EGCG Disrupts the LIN28B/Let-7 Interaction and Reduces Neuroblastoma Aggressiveness.

Neuroblastoma (NB) is the most commonly diagnosed extracranial solid tumor in children, accounting for 15% of all childhood cancer deaths. Although the 5-year survival rate of patients with a high-risk disease has increased in recent decades, NB remains a challenge in pediatric oncology, and the identification of novel potential therapeutic targets and agents is an urgent clinical need. The RNA-binding protein LIN28B has been identified as an oncogene in NB and is associated with a poor prognosis. Given that LIN28B acts by negatively regulating the biogenesis of the tumor suppressor let-7 miRNAs, we reasoned that selective interference with the LIN28B/let-7 miRNA interaction would increase let-7 miRNA levels, ultimately leading to reduced NB aggressiveness. Here, we selected (-)-epigallocatechin 3-gallate (EGCG) out of 4959 molecules screened as the molecule with the best inhibitory activity on LIN28B/let-7 miRNA interaction and showed that treatment with PLC/PLGA-PEG nanoparticles containing EGCG (EGCG-NPs) led to an increase in mature let-7 miRNAs and a consequent inhibition of NB cell growth. In addition, EGCG-NP pretreatment reduced the tumorigenic potential of NB cells in vivo. These experiments suggest that the LIN28B/let-7 miRNA axis is a good therapeutic target in NB and that EGCG, which can interfere with this interaction, deserves further preclinical evaluation.

Formation mechanism of quinoa protein hydrolysate-EGCG complexes at different pH conditions and its effect on the protein hydrolysate-lipid co-oxidation in emulsions.

This study aimed to investigate the interaction, structure, antioxidant, and emulsification properties of quinoa protein hydrolysate (QPH) complexes formed with (-)-epigallocatechin gallate (EGCG) at pH 3.0 and 7.0. Additionally, the effect of pH conditions and EGCG complexation on protein hydrolysate-lipid co-oxidation in QPH emulsions was explored. The results indicated that QPH primarily interacted with EGCG through hydrophobic interactions and hydrogen bonds. This interaction led to alterations in the secondary structure of QPH, as well as a decrease in surface hydrophobicity and free SH content. Notably, the binding affinity between QPH and EGCG was observed to be higher at pH 7.0 compared to pH 3.0. Consequently, QPH-EGCG complexes exhibited more significant enhancement in antioxidant and emulsification properties at pH 7.0 than pH 3.0. The pH level also influenced the droplet size, ζ-potential, and interfacial composition of emulsions formed by QPH and QPH-EGCG complexes. Compared to QPH stabilized emulsions, QPH-EGCG stabilized emulsions were more capable of mitigating destabilization during storage and displayed fewer lipid oxidation products, carbonyl generation, and sulfhydryl groups and fluorescence loss, which implied better oxidative stability of the emulsions. Furthermore, the QPH-EGCG complexes formed at pH 7.0 exhibited better inhibition of protein hydrolysate-lipid co-oxidation. Overall, these findings provide valuable insights into the potential application of QPH and its complexes with EGCG in food processing systems.

Simultaneous determination of six catechins and caffeine in tea and wine using salting-out assisted liquid-liquid extraction and high-performance liquid chromatography with ultraviolet detection.

Catechins, renowned for their antioxidant properties and health benefits, are commonly present in beverages, particularly tea and wine. An efficient and cost-effective salting-out assisted liquid-liquid extraction (SALLE) method has been developed and validated for the simultaneous determination of six catechins and caffeine in tea and wine samples using high-performance liquid chromatography-ultraviolet (HPLC-UV). This method demonstrates outstanding performance: linearity (1-120 µg/mL, r2 > 0.999), accuracy (96.5%-103.4% recovery), and precision (≤14.7% relative standard deviation), meeting validation requirements set by the US Food and Drug Administration. The reduced sample size (0.1 g) minimizes matrix interferences and costs without compromising sensitivity. All analytes were detected in Camellia sinensis teas, with green tea displaying the highest total catechin content (47.5-100.1 mg/mL), followed by white and black teas. Analysis of wine samples reveals the presence of catechin in all red and white wines, and epigallocatechin gallate in all red wine samples, highlighting the impact of winemaking processes on catechin content. The SALLE-HPLC-UV approach represents a green alternative by eliminating organic waste, surpassing conventional dilution methods in specificity and sensitivity for catechin determination. AGREEprep assessment emphasizes the strengths of the SALLE procedure, including material reusability, throughput efficiency, minimal sample requirements, low energy consumption, and the absence of organic waste generation.

