The incidence and mortality rates of lung cancer have remained high for several decades, necessitating the discovery of new drugs and the development of effective treatment strategies. This study ...identified matairesinoside (MTS) as a potent inhibitor of TMEM16A, a novel drug target for lung cancer. Molecular simulation combined with site-directed mutagenesis experiments confirmed the key binding sites of MTS and TMEM16A. Cell experiments demonstrated that MTS significantly inhibited the growth, migration, and invasion of lung cancer cells, while inducing apoptosis. Gene knockdown and overexpression studies further revealed that TMEM16A is the target for MTS in regulating lung cancer cell growth. Western blot analysis elucidated the signaling transduction network involved in MTS-mediated regulation of lung cancer. Building upon these findings, a biodegradable self-healing functional hydrogel was developed to load MTS, aiming to enhance therapeutic efficacy and minimize side effects in vivo. Animal experiments demonstrated that the hydrogel/MTS formulation exhibited satisfactory inhibitory effects on lung cancer and mitigated the side effects associated with direct MTS injection. This study identified MTS as a potential candidate for anti-lung cancer therapy with well-defined pharmacological mechanisms. Moreover, the targeted drug delivery system utilizing the hydrogel/MTS platform offers a promising approach for lung cancer treatment.
Serious side effects of chemotherapy drugs greatly limited the anticancer performance, while targeted drug delivery could improve the therapeutic effect and reduce side effects. In this work, ...biodegradable hydrogel was fabricated from pectin hydrazide (pec-H) and oxidized carboxymethyl cellulose (DCMC) for localized Silibinin delivery in lung adenocarcinoma treatment. The self-healing pec-H/DCMC hydrogel showed blood compatibility and cell compatibility both in vitro and in vivo, and could be degraded by enzymes. The hydrogel also formed fast fit for injectable applications and showed sustained drug release characteristic sensitive to pH based on acylhydrzone bond cross-linked networks. The Silibinin, as a specific lung cancer inhibiting drug targets TMEM16A ion channel, was loaded into the pec-H/DCMC hydrogel to treat the lung cancer in mice model. The results showed that the hydrogel loaded Silibinin significantly enhanced the anti-tumor efficiency in vivo and greatly reduced the toxicity of the Silibinin. Based on the dual effect of improving efficacy and reducing side effects, the pec-H/DCMC hydrogel with Silibinin loading have broad application prospects to inhibit lung tumor growth in clinic.
•Biodegradable self-healing hydrogel was prepared from hydrazide functional pectin (pec-H).•The pec-H could reacted with oxidized CMC (DCMC) to form self-healing hydrogel.•The pec-H/DCMC hydrogel formed fast fit for injectable applications.•The pec-H/DCMC hydrogel was used to loaded Silibinin targeting TMEM16A ion channel.•The Silibinin loaded in hydrogel enhanced anti-tumor efficacy and reduced the toxicity.
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•PNIPAM based thermo-responsive copolymers with ketone functional group was designed with profitable LCST.•PDAH with catechol moiety and hydrazide groups was used to cross-link the ...copolymer to fabricate thermo-responsive hydrogel.•The graphene oxide was incorporated to endow the hydrogel photothermal performance under NIR irradiation.•The vancomycin loading composite GO/hydrogel promoted burn wound repairing rate.
Thermo-responsive hydrogels with biodegradability have great application in biomedical areas, while the Poly(N-isopropylacrylamide) (PNIPAM) based hydrogels exhibiting lower critical solution temperature (LCST) around body temperature have shown promising applications in diverse areas such as drug delivery, tissue engineering, and wound repairing. In this study, PNIPAM based thermo-responsive copolymer with ketone functional group was polymerized and the LCST was regulated to body temperature, then biodegradable self-healing hydrogels with injectability were fabricated by cross-linking the thermo-responsive copolymers with dopamine functionalized pectin hydrazide (PDAH). The hydrogel exhibited good mechanical strength, excellent biocompatibility and thermo-responsive sustained drug release process. The nano-graphene oxide (GO) was incorporated to design near-infrared (NIR) sensitive nanocomposite hydrogel to serve as photothermal enhanced wound dressing with vancomycin loading. The composite hydrogel also showed pH-responsive drug release behavior and the NIR irradiation also accelerated the release rate based on photothermal induced phase transition. More importantly, the nanocomposite hydrogel with vancomycin loading and photothermal property can promoted burn wound repairing rate by inhibiting the bacterial growth. As a result, this GO composite hydrogel (GO/hydrogel) could act as NIR triggered photo-thermal enhanced drug delivery platform for promoted wound repairing in the near future.
