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Dopamine is one of the most important neurotransmitters and plays a crucial role in various neurological, renal, and cardiovascular systems. However, the abnormal levels of dopamine mainly point to Parkinson's, Alzheimer's, cardiovascular diseases, etc. Hydroxyapatite (HAp), owing to its catalytic nature, nanoporous structure, easy synthesis, and biocompatibility, is a promising matrix material. These characteristics make HAp a material of choice for doping metals such as cobalt. The synthesized cobalt-doped hydroxyapatite (Co-HAp) was used as a colorimetric sensing platform for dopamine. The successful synthesis of the platform was confirmed by characterization with FTIR, SEM, EDX, XRD, TGA, etc. The platform demonstrated intrinsic peroxidase-like activity in the presence of H2O2, resulting in the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). The proposed sensor detected dopamine in a linear range of 0.9-35 µM, a limit of detection of 0.51 µM, limit of quantification of 1.7 µM, and an R2 of 0.993. The optimization of the proposed sensor was done with different parameters, such as the amount of mimic enzyme, H2O2, pH, TMB concentration, and time. The proposed sensor showed the best response at 5 mg of the mimic enzyme, pH 5, 12 mM TMB, and 8 mM H2O2, with a short response time of only 2 min. The fabricated platform was successfully applied to detect dopamine in physiological solutions.
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Hydrogen peroxide (H2O2) is one of the main byproducts of most enzymatic reactions, and its detection is very important in disease conditions. Due to its essential role in healthcare, the food industry, and environmental research, accurate H2O2 determination is a prerequisite. In the present work, Morus nigra sawdust deposited zinc oxide (ZnO) nanoparticles (NPs) were synthesized by the use of Trigonella foenum extract via a hydrothermal process. The synthesized platform was characterized by various techniques, including UV-Vis, FTIR, XRD, SEM, EDX, etc. FTIR confirmed the presence of a ZnâO characteristic peak, and XRD showed the hexagonal phase of ZnO NPs with a 35 nm particle size. The EDX analysis confirmed the presence of Zn and O. SEM images showed that the as-prepared nanoparticles are distributed uniformly on the surface of sawdust. The proposed platform (acetic acid-capped ZnO NPs deposited sawdust) functions as a mimic enzyme for the detection of H2O2 in the presence of 3,3',5,5'-tetramethylbenzidine (TMB) colorimetrically. To get the best results, many key parameters, such as the amount of sawdust-deposited nanoparticles, TMB concentration, pH, and incubation time were optimized. With a linear range of 0.001-0.360 µM and an R2 value of 0.999, the proposed biosensor's 0.81 nM limit of quantification (LOQ) and 0.24 nM limit of detection (LOD) were predicted, respectively. The best response for the proposed biosensor was observed at pH 7, room temperature, and 5 min of incubation time. The acetic acid-capped sawdust deposited ZnO NPs biosensor was also used to detect H2O2 in blood serum samples of diabetic patients and suggest a suitable candidate for in vitro diagnostics and commercial purposes.
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Ascorbic acid is a vital biomolecule for human beings. When the body's level of ascorbic acid is abnormal, it can lead to a number of illnesses. Its appropriate concentration is necessary for the oxidation of prostaglandins and cyclic adenosine monophosphate, the production of dopamine, norepinephrine, epinephrine, and carnitine, and the expansion and durability of the collagen triple helix in humans. In the present work, silver nanoparticle synthesis was performed through a paracetamol-mediated approach. Different characterization techniques, such as X-ray diffractometry (XRD), energy dispersive X-ray (EDX), Fourier transform infrared (FTIR), and scanning electron microscopy (SEM), were used to confirm the prepared nanoparticles. Subsequently, the prepared Ag NPs functionalized with an ionic liquid were used as a sensing platform for ascorbic acid in blood serum samples. To achieve the best possible results, the proposed biosensor was optimized with different parameters such as TMB concentration, time, amount of capped nanoparticles (NPs), and pH. The proposed biosensor offers a sensitive and straightforward method for ascorbic acid with a linear range from 2 × 10-9 to 3.22 × 10-7 M, an LOD of 1.3 × 10-8 M, an LOQ of 4.3 × 10-8 M, and an R2 of 0.9996, Moreover, applications of the proposed biosensor were successfully used for the detection of ascorbic acid in samples of human plasma, suggesting that Ag NPs with high peroxidase-like activity, high stability, and facile synthesis exhibited promising applications in biomedical fields.