Phenolic compound profiling and antioxidant potential of different types of Schisandra henryi in vitro cultures.

Schisandra henryi is an endemic species of medicinal potential known from traditional Chinese medicine. As part of this study, a complex biotechnological and phytochemical assessment was conducted on S. henryi with a focus on phenolic compounds and antioxidant profiling. The following in vitro cultures were tested: microshoot agar and callus, microshoot agitated, and suspension, along with the microshoot culture in PlantForm bioreactors. Qualitative profiling was performed by ultra-high-performance liquid chromatography with a photodiode array detector coupled with ion-trap mass spectrophotometry with electrospray ionization and then quantitative analysis by high-performance liquid chromatography with a diode array detector using standards. In the extracts, mainly the compounds from procyanidins were identified as well as phenolic acids (neochlorogenic acid, caffeic acid, protocatechuic acid) and catechin. The highest content of phenolic compounds was found for in vitro agar microshoot culture (max. total content 229.87 mg/100 g DW) and agitated culture (max. total content 22.82 mg/100 g DW). The max. TPC measured using the Folin-Ciocalteu assay was equal to 1240.51 mg GAE/100 g DW (agar microshoot culture). The extracts were evaluated for their antioxidant potential by the DPPH, FRAP, and chelate iron ion assays. The highest potential was indicated for agar microshoot culture (90% of inhibition and 59.31 nM/L TEAC, respectively). The research conducted on the polyphenol profiling and antioxidant potential of S. henryi in vitro culture extracts indicates the high therapeutic potential of this species. KEY POINTS: • Different types of S. henryi in vitro cultures were compared for the first time. • The S. henryi in vitro culture strong antioxidant potential was determined for the first time. • The polyphenol profiling of different types of S. henryi in vitro cultures was shown.

Changes in amino acids, catechins and alkaloids during the storage of oolong tea and their relationship with antibacterial effect.

The storage process has a significant impact on tea quality. Few is known about effect of storage on quality of oolong tea. This study aimed to assess the effect of different storage times on the key chemical components of oolong tea by measuring changes in catechin, free amino acid, and alkaloid content. Variation in the main substances was determined by principal component analysis and heat map analysis. The results revealed notable effects of the storage process on the levels of theanine, epigallocatechin gallate (EGCG), and glutamine. These findings suggest that these compounds could serve as indicators for monitoring changes in oolong tea quality during storage. Additionally, the study observed an increase in the antibacterial ability of tea over time. Correlation analysis indicated that the antibacterial ability against Micrococcus tetragenus and Escherichia coli was influenced by metabolites such as aspartic acid, threonine, serine, gamma-aminobutyric acid, ornithine, alanine, arginine, and EGCG. Overall, this study presents an approach for identifying key metabolites to monitor tea quality effectively with relatively limited data.

Antibacterial Activity of Epigallocatechin-3-gallate (EGCG) Loaded Lipid-chitosan Hybrid Nanoparticle against Planktonic Microorganisms.

Epigallocatechin-3-gallate (EGCG), a polyphenol derived from Green Tea, is one of the sources of natural bioactive compounds which are currently being developed as medicinal ingredients. Besides other biological activities, this natural compound exhibits anti-cariogenic effects. However, EGCG has low physical-chemical stability and poor bioavailability. Thus, the purpose of this study was to develop and characterize lipid-chitosan hybrid nanoparticle with EGCG and to evaluate its in vitro activity against cariogenic planktonic microorganisms. Lipid-chitosan hybrid nanoparticle (LCHNP-EGCG) were prepared by emulsion and sonication method in one step and characterized according to diameter, polydispersity index (PdI), zeta potential (ZP), encapsulation efficiency (EE), mucoadhesion capacity and morphology. Strains of Streptococcus mutans, Streptococcus sobrinus and Lactobacillus casei were treated with LCHNP- EGCG, and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were evaluated. LCHNP-EGCG exhibited a size of 217.3 ± 5.1 nm with a low polydispersity index (0.17) and positive zeta potential indicating the presence of chitosan on the lipid nanoparticle surface (+33.7 mV). The LCHNP-EGCG showed a spherical morphology, high stability and a mucoadhesive property due to the presence of chitosan coating. In addition, the EGCG encapsulation efficiency was 96%. A reduction of almost 15-fold in the MIC and MBC against the strains was observed when EGCG was encapsulated in LCHNP, indicating the potential of EGCG encapsulation in lipid-polymer hybrid nanoparticles. Taking the results together, the LCHNP-EGCG could be an interesting system to use in dental care due to their nanometric size, mucoadhesive properties high antibacterial activity against relevant planktonic microorganisms.

