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1.
Cell Mol Biol (Noisy-le-grand) ; 70(7): 237-242, 2024 Jul 28.
Article in English | MEDLINE | ID: mdl-39097868

ABSTRACT

Recently, nanocarriers have been utilized for encapsulating and sustained release of agrochemicals specifically auxins. Due to their potential applications such as increased bioavailability and improved crop yield and nutritional quality. Herein, the efficacy of alginate/chitosan nanocapsules as a nanocarrier for the hormone indole-3-butyric acid (IBA) loading and its effect on rooting tobacco plants has been carried out in the present study. The average particle size of IBA-alginate/chitosan nanocapsules was measured by Dynamic light scattering analysis at 321 nm. Scanning electron microscope studies revealed the spherical shape of nanoparticles with an average size of 97 nm. The average particle size of IBA-alginate/chitosan nanocapsules was measured by Dynamic light scattering analysis at 321 nm. The characteristic peaks of IBA on alginate/chitosan nanocapsules were identified by Fourier transform infrared spectroscopic analysis. Also, high efficiency (35%) of IBA hormone loading was observed. The findings indicated that the concentration of 3 mgL-1 of IBA-alginate/chitosan nanocapsules has the highest efficiency in increasing the rooting in tobacco (Nicotiana tabacum) plants compared to other treatments. According to our results, we can introduce alginate/chitosan nanocapsules as an efficient nanocarrier in IBA hormone transfer applications and their use in agriculture.


Subject(s)
Alginates , Chitosan , Indoles , Nanocapsules , Nicotiana , Plant Roots , Chitosan/chemistry , Nicotiana/drug effects , Nicotiana/growth & development , Nicotiana/metabolism , Alginates/chemistry , Indoles/chemistry , Nanocapsules/chemistry , Plant Roots/drug effects , Plant Roots/growth & development , Particle Size , Spectroscopy, Fourier Transform Infrared , Hexuronic Acids/chemistry , Glucuronic Acid/chemistry , Plant Growth Regulators/pharmacology , Plant Growth Regulators/chemistry
2.
Sci Rep ; 14(1): 17856, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39090178

ABSTRACT

Surface display of functional groups with specific reactivity around living cells is an emerging, low cost and highly eco-compatible technology that serves multiple applications, ranging from basic biochemical studies to biomedicine, therapeutics and environmental sciences. Conversely to classical methods exploiting hazardous organic synthesis of precursors or monovalent functionalization via genetics, here we perform functional decoration of individual living microalgae using suitable biocoatings based on polydopamine, a melanin-like synthetic polymer. Here we demonstrate the one-pot synthesis of a functional polydopamine bearing phenylboronic units which can decorate the living cell surfaces via a direct ester formation between boronic units and surface glycoproteins. Furthermore, biosorption of fluorescent sugars on functionalized cell membranes is triggered, demonstrating that these organic coatings act as biocompatible soft shells, still functional and reactive after cell engineering.


Subject(s)
Boronic Acids , Indoles , Melanins , Polymers , Polymers/chemistry , Melanins/chemistry , Melanins/metabolism , Indoles/chemistry , Boronic Acids/chemistry , Microalgae/metabolism , Microalgae/chemistry
3.
Int J Nanomedicine ; 19: 7215-7236, 2024.
Article in English | MEDLINE | ID: mdl-39050875

ABSTRACT

Introduction: Current therapeutic strategies, including immune checkpoint blockade (ICB), exhibit limited efficacy in treating hepatocellular carcinoma (HCC). Nanoparticles, particularly those that can accumulate specifically within tumors and be activated by sonodynamic therapy (SDT), can induce immunogenic cell death (ICD); however, ICD alone has not achieved satisfactory therapeutic effectiveness. This study investigates whether combining ICB with ICD induced by nanoparticle-mediated SDT could enhance anti-tumor immunity and inhibit HCC growth. Methods: We developed an iron-based micelle nanodelivery system encapsulating the Near-Infrared Dye IR-780, which was surface-modified with a cyclic tripeptide composed of arginine-glycine-aspartic acid (cRGD). This led to the synthesis of targeted IR780@FOM-cRGD nanoparticles. These nanoparticles were specifically engineered to kill tumor cells under sonication, activate immunogenic cell death (ICD), and be used in conjunction with immune checkpoint blockade (ICB) for the treatment of hepatocellular carcinoma (HCC). Results: The synthesized IR780@FOM-cRGD nanoparticles had an average diameter of 28.23±1.750 nm and a Zeta potential of -23.95±1.926. Confocal microscopy demonstrated that IR780@FOM-cRGD could target HCC cells while minimizing toxicity to healthy cells. Upon sonodynamic activation, these nanoparticles consumed significant amounts of oxygen and generated substantial reactive oxygen species (ROS), effectively killing tumor cells and inhibiting the proliferation, invasion, and migration of H22 cells. Hemolysis assays confirmed the in vivo safety of the nanoparticles, and in vivo fluorescence imaging revealed significant accumulation in tumor tissues. Mouse model experiments showed that combining ICB(which induced by Anti-PD-L1) with ICD (which induced by IR780@FOM-cRGD), could effectively activated anti-tumor immunity and suppressed tumor growth. Discussion: This study highlights the potential of IR780@FOM-cRGD nanoparticles to facilitate tumor eradication and immune activation when used in conjunction with Anti-PD-L1 therapy. This combination represents a non-invasive, efficient, and targeted approach for the treatment of hepatocellular carcinoma (HCC). By integrating sonodynamic therapy with immunotherapy, this strategy promises to substantially improve the effectiveness of traditional treatments in combating HCC, offering new avenues for clinical application and therapeutic innovation.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Nanoparticles , Animals , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/immunology , Mice , Nanoparticles/chemistry , Liver Neoplasms/therapy , Liver Neoplasms/immunology , Cell Line, Tumor , B7-H1 Antigen/immunology , Humans , Indoles/chemistry , Indoles/pharmacology , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/chemistry , Ultrasonic Therapy/methods , Oligopeptides/chemistry , Oligopeptides/pharmacology , Immunogenic Cell Death/drug effects , Micelles , Combined Modality Therapy/methods , Mice, Inbred BALB C , Immunotherapy/methods
4.
J Biomed Mater Res B Appl Biomater ; 112(8): e35456, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39031923

