mesoporous silica-coated gold nanorods (Si-AuNRs) were functionalized with an arginine-rich peptide to create an organic template for the adsorption of ICG and fucoidan (Fu), an algae-derived anticoagulant. Uk was loaded into the SiO2 pores of the Si-AuNRs through the formation of a Fu-Uk-ICG complex on the peptide-functionalized template. The Fu-Uk/ICG@SiAu NRs nanocomposite increased the photostability of ICG and improved its targeting/accumulation at blood clot sites with a strong NIR fluorescence intensity for precise thrombus imaging. Furthermore, ICG incorporated into the nanocomposite enhanced the photothermal effect of Si-AuNRs. Fu, as a P-selectin-targeting ligand, enabled the nanocomposite to target a thrombus site where platelets were activated. The nanocomposite enabled a faster release of Uk for rapid clearing of blood clots and a slower release of Fu for longer lasting prevention of thrombosis regeneration. The nanocomposite with multiple functions, including thrombus-targeting drug delivery, photothermal thrombolysis, and NIR fluorescence imaging, is thus an advanced theranostic platform for thrombolytic therapy with reduced hemorrhaging risk and enhanced imaging/thrombolysis efficiency. STATEMENT OF SIGNIFICANCE: Herein, for the first time, a P-selectin specific, photothermal theranostic nanocomposite for thrombus-targeted co-delivery of urokinase and NIR fluorescence contrast agent indocyanine green (ICG) was developed. We evaluated the potential of this theranostic nanocomposite for thrombus imaging and enzyme/hyperthermia combined thrombolytic therapy. The nanocomposite showed multiple functions including thrombus targeting and imaging, and photothermal thrombolysis. Besides, it allowed faster release of the thrombolytic urokinase for rapidly clearing blood clots and slower release of a brown algae-derived anticoagulant fucoidan (also acting as a P-selectin ligand) for prevention of thrombosis regeneration. The nanocomposite is thus a new and advanced theranostic platform for targeted thrombolytic therapy.

Impact of Smoking-Related Chronic Obstruction Pulmonary Disease on Mortality of Invasive Ductal Carcinoma Patients Receiving Standard Treatments: Propensity Score-Matched, Nationwide, Population-Based Cohort Study.

PURPOSE: the survival effect of smoking-related chronic obstructive pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) is unclear for patients with invasive ductal carcinoma (IDC) receiving standard treatments. METHODS: we recruited women with clinical stage I-III IDC from the Taiwan Cancer Registry Database who had received standard treatments between 1 January 2009 and 31 December 2018. The time-dependent Cox proportional hazards model was used to analyze all-cause mortality. To reduce the effects of potential confounders when all-cause mortality between Groups 1 and 2 were compared, 1:2 propensity score matching (PSM) was performed. We categorized the patients into two groups based on COPD status to compare overall survival outcomes: Group 1 (current smokers with COPD) and Group 2 (nonsmokers without COPD group). RESULTS: PSM yielded 2319 patients with stage I-III IDC (773 and 1546 in Groups 1 and 2, respectively) eligible for further analysis. In the multivariate time-dependent Cox regression analyses, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) of all-cause mortality for Group 1 compared with Group 2 was 1.04 (0.83-1.22). The aHRs (95% CIs) of all-cause mortality for ≥1 hospitalization for COPDAE within one year before breast surgery was 1.51 (1.18-2.36) compared with no COPDAE. CONCLUSION: smoking-related COPD was not a significant independent risk factor for all-cause mortality in women with stage I-III IDC receiving standard treatments. Being hospitalized at least once for COPDAE within one year before breast surgery is highly associated with high mortality for women with IDC receiving standard treatments. The severity of smoking-related COPD before treatments for breast cancer might be an important prognostic factor of survival. Thus, the information of the severity of COPD before treatment for breast cancer might be valuable for increasing the survival rate in treatment of breast cancer, especially in the prevention of progress from COPD to COPDAE.

Nano-Strategies Targeting the Integrin αvß3 Network for Cancer Therapy.

Integrin αvß3, a cell surface receptor, participates in signaling transduction pathways in cancer cell proliferation and metastasis. Several ligands bind to integrin αvß3 to regulate proliferation and metastasis in cancer cells. Crosstalk between the integrin and other signal transduction pathways also plays an important role in modulating cancer proliferation. Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) activates the downstream integrin FAK to stimulate biological activities including cancer proliferation and metastasis. Blockage of signals related to integrin αvß3 was shown to be a promising target for cancer therapies. 3,3',5,5'-tetraiodothyroacetic acid (tetrac) completely binds to the integrin with the thyroid hormone to suppress cancer proliferation. The (E)-stilbene analog, resveratrol, also binds to integrin αvß3 to inhibit cancer growth. Recently, nanotechnologies have been used in the biomedical field for detection and therapeutic purposes. In the current review, we show and evaluate the potentiation of the nanomaterial carrier RGD peptide, derivatives of PLGA-tetrac (NDAT), and nanoresveratrol targeting integrin αvß3 in cancer therapies.