Integrated transcriptomics and metabolomics revealed the mechanism of catechin biosynthesis in response to lead stress in tung tree (Vernicia fordii).

Lead (Pb) affects gene transcription, metabolite biosynthesis and growth in plants. The tung tree (Vernicia fordii) is highly adaptive to adversity, whereas the mechanisms underlying its response to Pb remain uncertain. In this work, transcriptomic and metabolomic analyses were employed to study tung trees under Pb stress. The results showed that the biomass of tung seedlings decreased with increasing Pb doses, and excessive Pb doses resulted in leaf wilting, root rot, and disruption of Pb homeostasis. Under non-excessive Pb stress, a significant change in the expression patterns of flavonoid biosynthesis genes was observed in the roots of tung seedlings, leading to changes in the accumulation of flavonoids in the roots, especially the upregulation of catechins, which can chelate Pb and reduce its toxicity in plants. In addition, Pb-stressed roots showed a large accumulation of VfWRKY55, VfWRKY75, and VfLRR1 transcripts, which were shown to be involved in the flavonoid biosynthesis pathway by gene module analysis. Overexpression of VfWRKY55, VfWRKY75, and VfLRR1 significantly increased catechin concentrations in tung roots, respectively. These data indicate that Pb stress-induced changes in the expression patterns of those genes regulate the accumulation of catechins. Our findings will help to clarify the molecular mechanism of Pb response in plants.

Antibiofilm Activity of Combretum micranthum G. Don Catechin-Sugar Phytocomplex on Pseudomonas aeruginosa.

Clinicians often have to face infections caused by microorganisms that are difficult to eradicate due to their resistance and/or tolerance to antimicrobials. Among these pathogens, Pseudomonas aeruginosa causes chronic infections due to its ability to form biofilms on medical devices, skin wounds, ulcers and the lungs of patients with Cystic Fibrosis. In this scenario, the plant world represents an important reservoir of natural compounds with antimicrobial and/or antibiofilm properties. In this study, an extract from the leaves of Combretum micranthum G. Don, named Cm4-p, which was previously investigated for its antimicrobial activities, was assayed for its capacity to inhibit biofilm formation and/or to eradicate formed biofilms. The model strain P. aeruginosa PAO1 and its isogenic biofilm hyperproducer derivative B13 were treated with Cm4-p. Preliminary IR, UV-vis, NMR, and mass spectrometry analyses showed that the extract was mainly composed of catechins bearing different sugar moieties. The phytocomplex (3 g/L) inhibited the biofilm formation of both the PAO1 and B13 strains in a significant manner. In light of the obtained results, Cm4-p deserves deeper investigations of its potential in the antimicrobial field.

Insight into the structural characteristics of self-assembled liposome with epigallocatechin gallate/alcohol dehydrogenase.

In this study, the encapsulation and structural characteristics of the self-assembled liposome formed by epigallocatechin gallate (EGCG) and alcohol dehydrogenase (ADH) were studied. According to the results, EGCG significantly increased the catalytic activity of ADH with a 33.33 % activation rate and the liposomes were able to entrap EGCG-ADH with an effectiveness of 88.94 %. The self-assembled monolayers had nanometer-sized particles, and the excellent self-assembled system was demonstrated by the low PDI value and high surface absolute potential. The scanning electron microscope showed that the self-assembled liposome was honeycomb, groove-shaped, and rough. The spectroscopic results showed that EGCG-ADH complex was formed through hydrogen bond, which changed the secondary structure of the liposome, and verified EGCG-ADH liposome system was successfully prepared. In vitro digestion experiments showed that the gastrointestinal tolerance and antioxidant activity of EGCG-ADH liposomes were significantly higher than those of free EGCG-ADH.