ABSTRACT

Tissue engineered scaffolds aimed at the repair of critical-sized bone defects lack adequate consideration for our aging society. Establishing an effective aged in vitro model that translates to animals is a significant unmet challenge. The in vivo aged environment is complex and highly nuanced, making it difficult to model in the context of bone repair. In this work, 3D nanofibrous scaffolds generated by the thermally-induced self-agglomeration (TISA) technique were functionalized with polydopamine nanoparticles (PD NPs) as a tool to improve drug binding capacity and scavenge reactive oxygen species (ROS), an excessive build-up that dampens the healing process in aged tissues. PD NPs were reduced by ascorbic acid (rPD) to further improve hydrogen peroxide (H2O2) scavenging capabilities, where we hypothesized that these functionalized scaffolds could rescue ROS-affected osteoblastic differentiation in vitro and improve new bone formation in an aged mouse model. rPDs demonstrated improved H2O2 scavenging activity compared to neat PD NPs, although both NP groups rescued the alkaline phosphatase activity (ALP) of MC3T3-E1 cells in presence of H2O2. Additionally, BMP2-induced osteogenic differentiation, both ALP and mineralization, was significantly improved in the presence of PD or rPD NPs on TISA scaffolds. While in vitro data showed favorable results aimed at improving osteogenic differentiation by PD or rPD NPs, in vivo studies did not note similar improvements in ectopic bone formation an aged model, suggesting that further nuance in material design is required to effectively translate to improved in vivo results in aged animal models.


Subject(s)
Bone Regeneration , Indoles , Nanoparticles , Osteogenesis , Polymers , Reactive Oxygen Species , Tissue Scaffolds , Animals , Mice , Indoles/chemistry , Indoles/pharmacology , Osteogenesis/drug effects , Polymers/chemistry , Polymers/pharmacology , Tissue Scaffolds/chemistry , Bone Regeneration/drug effects , Nanoparticles/chemistry , Reactive Oxygen Species/metabolism , Nanofibers/chemistry , Hydrogen Peroxide/chemistry , Aging/metabolism , Free Radical Scavengers/pharmacology , Free Radical Scavengers/chemistry , Cell Differentiation/drug effects , Cell Line , Osteoblasts/metabolism
5.
Int J Nanomedicine ; 19: 6717-6730, 2024.
Article in English | MEDLINE | ID: mdl-38979530

ABSTRACT

Introduction: Immune regulatory small molecule JQ1 can block its downstream effector PD-L1 pathway and effectively reverse the PD-L1 upregulation induced by doxorubicin (DOX). So the synergistic administration of chemotherapeutic drug DOX and JQ1 is expected to increase the sensitivity of tumors to immune checkpoint therapy and jointly enhance the body's own immunity, thus effectively killing tumor cells. Therefore, a drug delivery system loaded with DOX and JQ1 was devised in this study. Methods: Polydopamine nanoparticles (PDA NPs) were synthesized through spontaneous polymerization. Under appropriate pH conditions, DOX and JQ1 were loaded onto the surface of PDA NPs, and the release of DOX and JQ1 were measured using UV-Vis or high performance liquid chromatography (HPLC). The mechanism of fabricated nanocomplex in vitro was investigated by cell uptake experiment, cell viability assays, apoptosis assays, and Western blot analysis. Finally, the tumor-bearing mouse model was used to evaluate the tumor-inhibiting efficacy and the biosafety in vivo. Results: JQ1 and DOX were successfully loaded onto PDA NPs. PDA-DOX/JQ1 NPs inhibited the growth of prostate cancer cells, reduced the expression of apoptosis related proteins and induced apoptosis in vitro. The in vivo biodistribution indicated that PDA-DOX/JQ1 NPs could accumulated at the tumor sites through the EPR effect. In tumor-bearing mice, JQ1 delivered with PDA-DOX/JQ1 NPs reduced PD-L1 expression at tumor sites, generating significant tumor suppression. Furthermore, PDA-DOX/JQ1 NPs could reduce the side effects, and produce good synergistic treatment effect in vivo. Conclusion: We have successfully prepared a multifunctional platform for synergistic prostate cancer therapy.


