Monitoring sulfur dioxide (SO2) derivatives in environment is of great significance due to their harmful effects to the environment and human health. In this study, a fluorescent probe (CZBT) for SO2 ...derivatives was prepared from 9-ethyl-9H-carbazole-3,6-dicarboxaldehyde and 2-methyl-benzothiazolium, which displayed a noticeable color change from yellow to colorless along with a remarkable fluorescence change from yellow to blue in response to HSO3−. The probe could quantitatively determine the concentration of HSO3− with excellent selectivity, high sensitivity and low limit of detection. 1H NMR and HR-MS spectra demonstrated that a selective 1, 4-nucleophilic addition occurred on the bridge double bond in CZBT. The probe was successfully used to determine the SO2 derivatives in several real water samples with good recovery. Furthermore, the probe was employed for monitoring the level of intracellular HSO3− in HeLa (human cervical cancer) cells by fluorescence imaging. These results indicated that CZBT has a good capability for monitoring SO2 derivatives in environment and living cells.
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•A colorimetric and ratiometric fluorescent probe has been developed for the specific detection of SO2 derivatives.•The probe can visualize environmentally harmful SO2 derivatives with low limit of detection (28nM).•The probe showed good recovery in the determination of SO2 derivatives in industrial wastewater and snow-broth.•The probe has been employed to visualize trace SO2 derivatives in living cells.
Thrombosis is one of the most important pathogenic factors related to cardiovascular diseases. Presently, thrombin inhibitors have gradually gained prominence in clinical practice due to their unique ...potential, such as dabigatran. Nevertheless, the risk of bleeding is not completely eliminated, and the threats of gastrointestinal bleeding are even increased in some cases. Therefore, developing new oral thrombin inhibitors with low side effects is urgent. In this paper, we summarized recent advances in the newly synthesized and isolated thrombin inhibitors from 2000 to 2019 and their structure-activity relationships (SARs) along with structure-dependent pharmacokinetic parameters, guiding the next generation of oral thrombin inhibitors.
The cell wall of brown algae contains alginate as a major constituent. This anionic polymer is a composite of β-d-mannuronate (M) and α-l-guluronate (G). Alginate can be degraded into ...oligosaccharides; both the polymer and its products exhibit antioxidative, antimicrobial, and immunomodulatory activities and, hence, find many commercial applications. Alginate is attacked by various enzymes, collectively termed alginate lyases, that degrade glycosidic bonds through β-elimination. Considering the abundance of brown algae in marine ecosystems, alginate is an important source of nutrients for marine organisms, and therefore, alginate lyases play a significant role in marine carbon recycling. Various marine microorganisms, particularly those that thrive in association with brown algae, have been reported as producers of alginate lyases. Conceivably, the marine-derived alginate lyases demonstrate salt tolerance, and many are activated in the presence of salts and, therefore, find applications in the food industry. Therefore, this review summarizes the structural and biochemical features of marine bacterial alginate lyases along with their applications. This comprehensive information can aid in the expansion of future prospects of alginate lyases.
Safe and efficient delivery of small interfering RNA (siRNA) is essential to gene therapy towards intervention of genetic diseases. Herein, we developed a novel cationic cholesterol lipid derivative ...(CEL) in which cholesterol hydrophobic skeleton was connected to L-lysine cationic headgroup via a hexanediol linker as the non-viral siRNA delivery carrier. Well-organized CEL/siRNA nanocomplexes (100-200 nm) were prepared by microfluidic-assisted assembly of CEL and siRNA at various N/P ratios. The CEL and CEL/siRNA nanocomplexes have lower cytotoxicity compared with bPEI25k. Delightfully, we disclosed that, in Hela-Luc and H1299-Luc cell lines, the micro-fluidic-based CEL/siRNA nanocomplexes exhibited high siRNA transfection efficiency under both serum-free condition (74-98%) and low-serum circumstances (80-87%), higher than that of lipofectamine 2000. These nanocomplexes also showed high cellular uptake through the caveolae/lipid-raft mediated endocytosis pathway, which may greatly contribute to transfection efficiency. Moreover, the time-dependent (0-12 h) dynamic intracellular imaging demonstrated the efficient delivery to cytoplasm after lysosomal co-localization. The results indicated that the microfluidic-based CEL/siRNA nanosystems possessed good stability, low cytotoxicity, high siRNA delivery efficiency, rapid cellular uptake and caveolae/lipid raft-dependent internalization. Additionally, this study provides a simple approach for preparing and applying a "helper lipid-free" cationic lipid siRNA delivery system as potential nanotherapeutics towards gene silencing treatment of (tumor) diseases.
Cancer immunotherapy is an effective antitumor approach through activating immune systems to eradicate tumors by immunotherapeutics. However, direct administration of “naked” immunotherapeutic agents ...(such as nucleic acids, cytokines, adjuvants or antigens without delivery vehicles) often results in: (1) an unsatisfactory efficacy due to suboptimal pharmacokinetics; (2) strong toxic and side effects due to low targeting (or off-target) efficiency. To overcome these shortcomings, a series of polysaccharide-based nanoparticles have been developed to carry immunotherapeutics to enhance antitumor immune responses with reduced toxicity and side effects. Polysaccharides are a family of natural polymers that hold unique physicochemical and biological properties, as they could interact with immune system to stimulate an enhanced immune response. Their structures offer versatility in synthesizing multifunctional nanocomposites, which could be chemically modified to achieve high stability and bioavailability for delivering therapeutics into tumor tissues. This review aims to highlight recent advances in polysaccharide-based nanomedicines for cancer immunotherapy and propose new perspectives on the use of polysaccharide-based immunotherapeutics.