Biophysical insight into the binding mechanism of epigallocatechin-3-gallate and cholecalciferol to albumin and its preventive effect against AGEs formation: An in vitro and in silico approach.

Advanced glycation end products (AGEs) are produced non-enzymatically through the process of glycation. Increased AGEs production has been linked to several diseases including polycystic ovary syndrome (PCOS). PCOS contributes to the development of secondary comorbidities, such as diabetes, cardiovascular complications, infertility, etc. Consequently, research is going on AGEs-inhibiting phytochemicals for their potential to remediate and impede the progression of hyperglycaemia associated disorders. In this study human serum albumin is used as a model protein, as albumin is predominantly present in follicular fluid. This article focusses on the interaction and antiglycating potential of (-)-Epigallocatechin-3-gallate (EGCG) and vitamin D in combination using various techniques. The formation of the HSA-EGCG and HSA-vitamin D complex was confirmed by UV and fluorescence spectroscopy. Thermodynamic analysis verified the spontaneity of reaction, and presence of hydrogen bonds and van der Waals interactions. FRET confirms high possibility of energy transfer. Cumulative antiglycation resulted in almost 60 % prevention in AGEs formation, decreased alterations at lysine and arginine, and reduced protein carbonylation. Secondary and tertiary structural changes were analysed by circular dichroism, Raman spectroscopy and ANS binding assay. Type and size of aggregates were confirmed by Rayleigh and dynamic light scattering, ThT fluorescence, SEM and SDS-PAGE. Effect on cellular redox status, DNA integrity and cytotoxicity was analysed in lymphocytes using dichlorofluorescein (DCFH-DA), DAPI and MTT assay which depicted an enhancement in antioxidant level by cumulative treatment. These findings indicate that EGCG and vitamin D binds strongly to HSA and have antiglycation ability which enhances upon synergism.

Polyphenol oxidase mediates (-)-epigallocatechin gallate to inhibit endogenous cathepsin activity in Apostichopus japonicus.

Apostichopus japonicus (A. japonicus) has rich nutritional value and is an important economic crop. Due to its rich endogenous enzyme system, fresh A. japonicus is prone to autolysis during market circulation and storage, resulting in economic losses. In order to alleviate this phenomenon, we investigated the effect of polyphenol oxidase (PPO) mediated (-)-epigallocatechin gallate (EGCG) on the activity and structure of endogenous cathepsin series protein (CEP) from A. japonicus. Research on cathepsin activity showed that PPO mediated EGCG could significantly reduce enzyme activity, resulting in a decrease in enzymatic reaction rate. SDS-PAGE and scanning electron microscopy results showed that PPO mediates EGCG could induce CEP aggregation to form protein aggregates. Various spectral results indicated that EGCG caused changes in the structure of CEP. Meanwhile, the conjugates formed by PPO mediated EGCG had lower thermal stability. In conclusion, PPO mediated EGCG was an effective method to inhibit the endogenous enzyme activity.

Enhancing the emulsion properties and bioavailability of loaded astaxanthin by selecting the reaction sequence of ternary conjugate emulsifiers in nanoemulsions.

This study investigated the effects of the conjugate reaction sequences of whey protein concentrate (WPC), epigallocatechin gallate (EGCG) and dextran (DEX) on the structure and emulsion properties of conjugates and the bioaccessibility of astaxanthin (AST). Two types of ternary covalent complexes were synthesised using WPC, EGCG and DEX, which were regarded as emulsifiers of AST nanoemulsions. Results indicated that the WPC-DEX-EGCG conjugate (referred to as 'con') exhibits a darker SDS-PAGE dispersion band and higher contents of α-helix (6%), ß-angle (24%) and random coil (32%), resulting in a greater degree of unfolding structure and fluorescence quenching. These findings suggested WPC-DEX-EGCG con had the potential to exhibit better emulsification properties than WPC-EGCG-DEX con. AST encapsulation efficiency (76.22%) and bioavailability (31.89%) also demonstrated the superior performance of the WPC-DEX-EGCG con emulsifier in nanoemulsion delivery systems. These findings indicate that altering reaction sequences changes protein conformation, enhancing the emulsification properties and bioavailability of AST.

