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31,321 result(s) for "Diagnostic agents"
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Transferrin Receptor Binding BBB-Shuttle Facilitates Brain Delivery of Anti-Aβ-Affibodies
Affibodies targeting amyloid-beta (Aβ) could potentially be used as therapeutic and diagnostic agents in Alzheimer’s disease (AD). Affibodies display suitable characteristics for imaging applications such as high stability and a short biological half-life. The aim of this study was to explore brain delivery and retention of Aβ protofibril-targeted affibodies in wild-type (WT) and AD transgenic mice and to evaluate their potential as imaging agents. Two affibodies, Z5 and Z1, were fused with the blood–brain barrier (BBB) shuttle single-chain variable fragment scFv8D3. In vitro binding of 125 I-labeled affibodies with and without scFv8D3 was evaluated by ELISA and autoradiography. Brain uptake and retention of the affibodies at 2 h and 24 h post injection was studied ex vivo in WT and transgenic (tg-Swe and tg-ArcSwe) mice. At 2 h post injection, [ 125 I]I-Z5 and [ 125 I]I-Z1 displayed brain concentrations of 0.37 ± 0.09% and 0.46 ± 0.08% ID/g brain, respectively. [ 125 I]I-scFv8D3-Z5 and [ 125 I]I-scFv8D3-Z1 showed increased brain concentrations of 0.53 ± 0.16% and 1.20 ± 0.35%ID/g brain. At 24 h post injection, brain retention of [ 125 I]I-Z1 and [ 125 I]I-Z5 was low, while [ 125 I]I-scFv8D3-Z1 and [ 125 I]I-scFv8D3-Z5 showed moderate brain retention, with a tendency towards higher retention of [ 125 I]I-scFv8D3-Z5 in AD transgenic mice. Nuclear track emulsion autoradiography showed greater parenchymal distribution of [ 125 I]I-scFv8D3-Z5 and [ 125 I]I-scFv8D3-Z1 compared with the affibodies without scFv8D3, but could not confirm specific affibody accumulation around Aβ deposits. Affibody-scFv8D3 fusions displayed increased brain and parenchymal delivery compared with the non-fused affibodies. However, fast brain washout and a suboptimal balance between Aβ and mTfR1 affinity resulted in low intrabrain retention around Aβ deposits.
The application and frontier progress of aptamers from targeted technology to clinical diagnosis and treatment
Aptamers, including nucleic acid and peptide aptamers, are small biological molecules whose development has consistently represented the forefront of science and technology. With advances in synthetic biology, bioinformatics, and cell biology, alongside the integration of multidisciplinary approaches, researchers have been able to construct aptamers of diverse structures and functions based on peptide self-assembly, thereby continuously driving innovation in this field. The maturation of various synthesis techniques has further facilitated the gradual translation of aptamers into the market. Supported by the establishment of aptamer information libraries, as well as their inherent excellent affinity and specificity, aptamers can now be synthesized, chemically modified, and applied across a broad spectrum of biomedical scenarios. They function not only as therapeutic agents and diagnostic probes, but also as biosensing tools and delivery vehicles for other drugs. These characteristics underscore the significance of aptamer development within the field of molecular recognition. In this paper, we conduct a comprehensive review of various research directions centered on their targeting properties, including their use as therapeutic and diagnostic agents, biosensors, platforms for new drug development, and drug delivery vehicles.
