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Indian Journal of Ophthalmology Jul 2024
Topics: Humans; Ethambutol; Antitubercular Agents; Male; Female; Adult; Electroretinography; Middle Aged; Visual Acuity; Tomography, Optical Coherence
PubMed: 38905470
DOI: 10.4103/IJO.IJO_494_23 -
International Journal of Medical... 2024Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease, characterized by dysregulated immune response. HDAC3 is reported to be an epigenetic brake...
Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disease, characterized by dysregulated immune response. HDAC3 is reported to be an epigenetic brake in inflammation, playing critical roles in macrophages. However, its role in IBD is unclear. In our study, we found HDAC3 was upregulated in CX3CR1-positive cells in the mucosa from IBD mice. Conditional knockout (cKO) of Hdac3 in CX3CR1 positive cells attenuated the disease severity of Dextran Sulfate Sodium (DSS)-induced colitis. In addition, inhibition of HDAC3 with RGFP966 could also alleviate the DSS-induced tissue injury and inflammation in IBD. The RNA sequencing results revealed that Hdac3 cKO restrained DSS-induced upregulation of genes in the pathways of cytokine-cytokine receptor interaction, complement and coagulation cascades, chemokine signaling, and extracellular matrix receptor interaction. We also identified that Guanylate-Binding Protein 5 (GBP5) was transcriptionally regulated by HDAC3 in monocytes by RNA sequencing. Inhibition of HDAC3 resulted in decreased transcriptional activity of interferon-gamma-induced expression of GBP5 in CX3CR1-positive cells, such as macrophages and microglia. Overexpression of HDAC3 upregulated the transcriptional activity of GBP5 reporter. Lastly, conditional knockout of Hdac3 in macrophages (Hdac3 mKO) attenuated the disease severity of DSS-induced colitis. In conclusion, inhibition of HDAC3 in macrophages could ameliorate the disease severity and inflammatory response in colitis by regulating GBP5-NLRP3 axis, identifying a new therapeutic avenue for the treatment of colitis.
Topics: Animals; Dextran Sulfate; Histone Deacetylases; Mice; Macrophages; NLR Family, Pyrin Domain-Containing 3 Protein; Mice, Knockout; Colitis; Humans; Signal Transduction; Inflammatory Bowel Diseases; GTP-Binding Proteins; Disease Models, Animal; CX3C Chemokine Receptor 1; Mice, Inbred C57BL; Histone Deacetylase Inhibitors; Intestinal Mucosa; Acrylamides; Phenylenediamines
PubMed: 38903915
DOI: 10.7150/ijms.94592 -
ACS Applied Polymer Materials Jun 2024Efficient treatment of wastewater contaminated with carcinogenic Cr(VI) has been a long-term challenge for both academic and industrial research efforts. Removal of...
Efficient treatment of wastewater contaminated with carcinogenic Cr(VI) has been a long-term challenge for both academic and industrial research efforts. Removal of Cr(VI) species by ion exchange is a relatively simple and efficient method, and its combination with highly tailorable nanomaterials is promising for the treatment of such wastewater. Here, we report a type of cationic porous organic polymer (POP), namely, PTPA-PIP, which can be prepared simply by converting the corresponding aromatic polyamine PTPA to its protonated form, thereby significantly increasing its hydrophilicity and ability to disperse homogeneously in water, crucial for application in water treatment. In addition to detailed characterization of the physicochemical properties of PTPA-PIP (including using Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), Brunauer-Emmett-Teller (BET), and solid-state NMR techniques), adsorption experiments demonstrate that PTPA-PIP removes low-concentration dichromate anions with very high performance, including excellent exchange capacity (maximum capacity of 230 mg CrO /g PTPA-PIP), ultrafast removal (initial adsorption rate of 83 mg g min), excellent selectivity (∼10% loss of adsorption capacity in the presence of 40-fold concentration of competing anions), as well as superior reusability (reusable for at least 5 cycles without compromised performance). These results demonstrate that PTPA-PIP is an outstanding candidate for application in industrial settings for the effective removal of harmful Cr(VI) pollutants in wastewater.
