Laccase-Mediated Oxidation of Phenolic Compounds from Wine Lees Extract towards the Synthesis of Polymers with Potential Applications in Food Packaging.

Laccase from Trametes versicolor was applied to produce phenolic polymeric compounds with enhanced properties, using a wine lees extract as the phenolic source. The influence of the incubation time on the progress of the enzymatic oxidation and the yield of the formed polymers was examined. The polymerization process and the properties of the polymeric products were evaluated with a variety of techniques, such as high-pressure liquid chromatography (HPLC) and gel permeation chromatography (GPC), Fourier-transform infrared (FTIR) and nuclear magnetic resonance (NMR) spectroscopies, differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). The enzymatic polymerization reaction resulted in an 82% reduction in the free phenolic compounds of the extract. The polymeric product recovery (up to 25.7%) and the molecular weight of the polymer depended on the incubation time of the reaction. The produced phenolic polymers exhibited high antioxidant activity, depending on the enzymatic oxidation reaction time, with the phenolic polymer formed after one hour of enzymatic reaction exhibiting the highest antioxidant activity (133.75 and 164.77 µg TE mg-1 polymer) towards the ABTS and DPPH free radicals, respectively. The higher thermal stability of the polymeric products compared to the wine lees phenolic extract was confirmed with TGA and DSC analyses. Finally, the formed phenolic polymeric products were incorporated into chitosan films, providing them with increased antioxidant activity without affecting the films' cohesion.

Activity of Lignin-Modifying Enzyme of Selected Medicinal Mushrooms in Submerged Fermentation of Lignocellulosic Materials.

In the present study, wide diversity in the set and activity of lignin-modifying enzymes (LME) was revealed during submerged fermentation of mandarin peel with 15 strains of white rot Basidiomycetes. Among them, Trametes pubescens BCC153 was distinguished by the simultaneous production of laccase, manganese peroxidase (MnP), and lignin peroxidase (LiP). Supplementation of CuSO4 at a concentration of 1 mM in the media for the cultivation of four Trametes species manifold increased the production of laccase. The diverse effects of chemically different lignocellulosic growth substrates and nitrogen sources on the production of individual LME have been established. The maximum laccase activity of T. pubescens was observed when the fungus was cultivated on media containing mandarin peel and wheat bran, whereas the highest MnP and LiP activities were detected in the submerged fermentation of tobacco residue. Peptone and casein hydrolysate appeared to be the best sources of nitrogen to produce laccase and both peroxidases by T. pubescens BCC153 whereas KNO3 was the worst nitrogen-containing compound for the production of all enzymes.

Huaier improves the efficacy of anti-PD-L1 Ab in the treatment of hepatocellular carcinoma by regulating tumor immune microenvironment.

BACKGROUND: Combination therapy is an effective method for augmenting the efficacy of immune checkpoint inhibitors (ICIs). Huaier is a commonly used Chinese patent medicine with substantial antitumor effects. The combination of Huaier and ICIs may increase the efficacy of ICIs against hepatocellular carcinoma (HCC). METHODS: The major components of Huaier were detected by high-performance liquid chromatography-mass spectrometry. The optimal antitumor dose of Huaier was investigated in H22-bearing mice. Next, Huaier was combined with anti-CD8α antibody (Ab) or anti-PD-L1 Ab to observe the antitumor effect. The safety of these combination drugs was evaluated through blood biochemical tests and hematoxylin and eosin staining of histological sections. RT-qPCR, immunohistochemistry, flow cytometry, and transcriptome sequencing were performed to investigate the potential action mechanism of anti-PD-L1 Ab combined with Huaier against HCC. RESULTS: HPLC-MS/MS identified 333 components of Huaier, including carboxylic acids and derivatives, thienothiophenes, phenols, flavonoids and so on. Huaier exhibited significant antitumor effects, with the strongest effect noted at a dose of 4 g/kg. Huaier boosted CD8+ T cells infiltration into the tumor. Next, CD8+ T cells were depleted by with anti-CD8α Ab, and the antitumor effect of Huaier was suppressed. Flow cytometry results revealed that CD8+ T cells were reduced in the Huaier+anti-CD8α Ab group, with the antitumor effect of this group being inhibited. This indicated that CD8+ T cells were key players in the antitumor activity of Huaier. Meanwhile, Huaier inhibited microvessel density (MVD), downregulated vascular endothelial growth factor A (VEGFA), and upregulated PD-L1 in tumor tissues. Finally, Huaier combined with anti-PD-L1 Ab exhibited a greater antitumor effect in the H22-bearing mice. And the results of liver and kidney function tests and histological section analysis unveiled that the safety of these drugs was excellent. According to the transcriptome sequencing results, Huaier combined with anti-PD-L1 Ab possibly exerted anti-HCC effects through immunomodulation, immune response, and so on. CONCLUSIONS: Huaier exhibited a significant antitumor effect. It promoted CD8+ T cells infiltration, upregulated PD-L1 expression, downregulated VEGFA expression, and inhibited MVD, thereby playing a significant antitumor immunoregulatory effect. The combination of Huaier and anti-PD-L1 Ab has significant antitumor effects, and this regimen has good safety. Therefore, Huaier combined with anti-PD-L1 Ab is a promising therapeutic approach against HCC.