Management and Prevention of Diabetic Foot Ulcers and Infections
Diabetic foot ulcers and infections are common and incur substantial economic burden for society, patients and families. We performed a comprehensive review, on a number of databases, of health economic evaluations of a variety of different prevention, diagnostic and treatment strategies in the area of diabetic foot ulcers and infections. We included English-language, peer-reviewed, cost-effectiveness, cost-minimization, cost-utility and cost-benefit studies that evaluated a treatment modality against placebo or comparator (i.e. drug, standard of care), regardless of year. Differences were settled through consensus. The search resulted in 1885 potential citations, of which 20 studies were retained for analysis (3 cost minimization, 13 cost effectiveness and 4 cost utility). Quality scores of studies ranged from 70.8% (fair) to 87.5% (good); mean = 78.4% ± 5.33%. In diagnosing osteomyelitis in patients with diabetic foot infection, magnetic resonance imaging (MRI) showed 82% sensitivity and 80% specificity. MRI cost less than 3-phase bone scanning + Indium (In)-111/Gallium (Ga)-67; however, when compared with prolonged antibacterials, MRI cost $US120 (year 1993 value) more without additional quality-adjusted life-expectancy. Prevention strategies improved life expectancy and QALYs and reduced foot ulcer rates and amputations. Ampicillin/sulbactam and imipenem/cilastatin were both 80% successful in treating diabetic foot infections but the latter cost $US2924 more (year 1994 value). Linezolid cure rates were higher (97.7%) than vancomycin (86.0%) and cost $US873 less (year 2004 value). Ertapenem costs were significantly lower than piperacillin/tazobactam ($US356 vs $US503, respectively; year 2005 values). Becaplermin plus good wound care may be cost effective in specific populations. Bioengineered living-skin equivalents increased ulcer-free months and ulcers healed, but costs varied between countries. Promogran® produced more ulcer-free months than wound care alone (3.75 vs 3.41 months, respectively). Treatment with cadexomer iodine resulted in higher rates of healed ulcer (29% vs 11%) and lower weekly treatment costs (Swedish krona [SEK]903 vs SEK1421; year 1993 values) than standard care. Filgrastim decreased hospital stays, time to resolution and costs (36% lower) compared with usual care. Adjunctive hyperbaric oxygen produced an incremental cost per QALY at year 1 of $US27 310 and $US2255 at year 12 (year 2001 values). Overall, preventive strategies were shown to be cost effective and potentially cost saving. Various antibacterial regimens are cost effective but empiric choices should be based on local resistance patterns. MRI was cost effective compared with three-phase bone scanning + In-111/Ga-67 but not against prolonged antibacterial therapy. Other innovations (becaplermin, bioengineered living-skin equivalents, filgrastim, cadexomer iodine ointment, hyperbaric oxygen, Promogran®) may be cost effective in this population but more studies are needed to confirm these findings.
Direct arene C–H fluorination with 18F⁻ via organic photoredox catalysis
Positron emission tomography (PET) plays key roles in drug discovery and development, as well as medical imaging. However, there is a dearth of efficient and simple radiolabeling methods for aromatic C–H bonds, which limits advancements in PET radiotracer development. Here, we disclose a mild method for the fluorine-18 (18F)–fluorination of aromatic C–H bonds by an [18F]F⁻ salt via organic photoredox catalysis under blue light illumination. This strategy was applied to the synthesis of a wide range of 18F-labeled arenes and heteroaromatics, including pharmaceutical compounds. These products can serve as diagnostic agents or provide key information about the in vivo fate of the labeled substrates, as showcased in preliminary tracer studies in mice.
Radiopharmaceuticals and their applications in medicine
Radiopharmaceuticals involve the local delivery of radionuclides to targeted lesions for the diagnosis and treatment of multiple diseases. Radiopharmaceutical therapy, which directly causes systematic and irreparable damage to targeted cells, has attracted increasing attention in the treatment of refractory diseases that are not sensitive to current therapies. As the Food and Drug Administration (FDA) approvals of [ 177 Lu]Lu-DOTA-TATE, [ 177 Lu]Lu-PSMA-617 and their complementary diagnostic agents, namely, [ 68 Ga]Ga-DOTA-TATE and [ 68 Ga]Ga-PSMA-11, targeted radiopharmaceutical-based theranostics (radiotheranostics) are being increasingly implemented in clinical practice in oncology, which lead to a new era of radiopharmaceuticals. The new generation of radiopharmaceuticals utilizes a targeting vector to achieve the accurate delivery of radionuclides to lesions and avoid off-target deposition, making it possible to improve the efficiency and biosafety of tumour diagnosis and therapy. Numerous studies have focused on developing novel radiopharmaceuticals targeting a broader range of disease targets, demonstrating remarkable in vivo performance. These include high tumor uptake, prolonged retention time, and favorable pharmacokinetic properties that align with clinical standards. While radiotheranostics have been widely applied in tumor diagnosis and therapy, their applications are now expanding to neurodegenerative diseases, cardiovascular diseases, and inflammation. Furthermore, radiotheranostic-empowered precision medicine is revolutionizing the cancer treatment paradigm. Diagnostic radiopharmaceuticals play a pivotal role in patient stratification and treatment planning, leading to improved therapeutic outcomes in targeted radionuclide therapy. This review offers a comprehensive overview of the evolution of radiopharmaceuticals, including both FDA-approved and clinically investigated agents, and explores the mechanisms of cell death induced by radiopharmaceuticals. It emphasizes the significance and future prospects of theranostic-based radiopharmaceuticals in advancing precision medicine.