Enhanced in vitro bioavailability of resveratrol-loaded emulsion stabilized by ß-lactoglobulin-catechin with excellent antioxidant activity.

The study aimed to fabricate ß-Lactoglobulin-catechin (ß-La-Ca) conjugates as a natural designed antioxidant emulsifier to improve the physicochemical stability of resveratrol emulsion delivery system. Fourier transform infrared (FT-IR) and fluorescence spectroscopy analysis confirmed the formation of conjugates using free radical grafting. The antioxidant ability of emulsion was evaluated by DPPH scavenging activities and ORAC experiments. The emulsion stabilized by ß-La-Ca conjugates exhibited strong antioxidant activity with ORAC value of 2541.39 ± 29.58 µmol TE/g, which was significantly higher than that by ß-Lactoglobulin alone with 387.96 ± 23.45 µmol TE/g or their mixture with 948.23 ± 32.77 µmol TE/g. During the whole simulated gastrointestinal digestion, emulsion stabilized by ß-La-Ca conjugates exhibited excellent oxidative stability that the lipid was mainly digested in the small intestine. This behavior attributed to the greater stability of resveratrol to chemical transformation leading to a higher overall bioavailability in vivo. These results suggested that the ß-La-Ca conjugates could be used to fabricate the emulsion-based delivery system to improve the oxidative stability and bioavailability of chemically labile hydrophobic bioactive compounds.

Improving structural and functional properties of starch-catechin-based green nanofiber mats for active food packaging by electrospinning and crosslinking techniques.

The hydrophilic and low mechanical properties limited the application of starch-based films. In this work, a hydrophobic starch-based nanofiber mat was first successfully prepared from aqueous solution at room temperature by using electrospinning and glutaraldehyde (GTA) vapor phase crosslinking techniques for active packaging applications. Catechin (CAT) was immobilized in the nanofibers by electrospinning, resulting in higher thermal stability (Tdmax = 315.23 °C), antioxidant (DPPH scavenging activity = 94.31 ± 2.70 %) and antimicrobial (inhibition zone diameter = 15.6 ± 0.3 mm) of the fibers, which further demonstrated hydrogen bonding and electrostatic interaction between CAT and fibers. Nanofibers after GTA vapor phase crosslinking exhibited enhanced hydrophobicity (water contact angle: 15.6 ± 1.5° â†’ 93.5 ± 2.3°) and mechanical properties (tensile strength: 1.82 ± 0.06 MPa â†’ 7.64 ± 0.24 MPa, elastic modulus: 19.35 ± 0.63 MPa â†’ 45.34 ± 0.51 MPa). The results demonstrated that preparation of starch-based electrospun nanofiber mats in aqueous system at room temperature overcame the challenges of organic solvent pollution and thermosensitive material encapsulation, while GTA vapor phase crosslinking technique improved the hydrophobicity and mechanical properties of nanofiber mats, which facilitated the application of starch-based materials in the field of packaging.

EGCG suppresses PD-1 expression of T cells via inhibiting NF-κB phosphorylation and nuclear translocation.

Epigallocatechin-3-gallate (EGCG) is an important tea polyphenol with anti-tumor potential. Our previous studies revealed that EGCG was a promising immune checkpoint inhibitor (ICI) as it could downregulate expression of programmed cell death 1 ligand 1 (PD-L1) in tumor cells, thereby resulting tumor killing effect. In particular, EGCG can effectively avoid the inflammatory storm caused by anti-tumor therapy, which is a healthy green capacity absent from many ICIs. However, the relationship between EGCG and programmed cell death 1 (PD-1) of T cells remains unclear. In this work, we explored the effect of EGCG on T cells and found that EGCG suppressed PD-1 via inhibiting NF-κB phosphorylation and nuclear translocation. Furtherly, the capability of EGCG was confirmed in tumor-bearing mice to inhibit PD-1 expression in T cells and enhance apoptosis in tumor cells. These results implied that EGCG could inhibit the expression of PD-1 in T cells, thereby promoting anti-tumor effects of T cells. EGCG will be a promising candidate in anti-tumor therapy.

Polyphenol-Assisted Biomineralization of Metal-Organic Framework Nanoparticles for Precision Delivery of Therapeutic Proteins to Cancer Cells.