PubMed: 38903399
DOI: 10.1021/acsapm.4c00658 -
Asian Journal of Pharmaceutical Sciences Jun 2024Polyamine metabolism dysregulation is a hallmark of many cancers, offering a promising avenue for early tumor theranostics. This study presents the development of a...
Polyamine metabolism dysregulation is a hallmark of many cancers, offering a promising avenue for early tumor theranostics. This study presents the development of a nuclear probe derived from spermidine (SPM) for dual-purpose tumor PET imaging and internal radiation therapy. The probe, radiolabeled with either [Ga]Ga for diagnostic applications or [Lu]Lu for therapeutic use, was synthesized with exceptional purity, stability, and specific activity. Extensive testing involving 12 different tumor cell lines revealed remarkable specificity towards B16 melanoma cells, showcasing outstanding tumor localization and target-to-non-target ratio. Mechanistic investigations employing polyamines, non-labeled precursor, and polyamine transport system (PTS) inhibitor, consistently affirmed the probe's targetability through recognition of the PTS. Notably, while previous reports indicated PTS upregulation in various tumor types for targeted therapy, this study observed no positive signals, highlighting a concentration-dependent discrepancy between targeting for therapy and diagnosis. Furthermore, when labeled with [Lu], the probe demonstrated its therapeutic potential by effectively controlling tumor growth and extending mouse survival. Investigations into biodistribution, excretion, and biosafety in healthy humans laid a robust foundation for clinical translation. This study introduces a versatile SPM-based nuclear probe with applications in precise tumor theranostics, offering promising prospects for clinical implementation.
PubMed: 38903130
DOI: 10.1016/j.ajps.2024.100924 -
Blood Jun 2024
Azab AK, Runnels JM, Pitsillides C, et al. CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy. Blood. 2009;113(18):4341-4351.
Topics: Cyclams; Humans; Multiple Myeloma; Receptors, CXCR4; Benzylamines; Heterocyclic Compounds; Bone Marrow; Tumor Microenvironment
PubMed: 38900482
DOI: 10.1182/blood.2024025275 -
Mikrochimica Acta Jun 2024Ratiometric fluorescence and colorimetric strategies for detecting activity of butyrylcholinesterase (BChE) in human serum were developed by using g-CN nanosheets,...
Ratiometric fluorescence and colorimetric strategies for assessing activity of butyrylcholinesterase in human serum using g-CN nanosheets, silver ion and o-phenylenediamine.
Ratiometric fluorescence and colorimetric strategies for detecting activity of butyrylcholinesterase (BChE) in human serum were developed by using g-CN nanosheets, silver ion (Ag) and o-phenylenediamine (OPD) as chromogenic agents. The oxidation-reduction reaction of OPD and Ag generates 2,3-diaminophenazine (oxOPD). Under exciation at 370 nm, g-CN nanosheets and oxOPD emit fluorescence at 440 nm (F) and 560 nm (F), respectively. Additionally, oxOPD exhibits quenching ability towards g-CN nanosheets via photoinduced electron transfer (PET) process. Thiocholine (TCh), as a product of BChE-catalyzed hydrolysis reaction of butylthiocholine iodide (BTCh), can coordinate with Ag intensively, and consequently diminish the amount of free Ag in the testing system. Less amount of free Ag leads to less production of oxOPD, resulting in less fluorescence quenching towards g-CN nanosheets as well as less fluorescence emission of oxOPD. Therefore, by using g-CN nanosheets and oxOPD as fluorescence indicators, the intensity ratio of their fluorescence (F/F) was calculated and employed to evaluate the activity of BChE. Similarly, the color variation of oxOPD indicated by the absorbance at 420 nm (ΔA) was monitored for the same purpose. These strategies were validated to be sensitive and selective for detecting BChE activity in human serum, with limits of detection (LODs) of 0.1 U L for ratiometric fluorescence mode and 0.7 U L for colorimetric mode.
