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Objective Based on previous studies on a class of tumor-targeted indocyanine small molecules, we aimed to synthesize a new analog modified with water-soluble polyethylene glycol (PEG) and then investigated its physicochemical properties and role in tumor targeting photodynamic therapy. Methods PEG-modified indocyanine small molecules were designed and synthesized by using 2, 3, 3-trimethylindole and polyethylene glycol monomethyl ether as raw materials. Its chemical structure was characterized by nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS); its physicochemical properties and cancer targeting photodynamic effect were investigated by determining its water solubility, optical spectra, cell uptake, cell viability, singlet oxygen, and reactive oxygen production. Results Based on a converging strategy of synthesis and through 6 steps of chemical reactions, a PEG-modified indocyanine small molecule (PEG-808-NM2) was successfully produced. Its structure was confirmed by NMR spectroscopy and MS. Compared to 808-NM2, PEG-808-NM2 significantly increased water solubility and exhibited excellent near-infrared fluorescence property in both methanol and water solution. PEG-808-NM2 preferentially accumulated in RENCA cells (a mouse renal adenocarcinoma cell line) rather than HK-2 cells (a tubular cell line from normal human kidneys). Under 808 nm-laser irradiation, PEG-808-NM2 induced a great amount of singlet oxygen and intracellular reactive oxygen species. Conclusion Our synthesized PEG-modified indocyanine small molecules not only keep the cancer preferential accumulation and the role in near-infrared imaging as original indocyanine, but also obtain significantly improved physicochemical properties and photosensitizing effect. They exert significant photodynamic therapeutic effect on renal cell carcinoma cells.

Background Obesity is a crucial risk factor for asthma. Observational studies have examined the association between abdominal obesity and asthma symptoms. This study aimed to investigate the causal relationship between visceral adipose tissue (VAT) and asthma and its potential as an independent indicator. Methods This study utilized data from the National Health and Nutrition Examination Survey spanning 2011–8. Multivariable logistic regression and stratified variable selection were employed to identify associations between asthma and VAT. Moreover, a two-sample Mendelian randomization analysis, using 221 genetic variants as instrumental variables, was conducted to assess this relationship further. Results Our findings indicated that individuals with higher VAT levels were more likely to develop asthma. Visceral obesity remained a significant risk factor for asthma after adjusting for demographic characteristics. Genetic predictions suggest a positive association between VAT and an elevated risk of asthma (odds ratio [OR] = 1.393, 95% confidence interval [CI]: 1.266–1.534, and P  = 1.43E−11). No significant polymorphisms were detected using the Mendelian randomization-Egger intercept test. Conclusions This study presents potential evidence supporting the causal role of VAT in asthma development. Furthermore, the findings from the Mendelian randomization analysis further reinforce the relationship between VAT and asthma risk. Key message What is already known on this topic Obesity is a well-established risk factor for asthma, with previous observational studies examining the association between abdominal obesity and asthma symptoms. What this study adds Individuals with higher visceral fat are more likely to develop asthma. Furthermore, even after adjusting for demographic factors, visceral obesity remains a significant risk factor for asthma. How this study might affect research, practice, or policy This study offers additional evidence associating visceral fat with asthma and further validates the causal relationship between the two conditions. [ABSTRACT FROM AUTHOR]