Nanoparticles as Novel Emerging Therapeutic Antibacterial Agents in the Antibiotics Resistant Era
Microorganisms are highly resistant to the antibiotics that are commonly used and thus are becoming serious public health problem. There is an urgent need for new approaches to monitor microbial behavior, and hence, nanomaterial can be a very promising solution. Nanotechnology has led to generation of novel antimicrobial agents such as gold, silver, zinc, copper, poly-£-lysine, iron, and chitosan which have shown remarkable potential, demonstrating their applicability as proficient antibiotic agents against various pathogenic bacterial species. The antimicrobial nanoproduct physically kills the organism’s cell membranes that prevent the production of drug-resistant microorganisms. These nanosized particles can also be used as diagnostic agents, targeted drug delivery vehicle, noninvasive imaging technologies, and in vivo visual monitoring of tumors angiogenesis. These nanomaterials provide a promising platform for diagnostics, prognostic, drug delivery, and treatment of diseases by means of nanoengineered products/devices. This owes to their small size, prolonged antimicrobial efficacy with insignificant toxicity creating less environmental hazard or toxicity. Scientists address several problems such as health, bioethical problems, toxicity risks, physiological, and pharmaceutical concerns related with the usage of NPs as antimicrobial agents as current research lack adequate data and information on the safe use of certain tools and materials.
Aggregation induced emission luminogen bacteria hybrid bionic robot for multimodal phototheranostics and immunotherapy
Multimodal phototheranostics utilizing single molecules offer a “one-and-done” approach, presenting a convenient and effective strategy for cancer therapy. However, therapies based on conventional photosensitizers often suffer from limitations such as a single photosensitizing mechanism, restricted tumor penetration and retention, and the requirement for multiple irradiations, which significantly constrain their application. In this report, we present an aggregation-induced emission luminogen (AIEgen) bacteria hybrid bionic robot to address above issues. This bionic robot is composed of multifunctional AIEgen (INX-2) and Escherichia coli Nissle 1917 (EcN), i.e., EcN@INX-2. The EcN@INX-2 bionic robot exhibits near-infrared II (NIR-II) fluorescence emission and demonstrates efficient photodynamic and photothermal effects, as well as tumor-targeting capabilities. These features are facilitated by the complementary roles of INX-2 and EcN. The robot successfully enables in vivo multimodal imaging and therapy of colon cancer models in female mice through various mechanisms, including the activation of anti-tumor immunity, as well as photodynamic and photothermal therapy. Our study paves an avenue for designing multifunctional diagnostic agents for targeted colon cancer therapy through image-guided combinational immunotherapy. The utility of photosensitizers for cancer therapies is often hindered by a single photosensitizing mechanism, the need of multiple irradiations, and limited tumor penetration and retention. Here, the authors address these issues by developing an aggregation-induced emission luminogen bacteria hybrid bionic robot that enables multimodal imaging and therapy and activates anti-tumor immunity.
Efficient radioactive gas detection by scintillating porous metal–organic frameworks
Natural and anthropogenic gas radionuclides such as radon, xenon, hydrogen and krypton isotopes must be monitored to be managed as pathogenic agents, radioactive diagnostic agents or nuclear activity indicators. State-of-the-art detectors based on liquid scintillators suffer from laborious preparation and limited solubility for gases, which affect the accuracy of the measurements. The actual challenge is to find solid scintillating materials simultaneously capable of concentrating radioactive gases and efficiently producing visible light revealed with high sensitivity. The high porosity, combined with the use of scintillating building blocks in metal–organic frameworks (MOFs), offers the possibility to satisfy these requisites. We demonstrate the capability of a hafnium-based MOF incorporating dicarboxy-9,10-diphenylanthracene as a scintillating conjugated ligand to detect gas radionuclides. Metal–organic frameworks show fast scintillation, a fluorescence yield of ∼40%, and accessible porosity suitable for hosting noble gas atoms and ions. Adsorption and detection of 85Kr, 222Rn and 3H radionuclides are explored through a newly developed device that is based on a time coincidence technique. Metal–organic framework crystalline powder demonstrated an improved sensitivity, showing a linear response down to a radioactivity value below 1 kBq m−3 for 85Kr, which outperforms commercial devices. These results support the possible use of scintillating porous MOFs to fabricate sensitive detectors of natural and anthropogenic radionuclides.Detection of gas radionuclides is limited in sensitivity with present methods, but may be useful in energy, security, medical and other sectors. In this work, gas-concentrating porous scintillating metal–organic frameworks are demonstrated for gas radionuclide detection.