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Uric acid (UA) is a metabolic byproduct of purine nucleotides and is excreted as a urine component. Abnormalities in UA metabolism cause localized inflammation due to crystal deposition and can lead to various diseases. In the current study, we successfully fabricated a biosensor based on 1-H-3-methylimidazolium acetate (ionic liquid, IL)-capped nickel nanoparticles (NiNPs) for the detection of uric acid in test samples. The structures of IL-capped NiNPs and their precursors were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and X-ray diffraction. The IL-capped NiNPs possessed intrinsic peroxidase-like properties and displayed selective UA quenching after interacting with 3,3',5,5'-tetramethylbenzidine (TMB) solution. Different parameters such as pH, time, IL, TMB, and UA concentration were optimized to obtain the best results for the proposed sensor. The UA biosensor shows good responses in the linear range from 1 × 10-8 to 2.40 × 10-6 M, with a lower limit of detection of 1.30 × 10-7 M, a limit of quantification of 4.3 × 10-7 M, and an R 2 value of 0.9994. For the colorimetric detection of UA, the proposed sensor gave a short time response of 4 min at room temperature and pH 7.5. The proposed sensing probe detects UA in real serum samples and could be used as a selective sensor for UA in the real sample detection.
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The regulatory T cells (Treg cells) expressing CD4 + CD25 + FOXP3 + markers are indispensable for the initiation of immune homeostasis and tolerance to self-antigens in both mice and humans. A decrease in regulatory T cells leads to various autoimmune pathologies. Herein, we report three low molecular weight, small organic molecules as a new series of Treg proliferators TRP-1-3. These small molecules were tested for their proliferative effect on regulatory T cells. It was found that TRP-1 (Oleracein E) strongly accelerates the Treg proliferation in vitro in a concentration-dependent manner. The effect was evident for all subsets of Treg cells tested, including naturally occurring, thymus-derived and peripherally-induced or adaptive Treg, indicating an effect independent of the maturation site. Importantly, increased Treg cells numbers by TRP-1 correlated with improved CD4 + CD25 + FOXP3 + expression in vitro, while propidium iodide-based staining showed low TRP-1-induced cytotoxicity. Molecular docking plus simulation studies of these TRP-1-3 with IL-2R, mTOR and TCR receptors suggest a TCR-based Treg cells activation mechanism. Because of its high Treg cells activities and low cellular cytotoxicity, TRP-1-3 may be useful in stimulating ex-vivo/in-vivo, Treg cell-specific responses for therapeutic applications.
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Alcaloides/farmacologia , Fenóis/farmacologia , Bibliotecas de Moléculas Pequenas/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Alcaloides/química , Animais , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Simulação de Acoplamento Molecular , Estrutura Molecular , Células NIH 3T3 , Fenóis/química , Bibliotecas de Moléculas Pequenas/química , Relação Estrutura-AtividadeRESUMO
Diverse immune cells in the tumor microenvironment form a complex ecosystem, but our knowledge of their heterogeneity and dynamics within hepatocellular carcinoma (HCC) still remains limited. To assess the plasticity and phenotypes of immune cells within HBV/HCV-related HCC microenvironment at single-cell level, we performed single-cell RNA sequencing on 41,698 immune cells from seven pairs of HBV/HCV-related HCC tumors and non-tumor liver tissues. We combined bio-informatic analyses, flow cytometry, and multiplex immunohistochemistry to assess the heterogeneity of different immune cell subsets in functional characteristics, transcriptional regulation, phenotypic switching, and interactions. We identified 29 immune cell subsets of myeloid cells, NK cells, and lymphocytes with unique transcriptomic profiles in HCC. A highly complex immunological network was shaped by diverse immune cell subsets that can transit among different states and mutually interact. Notably, we identified a subset of M2 macrophage with high expression of CCL18 and transcription factor CREM that was enriched in advanced HCC patients, and potentially participated in tumor progression. We also detected a new subset of activated CD8+ T cells highly expressing XCL1 that correlated with better patient survival rates. Meanwhile, distinct transcriptomic signatures, cytotoxic phenotypes, and evolution trajectory of effector CD8+ T cells from early-stage to advanced HCC were also identified. Our study provides insight into the immune microenvironment in HBV/HCV-related HCC and highlights novel macrophage and T-cell subsets that could be further exploited in future immunotherapy.