Subject(s)
Apoptosis , Azepines , Doxorubicin , Indoles , Nanoparticles , Polymers , Prostatic Neoplasms , Male , Animals , Doxorubicin/chemistry , Doxorubicin/pharmacology , Doxorubicin/pharmacokinetics , Doxorubicin/administration & dosage , Indoles/chemistry , Indoles/pharmacology , Indoles/pharmacokinetics , Polymers/chemistry , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Nanoparticles/chemistry , Humans , Mice , Cell Line, Tumor , Apoptosis/drug effects , Azepines/chemistry , Azepines/pharmacology , Azepines/pharmacokinetics , Drug Synergism , Cell Survival/drug effects , Tissue Distribution , Xenograft Model Antitumor Assays , Drug Liberation , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , B7-H1 Antigen/metabolism , Triazoles
6.
ACS Appl Mater Interfaces ; 16(28): 36168-36193, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38954488

ABSTRACT

In the intricate landscape of Traumatic Brain Injury (TBI), the management of TBI remains a challenging task due to the extremely complex pathophysiological conditions and excessive release of reactive oxygen species (ROS) at the injury site and the limited regenerative capacities of the central nervous system (CNS). Existing pharmaceutical interventions are limited in their ability to efficiently cross the blood-brain barrier (BBB) and expeditiously target areas of brain inflammation. In response to these challenges herein, we designed novel mussel inspired polydopamine (PDA)-coated mesoporous silica nanoparticles (PDA-AMSNs) with excellent antioxidative ability to deliver a new potential therapeutic GSK-3ß inhibitor lead small molecule abbreviated as Neuro Chemical Modulator (NCM) at the TBI site using a neuroprotective peptide hydrogel (PANAP). PDA-AMSNs loaded with NCM (i.e., PDA-AMSN-D) into the matrix of PANAP were injected into the damaged area in an in vivo cryogenic brain injury model (CBI). This approach is specifically built while keeping the logic AND gate circuit as the primary focus. Where NCM and PDA-AMSNs act as two input signals and neurological functional recovery as a single output. Therapeutically, PDA-AMSN-D significantly decreased infarct volume, enhanced neurogenesis, rejuvenated BBB senescence, and accelerated neurological function recovery in a CBI.


Subject(s)
Antioxidants , Bivalvia , Brain Injuries, Traumatic , Indoles , Nanocomposites , Neurogenesis , Oxidative Stress , Polymers , Indoles/chemistry , Indoles/pharmacology , Brain Injuries, Traumatic/drug therapy , Brain Injuries, Traumatic/pathology , Brain Injuries, Traumatic/metabolism , Polymers/chemistry , Polymers/pharmacology , Animals , Oxidative Stress/drug effects , Antioxidants/chemistry , Antioxidants/pharmacology , Nanocomposites/chemistry , Bivalvia/chemistry , Neurogenesis/drug effects , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacology , Silicon Dioxide/chemistry , Blood-Brain Barrier/drug effects , Blood-Brain Barrier/metabolism , Male
7.
ACS Appl Mater Interfaces ; 16(28): 37087-37099, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38958653

ABSTRACT

Hydrogels, as flexible materials, have been widely used in the field of flexible sensors. Human sweat contains a variety of biomarkers that can reflect the physiological state of the human body. Therefore, it is of great practical significance and application value to realize the detection of sweat composition and combine it with human motion sensing through a hydrogel. Based on mussel-inspired chemistry, polydopamine (PDA) and gold nanoparticles (AuNPs) were coated on the surface of cellulose nanocrystals (CNCs) to obtain CNC-based nanocomposites (CNCs@PDA-Au), which could simultaneously enhance the mechanical, electrochemical, and self-healing properties of hydrogels. The CNCs@PDA-Au was composited with poly(vinyl alcohol) (PVA) hydrogel to obtain the nanocomposite hydrogel (PVA/CNCs@PDA-Au) by freeze-thaw cycles. The PVA/CNCs@PDA-Au has excellent mechanical strength (7.2 MPa) and self-healing properties (88.3%). The motion sensors designed with PVA/CNCs@PDA-Au exhibited a fast response time (122.9 ms), wide strain sensing range (0-600.0%), excellent stability, and fatigue resistance. With the unique electrochemical redox properties of uric acid, the designed hydrogel sensor successfully realized the detection of uric acid in sweat with a wide detection range (1.0-100.0 µmol/L) and low detection limit (0.42 µmol/L). In this study, the dual detection of human motion and uric acid in sweat was successfully realized by the designed PVA/CNCs@PDA-Au nanocomposite hydrogel.