Treatment of Non-Infectious Corneal Injury: Review of Diagnostic Agents, Therapeutic Medications, and Future Targets
Corneal injuries can occur secondary to traumatic, chemical, inflammatory, metabolic, autoimmune, and iatrogenic causes. Ocular infection may frequently occur concurrent to corneal injury; however, antimicrobial agents are excluded from this present review. While practitioners may primarily rely on clinical examination techniques to assess these injuries, several pharmacological agents, such as fluorescein, lissamine green, and rose bengal, can be used to formulate a diagnosis and develop effective treatment strategies. Practitioners may choose from several analgesic medications to help with patient comfort without risking further injury or delaying ocular healing. Atropine, cyclopentolate, scopolamine, and homatropine are among the most frequently used medications for this purpose. Additional topical analgesic agents may be used judiciously to augment patient comfort to facilitate diagnosis. Steroidal anti-inflammatory agents are frequently used as part of the therapeutic regimen. A variety of commonly used agents, including prednisolone acetate, loteprednol, difluprednate, dexamethasone, fluorometholone, and methylprednisolone are discussed. While these medications are effective for controlling ocular inflammation, side effects, such as elevated intraocular pressure and cataract formation, must be monitored by clinicians. Non-steroidal medications, such as ketorolac, bromfenac, nepafenac, and diclofenac, are additionally used for their efficacy in controlling ocular inflammation without incurring side effects seen with steroids. However, these agents have their own respective side effects, warranting close monitoring by clinicians. Additionally, ophthalmologists routinely employ several agents in an off-label manner for supplementary control of inflammation and treatment of corneal injuries. Patients with corneal injuries not infrequently have significant ocular surface disease, either as a concurrent pathology or as an exacerbation of previously existing disease. Several agents used in the management of ocular surface disease have also been found to be useful as part of the therapeutic armamentarium for treatment of corneal injuries. For example, several antibiotics, such as doxycycline and macrolides, have been used for their anti-inflammatory effects on specific cytokines that are upregulated during acute injuries. There has been a recent wave of interest in amniotic membrane therapies (AMTs), including topical, cryopreserved and dehydrated variants. AMT is particularly effective in ocular injuries with violation of corneal surface integrity due to its ability to promote re-epithelialization of the corneal epithelium. Blood-based therapies, including autologous serum tears, plasma-enriched growth factor eyedrops and autologous blood drops, have additionally been explored in small case series for effectiveness in challenging and recalcitrant cases. Protection of the ocular surface is also a vital component in the treatment of corneal injuries. Temporary protective methods, such as bandage contact lenses and mechanical closure of the eyelids (tarsorrhaphy) can be particularly helpful in selective cases. Glue therapies, including biologic and non-biologic variants, can also be used in cases of severe injury and risk of corneal perforation. Finally, there are a variety of recently introduced and in-development agents that may be used as adjuvant therapies in challenging patient populations. Neurotrophic corneal disease may occur as a result of severe or chronic injury. In such cases, recombinant human nerve growth factor (cenegermin), topical insulin, and several other novel agents may be an alternate and effective option for clinicians to consider.
Cell-Penetrating Peptides (CPPs) as Therapeutic and Diagnostic Agents for Cancer
Cell-Penetrating Peptides (CPPs) are short peptides consisting of <30 amino acids. Their ability to translocate through the cell membrane while carrying large cargo biomolecules has been the topic of pre-clinical and clinical trials. The ability to deliver cargo complexes through membranes yields potential for therapeutics and diagnostics for diseases such as cancer. Upon cellular entry, some CPPs have the ability to target specific organelles. CPP-based intracellular targeting strategies hold tremendous potential as they can improve efficacy and reduce toxicities and side effects. Further, recent clinical trials show a significant potential for future CPP-based cancer treatment. In this review, we summarize recent advances in CPPs based on systematic searches in PubMed, Embase, Web of Science, and Scopus databases until 30 September 2022. We highlight targeted delivery and explore the potential uses for CPPs as diagnostics, drug delivery, and intrinsic anti-cancer agents.