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Regulatory T cells (Tregs) are crucial for the maintenance of peripheral tolerance, but they also limit beneficial responses through cancer-induced immunoediting. The roles of Treg subsets in cervical squamous cell carcinoma (CSCC) are currently unknown. Here, we aimed to perform an extensive study with an increased resolution of the Treg compartment in the peripheral blood and tumor tissues of CSCC patients. We first identified that an HLADRhi Treg population in the peripheral blood was significantly increased in CSCC patients compared to precancer patients and healthy donors. We found that HLADRhi Tregs express high levels of a panel of inhibition and activation markers and the TCR-responsive transcription factors BATF and IRF4. However, this Treg subset showed reduced calcium influx after TCR crosslinking. In addition, HLADRhi Tregs are highly proliferative and vulnerable to apoptosis. Further studies demonstrated that the HLADRhi Tregs display high levels of suppressive activity. Quantitative multiplexed immunohistochemistry revealed that an increase in the number of tumor-infiltrating HLADRhi Tregs is associated with unfavorable classical risk parameters of advanced disease stage and stromal invasion. Context-based quantification revealed that a high frequency of stromal HLADRhi Tregs in patients is significantly associated with worse progression-free survival. In the current study, we characterized a population of highly activated and immunosuppressive HLADRhi Tregs in CSCC patients. An increased HLADRhi Treg frequency may be a potential biomarker to stratify CSCC patients and evaluate therapeutic efficacies in personalized immuno-oncology studies.
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Antígenos HLA-DR/metabolismo , Imunomodulação , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/metabolismo , Apoptose , Biomarcadores , Progressão da Doença , Feminino , Antígenos HLA-DR/imunologia , Humanos , Imuno-Histoquímica , Ativação Linfocitária , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/patologia , Fenótipo , Prognóstico , Microambiente Tumoral/imunologia , Neoplasias do Colo do Útero/mortalidadeRESUMO
Cedrus deodara (deodar) is practically used, as insect repellent, in the northern areas of Pakistan but no data available therefore this study was conducted to evaluate the effectiveness of deodar oil as an alternate of conventional insecticides against the larval pest stage of mealworm beetle (Tenebrio molitor), by feeding method. The aim of the study was to investigate the effectiveness of deodar oil as an alternate of conventional insecticides against the larval pest stage of mealworm beetle (Tenebrio molitor), by feeding method. All tested chemicals showed efficacy against the pests. The LC50 was determined by probit analysis and was found to be 3.41, 0.086 and 0.023% of larvae treated with deodar oil, Carbosulfan and Imidacloprid respectively The LC50 treated larvae were subjected to the evaluation of protein activity, qualitatively and quantitatively. The protein level in tested insects was enhanced when treated with Imidacloprid, Carbosulfan and deodar oil. The electrophoretic profile of treated insects showed more bands in insects treated with Cedrus deodara oil. This electrophoretic profile appeared in 4, 5, 7 and 8 bands for tested chemicals including control. Antifeedant activity was observed for C. deodara as larvae were deterred to feed on the food found in the container.