Subject(s)
Cellulose , Gold , Hydrogels , Nanocomposites , Polymers , Sweat , Cellulose/chemistry , Nanocomposites/chemistry , Humans , Hydrogels/chemistry , Gold/chemistry , Sweat/chemistry , Polymers/chemistry , Metal Nanoparticles/chemistry , Polyvinyl Alcohol/chemistry , Nanoparticles/chemistry , Indoles/chemistry , Biosensing Techniques/methods , Electrochemical Techniques/methods , Limit of Detection , Motion
8.
Theranostics ; 14(10): 4014-4057, 2024.
Article in English | MEDLINE | ID: mdl-38994032

ABSTRACT

Background: The comprehensive management of diabetic bone defects remains a substantial clinical challenge due to the hostile regenerative microenvironment characterized by aggravated inflammation, excessive reactive oxygen species (ROS), bacterial infection, impaired angiogenesis, and unbalanced bone homeostasis. Thus, an advanced multifunctional therapeutic platform capable of simultaneously achieving immune regulation, bacterial elimination, and tissue regeneration is urgently designed for augmented bone regeneration under diabetic pathological milieu. Methods and Results: Herein, a photoactivated soft-hard combined scaffold system (PGCZ) was engineered by introducing polydopamine-modified zeolitic imidazolate framework-8-loaded double-network hydrogel (soft matrix component) into 3D-printed poly(ε-caprolactone) (PCL) scaffold (hard matrix component). The versatile PGCZ scaffold based on double-network hydrogel and 3D-printed PCL was thus prepared and features highly extracellular matrix-mimicking microstructure, suitable biodegradability and mechanical properties, and excellent photothermal performance, allowing long-term structural stability and mechanical support for bone regeneration. Under periodic near-infrared (NIR) irradiation, the localized photothermal effect of PGCZ triggers the on-demand release of Zn2+, which, together with repeated mild hyperthermia, collectively accelerates the proliferation and osteogenic differentiation of preosteoblasts and potently inhibits bacterial growth and biofilm formation. Additionally, the photoactivated PGCZ system also presents outstanding immunomodulatory and ROS scavenging capacities, which regulate M2 polarization of macrophages and drive functional cytokine secretion, thus leading to a pro-regenerative microenvironment in situ with enhanced vascularization. In vivo experiments further demonstrated that the PGCZ platform in conjunction with mild photothermal therapeutic activity remarkably attenuated the local inflammatory cascade, initiated endogenous stem cell recruitment and neovascularization, and orchestrated the osteoblast/osteoclast balance, ultimately accelerating diabetic bone regeneration. Conclusions: This work highlights the potential application of a photoactivated soft-hard combined system that provides long-term biophysical (mild photothermal stimulation) and biochemical (on-demand ion delivery) cues for accelerated healing of diabetic bone defects.


Subject(s)
Bone Regeneration , Hydrogels , Photothermal Therapy , Tissue Scaffolds , Animals , Mice , Bone Regeneration/drug effects , Photothermal Therapy/methods , Tissue Scaffolds/chemistry , Hydrogels/chemistry , Indoles/chemistry , Indoles/pharmacology , Neovascularization, Physiologic/drug effects , Printing, Three-Dimensional , Osteogenesis/drug effects , Polyesters/chemistry , Diabetes Mellitus, Experimental/therapy , Male , Rats , Polymers/chemistry , Reactive Oxygen Species/metabolism , Wound Healing/drug effects , Angiogenesis
9.
J Am Chem Soc ; 146(28): 19030-19041, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38976645

ABSTRACT

Artificial photoenzymes with novel catalytic modes not found in nature are in high demand; yet, they also present significant challenges in the field of biocatalysis. In this study, a chemogenetic modification strategy is developed to facilitate the rapid diversification of photoenzymes. This strategy integrates site-specific chemical conjugation of various artificial photosensitizers into natural protein cavities and the iterative mutagenesis in cell lysates. Through rounds of directed evolution, prominent visible-light-activatable photoenzyme variants were developed, featuring a thioxanthone chromophore. They successfully enabled the enantioselective [2 + 2] photocycloaddition of 2-carboxamide indoles, a class of UV-sensitive substrates that are traditionally challenging for known photoenzymes. Furthermore, the versatility of this photoenzyme is demonstrated in enantioselective whole-cell photobiocatalysis, enabling the efficient synthesis of enantioenriched cyclobutane-fused indoline tetracycles. These findings significantly expand the photophysical properties of artificial photoenzymes, a critical factor in enhancing their potential for harnessing excited-state reactivity in stereoselective transformations.


Subject(s)
Cycloaddition Reaction , Stereoisomerism , Indoles/chemistry , Indoles/chemical synthesis , Indoles/metabolism , Photochemical Processes , Biocatalysis , Directed Molecular Evolution , Photosensitizing Agents/chemistry , Photosensitizing Agents/chemical synthesis , Light , Escherichia coli/enzymology , Molecular Structure
10.
Molecules ; 29(13)2024 Jun 23.
Article in English | MEDLINE | ID: mdl-38998940

