Meeting current decarbonization targets requires a shift to a hydrogen energy nexus, yet, water is a valuable resource for hydrogen production, shifting the perspective to the use of HS instead within the context of circular economy. A comprehensive understanding of the environmental impacts, using a cradle-to-gate life cycle assessment (LCA), was developed focusing on the operation of hydrogen sulfide-methane reforming (HSMR) for H production benchmarked to conventional technologies, steam methane reforming (SMR) and SMR + carbon capture (CC), as feedstock to produce sustainable fuels (i.e.
View Article and Find Full Text PDFLocal re-occurrence of cancer in patients with solid tumors is currently the most common reason for failure of treatment strategies. This fact indicates that prevailing approaches for tumor resection can cure only 50% of patients. A major cause of failure in tumor resection is off-target drug cytotoxicity and lack of sensitivity in tumor detection methods.
View Article and Find Full Text PDFProstate-specific membrane antigen (PSMA) is a viable diagnostic biomarker for the detection and treatment of prostate cancer. Although numerous imaging techniques and fluorescent probes have been developed, targeted imaging and intraoperative surgery continue to remain as a proof-of-concept with a severe lack of tools having high affinity and penetrative capacity. three-dimensional cell culture has gained immense interest in cancer research and drug discovery programs as it yields important physiological information and serves an excellent model for bioimaging and penetration analysis studies.
View Article and Find Full Text PDFCOVID-19 has emerged as global pandemic with largest damage to the public health, economy and human psyche.The genome sequence data obtained during the ongoing pandemic are valuable to understand the virus evolutionary patterns and spread across the globe. Increased availability of genome information of circulating SARS-CoV-2 strains in India will enable the scientific community to understand the emergence of new variants and their impact on human health.
View Article and Find Full Text PDFIn recent years, 3D culture of tumor spheroids has managed to revolutionize cancer research and drug discovery. 2D monolayer cells grown in cell culture flasks undergo radical changes in cell behavior, structure, and function owing to varying environmental cues and are unable to provide predictive data for preclinical evaluation. 3D tumor spheroids can better recapitulate tumor architecture, cell-cell and cell-matrix connectivity, and the tissue complexity of tumors grown in animal models.
View Article and Find Full Text PDF1,5Disubstituted indole-2-carboxaldehyde derivatives - and glycine alkyl esters - are shown to undergo a novel cascade imination-heterocylization in the presence of the organic base DIPEA to provide 1-indolyl-3,5,8-substituted γ-carbolines - in good yields. The γ-carbolines are fluorescent and exhibit anticancer activities against cervical, lung, breast, skin, and kidney cancer cells.
View Article and Find Full Text PDFEarly diagnosis of prostate cancer (PCa) is crucial for staging, treatment and management of patients. Prostate specific membrane antigen (PSMA), highly over-expressed on PCa cells, is an excellent target for selective imaging of PCa. In recent years, various scaffolds have been explored as potential carriers to target diagnostic and therapeutic agents to PSMA tumour cells.
View Article and Find Full Text PDFThe current challenge in fluorescence guided surgery (FGS) for prostate cancer (PCa) is in the design of imaging probes with high selectivity, clear visualization of tumour margins, and minimal toxicity. This report aims to design and develop a novel NIR-nanoprobe, and evaluate its potential in the penetration of PCa tumour tissues. The PSMA receptor-targeted quantum dot (PSMA-QD655) is a NIR, deep-tissue imaging agent, which has the potential for intraoperative navigation during surgery and improved detection specificity for PCa.
View Article and Find Full Text PDFBackground: Prostate-specific membrane antigen (PSMA), overexpressed on prostate cancer (PCa), is a well-characterized cell surface protein to selectively diagnose PCa. PSMA's unique characteristics and its 1000-fold higher expression in PCa compared with other tissues renders it as a suitable biomarker for detection of PCa in its early stage. In this report, we critically analyze and recommend the requirements needed for the development of variety of PSMA-targeted molecular imaging agents based on antibodies, small molecule ligands, peptides, and aptamers.
View Article and Find Full Text PDFA serendipitous discovery of a novel one-pot synthesis of 4,6-disubstituted 5-azaindoles is reported herein. In the presence of Hunig's base, various N-substituted pyrrole-2-carboxaldehydes have been efficiently transformed into their corresponding 4,6-disubstituted 5-azaindoles through an imine mediated cascade condensation-heteroannulation. The synthetic value of the methodology is established by preparing a novel chemical analogue of a cannabinoid receptor type 2 (CB2) agonist.
View Article and Find Full Text PDFIn this article, we have explored the chemical interactions of tyrosine-based asymmetric urea ligands in the binding pockets of prostate specific membrane antigen (PSMA) through in silico studies. The S1 pocket of the PSMA protein offers better scope for modifications in the urea ligands to improve the binding affinity. Accordingly, tyrosine-based (S)-2-(3-((S)-1-carboxy-2-(4-(carboxymethoxy)phenyl)ethyl)ureido)pentanedioic acid (CYUE, 3) ligand was designed, synthesized and predicted to possess inhibition constant (Ki) of 55 nM with PSMA protein.
View Article and Find Full Text PDFIn this article, we have successfully designed and demonstrated a novel continuous process for assembling targeting ligands, peptidic spacers, fluorescent tags and a chelating core for the attachment of cytotoxic molecules, radiotracers, nanomaterials in a standard Fmoc solid-phase peptide synthesis in high yield and purity. The differentially protected Fmoc-Lys-(Tfa)-OH plays a vital role in attaching fluorescent tags while growing the peptide chain in an uninterrupted manner. The methodology is versatile for solid-phase resins that are sensitive to mild and strong acidic conditions when acid-sensitive side chain amino protecting groups such as Trt (chlorotrityl), Mtt (4-methyltrityl), Mmt (4-methoxytrityl) are employed to synthesise the ligand targeted fluorescent tagged bioconjugates.