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In the current work, we report the discovery of new sulfonate and sulfamate derivatives of benzofuran- and benzothiophene as potent inhibitors of human carbonic anhydrases (hCAs) II, IX and XII. A set of derivatives, 1a-t, having different substituents on the fused benzofuran and benzothiophene rings (Râ¯=â¯alkyl, cyclohexyl, aryl, NH2, NHMe, or NMe2) was designed and synthesized. Most of the derivatives exhibited higher potency than acetazolamide as inhibitors of the purified hCAII, IX and XII isoforms. The most potent inhibitors for hCAII, hCAIX and hCAXII were 1g, 1b and 1d with an IC50⯱â¯SEM values of 0.14⯱â¯0.03, 0.13⯱â¯0.03 and 0.17⯱â¯0.06⯵M, respectively. In addition, compounds 1d and 1n exerted preferential inhibitory effect against hCAXII isozyme with good potencies. Some selected compounds were docked within the active pocket of these isozymes and binding of the molecules revealed that sulfonate and sulfamate rings were located towards the active cavity and compounds coordinated to zinc ions.
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Benzofuranos/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Ácidos Sulfônicos/farmacologia , Tiofenos/farmacologia , Benzofuranos/síntese química , Benzofuranos/química , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Anidrases Carbônicas/isolamento & purificação , Relação Dose-Resposta a Droga , Células HEK293 , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/isolamento & purificação , Isoenzimas/metabolismo , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Ácidos Sulfônicos/síntese química , Ácidos Sulfônicos/química , Tiofenos/síntese química , Tiofenos/químicaRESUMO
BACKGROUND: Alzheimer's Disease (AD) is the leading cause of dementia among the aging population. This devastating disorder is generally associated with the gradual memory loss, specified by a decrease of acetylcholine level in the cortex hippocampus of the brain due to hyperactivation of cholinesterases (acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)). OBJECTIVE: Therefore, inactivation of AChE and BChE by inhibitors can increase the acetylcholine level and hence may be an encouraging strategy for the treatment of AD and related neurological problems. METHOD: In this contribution, two series of chromenone-based derivatives were tested by Ellmann's calorimetric method for AChE and BChE inhibition. RESULTS: All the compounds showed inhibitory activity against cholinesterases and some of them exhibited dual inhibition of AChE as well as BChE. The most potent inhibitor of AChE was 2l having an IC50 value of 0.08 ± 0.03 µM, while 3q inhibited the BChE with an IC50 value of 0.04 ± 0.01 µM. In case of dual inhibition, 3h showed an inhibitory concentration of 0.15 ± 0.01 µM for AChE, and 0.09 ± 0.01 µM for BChE. Molecular docking studies were performed to explore the probable binding modes of the most potent dual inhibitors. CONCLUSION: It can be hypothesized that the inhibitors are able to target cholinesterase pathways and may emerge as a suitable outset for the further development process.
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Inibidores da Colinesterase/química , Cumarínicos/química , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Doença de Alzheimer/tratamento farmacológico , Butirilcolinesterase/química , Butirilcolinesterase/metabolismo , Domínio Catalítico , Inibidores da Colinesterase/metabolismo , Cumarínicos/metabolismo , Humanos , Simulação de Acoplamento Molecular , Ligação Proteica , Tacrina/químicaRESUMO
In the current study, electrostatically-driven pH responsive, supramolecular hydrogels of the trilacunary Wells-Dawson-type 15-tungsto-2-phosphate polyanion (P2W15) and chitosan hydrochloride (ChCl) were prepared, using methacrylic acid as pH responsive agent using benzoyl peroxide (BPO) as initiator. The prepared hydrogels were characterized by FT-IR, SEM, XRD and thermal analyses (TGA-DSC). The swelling and pH based P2W15 release profile of the hydrogels showed maximum swellability and release at pH 7.4. Different mathematical models were applied, showing that P2W15 release followed supercase transport-II mechanism and zero-order kinetics. The cytotoxicity results showed that free and embedded P2W15 exhibited dose-dependent cytotoxicity against cancer cell lines (MCF-7; HeLa) with minimal effects on normal cells (Vero). The developed hydrogels were administered to the rabbits for determining the pharmacokinetic behavior of the polyanion. Moreover, the developed hydrogel system as well as polyanion concentration used were also checked for its oral tolerability and safety evaluation in rabbits. The histopathological studies, serum chemistry (except blood glucose level) and hematological investigations exhibited that administered hydrogel suspension at maximal tolerable dose (4000mg/kg body weight) and polyanion concentration used (20mg) were safe from in-vivo point of view. The developed hydrogels exhibited desirable qualities of a drug delivery system that can be used for the delivery of the embedded polyanion.