ABSTRACT

Aryl Hydrocarbon Receptor (AHR) ligands, upon binding, induce distinct gene expression profiles orchestrated by the AHR, leading to a spectrum of pro- or anti-inflammatory effects. In this study, we designed, synthesized and evaluated three indole-containing potential AHR ligands (FluoAHRL: AGT-4, AGT-5 and AGT-6). All synthesized compounds were shown to emit fluorescence in the near-infrared. Their AHR agonist activity was first predicted using in silico docking studies, and then confirmed using AHR luciferase reporter cell lines. FluoAHRLs were tested in vitro using mouse peritoneal macrophages and T lymphocytes to assess their immunomodulatory properties. We then focused on AGT-5, as it illustrated the predominant anti-inflammatory effects. Notably, AGT-5 demonstrated the ability to foster anti-inflammatory regulatory T cells (Treg) while suppressing pro-inflammatory T helper (Th)17 cells in vitro. AGT-5 actively induced Treg differentiation from naïve CD4+ cells, and promoted Treg proliferation, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) expression and interleukin-10 (IL-10) production. The increase in IL-10 correlated with an upregulation of Signal Transducer and Activator of Transcription 3 (STAT3) expression. Importantly, the Treg-inducing effect of AGT-5 was also observed in human tonsil cells in vitro. AGT-5 showed no toxicity when applied to zebrafish embryos and was therefore considered safe for animal studies. Following oral administration to C57BL/6 mice, AGT-5 significantly upregulated Treg while downregulating pro-inflammatory Th1 cells in the mesenteric lymph nodes. Due to its fluorescent properties, AGT-5 could be visualized both in vitro (during uptake by macrophages) and ex vivo (within the lamina propria of the small intestine). These findings make AGT-5 a promising candidate for further exploration in the treatment of inflammatory and autoimmune diseases.


Subject(s)
Receptors, Aryl Hydrocarbon , T-Lymphocytes, Regulatory , Animals , Receptors, Aryl Hydrocarbon/metabolism , Receptors, Aryl Hydrocarbon/agonists , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , Mice , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/chemical synthesis , Humans , Zebrafish , Fluorescent Dyes/chemistry , Ligands , Mice, Inbred C57BL , Indoles/pharmacology , Indoles/chemistry , Cell Differentiation/drug effects
11.
Int J Mol Sci ; 25(13)2024 Jun 25.
Article in English | MEDLINE | ID: mdl-39000062

ABSTRACT

The present work focuses on the synthesis of a vanadium nitride (VN)/carbon nanocomposite material via the thermal decomposition of vanadyl phthalocyanine (VOPC). The morphology and chemical structure of the synthesized compounds were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), Fourier transformed infrared spectroscopy (FTIR), X-ray diffraction (XRD), and X-ray photoemission spectroscopy (XPS). The successful syntheses of the VOPC and non-metalated phthalocyanine (H2PC) precursors were confirmed using FTIR and XRD. The VN particles present a needle-like morphology in the VN synthesized by the sol-gel method. The morphology of the VN/C composite material exhibited small clusters of VN particles. The XRD analysis of the thermally decomposed VOPC indicated a mixture of amorphous carbon and VN nanoparticles (VN(TD)) with a cubic structure in the space group FM-3M consistent with that of VN. The XPS results confirmed the presence of V(III)-N bonds in the resultant material, indicating the formation of a VN/C nanocomposite. The VN/C nanocomposite synthesized through thermal decomposition exhibited a high carbon content and a cluster-like distribution of VN particles. The VN/C nanocomposite was used as an anode material in LIBs, which delivered a specific capacity of 307 mAh g-1 after 100 cycles and an excellent Coulombic efficiency of 99.8 at the 100th cycle.


Subject(s)
Carbon , Nanocomposites , Nanocomposites/chemistry , Carbon/chemistry , Spectroscopy, Fourier Transform Infrared , X-Ray Diffraction , Indoles/chemistry , Vanadium/chemistry , Vanadium Compounds/chemistry , Photoelectron Spectroscopy
12.
J Agric Food Chem ; 72(28): 15725-15739, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38973111

ABSTRACT

Indole-3-lactic acid (ILA) has exhibited antimicrobial properties. However, its role in inhibiting Helicobacter pylori infection remains elusive. This study investigated the inhibitory effect of ILA produced by Lacticaseibacillus paracasei on H. pylori, which was further confirmed by cell and animal experiments. 5 mg/mL ILA was sufficient to directly inhibit the growth of H. pylori in vitro, with a urease inhibitory activity reaching 60.94 ± 1.03%, and the cell morphology and structure were destroyed. ILA inhibited 56.5% adhesion of H. pylori to GES-1 and significantly reduced the number of apoptotic cells. Furthermore, ILA suppresses H. pylori colonization by approximately 38% to 63%, reduced inflammation and oxidative stress in H. pylori-infected mice, and enhanced the enrichment and variety of gut microbiota, notably fostering the growth of beneficial bacteria such as Lactobacillus and Bifidobacterium strains. The results support that ILA derived from Lactobacillus can be applicated as a novel prebiotic in anti-H. pylori functional foods.