Galectin-3 as a Biomarker for Stratifying Abdominal Aortic Aneurysm Size in a Taiwanese Population.

Abdominal aortic aneurysm (AAA) ruptures are unpredictable and lethal. A biomarker predicting AAA rupture risk could help identify patients with small, screen-detected AAAs. Galectin-3 (Gal-3), a ß-galactosidase-binding lectin, is involved in inflammatory processes and may be associated with AAA incidence. We investigated whether Gal-3 can be used as a biomarker of AAA size. Plasma Gal-3 protein concentrations were examined in patients with AAA (n = 151) and control patients (n = 195) using Human ProcartaPlex multiplex and simplex kits. Circulating Gal-3 levels were significantly higher in patients with AAA than in control patients. The area under the receiver operating characteristic curve for Gal-3 was 0.91. Multivariate logistic regression analysis revealed a significant association between Gal-3 level and the presence of AAA. Circulating Gal-3 levels were significantly correlated with aortic diameter in a concentration-dependent manner. In conclusion, higher plasma Gal-3 concentrations may be a useful biomarker of AAA progression.

Migration and invasion of NSCLC suppressed by the downregulation of Src/focal adhesion kinase using single, double and tetra domain anti- CEACAM6 antibodies.

Carcinoembryonic antigen-related cell adhesion molecules 6 (CEACAM6) is a cell adhesion receptor. Expression of CEACAM6 in non-small cell lung cancer (NSCLC) associated with tumor progression and metastatic condition via Src/FAK signaling pathway. We established three anti-CEACAM6 antibodies with valences, which were designed to be monomeric sdAb, bivalent sdAb (2Ab), and tetravalent sdAb (4Ab). The anti-CEACAM6 antibodies can be used to target CEACAM6 overexpressing NSCLC. Anti-CEACAM6 antibodies, sdAb, 2Ab and 4Ab, were modified with different valency via protein engineering. sdAb and multivalent sdAbs (2Ab & 4Ab) were expressed and purified from E.coli and CHO cells, respectively. We compared the effect of anti-CEACAM6 antibodies with doxorubicin in NSCLC cell line both in vitro and in vivo. The 4Ab showed significant effect on cell viability. In addition, A549 cells treated with 2Ab and 4Ab inhibited the invasion and migration. In western blot, the 2Ab and 4Ab showed significant inhibition of phospho FAK domain Ty397 that is essential for activation of Src kinase family. Meanwhile, overall protein analysis revealed that 2Ab and 4Ab potently inhibited the phosphorylation of pSRC, pERK, pFAK, pAKT, MMP-2, MMP-9 and N-cadherin. Anti-tumor effect was observed in an A549 NSCLC xenograft model treated with 2Ab or 4Ab compared with doxorubicin. Confocal analysis showed higher targeting ability of 4Ab than that of 2Ab at 4 h incubation. Our data suggests that 2Ab and 4Ab inhibits EMT-mediated migration and invasion via suppression of Src/FAK signaling, which exhibits therapeutic efficiency for NSCLC treatment.

Galectin-3 Modulates Macrophage Activation and Contributes Smooth Muscle Cells Apoptosis in Abdominal Aortic Aneurysm Pathogenesis.

Galectin-3 (Gal-3) is a 26-kDa lectin that regulates many aspects of inflammatory cell behavior. We assessed the hypothesis that increased levels of Gal-3 contribute to abdominal aortic aneurysm (AAA) progression by enhancing monocyte chemoattraction through macrophage activation. We analyzed the plasma levels of Gal-3 in 76 patients with AAA (AAA group) and 97 controls (CTL group) as well as in angiotensin II (Ang-II)-infused ApoE knockout mice. Additionally, conditioned media (CM) were used to polarize THP-1 monocyte to M1 macrophages with or without Gal-3 inhibition through small interfering RNA targeted deletion to investigate whether Gal-3 inhibition could attenuate macrophage-induced inflammation and smooth muscle cell (SMC) apoptosis. Our results showed a markedly increased expression of Gal-3 in the plasma and aorta in the AAA patients and experimental mice compared with the CTL group. An in vitro study demonstrated that the M1 cells exhibited increased Gal-3 expression. Gal-3 inhibition markedly decreased the quantity of macrophage-induced inflammatory regulators, including IL-8, TNF-α, and IL-1ß, as well as messenger RNA expression and MMP-9 activity. Moreover, Gal-3-deficient CM weakened SMC apoptosis through Fas activation. These findings prove that Gal-3 may contribute to AAA progression by the activation of inflammatory macrophages, thereby promoting SMC apoptosis.