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Quitosana/administração & dosagem , Sistemas de Liberação de Medicamentos , Hidrogéis/administração & dosagem , Ácidos Polimetacrílicos/administração & dosagem , Compostos de Tungstênio/administração & dosagem , Animais , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Quitosana/farmacocinética , Chlorocebus aethiops , Liberação Controlada de Fármacos , Feminino , Células HeLa , Humanos , Hidrogéis/química , Hidrogéis/farmacocinética , Concentração de Íons de Hidrogênio , Células MCF-7 , Masculino , Ácidos Polimetacrílicos/química , Ácidos Polimetacrílicos/farmacocinética , Coelhos , Compostos de Tungstênio/química , Compostos de Tungstênio/farmacocinética , Células VeroRESUMO
BACKGROUND: More than a century ago, Paul Ehrlich proposed the idea of a drug working as a "magic bullet" that selectively eliminates diseased cells without harming the surrounding normal cells. Since then, much progress has been made in this field to broaden the scope for targeted delivery of drugs. A major problem remain the toxic effects of targeted drugs on healthy cells. In order to reduce the adverse effects of chemotherapy on healthy tissues, we survey the use of recent drug delivery systems for targeted therapy. OBJECTIVE: The selective delivery of the drugs to specific diseased cells or tissues still is a daunting task. Ideally, for target drug delivery systems, the system should be made up of carriers and drugs, where carriers precisely target the desired drug. This issue covers the recent advancements in modern techniques for such purposes. RESULT AND CONCLUSION: It encompasses advances, benefits and limitations in state of art work of targeted drug delivery through hydrogels, microfluidics, nanoparticles, carbon nanotubes, polymeric micelles, liposomes, lipoprotein based drug carriers and dendrites.
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Antineoplásicos/administração & dosagem , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Doenças do Sistema Imunitário/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológico , Humanos , Hidrogéis , Doenças do Sistema Imunitário/patologia , Micelas , Terapia de Alvo Molecular/efeitos adversos , NanopartículasRESUMO
Super-activation of cholinesterases (acetylcholinesterase and butyrylcholinesterase) are linked to various neurological problems most precisely Alzheimer's disease (AD), which leads to senile dementia. Therefore, cholinesterases (AChE & BChE) inhibition are considered as a promising strategy for the treatment of Alzheimer's disease. FDA approved drugs for the treatment of AD, belong to a group of cholinesterase inhibitors. However, none of them is able to combat or completely abrogate the disease progression. Herein, we report a series of newly synthesized chalcone derivatives with anti-AD potential. For this purpose, a series of piperidyl-thienyl and 2-pyrazoline derivatives of chalcones were tested for their cholinesterases (AChE & BChE) inhibitory activity. All compounds were found as selective inhibitor of AChE. In piperidyl chalcones derivatives compound 1e having IC50 of 0.16 ± 0.008 µM and 2m in 2-pyrazoline chalcones with IC50 of 0.13 ± 0.006 µM, were found to be the most potent inhibitors of AChE, exhibiting ≈142 and ≈ 173-fold greater inhibitory potential compared to the reference inhibitor i.e., Neostigmine (IC50 ± SEM = 22.2 ± 3.2 µM). Molecular docking studies of most potent inhibitors were carried out to investigate the binding interactions inside the active site. Molecular docking study revealed that potent compounds and co-crystalized ligand had same binding orientation within the active site of target enzyme. Most of these compounds are selective inhibitors of AChE with a potential use against progressive neurodegenerative disorder and age related problems.