The delivery of proteins into the cytosol holds great promise for cell signaling manipulation and the development of precision medicine. However, this potency is challenged by achieving targeted and controlled delivery, specifically within diseased cells. In this study, we introduce a versatile and effective method for the precision delivery of therapeutic proteins to cancer cells by designing polyphenol-assisted biomineralization of zeolite imidazole framework-8 (ZIF-8). We demonstrate that by leveraging the strong noncovalent binding affinity of epigallocatechin gallate (EGCG) with both proteins and ZIF-8, our approach significantly enhances the biomineralization of ZIF-8, which in turn improves the efficiency of protein encapsulation and intracellular delivery. Moreover, the incorporation of EGCG within ZIF-8 enables controlled degradation of the nanoparticles and the selective release of the encapsulated proteins in cancer cells. This selective release is triggered by the oxidation of EGCG in response to the high levels of reactive oxygen species (ROS) found within cancer cells that destabilize the EGCG/ZIF-8 nanoparticles. We have further demonstrated the ability of EGCG/ZIF-8 to deliver a wide range of proteins into cancer cells, including bacterial virulence protein, to rewire cell signaling and prohibit tumor cell growth in a mouse xenograft model. Our strategy and findings underscore the potential of designing the EGCG/ZIF-8 interface for specific and controlled protein delivery for targeted cancer therapy.

Study on the interaction mechanism between (-)-epigallocatechin-3-gallate and myoglobin: Multi-spectroscopies and molecular simulation.

(-)-Epigallocatechin-3-gallate (EGCG) is remarkably efficacious in inhibiting the browning of red meat. We therefore propose a hypothesis that EGCG forms complexes with myoglobin, thereby stabilizing its structure and thus preventing browning. This study investigated the interaction mechanism between EGCG and myoglobin. EGCG induced static quenching of myoglobin. Noncovalent forces, including hydrogen bonds and van der Waals, primarily governing the interactions between myoglobin and EGCG. The interactions primarily disrupted myoglobin's secondary structure, thus significantly reducing surface hydrophobicity by 53% (P < 0.05). The modification augmented the solubility and thermal stability of myoglobin. The radius of gyration (Rg) value fluctuated between 1.47 and 1.54 nm, and the hydroxyl groups in EGCG formed an average of 2.93 hydrogen bonds with myoglobin. Our findings elucidated the formation of stable myoglobin-EGCG complexes and the myoglobin-EGCG interaction, thus confirming our initial hypothesis.

Selection of Catechin Biosynthesis-Related Genes and Functional Analysis from Chromosome-Level Genome Assembly in C. sinensis L. Variety 'Sangmok'.

Camellia is an important plant genus that includes well-known species such as C. sinensis, C. oleifera, and C. japonica. The C. sinensis cultivar 'Sangmok', one of Korea's standard types of tea landraces, is a small evergreen tree or shrub. Genome annotation has shown that Korean tea plants have special and unique benefits and superior components, such as catechin. The genome of Camellia sinensis cultivar 'Sangmok' was assembled on the chromosome level, with a length of 2678.62 Mbp and GC content of 38.16%. Further, 15 chromosome-scale scaffolds comprising 82.43% of the assembly (BUSCO completeness, 94.3%) were identified. Analysis of 68,151 protein-coding genes showed an average of 5.003 exons per gene. Among 82,481 coding sequences, the majority (99.06%) were annotated by Uniprot/Swiss-Prot. Further analysis revealed that 'Sangmok' is closely related to C. sinensis, with a divergence time of 60 million years ago. A total of 3336 exclusive gene families in 'Sangmok' were revealed by gene ontology analysis to play roles in auxin transport and cellular response mechanisms. By comparing these exclusive genes with 551 similar catechin genes, 17 'Sangmok'-specific catechin genes were identified by qRT-PCR, including those involved in phytoalexin biosynthesis and related to cytochrome P450. The 'Sangmok' genome exhibited distinctive genes compared to those of related species. This comprehensive genomic investigation enhances our understanding of the genetic architecture of 'Sangmok' and its specialized functions. The findings contribute valuable insights into the evolutionary and functional aspects of this plant species.