The Importance of Traditional Chinese Medicine in the Intervention and Treatment of HIV while Considering its Safety and Efficacy.

Natural products have been considered a potential resource for the development of novel therapeutic agents, since time immemorial. It is an opportunity to discover cost-effective and safe drugs at the earliest, with the goal to hit specific targets in the HIV life cycle. Natural products with inhibitory activity against human immunodeficiency virus are terpenes, coumarins, flavonoids, curcumin, proteins, such as lectins, laccases, bromotyrosines, and ribosome-inactivating proteins. Terpenes inhibit virus fusion, lectins and flavonoids have an inhibitory impact on viral binding, curcumin and flavonoids inhibit viral DNA integration. The most important medicinal plants which have been used in traditional Chinese medicinal sciences with anti-HIV properties are Convallaria majalis, Digitalis lanata, Cassia fistula, Croton macrostachyus, Dodonaea angustifolia, Ganoderma lucidum, Trametes versicolor, Coriolus versicolor, Cordyceps sinensis, Gardenia jasminoides, Morus alba, Scutellaria baicalensis, Ophiopogon japonicus, Platycodon grandiflorus, Fritillaria thunbergii, Anemarrhena asphodeloides, Trichosanthes kirilowii, Citrus reticulata, Glycyrrhiza uralensis, Rheum officinale, Poria cocos, Rheum palmatum, Astragalus membranaceus, Morinda citrifolia, Potentilla kleiniana, Artemisia capillaris, Sargassum fusiforme, Piperis longi fructus, Stellera chamaejasme, Curcumae rhizoma, Dalbergia odorifera lignum, Arisaematis Rhizoma preparatum, and Phellodendron amurense. The information provided is gathered from randomized control experiments, review articles, and analytical studies and observations, which are obtained from different literature sources, such as Scopus, Google Scholar, PubMed, and Science Direct from July 2000 to August 2023. The aim of this review article is to survey and introduce important medicinal plants and herbs that have been used for the treatment of HIV, especially the medicinal plants that are common in traditional Chinese medicine, as research to date is limited, and more evidence is required to confirm TCM,s efficacy.

Durability of heat-treated Paulownia tomentosa and Pinus koraiensis woods in palm oil and air against brown- and white-rot fungi.

This study aimed to evaluate and compare the effects of oil- and air-heat treatments on the durability of Paulownia tomentosa and Pinus koraiensis woods against Fomitopsis palustris and Trametes versicolor. The wood samples were treated in palm oil and air at 180, 200, and 220 °C for 2 h. The weight loss, morphology, crystalline properties, and chemical compounds of untreated and heat-treated wood after fungal attack were investigated. The significant difference in weight loss between oil- and air-heat-treated samples was shown at 220 °C. Heat-treated wood exposed to white-rot fungus showed a lower weight loss than that exposed to brown-rot fungus. The cell components in the untreated- and heat-treated Paulownia tomentosa and Pinus koraiensis at 180 °C were severely damaged due to fungal exposure compared to those at 220 °C. A fungal effect on the relative crystallinity was observed in heat-treated wood at 180 °C, whereas the effect was not observed at 220 °C. Following brown-rot fungus exposure, untreated- and heat-treated wood at 180 °C showed a notable change in the Fourier transform infrared (FTIR) peaks of polysaccharides, whereas no noticeable change in lignin peaks was observed. Heat-treated wood at 220 °C showed no noticeable change in the FTIR spectra owing to brown-rot fungus exposure. Exposure to white-rot fungus did not noticeably change the FTIR spectra of untreated and heat-treated wood.

Detection of Mitogenic and Genotoxic Effects of the Turkey Tail Medicinal Mushroom (Trametes versicolor, Agaricomycetes) Extracts from Mexico on Human Lymphocyte Cultures.