View Article and Find Full Text PDFCurr Protoc Chem Biol
December 2018
The development of small molecule ligand-targeted therapeutics is currently of paramount importance for treatment of cancer due to their potential to reduce system toxicity and increase potency of a delivered chemotherapeutic drug. The main aim of a targeted drug-delivery technique is to release the drug cargo selectively into tumor tissues, avoiding off-site toxicity to healthy tissues and organs during chemotherapy. In this strategy, a chemotherapeutic drug is conjugated to a homing ligand, which has high affinity for proteins over-expressed on cancer cells, via a peptide linker and a self-immolative segment that facilitates intracellular release of drug cargo.
View Article and Find Full Text PDFCurr Protoc Chem Biol
December 2018
Present treatment strategies focus on minimizing unwanted toxicity to healthy cells during chemotherapeutic treatment. This is achieved by developing strategies to selectively deliver drugs to malignant cells over-expressing specific protein biomarkers. The drugs are attached via a self-immolative linker to a small molecule homing ligand having affinity for protein biomarkers over-expressed during disease states.
View Article and Find Full Text PDFThe Gram-negative bacterium Vibrio cholerae is a unique pathogen with an ability to colonize human intestine as well as outside environments. The biofilm, an organized polymeric structure produced by this bacterium known to be a significant factor for the survival and persistence in hostile conditions. However, the direct role of biofilm formation by this bacterium in environmental persistence, in vivo colonization, and pathogenesis remains unexplored.
View Article and Find Full Text PDFBackground: Vibrio cholerae, the aetiological agent of the deadly diarrhoeal disease cholera, is known to form biofilm. The antibiotic susceptibility status of biofilm of V. cholerae O139, an important epidemic strain in India and other countries, has not previously been studied in detail.
View Article and Find Full Text PDFAlthough peptides, antibodies/antibody fragments, siRNAs, antisense DNAs, enzymes, and aptamers are all under development as possible therapeutic agents, the breadth of their applications has been severely compromised by their inability to reach intracellular targets. Thus, while macromolecules can often enter cells by receptor-mediated endocytosis, their missions frequently fail due to an inability to escape their entrapping endosomes. In this paper, we describe a general method for promoting release of any biologic material from any entrapping endosome.
View Article and Find Full Text PDFActivated macrophages play a key role in the development and maintenance of inflammatory diseases such as atherosclerosis, lupus, psoriasis, rheumatoid arthritis, ulcerative colitis, and many others. These activated macrophages, but not resting or quiescent macrophages highly up-regulate folate receptor beta (FR-β). This differential expression of FR-β provides a mechanism to selectively deliver imaging and therapeutic agents utilizing folate as a targeting molecule.
View Article and Find Full Text PDFAim: We endeavored to create a folate-targeted liposome (Fol-liposome) that could selectively target areas of inflammation.
Materials & Methods: Fol-liposomes were prepared with encapsulated DiD fluorophore or betamethasone (BM) to image and treat an adjuvant-induced rat model of rheumatoid arthritis.
Results: Fol-liposomes selectively accumulated in arthritic rat paws to a greater extent than nontargeted liposomes.
Almost all cells are easily killed by exposure to potent oxidants. Indeed, major pathogen defense mechanisms in both animal and plant kingdoms involve production of an oxidative burst, where host defense cells show an invading pathogen with reactive oxygen species (ROS). Although cancer cells can be similarly killed by ROS, development of oxidant-producing chemotherapies has been limited by their inherent nonspecificity and potential toxicity to healthy cells.
View Article and Find Full Text PDFMany cancer cells over-express folate receptors, and this provides an opportunity for both folate-targeted fluorescence imaging and the development of targeted anti-cancer drugs. We present an optical imaging modality that allows for the monitoring and evaluation of drug delivery and release through disulfide bond reduction inside a tumor in vivo for the first time. A near-infrared folate-targeting fluorophore pair was synthesized and used to image a xenograft tumor grown from KB cells in a live mouse.
View Article and Find Full Text PDFAim: The vast majority of nanomedicine research is focused on the use of nanoparticles for the diagnosis and treatment of cancer. However, the dense extracellular matrix of solid tumors restricts nanoparticle penetration, raising the question of whether the best applications of nanomedicines lie in oncology.
Materials & Methods: In this study, the uptake of folate-conjugated liposomes was compared between folate receptor-expressing tumors and folate receptor+ inflammatory lesions within the same mouse.
West Indian Med J
March 2014
Neisseria meningitidis infection should be considered in patients presenting with septic arthritis especially if Gram-negative diplococcic are observed on Gram-stain.
View Article and Find Full Text PDFJ Opt Soc Am A Opt Image Sci Vis
June 2013
Despite the broad impact in medicine that optics can bring, thus far practical approaches are limited to weak scatter or near-surface monitoring. We show a method that utilizes a laser topography scan and a diffusion equation model to describe the photon transport, together with a multiresolution unstructured grid solution to the nonlinear optimization measurement functional, that overcomes these limitations. We conclude that it is possible to achieve whole body optical imaging with a resolution suitable for finding cancer nodules within an organ during surgery, with the aid of a targeted imaging agent.
View Article and Find Full Text PDFComplete surgical resection of malignant disease is the only reliable method to cure cancer. Unfortunately, quantitative tumor resection is often limited by a surgeon's ability to locate all malignant disease and distinguish it from healthy tissue. Fluorescence-guided surgery has emerged as a tool to aid surgeons in the identification and removal of malignant lesions.
View Article and Find Full Text PDF