Topics: Humans; Colorimetry; Silver; Phenylenediamines; Butyrylcholinesterase; Spectrometry, Fluorescence; Nanostructures; Nitrogen Compounds; Limit of Detection; Nitriles; Graphite; Phenazines
PubMed: 38900245
DOI: 10.1007/s00604-024-06488-w -
Trends in Endocrinology and Metabolism:... Jun 2024Intracellular metabolism is a crucial regulator of macrophage function. Recent evidence revealed that the polyamine pathway and subsequent hypusination of eukaryotic... (Review)
Review
Intracellular metabolism is a crucial regulator of macrophage function. Recent evidence revealed that the polyamine pathway and subsequent hypusination of eukaryotic initiation factor 5A (eIF5A) are master regulators of immune cell functions. In brown adipose tissue (BAT), macrophages show an impressive degree of heterogenicity, with specific subsets supporting adaptive thermogenesis during cold exposure. In this review, we discuss the impact of polyamine metabolism on macrophage diversity and function, with a particular focus on their role in adipose tissue homeostasis. Thus, we highlight the exploration of how polyamine metabolism in macrophages contributes to BAT homeostasis as an attractive and exciting new field of research.
PubMed: 38897879
DOI: 10.1016/j.tem.2024.05.008 -
International Journal of Molecular... Jun 2024Phenotypic susceptibility testing of the complex (MTBC) isolate requires culture growth, which can delay rapid detection of resistant cases. Whole genome sequencing...
Phenotypic susceptibility testing of the complex (MTBC) isolate requires culture growth, which can delay rapid detection of resistant cases. Whole genome sequencing (WGS) and data analysis pipelines can assist in predicting resistance to antimicrobials used in the treatment of tuberculosis (TB). This study compared phenotypic susceptibility testing results and WGS-based predictions of antimicrobial resistance (AMR) to four first-line antimicrobials-isoniazid, rifampin, ethambutol, and pyrazinamide-for MTBC isolates tested between the years 2018-2022. For this 5-year retrospective analysis, the WGS sensitivity for predicting resistance for isoniazid, rifampin, ethambutol, and pyrazinamide using Mykrobe was 86.7%, 100.0%, 100.0%, and 47.8%, respectively, and the specificity was 99.4%, 99.5%, 98.7%, and 99.9%, respectively. The predictive values improved slightly using Mykrobe corrections applied using TB Profiler, i.e., the WGS sensitivity for isoniazid, rifampin, ethambutol, and pyrazinamide was 92.31%, 100%, 100%, and 57.78%, respectively, and the specificity was 99.63%. 99.45%, 98.93%, and 99.93%, respectively. The utilization of WGS-based testing addresses concerns regarding test turnaround time and enables analysis for MTBC member identification, antimicrobial resistance prediction, detection of mixed cultures, and strain genotyping, all through a single laboratory test. WGS enables rapid resistance detection compared to traditional phenotypic susceptibility testing methods using the WHO TB mutation catalog, providing an insight into lesser-known mutations, which should be added to prediction databases as high-confidence mutations are recognized. The WGS-based methods can support TB elimination efforts in Canada and globally by ensuring the early start of appropriate treatment, rapidly limiting the spread of TB outbreaks.
Topics: Whole Genome Sequencing; Mycobacterium tuberculosis; Antitubercular Agents; Humans; Microbial Sensitivity Tests; Retrospective Studies; Drug Resistance, Bacterial; Genome, Bacterial; Ethambutol; Isoniazid; Pyrazinamide; Tuberculosis; Rifampin
PubMed: 38892433
DOI: 10.3390/ijms25116245 -
Cells Jun 2024Ferroptosis hallmarked by lipid peroxidation and iron homeostasis imbalance is involved in the occurrence and development of various diseases. The plant growth regulator...