Diseases caused by a compromised immune system, characterized by decreased production and diversification of T lymphocytes, such as immunodeficiencies or chronic infections, are becoming increasingly prominent. These diseases lead to increased vulnerability to infections caused by parasites, viruses, bacteria, fungi, and other microorganisms. According to various articles, Trametes versicolor has been used as immunotherapy and cancer treatment due to its polysaccharides, which have shown their value in traditional medicine. However, most of the studies have been done with Asian samples. For this reason, the aim of this study was to evaluate the effect of samples of Mexican T. versicolor on human lymphoid cells. Of various extracts, the one with the best T cell proliferative response was the extract produced by maceration in water at room temperature, but all treatments in aqueous and ethanolic extracts increased the lymphocyte count, showing that extracts of Mexican T. versicolor also have compounds that stimulate T cells. Unfortunately, genetic damage expressed as an increment in micronuclei count was identified, so using these fungus extracts in traditional medicine would require careful control of recommended doses.

Characterization of white rot fungi from wood decayed for lignin degradation.

The present study was conducted to isolate and identify white rot fungi (WRF) from wood decayed and to determine their ability to produce lignin-modifying enzymes (LMEs), specifically laccase (Lac), lignin peroxidase (LiP), and manganese peroxidase (MnP), on solid and liquid media supplemented with synthetic dyes namely 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), azure B, and phenol red. A total of 23 isolates of WRF were isolated from decayed wood and identified as eight different species namely Phanerochaete australis, Perenniporia tephropora, Lentinus squarrosulus, Ganoderma australe, Trametes polyzona, Lentinus sajor-caju, Gymnopilus dilepis, and Fomitopsis palustris based on morphological characteristics, DNA sequences of the internal transcribed spacer (ITS) region, and phylogenetic inference. The fungal isolates can be divided into four groups based on the type of LMEs produced, namely A (Lac-LiP-MnP) with 16 isolates, B (Lac-MnP) (three isolates), C (Lac) (three isolates), and D (MnP) (one isolate). This study highlights P. australis (BJ38) as the best producer of Lac and LiP, while L. squarrosulus (IPS72) is the best producer of MnP. The present study is the first reported P. australis as an efficient lignin degrader by demonstrating the highest activity of two important LMEs.

Antioxidant Potential of Several Polypores Mushrooms from the South of France.

We selected polypore mushrooms growing in the Mediterranean area of France to screen their antioxidant activity: Ganoderma applanatum, G. lucidum, Inonotus cuticularis, I. hispidus, Trametes hirsuta, and T. versicolor. Our work also evaluated antioxidant capacity from wild and cultivated G. lucidum fruiting bodies to optimize this biological property on human health. Dried fungal materials were sequentially extracted using cyclohexane, dichloromethane, ethanol, and water. Folin-Ciocalteu assay, oxygen radical absorbance capacity using DPPH and ORAC tests of the polypore extracts were assessed and compared. Among the 28 mushroom extracts tested, four exhibited significant antioxidant activity as ethanol extracts of I. cuticularis, T. hirsuta and wild and cultivated G. lucidum. The ethanol extracts of I. cuticularis and T. hirsuta revealed the highest values for the ORAC test, while the highest values for the Folin-Ciocalteu and DPPH tests were found for the ethanol extracts of cultivated G. lucidum and I. cuticularis. Further studies are needed to identify potential bioactive compounds, especially from I. cuticularis and G. lucidum grown under selected conditions and explore their benefits in the pharmaceutical and food industries.

Smartphone-Based Electrochemical Biosensor for On-Site Nutritional Quality Assessment of Coffee Blends.

This work aimed to develop an easy-to-use smartphone-based electrochemical biosensor to quickly assess a coffee blend's total polyphenols (Phs) content at the industrial and individual levels. The device is based on a commercial carbon-based screen-printed electrode (SPE) modified with multi-walled carbon nanotubes (CNTs) and gold nanoparticles (GNPs). At the same time, the biological recognition element, Laccase from Trametes versicolor, TvLac, was immobilized on the sensor surface by using glutaraldehyde (GA) as a cross-linking agent. The platform was electrochemically characterized to ascertain the influence of the SPE surface modification on its performance. The working electrode (WE) surface morphology characterization was obtained by scanning electron microscopy (SEM) and Fourier-transform infrared (FT-IR) imaging. All the measurements were carried out with a micro-potentiostat, the Sensit Smart by PalmSens, connected to a smartphone. The developed biosensor provided a sensitivity of 0.12 µA/µM, a linear response ranging from 5 to 70 µM, and a lower detection limit (LOD) of 2.99 µM. Afterward, the biosensor was tested for quantifying the total Phs content in coffee blends, evaluating the influence of both the variety and the roasting degree. The smartphone-based electrochemical biosensor's performance was validated through the Folin-Ciocâlteu standard method.

