Blood transfusion is a common therapeutic intervention in hospitalized patients. There are numerous indications for transfusion, including anemia and coagulopathy with deficiency of single or multiple coagulation components such as platelets or coagulation factors. Nevertheless, the practice of transfusion in critically ill patients has been controversial mainly due to a lack of evidence and the need to consider the appropriate clinical context for transfusion.
View Article and Find Full Text PDFRegulatory T cells (Tregs) play a crucial role in mediating immunosuppression in the tumor microenvironment. Furthermore, Tregs contribute to the lack of efficacy and hyperprogressive disease upon Programmed cell death protein 1 (PD-1) blockade immunotherapy. Thus, Tregs are considered a promising therapeutic target, especially when combined with PD-1 blockade.
View Article and Find Full Text PDFHeptamethine cyanine dyes enable deep tissue fluorescence imaging in the near infrared (NIR) window. Small molecule conjugates of the benchmark dye ZW800-1 have been tested in humans. However, long-term imaging protocols using ZW800-1 conjugates are limited by their instability, primarily because the chemically labile C4'-O-aryl linker is susceptible to cleavage by biological nucleophiles.
View Article and Find Full Text PDFHeptamethine (Cy7) dyes with meso-Cl substituents injected intravenously (iv) into mice accumulate in tumors and persist there over several days. We believe this occurs via meso-Cl displacement by the only free cysteine residues of albumin; therefore, conjugating tumor-seeking dyes with fragments can increase selective therapeutic delivery to tumors and drug residence. This strategy has elevated significance recently because the first tumor-seeking dye-drug conjugate has moved into clinical trials.
View Article and Find Full Text PDFBiosens Bioelectron
December 2022
Activatable fluorophores with emission beyond 1000 nm have the potential to enable high contrast imaging in complex in vivo settings. However, there are few scaffolds that can be applied to this challenge. Here we detail the synthesis and evaluation of benzo[c,d]indole-substituted norcyanines that enable pH responsive fluorescence imaging in the long wavelength (>1150 nm) range.
View Article and Find Full Text PDFPhotoconvertible tracking strategies assess the dynamic migration of cell populations. Here we develop hototruncation-ssisted ell racking (PACT) and apply it to evaluate the migration of immune cells into tumor-draining lymphatics. This method is enabled by a recently discovered cyanine photoconversion reaction that leads to the two-carbon truncation and consequent blue-shift of these commonly used probes.
View Article and Find Full Text PDFMolecular imaging is an emerging non-invasive method to qualitatively and quantitively visualize and characterize biological processes. Among the imaging modalities, PET/SPECT and near-infrared (NIR) imaging provide synergistic properties that result in deep tissue penetration and up to cell-level resolution. Dual-modal PET/SPECT-NIR agents are commonly combined with a targeting ligand (e.
View Article and Find Full Text PDFConjugates of small molecules and antibodies are broadly employed diagnostic and therapeutic agents. Appending a small molecule to an antibody often significantly impacts the properties of the resulting conjugate. Here, we detail a systematic study investigating the effect of various functional groups on the properties of antibody-fluorophore conjugates.
View Article and Find Full Text PDFMHI-I () and QuatCy-I () were compared in terms of properties important for early-stage photodynamic therapy preclinical candidates. Thus, experiments were performed to monitor dark cytotoxicities, light/dark cytotoxicity ratios, selectivity of localization in tumors over other organs, and clearance from the plasma.
View Article and Find Full Text PDFNear-infrared (NIR) emitting fluorophores are powerful tools for optical imaging. However, there are only a handful of broadly employed NIR-emitting scaffolds, and the synthetic methods to prepare these molecules are often problematic. Here, we describe a novel, three-step synthesis of chromene-containing hemicyanine probes exhibiting large Stokes shifts and NIR emissions.
View Article and Find Full Text PDFFluorescent dyes attached to kinase inhibitors (KIs) can be used to probe kinases in vitro, in cells, and in vivo. Ideal characteristics of the dyes vary with their intended applications. Fluorophores used in vitro may inform on kinase active site environments, hence the dyes used should be small and have minimal impact on modes of binding.
View Article and Find Full Text PDFActive targeting uses molecular fragments that bind receptors overexpressed on cell surfaces to deliver cargoes, and this selective delivery to diseased over healthy tissue is valuable in diagnostic imaging and therapy. For instance, targeted near-infrared (near-IR) dyes can mark tissue to be excised in surgery, and radiologists can use active targeting to concentrate agents for positron emission tomography (PET) in tumor tissue to monitor tumor metastases. Selective delivery to diseased tissue is also valuable in some treatments wherein therapeutic indexes (toxic/effective doses) are key determinants of efficacy.
View Article and Find Full Text PDFThe combination of targeting ligands and fluorescent dyes is a powerful strategy to observe cell types and tissues of interest. Conjugates of peptides, proteins, and, in particular, monoclonal antibodies (mAbs) exhibit excellent tumor targeting in various contexts. This approach has been translated to a clinical setting to provide real-time molecular insights during the surgical resection of solid tumors.
View Article and Find Full Text PDFIntroduction The constellation of the physical and psychological symptoms that appear several days before menstrual period is regarded as the premenstrual syndrome (PMS). The current study evaluated the symptoms associated with PMS and their impact on the day-to-day activities of women. Methodology An observational cross-sectional study was conducted at a squatter settlement in Karachi, Pakistan, from January 2019 to February 2020.
View Article and Find Full Text PDFIntroduction: Self-care activities are behaviors adopted in order to enhance one's health. Self-care behaviors and activities are studied in their role to enhance glycemic control, reduce diabetes-related complications, and contribute to enhancing overall quality of life in people with diabetes. The aim of this observational study was to evaluate the impact of diabetes self-care activities and behaviors on glycemic control in people with diabetes.
View Article and Find Full Text PDFSome heptamethine cyanine dyes accumulate in solid tumors and persist there for several days. The reasons why they accumulate and persist in tumors were incompletely defined, but explanations based on uptake into cancer cells via organic anion transporting polypeptides (OATPs) have been widely discussed. All cyanine-based "tumor-seeking dyes" have a chloride centrally placed on the heptamethine bridge (a "-chloride").
View Article and Find Full Text PDFIntroduction: Chronic headaches account for a significant proportion of people leading a poor quality of life. Chronic cluster headaches can be defined as episodes of headache usually around the eye in the pattern of a cluster lasting 15-180 minutes each followed by multiple similar episodes occurring at a frequency of 1-8 times per day.
Method: This cross-sectional study was conducted in Jinnah Postgraduate Medical Center, Karachi.
Introduction Thalassemia is a common genetic disorder worldwide, also occurring frequently in Karachi, Pakistan. Beta (β)-thalassemia major patients need repeated transfusions which cause iron overload. Patients are treated with chelating agents to reduce the high serum ferritin level and to decrease morbidity and mortality due to increased iron levels.
View Article and Find Full Text PDFA small subset of heptamethine dyes (cyanine-7 or Cy7) share an intriguing characteristic: preferential tumor accumulation and retention. These dyes absorb in the near-infrared (NIR) region (above 750 nm) and perform active targeting to deliver therapeutic and toxic cargoes to various tumor models in vivo. In this work, four heptamethines were synthesized, which have a gemcitabine fragment attached to the -position of the Cy7 core.
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