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Acetilcolinesterase/metabolismo , Butirilcolinesterase/metabolismo , Chalconas/química , Chalconas/farmacologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/enzimologia , Animais , Electrophorus , Humanos , Simulação de Acoplamento Molecular , Pirazóis/química , Pirazóis/farmacologiaRESUMO
Major histocompatibility complex (MHC) class II molecules are expressed by antigen-presenting cells and stimulate CD4(+) T cells, which initiate humoral immune responses. Over the past decade, interest has developed to therapeutically impact the peptides to be exposed to CD4(+) T cells. Structurally diverse small molecules have been discovered that act on the endogenous peptide exchanger HLA-DM by different mechanisms. Exogenously delivered peptides are highly susceptible to proteolytic cleavage in vivo; however, it is only when successfully incorporated into stable MHC II-peptide complexes that these peptides can induce an immune response. Many of the small molecules so far discovered have highlighted the molecular interactions mediating the formation of MHC II-peptide complexes. As potential drugs, these small molecules open new therapeutic approaches to modulate MHC II antigen presentation pathways and influence the quality and specificity of immune responses. This review briefly introduces how CD4(+) T cells recognize antigen when displayed by MHC class II molecules, as well as MHC class II-peptide-loading pathways, structural basis of peptide binding and stabilization of the peptide-MHC complexes. We discuss the concept of MHC-loading enhancers, how they could modulate immune responses and how these molecules have been identified. Finally, we suggest mechanisms whereby MHC-loading enhancers could act upon MHC class II molecules.
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Antígenos/metabolismo , Linfócitos T CD4-Positivos/imunologia , Antígenos HLA-D/metabolismo , Antígenos de Histocompatibilidade Classe II/metabolismo , Peptídeos/metabolismo , Animais , Apresentação de Antígeno , Humanos , Ativação Linfocitária , Ligação Proteica , Estabilidade Proteica , Transporte ProteicoRESUMO
A novel fluorescent bis-calix[4]arene macrocycle 9 incorporating metal-binding pockets was successfully prepared. The structure of macrocycle 9 and its precursors were characterized via EI-MS, MALDI-TOF-MS, ESI-MS, (1)H NMR, (13)CNMR, 2D NMR, and X-ray crystallography. The macrocycle 9 displayed selective fluorescence quenching after interacting with Cu(2+) in the presence competing metal cations including Mg(2+), Ca(2+), Ba(2+), Ag(+), Zn(2+), Ti(4+),Cd(2+), Hg(2+), Pb(2+), In(3+), La(3+), Cr(3+), Ni(2+), Sb(3+), V(5+), Fe(3+), Co(2+), Sn(2+), Sn(2+), and Tl(+). The Cu(2+) limit of detection was found to be 40 nM much lower than its threshold level (â¼ 20 µM) in drinking water permitted by the U.S Environmental Protection Agency (EPA). Furthermore, drinking water samples from Karachi University (Pakistan) spiked with Cu(2+) were analysed with the sensing system and the results showed an excellent agreement with the fluorescence quenching phenomenon of macrocycle 9 examined in deionized water. Importantly, the chemosensor 9 could be used to detect Cu(2+) in living cells.
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Major histocompatibility complex (MHC)-loading enhancers (MLE) have recently attracted attention because of their ability to enhance the efficacy of peptide immunotherapeutics. As small molecular weight compounds, they influence the loading of peptides in MHC molecules by converting them from a non-receptive to a receptive state. Herein, we report a 14-mer cyclic peptide 1 (CP-1) as a new class of MLE-peptide. This peptide was used to investigate its loading on human leukocyte antigen (HLA)-DR molecules. It was found that CP-1 strongly accelerates peptide-loading on both soluble and cell surface HLA-DR molecules in a dose-dependent manner. The effect was evident for all subsets of HLA-DR tested, including HLA-DRB1*1501, indicating that it acts independently of P1-pocket size, which is the canonical MLE-binding site. Importantly, increased peptide-loading by CP-1 was correlated with improved CD4(+) T cell responses in vitro, while propidium iodide staining indicated low peptide-induced cytotoxicity. Thus, this study revealed a new class of peptide-based enhancers that catalyze peptide-loading by allosteric interactions with MHC molecules. Because of its low cellular cytotoxicity and high MLE activity, it may be useful in stimulating antigen-specific T cell responses for therapeutic purposes.