Phase I/II clinical trial of efficacy and safety of EGCG oxygen nebulization inhalation in the treatment of COVID-19 pneumonia patients with cancer.

BACKGROUND: The antiviral drug Nirmatrelvir was found to be a key drug in controlling the progression of pneumonia during the infectious phase of COVID-19. However, there are very few options for effective treatment for cancer patients who have viral pneumonia. Glucocorticoids is one of the effective means to control pneumonia, but there are many adverse events. EGCG is a natural low toxic compound with anti-inflammatory function. Thus, this study was designed to investigate the safety and efficacy of epigallocatechin-3-gallate (EGCG) aerosol to control COVID-19 pneumonia in cancer populations. METHODS: The study was designed as a prospective, single-arm, open-label phase I/II trial at Shandong Cancer Hospital and Institute, between January 5, 2023 to March 31,2023 with viral pneumonia on radiographic signs after confirmed novel coronavirus infection. These patients were treated with EGCG nebulization 10 ml three times daily for at least seven days. EGCG concentrations were increased from 1760-8817umol/L to 4 levels with dose escalation following a standard Phase I design of 3-6 patients per level. Any grade adverse event caused by EGCG was considered a dose-limiting toxicity (DLT). The maximum tolerated dose (MTD) is defined as the highest dose with less than one-third of patients experiencing dose limiting toxicity (DLT) due to EGCG. The primary end points were the toxicity of EGCG and CT findings, and the former was graded by Common Terminology Criteria for Adverse Events (CTCAE) v. 5.0. The secondary end point was the laboratory parameters before and after treatment. RESULT: A total of 60 patients with high risk factors for severe COVID-19 pneumonia (factors such as old age, smoking and combined complications)were included in this phase I-II study. The 54 patients in the final analysis were pathologically confirmed to have tumor burden and completed the whole course of treatment. A patient with bucking at a level of 1760 umol/L and no acute toxicity associated with EGCG has been reported at the second or third dose gradients. At dose escalation to 8817umol/L, Grade 1 adverse events of nausea and stomach discomfort occurred in two patients, which resolved spontaneously within 1 hour. After one week of treatment, CT showed that the incidence of non-progression of pneumonia was 82% (32/39), and the improvement rate of pneumonia was 56.4% (22/39). There was no significant difference in inflammation-related laboratory parameters (white blood cell count, lymphocyte count, IL-6, ferritin, C-reactive protein and lactate dehydrogenase) before and after treatment. CONCLUSION: Aerosol inhalation of EGCG is well tolerated, and preliminary investigation in cancer population suggests that EGCG may be effective in COVID-19-induced pneumonia, which can promote the improvement of patients with moderate pneumonia or prevent them from developing into severe pneumonia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05758571. Date of registration: 8 February 2023.

Epigallocatechin-3-gallate derived polymer coated Prussian blue for synergistic ROS elimination and antibacterial therapy.

Reactive oxygen species (ROS) play a vital role in wound healing process by fighting against invaded bacteria. However, excess ROS at the wound sites lead to oxidative stress that can trigger deleterious effects, causing cell death, tissue damage and chronic inflammation. Therefore, we fabricated a core-shell structured nanomedicine with antibacterial and antioxidant properties via a facile and green strategy. Specifically, Prussian blue (PB) nanozyme was fabricated and followed by coating a layer of epigallocatechin-3-gallate (EGCG)-derived polymer via polyphenolic condensation reaction and self-assembly process, resulting in PB@EGCG. The introduction of PB core endowed EGCG-based polyphenol nanoparticles with excellent NIR-triggered photothermal properties. Besides, owing to multiple enzyme-mimic activity of PB and potent antioxidant capacity of EGCG-derived polymer, PB@EGCG exhibited a remarkable ROS-scavenging ability, mitigated intracellular ROS level and protected cells from oxidative damage. Under NIR irradiation (808 nm, 1.5 W/cm2), PB@EGCG (50 µg/mL) exerted synergistic EGCG-derived polymer-photothermal antibacterial activity against Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus). In vivo therapeutic effect was evaluated using a S. aureus-infected rat model indicated PB@EGCG with a prominent bactericidal ability could modulate the inflammatory microenvironment and accelerate wound healing. Overall, this dual-functional nanomedicine provides a promising strategy for efficient antibacterial therapy.