Ferroptosis hallmarked by lipid peroxidation and iron homeostasis imbalance is involved in the occurrence and development of various diseases. The plant growth regulator chlormequat chloride (CCC) can contribute to the causality and exacerbation of reproductive disorders. However, the mechanism by which CCC may cause Leydig cell attenuation remains poorly understood. In this study, TM3 Leydig cells were used to investigate the inhibitory effect of CCC on cell growth and its possible mechanism. The results showed that CCC caused apoptosis, pyroptosis, ferroptosis and necroinflammation in TM3 cells. By comparing the effects of ferroptosis inhibitor Ferrostatin-1 (Fer-1) and pan-Caspase inhibitor Z-VAD-FMK (ZVF) on lipid peroxidation and Caspase-mediated regulated cell death (RCD), we found that Fer-1 was better at rescuing the growth of TM3 cells than ZVF. Although ZVF reduced mitochondrial ROS level and inhibited the activation of Caspase3 and Caspase1, it could not significantly ameliorate lipid peroxidation and the levels of IL-1β and HMGB1 like Fer-1. Therefore, ferroptosis might be a key non apoptotic RCD mode responsible for CCC-driven inflammation, leading to weakened viability and proliferation of TM3 cells. In addition, overexpression of ferritin light chain (FTL) promoted the resistance of TM3 cells to CCC-induced ferroptosis-mediated inflammation and to some extent improved the inhibition of viability and proliferation. Altogether, ferroptosis-initiated inflammation might play a key role in CCC-impaired TM3 cell growth.
Topics: Ferroptosis; Animals; Male; Mice; Leydig Cells; Inflammation; Cell Proliferation; Lipid Peroxidation; Reactive Oxygen Species; Cell Line; Apoptosis; Mitochondria; Amino Acid Chloromethyl Ketones; Cyclohexylamines; Phenylenediamines
PubMed: 38891111
DOI: 10.3390/cells13110979 -
International Journal of Nanomedicine 2024Phototherapy, known for its high selectivity, few side effects, strong controllability, and synergistic enhancement of combined treatments, is widely used in treating...
Tumor Cell-Targeting and Tumor Microenvironment-Responsive Nanoplatforms for the Multimodal Imaging-Guided Photodynamic/Photothermal/Chemodynamic Treatment of Cervical Cancer.
PURPOSE
Phototherapy, known for its high selectivity, few side effects, strong controllability, and synergistic enhancement of combined treatments, is widely used in treating diseases like cervical cancer.
METHODS
In this study, hollow mesoporous manganese dioxide was used as a carrier to construct positively charged, poly(allylamine hydrochloride)-modified nanoparticles (NPs). The NP was efficiently loaded with the photosensitizer indocyanine green (ICG) via the addition of hydrogen phosphate ions to produce a counterion aggregation effect. HeLa cell membrane encapsulation was performed to achieve the final M-HMnO@ICG NP. In this structure, the HMnO carrier responsively degrades to release ICG in the tumor microenvironment, self-generates O for sensitization to ICG-mediated photodynamic therapy (PDT), and consumes GSH to expand the oxidative stress therapeutic effect [chemodynamic therapy (CDT) + PDT]. The ICG accumulated in tumor tissues exerts a synergistic PDT/photothermal therapy (PTT) effect through single laser irradiation, improving efficiency and reducing side effects. The cell membrane encapsulation increases nanomedicine accumulation in tumor tissues and confers an immune evasion ability. In addition, high local temperatures induced by PTT can enhance CDT. These properties of the NP enable full achievement of PTT/PDT/CDT and targeted effects.
RESULTS
Mn can serve as a magnetic resonance imaging agent to guide therapy, and ICG can be used for photothermal and fluorescence imaging. After its intravenous injection, M-HMnO@ICG accumulated effectively at mouse tumor sites; the optimal timing of in-vivo laser treatment could be verified by near-infrared fluorescence, magnetic resonance, and photothermal imaging. The M-HMnO@ICG NPs had the best antitumor effects among treatment groups under near-infrared light conditions, and showed good biocompatibility.
CONCLUSION
In this study, we designed a nano-biomimetic delivery system that improves hypoxia, responds to the tumor microenvironment, and efficiently loads ICG. It provides a new economical and convenient strategy for synergistic phototherapy and CDT for cervical cancer.
Topics: Uterine Cervical Neoplasms; Female; Tumor Microenvironment; Humans; Indocyanine Green; Photochemotherapy; Animals; HeLa Cells; Photosensitizing Agents; Nanoparticles; Manganese Compounds; Mice; Multimodal Imaging; Photothermal Therapy; Oxides; Mice, Inbred BALB C; Polyamines; Magnetic Resonance Imaging
PubMed: 38887692
DOI: 10.2147/IJN.S466042