Hemoglobin-Conjugated Gold Nanoclusters for Qualitative Analysis of Haptoglobin Phenotypes.

Designing a facile and rapid detection method for haptoglobin (Hp) phenotypes in human blood plasma is urgently needed to meet clinic requirements in hemolysis theranostics. In this work, a novel approach to qualitatively analyze Hp phenotypes was developed using a fluorescent probe of gold nanoclusters (AuNCs). Hemoglobin-conjugated (Hb)-AuNCs were successfully synthesized with blue-green fluorescence and high biocompatibility via one-pot synthesis. The fluorescence of Hb-AuNCs comes from the ligand-metal charge transfer between surface ligands of Hb and the gold cores with high oxidation states. The biocompatibility assays including cell viability and fluorescence imaging, demonstrated high biocompatibility of Hb-AuNCs. For the qualitative analysis, three Hp phenotypes in plasma, Hp 1-1, Hp 2-1, and Hp 2-2, were successfully discriminated according to changes in the fluorescence intensity and peak position of the maximum intensity of Hb-AuNCs. Our work provides a practical method with facile and rapid properties for the qualitative analysis of three Hp phenotypes in human blood plasma.

Synthesis and characterization of Gd-DTPA/fucoidan/peptide complex nanoparticle and in vitro magnetic resonance imaging of inflamed endothelial cells.

P-selectin overexpressed on activated endothelial cells and platelets is a new target for treatment of cancers and cardiovascular diseases such as atherosclerosis and thrombosis. In this study, depolymerized low molecular weight fucoidan (LMWF8775) and a thermolysin-hydrolyzed protamine peptide (TPP1880) were prepared. TPP1880 and LMWF8775 were able to form self-assembled complex nanoparticles (CNPs). The formation of TPP1880/LMWF8775 CNPs was characterized by Fourier-transform infrared spectra, circular dichroism spectra and isothermal titration calorimetry. The CNPs selectively targeted PMA-stimulated, inflamed endothelial cells (HUVECs) with high expression of P-selectin. Gd-DTPA MRI contrast agent was successfully loaded in the CNPs with better T1 relaxivity and selectively accumulated in the activated HUVECs with increased MRI intensity and reduced cytotoxicity as compared to free Gd-DTPA. Our results suggest that the TPP1880/LMWF8775 CNPs may have potential in future for early diagnosis of cardiovascular diseases and cancers in which the endothelium is inflamed or activated.

Nanomaterials for the Photothermal Killing of Bacteria.

An upsurge in the multidrug-resistant (MDR) bacterial pestilence is a global cause for concern in terms of human health. Lately, nanomaterials with photothermal effects have assisted in the efficient killing of MDR bacteria, attributable to their uncommon plasmonic, photocatalytic, and structural properties. Examinations of substantial amounts of photothermally enabled nanomaterials have shown bactericidal effects in an optimized time under near-infrared (NIR) light irradiation. In this review, we have compiled recent advances in photothermally enabled nanomaterials for antibacterial activities and their mechanisms. Photothermally enabled nanomaterials are classified into three groups, including metal-, carbon-, and polymer-based nanomaterials. Based on substantial accomplishments with photothermally enabled nanomaterials, we have inferred current trends and their prospective clinical applications.

Microtube Array Membrane (MTAM)-Based Encapsulated Cell Therapy for Cancer Treatment.

The treatment of cancer has evolved significantly in recent years with a strong focus on immunotherapy. Encapsulated Cell Therapy (ECT) for immunotherapy-based anti-cancer treatment is a unique niche within this landscape, where molecules such as signaling factors and antibodies produced from cells are encapsulated within a vehicle, with a host amount of benefits in terms of treatment efficacy and reduced side effects. However, traditional ECTs generally lie in two extremes; either a macro scale vehicle is utilized, resulting in a retrievable system but with limited diffusion and surface area, or a micro scale vehicle is utilized, resulting in a system that has excellent diffusion and surface area but is unretrievable in the event of side effects occurring, which greatly compromises the biosafety of patients. In this study we adapted our patented and novel electrospun Polysulfone (PSF) Microtube Array Membranes (MTAMs) as a 'middle' approach to the above dilemma, which possess excellent diffusion and surface area while being retrievable. Hybridoma cells were encapsulated within the PSF MTAMs, where they produced CEACAM6 antibodies to be used in the suppression of cancer cell line A549, MDA-MB-468 and PC 3 (control). In vitro and in vivo studies revealed excellent cell viability of hybridoma cells with continuous secretion of CEACAM6 antibodies which suppressed the MDA-MB-468 throughout the entire 21 days of experiment. Such outcome suggested that the PSF MTAMs were not only an excellent three-dimensional (3D) cell culture substrate but potentially also an excellent vehicle for the application in ECT systems. Future research needs to include a long term in vivo >6 months study before it can be used in clinical applications.