Subject(s)
Epithelial Cells , Gastric Mucosa , Helicobacter Infections , Helicobacter pylori , Indoles , Lacticaseibacillus paracasei , Helicobacter pylori/drug effects , Animals , Mice , Helicobacter Infections/drug therapy , Helicobacter Infections/microbiology , Humans , Gastric Mucosa/microbiology , Gastric Mucosa/drug effects , Indoles/pharmacology , Indoles/chemistry , Lacticaseibacillus paracasei/chemistry , Epithelial Cells/drug effects , Epithelial Cells/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Inflammation/prevention & control , Gastrointestinal Microbiome/drug effects , Male , Bacterial Adhesion/drug effects
13.
Mikrochim Acta ; 191(8): 456, 2024 07 09.
Article in English | MEDLINE | ID: mdl-38980419

ABSTRACT

Polydopamine (PDA) has garnered significant interest for applications in biosensors, drug delivery, and tissue engineering. However, similar polycatecholamines like polynorepinephrine (PNE) with additional hydroxyl groups and poly-α-methylnorepinephrine (PAMN) with additional hydroxyl and methyl groups remain unexplored in the biosensing domain. This research introduces three innovative biosensing platforms composed of ternary nanocomposite based on reduced graphene oxide (RGO), gold nanoparticles (Au NPs), and three sister polycatecholamine compounds (PDA, PNE, and PAMN). The study compares and evaluates the performance of the three biosensing systems for the ultrasensitive detection of Mycobacterium tuberculosis (MTB). The formation of the nanocomposites was meticulously examined through UV-Visible, Raman, XRD, and FT-IR studies with FE-SEM and HR-TEM analysis. Cyclic voltammetry and differential pulse voltammetry measurements were also performed to determine the electrochemical characteristics of the modified electrodes. Electrochemical biosensing experiments reveal that the RGO-PDA-Au, RGO-PNE-Au, and RGO-PAMN-Au-based biosensors detected target DNA up to a broad detection range of 0.1 × 10-8 to 0.1 × 10-18 M, with a low detection limit (LOD) of 0.1 × 10-18, 0.1 × 10-16, and 0.1 × 10-17 M, respectively. The bioelectrodes were proved to be highly selective with excellent sensitivities of 3.62 × 10-4 mA M-1 (PDA), 7.08 × 10-4 mA M-1 (PNE), and 6.03 × 10-4 mA M-1 (PAMN). This study pioneers the exploration of two novel mussel-inspired polycatecholamines in biosensors, opening avenues for functional nanocoatings that could drive further advancements in this field.


Subject(s)
Biosensing Techniques , Electrochemical Techniques , Gold , Graphite , Indoles , Limit of Detection , Metal Nanoparticles , Polymers , Biosensing Techniques/methods , Indoles/chemistry , Polymers/chemistry , Electrochemical Techniques/methods , Graphite/chemistry , Gold/chemistry , Animals , Metal Nanoparticles/chemistry , Mycobacterium tuberculosis , Bivalvia/chemistry , Nanocomposites/chemistry , Electrodes , Norepinephrine/analysis
14.
Org Lett ; 26(27): 5764-5769, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38958211

ABSTRACT

The structure-activity relationship of the unusual indolosesquiterpenoid mycoleptodiscin A is unknown due to natural scarcity and inefficient synthesis. A modular approach leveraging Larock indole synthesis has been established to access mycoleptodiscin A and a divergent collection of drimenyl indoles. It features the utilization of an inexpensive (+)-sclareolide, modularity, purification-economy, and scalability, which facilitates the first biological evaluation of mycoleptodiscin A and related precursors.


Subject(s)
Indoles , Indoles/chemistry , Indoles/pharmacology , Indoles/chemical synthesis , Molecular Structure , Structure-Activity Relationship , Sesquiterpenes/chemistry , Sesquiterpenes/chemical synthesis , Sesquiterpenes/pharmacology , Microbial Sensitivity Tests , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/chemistry , Stereoisomerism
15.
Dalton Trans ; 53(28): 11995-12006, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38963284

ABSTRACT

The spontaneous aggregation of infectious or misfolded forms of prion protein is known to be responsible for neurotoxicity in brain cells, which ultimately leads to the progression of prion disorders. Bovine spongiform encephalopathy (BSE) in animals and Creutzfeldt-Jakob disease (CJD) in humans are glaring examples in this regard. Square-planar complexes with labile ligands and indole-based compounds are found to be efficiently inhibitory against protein aggregation. Herein, we report the synthesis of an indole-based cyclometallated palladium complex. The ligand and complex were characterized by various spectroscopic techniques such as UV-visible, NMR, IR, and HRMS. The molecular structure of the complex was confirmed by single-crystal X-ray crystallography. The interaction of the complex with PrP106-126 was studied using UV-visible spectroscopy, CD spectroscopy, MALDI-TOF MS, and molecular docking. The inhibition effects of the complex on the PrP106-126 aggregation, fibrillization and amyloid formation phenomena were analysed through the ThT assay, CD, TEM and AFM. The effect of the complex on the aggregation process of PrP106-126 was determined kinetically through the ThT assay. The complex presented high binding affinity with the peptide and influenced the peptide's conformation and aggregation in different modes of binding. Furthermore, the MTT assay on neuronal HT-22 cells showed considerable protective properties of the complex against PrP106-126-mediated cytotoxicity. These findings suggest that the compound influences peptide aggregation in different ways, and the anti-aggregation action is primarily associated with the metal's physicochemical properties and the reactivity rather than the ligand. As a result, we propose that this compound be investigated as a potential therapeutic molecule in metallopharmaceutical research to treat prion disease (PD).