Radionuclide uranium has both a chemical and radioactive toxicity, leading to severe nephrotoxicity as it predominantly deposits itself in the kidneys after entering into human bodies. It crosses renal cell membranes, accumulates in mitochondria and causes mitochondrial oxidative damage and dysfunction. In this study, a mitochondria-targeted heptamethine indocyanine small molecule chelator modified with gallic acid (IR-82) is synthesized for uranium detoxication. Both gallic acid and sulfonic acid, as two hydrophilic endings, make IR-82, being excreted feasibly through kidneys. Gallic acid with polyphenol groups has a steady metal chelation effect and potent antioxidant ability, which may facilitate IR-82-alleviated uranium nephrotoxicity simultaneously by enhancing uranium decorporation from the kidneys and reducing mitochondrial oxidative damage. Cell viability assays demonstrate that IR-82 can significantly improve the cell viability of uranium-exposed human renal (HK-2) cells. It is also demonstrated to accumulate in mitochondria and reduce mitochondrial ROS and total intracellular ROS, as well as intracellular uranium content. In vivo imaging experiments in mice show that IR-82 could be excreted out through kidneys. ICP-MS tests further reveal that IR-82 can efficiently decrease the uranium deposition in mouse kidneys. IR-82 treatment improves the animal survival rate and renal function of experimental mice after high-dose uranium exposure. Collectively, our study may evidence that the development of uranium decorporation agents with kidney–mitochondrion dual targeting abilities is a promising strategy for attenuating uranium-induced nephrotoxicity. [ABSTRACT FROM AUTHOR]

We proposed a sensor architecture for surface-enhanced Raman scattering (SERS) based on Fe ion doped LN (FLN) crystal, which was modified by large-area laser-induced periodic surface structures (LIPSS) and subsequently decorated with Ag nanoparticles (Ag NPs). Based on such a FLN/LIPSS/Ag substrate, strikingly boosted SERS enhancement was obtained at constant temperature owing to the LIPSS-related hot spot improvement. Benefiting from the pyroelectric effect of the FLN crystal, further enhanced SERS was achieved under heating and cooling processes, which can be ascribed to the additional charge transfer between molecules and Ag NPs triggered by pyroelectric potential. The experimental results highlight the high fabrication efficiency, ultrasensitivity, high uniformity, and high universality of the substrate, integrating the advantages of both LIPSS and the FLN crystal. More interestingly, selective suppression of Raman signals under cooling processes was observed, which further extends the applications of the FLN/LIPSS/Ag substrate for the detection of molecule complexes such as lake water polluted by crystal violet and 4-aminothiophenol molecules. [ABSTRACT FROM AUTHOR]

Major causes of the radiation-induced disease include nuclear accidents, war-related nuclear explosions, and clinical radiotherapy. While certain radioprotective drug or bioactive compounds have been utilized to protect against radiation-induced damage in preclinical and clinical settings, these strategies are hampered by poor efficacy and limited utilization. Hydrogel-based materials are effective carriers capable of enhancing the bioavailability of compounds loaded therein. As they exhibit tunable performance and excellent biocompatibility, hydrogels represent promising tools for the design of novel radioprotective therapeutic strategies. This review provides an overview of common approaches to radioprotective hydrogel preparation, followed by a discussion of the pathogenesis of radiation-induced disease and the current states of research focused on using hydrogels to protect against these diseases. These findings ultimately provide a foundation for discussions of the challenges and future prospects associated with the use of radioprotective hydrogels. [ABSTRACT FROM AUTHOR]

Enhancer of zeste homolog 2 (EZH2) is responsible for the methylation of lysine 27 of histone H3 (H3K27) leading to transcriptional repression. Consequently, EZH2 is related with several diseases including cancers, as overexpressed EZH2 can down-regulate cancer suppressor genes. Therefore, EZH2 became a promising target for cancer treatment and diagnosis and in vivo imaging of EZH2 is critical for diagnosis and treatment monitor. In the present work, we radiolabeled a specific inhibitor of EZH2, [11C]EI1, investigated its pharmacokinetics and performed micro PET/CT imaging. Results showed that the half-life of the [11C]EI1 in blood was 3.4 min. Micro PET/CT imaging showed that the [11C]EI1 can enter the major organs including liver, stomach, and intestine and can be blocked by the unlabeled EI1 resulting in a significant distinct between apparent distribution volumes (Vd, 2.8 mL for blocking versus 17.4 ml for baseline), which validated the specific affinity of the [11C]EI1 against EZH2 and illustrated the distribution of EZH2 in major organs. The results indicated that the [11C]EI1 can be a tracer for EZH2 PET imaging used in diagnosis and therapy monitor of EZH2 related diseases especially cancers. [ABSTRACT FROM AUTHOR]