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•Cancer immunotherapy is an emerging antitumor approach but with drawbacks.•Polysaccharides can interact with the immune system to enhance immune response.•Polysaccharides can be applied as nano-carriers for cancer immunotherapeutics with enhanced anti-tumor efficacy.•Polysaccharide-based nanomedicines can relieve the toxic and side effect of cancer immunotherapy.
Developing natural product-based anti-cancer drugs/agents is a promising way to overcome the serious side effects and toxicity of traditional chemotherapeutics for cancer treatment. However, rapid ...assessment of the in vivo anti-cancer activities of natural products is a challenge. Alternatively, zebrafish are useful model organisms and perform well in addressing this challenging issue. Nowadays, a growing number of studies have utilized zebrafish models to evaluate the in vivo activities of natural compounds. Herein, we reviewed the application of zebrafish models for evaluating the anti-cancer activity and toxicity of natural products over the past years, summarized its process and benefits, and provided future outlooks for the development of natural product-based anti-cancer drugs.
Herein, a novel phototheranostic nanocomplex that is self-assembled from bovine serum albumin (BSA) and indocyanine green (ICG) is developed for enhanced near-infrared (NIR) fluorescence imaging, ...which benefits the guidance on in vivo cancer photothermal therapy (PTT). The study confirms that the binding of ICG with the bind sits on the albumin will result in improved hydrolytic stability and high photoluminescence quantum yield (PLQY). The ICG loading ratio in the nanocomplex is optimized and confirms the loading ratio of 0.5% ICG to be the optimal content. The optimized ICG-BSA nanocomplex (ICG-BSA NC) possesses a higher PLQY of 16.8% than that of free ICG (2.7%). The high PLQY and efficient passive targeting ability of ICG-BSA NC help improve its in vivo tumor accumulation and NIR fluorescence imaging significantly. Under laser irradiation, efficient PTT with obvious tumor growth suppression on a triple negative breast tumor model can be observed in the ICG-BSA NC treated group.
Compound 1 (SMTP-7, also FGFC1), an isoindolone alkaloid from marine fungi Starchbotrys longispora FG216 and fungi Stachybotrys microspora IFO 30018, possessed diverse bioactivities such as ...thrombolysis, anti-inflammatory and anti-oxidative properties, and so on. It may be widely used for the treatment of various diseases, including cerebral infarction, stroke, ischemia/reperfusion damage, acute kidney injury, etc. Especially in cerebral infarction, compound 1 could reduce hemorrhagic transformation along with thrombolytic therapy, as the traditional therapies are accompanied with bleeding risks. In the latest studies, compound 1 selectively inhibited the growth of NSCLC cells with EGFR mutation, thus demonstrating its excellent anti-cancer activity. Herein, we summarized pharmacological activities, preparation of staplabin congeners—especially compound 1—and the mechanism of compound 1, with potential therapeutic applications.
For achieving successful chemotherapy against cancer, designing biocompatible drug delivery systems (DDSs) with long circulation times, high cellular endocytosis efficiency, and targeted drug release ...is of upmost importance. Herein, a well-defined PEG-b-P(MASSChol-co-MANBoc) block copolymer bearing redox-sensitive cholesteryl-side group was prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization (with non-redox PEG-b-P(MACCChol-co-MAN-DCA) as the reference), and 1,2-dicarboxylic-cyclohexene acid (DCA) was then grafted onto the hydrophobic block to endow it with charge-convertible characteristics under a tumor microenvironment. The amphiphilic copolymer could be assembled into polymeric spherical micelles (SSMCs) with polyethylene glycol (PEG) as the corona/shell, and anti-cancer drug doxorubicin (DOX) was successfully encapsulated into the micellar core via strong hydrophobic and electrostatic interactions. This nanocarrier showed high stability in the physiological environment and demonstrated “smart” surface charge conversion from negative to positive in the slightly acidic environment of tumor tissues (pH 6.5~6.8), as determined by dynamic light scattering (DLS). Moreover, the cleavage of a disulfide bond linking the cholesterol grafts under an intracellular redox environment (10 mM GSH) resulted in micellar dissociation and accelerated drug release, with the non-redox-responsive micelles (CCMCs) as the control. Additionally, a cellular endocytosis and tumor proliferation inhibition study against MCF-7 tumor cells demonstrated the enhanced endocytosis and tumor cell inhibitory efficiency of dual-responsive SSMCs/DOX nanomedicines, revealing potentials as multifunctional nanoplatforms for effective oncology treatment.
•The common dental diseases and their treatment methods are introduced.•Various cells and materials used to realize tooth regeneration are summarized.•The mechanisms of tooth regeneration were also ...summarized and discussed.•Clinical applications and clinical trials have been discussed.•Perspectives for future development of tooth regeneration strategies are proposed.
Tooth defect and loss are common clinical diseases in stomatology. With the extension of life expectancy, there is an increasing demand for tooth tissue and whole tooth regeneration. Compared with traditional oral prosthetic treatment, tooth regeneration has unique advantages and has become one of the hotspots towards oral biomedical treatment. In this review, we discussed the development and challenges of tooth regeneration based on cells and materials, including tooth enamel, dentin, dental pulp, cementum, dentin-pulp complex, and the whole tooth regeneration, in order to provide a comprehensive, up-to-date, illustrative overview of tooth regeneration issues. The mechanisms of the regeneration were also summarized and discussed. Moreover, this review hints the future perspective and research direction of tooth regeneration in the challenging field of regenerative dentistry.
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