Subject(s)
Coordination Complexes , Indoles , Palladium , Protein Aggregates , Palladium/chemistry , Palladium/pharmacology , Humans , Indoles/chemistry , Indoles/pharmacology , Protein Aggregates/drug effects , Coordination Complexes/pharmacology , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Molecular Docking Simulation , Peptide Fragments/chemistry , Peptide Fragments/pharmacology , Peptide Fragments/metabolism , Prion Proteins/chemistry , Prion Proteins/metabolism , Prion Proteins/antagonists & inhibitors , Prions
16.
Eur J Med Chem ; 275: 116617, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-38959729

ABSTRACT

Agents that cause apoptotic cell death by interfering with tubulin dynamics, such as vinblastine and paclitaxel, are an important class of chemotherapeutics. Unfortunately, these compounds are substrates for multidrug resistance (MDR) pumps, allowing cancer cells to gain resistance to these chemotherapeutics. The indolesulfonamide family of tubulin inhibitors are not excluded by MDR pumps and have a promising activity profile, although their high lipophilicity is a pharmacokinetic limitation for their clinical use. Here we present a new family of N-indolyl-3,4,5-trimethoxybenzenesulfonamide derivatives with modifications on the indole system at positions 1 and 3 and on the sulfonamide nitrogen. We synthesized and screened against HeLa cells 34 novel indolic benzenesulfonamides. The most potent derivatives (1.7-109 nM) were tested against a broad panel of cancer cell lines, which revealed that substituted benzenesulfonamides analogs had highest potency. Importantly, these compounds were only moderately toxic to non-tumorigenic cells, suggesting the presence of a therapeutic index. Consistent with known clinical anti-tubulin agents, these compounds arrested the cell cycle at G2/M phase. Mechanistically, they induced apoptosis via caspase 3/7 activation, which occurred during M arrest. The substituents on the sulfonamide nitrogen appeared to determine different mechanistic results and cell fates. These results suggest that the compounds act differently depending on the bridge substituents, thus making them very interesting as mechanistic probes as well as potential drugs for further development.


Subject(s)
Antineoplastic Agents , Apoptosis , Benzenesulfonamides , Cell Proliferation , Drug Screening Assays, Antitumor , Indoles , Sulfonamides , Humans , Sulfonamides/chemistry , Sulfonamides/pharmacology , Sulfonamides/chemical synthesis , Cell Proliferation/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Structure-Activity Relationship , Apoptosis/drug effects , Molecular Structure , Indoles/chemistry , Indoles/pharmacology , Indoles/chemical synthesis , Dose-Response Relationship, Drug , Nitrogen/chemistry , Cell Line, Tumor , HeLa Cells , Tubulin Modulators/pharmacology , Tubulin Modulators/chemistry , Tubulin Modulators/chemical synthesis
17.
Anal Chim Acta ; 1317: 342920, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-39030014

ABSTRACT

BACKGROUND: As a broad-spectrum tetracycline antibiotic, Oxytetracycline (OTC) was widely used in a variety of applications. But, the overuse of OTC had led to the detection of it in food, water and soil, which could present significance risk to human health and cause damage to ecosystem. It was of great significance to develop sensitive detection methods for OTC. Herein, an environmentally friendly photoelectrochemical (PEC) aptasensor was constructed for the sensitive detection of OTC based on CuO-induced BiOBr/Ag2S/PDA (Polydopamine) photocurrent polarity reversal. RESULTS: BiOBr/Ag2S/PDA composites modified electrode not only produced stable initial anodic photocurrent but also provided attachment sites for the aptamer S1 of OTC by the strong adhesion of PDA. On the other hand, CuO loaded OTC aptamer S2 (Cu-S2) was got through Cu-S bonds. After the target OTC was identified on the electrode surface, CuO was introduced to the surface of ITO/BiOBr/Ag2S/PDA through the specific binding of OTC to S2. This identification process formed dual Z-type heterojunctions and resulted in a remarkable reversal of photocurrent polarity from anodic to cathodic. Under optimization conditions, the PEC aptasensor showed a wide linear range (50 fM âˆ¼ 100 nM), low detection limit (1.9 fM), excellent selectivity, stability and reproducibility for the detection of OTC. Moreover, it was successfully used for the analysis of OTC in real samples of tap water, milk and honey, and had the potential for practical application. SIGNIFICANCE: This work developed an environmentally friendly photocurrent-polarity-switching PEC aptasensor with excellent selectivity, reproducibility, stability, low LOD and wide linear range for OTC detection. This sensitive system, which was including BiOBr, Ag2S, PDA and CuO were low toxicity, not only reduced the risk of traditional toxic semiconductors to operators and the environment, but can also be used for the detection of real samples, broadening the wider range of applications for BiOBr, Ag2S, PDA and CuO.


Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , Bismuth , Copper , Electrochemical Techniques , Oxytetracycline , Oxytetracycline/analysis , Copper/chemistry , Aptamers, Nucleotide/chemistry , Electrochemical Techniques/methods , Bismuth/chemistry , Photochemical Processes , Silver Compounds/chemistry , Polymers/chemistry , Electrodes , Animals , Limit of Detection , Indoles/chemistry , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/chemistry
18.
World J Microbiol Biotechnol ; 40(9): 270, 2024 Jul 20.
Article in English | MEDLINE | ID: mdl-39030429

ABSTRACT

Bacterial pigments stand out as exceptional natural bioactive compounds with versatile functionalities. The pigments represent molecules from distinct chemical categories including terpenes, terpenoids, carotenoids, pyridine, pyrrole, indole, and phenazines, which are synthesized by diverse groups of bacteria. Their spectrum of physiological activities encompasses bioactive potentials that often confer fitness advantages to facilitate the survival of bacteria amid challenging environmental conditions. A large proportion of such pigments are produced by bacterial pathogens mostly as secondary metabolites. Their multifaceted properties augment potential applications in biomedical, food, pharmaceutical, textile, paint industries, bioremediation, and in biosensor development. Apart from possessing a less detrimental impact on health with environmentally beneficial attributes, tractable and scalable production strategies render bacterial pigments a sustainable option for novel biotechnological exploration for untapped discoveries. The review offers a comprehensive account of physiological role of pigments from bacterial pathogens, production strategies, and potential applications in various biomedical and biotechnological fields. Alongside, the prospect of combining bacterial pigment research with cutting-edge approaches like nanotechnology has been discussed to highlight future endeavours.


Subject(s)
Bacteria , Pigments, Biological , Pigments, Biological/chemistry , Pigments, Biological/metabolism , Bacteria/metabolism , Biotechnology/methods , Carotenoids/metabolism , Carotenoids/chemistry , Indoles/metabolism , Indoles/chemistry , Terpenes/metabolism , Terpenes/chemistry , Pyridines/metabolism , Pyridines/chemistry , Pyrroles/metabolism , Pyrroles/chemistry , Biosensing Techniques , Phenazines/metabolism , Phenazines/chemistry
19.
Bioorg Med Chem Lett ; 110: 129877, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38964518

ABSTRACT

Small cell lung cancer (SCLC) keeps on the leading cause of cancer mortality world widely, while there is lack of efficient therapeutic drugs especially for the resistant ones. In this work, a compound named penindolone (PND) with new skeleton was found to show weak inhibitory effect (IC50 = 42.5 µM) on H69AR cells (SCLC, adriamycin-resistant) proliferation by screening our in-house compound library. With the aim of improving its low potency, a series of PND derivatives were synthesized and biologically evaluated by the Sulforhodamine B (SRB) assay. Among all tested derivatives, compound 5h possessed higher antiproliferation potency (IC50 = 1.6 µM). Furthermore, preliminary mechanism investigation revealed that 5h was able to induce apoptosis and arrest the cell cycle at G0/G1 phase. These findings suggest that this novel skeleton has expanded the anti-SCLC compound reservoir and provided a new drug lead.


Subject(s)
Antineoplastic Agents , Apoptosis , Cell Proliferation , Drug Screening Assays, Antitumor , Lung Neoplasms , Humans , Cell Proliferation/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Structure-Activity Relationship , Cell Line, Tumor , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Apoptosis/drug effects , Molecular Structure , Small Cell Lung Carcinoma/drug therapy , Small Cell Lung Carcinoma/pathology , Dose-Response Relationship, Drug , Indoles/pharmacology , Indoles/chemistry , Indoles/chemical synthesis , Indenes
20.
Int J Nanomedicine ; 19: 6377-6397, 2024.
Article in English | MEDLINE | ID: mdl-38952677

ABSTRACT

Background: How to ingeniously design multi-effect photosensitizers (PSs), including multimodal imaging and multi-channel therapy, is of great significance for highly spatiotemporal controllable precise phototherapy of malignant tumors. Methods: Herein, a novel multifunctional zinc(II) phthalocyanine-based planar micromolecule amphiphile (ZnPc 1) was successfully designed and synthesized, in which N atom with photoinduced electron transfer effect was introduced to enhance the near-infrared absorbance and nonradiative heat generation. After simple self-assembling into nanoparticles (NPs), ZnPc 1 NPs would exhibit enhanced multimodal imaging properties including fluorescence (FL) imaging (FLI) /photoacoustic (PA) imaging (PAI) /infrared (IR) thermal imaging, which was further used to guide the combined photodynamic therapy (PDT) and photothermal therapy (PTT). Results: It was that under the self-guidance of the multimodal imaging, ZnPc 1 NPs could precisely pinpoint the tumor from the vertical and horizontal boundaries achieving highly efficient and accurate treatment of cancer. Conclusion: Accordingly, the integration of FL/PA/IR multimodal imaging and PDT/PTT synergistic therapy pathway into one ZnPc 1 could provide a blueprint for the next generation of phototherapy, which offered a new paradigm for the integration of diagnosis and treatment in tumor and a promising prospect for precise cancer therapy.


Subject(s)
Indoles , Isoindoles , Multimodal Imaging , Nanoparticles , Photochemotherapy , Photosensitizing Agents , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Multimodal Imaging/methods , Animals , Humans , Indoles/chemistry , Indoles/pharmacology , Photochemotherapy/methods , Nanoparticles/chemistry , Mice , Zinc Compounds/chemistry , Organometallic Compounds/chemistry , Organometallic Compounds/pharmacology , Cell Line, Tumor , Photoacoustic Techniques/methods , Photothermal Therapy/methods , Neoplasms/diagnostic imaging , Neoplasms/therapy , Neoplasms/drug therapy , Mice, Inbred BALB C , Phototherapy/methods , Female
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