Leucettamine B analogs and their carborane derivative as potential anti-cancer agents: Design, synthesis, and biological evaluation.

Leucettamine B is a natural product found in marine sponge Leucetta microraphis. Several of analogs of its family, such as aplysinopsine and clathridine, are medicinally active molecules which have applications in many pharmaceuticals and healthcare products; however, thus far, leucettamine B has not been studied. In this report, we describe the synthesis of a new class of analogs of leucettamine B obtained by Knoevenagel condensation using a microwave reactor. The 25 newly synthesized compounds were tested against MDA-MB-468, SW480, and Mahlavu cell lines for anticancer activity. Among them, the carborane-based compound (Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-3-(1-closo-carboranyl)-2-thioxo -thiazolidin-4-one (49) and (Z)-5-(benzo[d][1,3]dioxol-5-ylmethylene)-3-(2-(pyrrolidin-1-yl)ethyl)-2-thioxothiazolidin-4-one (31) derivatives were found to have the most potential for use against tumor cells. The carborane derivative 49 had the lowest IC50 value against the SW480 cell line (4.7 µM) and the Mahlavu (6.6 µM) cell line. Furthermore, compound 31 also had a low IC50 value against SW480 (7.5 µM). Our research shows that leucettamine B analogs might have potential for use in cancer chemotherapy.

Two new, near-infrared, fluorescent probes as potential tools for imaging bone repair.

A precise imaging technique to evaluate osteogenesis, osteodifferentiation, and osseointegration following peri-implant surgery is in high clinical demand. Herein, we report the generation of two new, near-infrared (NIR) fluorescent probes for use in the molecular imaging of bone repair. The first probe aims to monitor the in vitro differentiation of human mesenchymal stem cells (MSCs) into osteoblasts. A NIR fluorochrome was conjugated to a cyclic peptide that binds to integrin α5ß1, a factor that promotes osteogenesis in MSCs and therefore functioned as an osteoblast-specific marker. The second probe aims to monitor osteogenesis, and was generated by conjugating the drug pamidronate to a NIR fluorescent gold nanocluster. Pamidronate specifically binds to hydroxyapatite (HA), a mineral present in bone that is produced by osteoblasts, and therefore provides a functional marker for new bone formation. Our results show that both probes bind to their specific targets in vitro-differentiated osteoblasts, and not to undifferentiated MSCs, and emit NIR fluorescence for functional detection. This in vitro work demonstrates the ability of these probes to bind to active osteoblasts and their mineral deposits and highlight their potential utility as clinical tools for the imaging of the osseointegration process at the molecular level.

Haptoglobin phenotype influences the effectiveness of diet-induced weight loss in middle-age abdominally obese women with metabolic abnormalities.

BACKGROUND & AIMS: Haptoglobin (Hp) is associated with risks of obesity and cardiometabolic dysfunction; however, the role of the Hp phenotype in diet-induced weight loss remains to be elucidated. This study investigated whether the Hp phenotype contributes to inter-individual variations in body weight reduction as well as changes in the metabolic profile. METHODS: Secondary data analysis from a randomized controlled trial. In total, 151 abdominally obese Taiwanese women with ≥2 metabolic components were randomized to each of four dietary programs [calorie restriction (CR), calorie restriction plus fish oil supplementation (CRF), calorie restricted meal replacement (CRMR), and calorie restricted meal replacement with fish oil supplementation (CRMRF)] for 12 weeks. Abdominal obesity was defined as a waist circumference (WC) ≥ 80 cm in women. Hp phenotyping was performed by plasma gel electrophoresis. RESULTS: The prevalence of the Hp 1-1, 2-1, and 2-2 phenotypes were 12.58%, 41.06% and 46.35%, respectively. The mean age was 50.59 ± 12.22 years, and mean reduction in the percent body weight was 4.7% ± 3.8%. The Hp 1-1 phenotype exhibited significant decreases in the WC, body fat mass, plasma insulin levels, free hemoglobin and homeostatic model assessment of insulin resistance (HOMA-IR) compared to the Hp 2-1 or Hp 2-2 phenotypes after adjusting for the baseline age, WC, metabolic syndrome (MetS), and dietary programs (all adjusted p < 0.05). A greater improvement in the prevalence of central obesity and, to a lesser extent, MetS was also found in women with the Hp 1-1 phenotype. CONCLUSIONS: Obese women with the Hp 1-1 phenotype might obtain greater benefits in terms of reducing abdominal fat and improving insulin sensitivity in response to hypocaloric diet-induced weight reduction. The findings from this study support potential gene-diet interactions affecting weight loss. This trial was registered at ClinicalTrials.gov as NCT01768169. CLINICAL TRIAL REGISTRY: This trial was registered at ClinicalTrials.gov as NCT01768169.