Diabetic wound is considered as a kind of chronic wound prone to infection and difficult to repair due to high glucose level in the blood of patients. In this research, a biodegradable self-healing ...hydrogel with mussel inspired bioadhesion and anti-oxidation properties is fabricated based on Schiff-base cross-linking. The hydrogel was designed from dopamine coupled pectin hydrazide (Pec-DH) and oxidized carboxymethyl cellulose (DCMC) for mEGF loading as a diabetic wound repair dressing. The Pectin and CMC as natural feedstock endowed the hydrogel with biodegradability to avoid possible side effects, while the coupled catechol structure could enhance the tissue adhesion of the hydrogel for hemostasis. The results showed the Pec-DH/DCMC hydrogel formed fast and can cover irregular wounds with good sealing effect. The catechol structure also improved the reactive oxygen species (ROS) scavenging ability of the hydrogel, which can eliminate the negative effect of ROS during wound healing. The in vivo diabetic wound healing experiment revealed the hydrogel as mEGF loading vehicle greatly enhanced the diabetic wound repairing rate in mice model. As a result, the Pec-DH/DCMC hydrogel could show advantages as EGF carrier in wound healing applications.
Biodegradable self-healing hydrogels with antibacterial property attracted growing attentions in biomedication as wound dressings since they can prevent bacterial infection and promote wound healing ...process. In this research, a biodegradable self-healing hydrogel with ROS scavenging performance and enhanced tissue adhesion was fabricated from dopamine grafted oxidized pectin (OPD) and naphthoate hydrazide terminated PEO (PEO NH). At the same time, Fe3+ ions were incorporated to endow the hydrogel with near-infrared (NIR) triggered photothermal property to obtain antibacterial activity. The composite hydrogel showed good hemostasis performance based on mussel inspired tissue adhesion with biocompatibility well preserved. As expected, the composition of FeCl3 improved conductivity and endowed photothermal property to the hydrogel. The in vivo wound repairing experiment revealed the 808 nm NIR light triggered photothermal behavior of the hydrogel reduced the inflammation response and promoted wound repairing rate. As a result, this composite FeCl3/hydrogel shows great potential to be an excellent wound dressing for the treatment of infection prong wounds with NIR triggers.
Accumulation of mutant proteins is a major cause of many diseases (collectively called proteopathies), and lowering the level of these proteins can be useful for treatment of these diseases. We ...hypothesized that compounds that interact with both the autophagosome protein microtubule-associated protein 1A/1B light chain 3 (LC3)
and the disease-causing protein may target the latter for autophagic clearance. Mutant huntingtin protein (mHTT) contains an expanded polyglutamine (polyQ) tract and causes Huntington's disease, an incurable neurodegenerative disorder
. Here, using small-molecule-microarray-based screening, we identified four compounds that interact with both LC3 and mHTT, but not with the wild-type HTT protein. Some of these compounds targeted mHTT to autophagosomes, reduced mHTT levels in an allele-selective manner, and rescued disease-relevant phenotypes in cells and in vivo in fly and mouse models of Huntington's disease. We further show that these compounds interact with the expanded polyQ stretch and could lower the level of mutant ataxin-3 (ATXN3), another disease-causing protein with an expanded polyQ tract
. This study presents candidate compounds for lowering mHTT and potentially other disease-causing proteins with polyQ expansions, demonstrating the concept of lowering levels of disease-causing proteins using autophagosome-tethering compounds.
Toll-like receptor (TLR) activation is central to immunity, wherein the activation of the TLR9 subfamily members TLR9 and TLR7 results in the robust induction of type I IFNs (IFN-α/β) by means of the ...MyD88 adaptor protein. However, it remains unknown how the TLR signal "input" can be processed through MyD88 to "output" the induction of the IFN genes. Here, we demonstrate that the transcription factor IRF-7 interacts with MyD88 to form a complex in the cytoplasm. We provide evidence that this complex also involves IRAK4 and TRAF6 and provides the foundation for the TLR9-dependent activation of the IFN genes. The complex defined in this study represents an example of how the coupling of the signaling adaptor and effector kinase molecules together with the transcription factor regulate the processing of an extracellular signal to evoke its versatile downstream transcriptional events in a cell. Thus, we propose that this molecular complex may function as a cytoplasmic transductional-transcriptional processor.
, the gram-negative bacteria belonging to the family
, lacks the ability to synthesize chemicals. However, in this study, a strain of
NJ1023 screened from the soil containing petrochemicals was found ...to be capable of producing extracellular polysaccharides (EPSs). After purification of the polysaccharide, the chemical composition and physicochemical properties of the polysaccharide were analyzed by UV-Vis spectra, FTIR spectroscopy and GC-MS, etc. The results showed that: The molecular weight of the polysaccharide produced by this strain was only 2.7×10
Da, which was lower than that reported in other polysaccharides from the same genus. The polysaccharide produced by
NJ1023 mainly comprised xylose, glucose, galactose, and N-acetylglucosamine with a molar ratio of 0.27: 4.52: 1.74: 0.2, which differed from those reported from the same genus. The results demonstrated that lower incubation temperatures and shaking speeds were more favorable for EPSs synthesis, while higher incubation temperatures and shaking speeds favored cell growth. Additionally, the EPSs produced by
NJ1023 significantly protected the
cells against cadaverine stress. Overall, the discovery of EPSs produced by
increased the diversity of bacterial polysaccharides and broadened the potential applications of this species.
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