Immunoregulatory effects of Huaier (Trametes robiniophila Murr) and relevant clinical applications.

Huaier (Trametes robiniophila Murr) is a medicinal fungus of traditional Chinese medicine with more than 1000 years of history of clinical application. Its remarkable anticancer activities has led to its application in treating diverse malignancies. In recent years, the immunomodulatory effects of Huaier have been uncovered and proved to be beneficial in a plethora of immune-related diseases including cancer, nephropathy, asthma, etc. In this review, we comprehensively summarized the active components of Huaier, its regulatory activities on multifaceted aspects of the immune system, its application in various clinical settings as well as toxicologic evidence. Based on currently available literature, Huaier possesses broad-spectrum regulatory activities on various components of the innate and adaptive immune system, including macrophages, dendritic cells, natural killer cells, T and B lymphocytes, etc. Versatile immunologic reactions are under the regulation of Huaier from expression of damage-associated molecular patterns, immune cell activation and maturation to cell proliferation, differentiation, antibody production, expression of cytokines and chemokines and terminal intracellular signal transduction. Moreover, some modulatory activities of Huaier might be context-dependent, typically promoting the restoration toward normal physiological status. With excellent efficacy and minimal side effects, we foresee more extensive application of Huaier for treating immune-related disorders.

Optimization of dye-contaminated wastewater treatment by fungal Mycelial-light expanded clay aggregate composite.

Dye-contaminated wastewaters from the printing batik industry are hazardous if discharged into the environment without any treatment. Finding an optimization and reusability assessment of a new fungal-material composite for dye-contaminated wastewater treatment is important for efficiency. The study purposes to optimize fungal mycelia Trametes hirsuta EDN 082 - light expanded clay aggregate (myco-LECA) composite for real priting batik dye wastewater treatment by using Response Surface Methodology with Central Composite Design (RSM-CCD). The factors included myco-LECA weight (2-6 g), wastewater volume (20-80 mL), and glucose concentration (0-10%) were applied for 144 h of incubation time. The result showed that the optimum condition was achieved at 5.1 g myco-LECA, at 20 mL wastewater, and at 9.1% glucose, respectively. In this condition, the decolorization values with an incubation time of 144 h were 90, 93, and 95%, at wavelengths 570, 620, and 670 nm, respectively. A reusability assessment was conducted for 19 cycles and the result showed that decolorization effectiveness was still above 96%. GCMS analysis showed the degradation of most compounds in the wastewater and the degradation products of the wastewater demonstrated detoxification against Vigna radiata and Artemia salina. The study suggests that myco-LECA composite has a good performance and therefore is a promising method for the treatment of printing batik wastewater.

Effects of dietary co-exposure to fungal and herbal functional feed additives on immune parameters and microbial intestinal diversity in rainbow trout (Oncorhynchus mykiss).

Misuse and overuse of antibiotics in aquaculture has proven to be an unsustainable practice leading to increased bacterial resistance. An alternative strategy involves the inclusion of immunostimulants in fish diets, especially fungal and herbal compounds already authorized for human consumption, hence without environmental or public health concerns. In this study, we used a holistic and cross-disciplinary pipeline to assess the immunostimulatory properties of two fungi: Trametes versicolor and Ganoderma lucidum; one herbal supplement, capsaicin in the form of Espelette pepper (Capsicum annuum), and a combination of these fungal and herbal additives on rainbow trout (Oncorhynchus mykiss). We investigated the impact of diet supplementation for 7 weeks on survival, growth performance, cellular, humoral, and molecular immune parameters, as well as the intestinal microbial composition of the fish. Uptake of herbal and fungal compounds influenced the expression of immune related genes, without generating an inflammatory response. Significant differences were detected in the spleen-tlr2 gene expression. Supplementation with herbal additives correlated with structural changes in the fish intestinal microbiota and enhanced overall intestinal microbial diversity. Results demonstrated that the different treatments had no adverse effect on growth performance and survival, suggesting the safety of the different feed additives at the tested concentrations. While the mechanisms and multifactorial interactions remain unclear, this study provides insights not only in regard to nutrition and safety of these compounds, but also how a combined immune and gut microbiota approach can shed light on efficacy of immunostimulant compounds for potential commercial inclusion as feed supplements.

Medicinal Mushroom Supplements in Cancer: A Systematic Review of Clinical Studies.

PURPOSE OF REVIEW: Patients seek clinical guidance on mushroom supplements that can be given alongside conventional treatments, but most research on such fungi has been preclinical. The current systematic review focused on clinical studies of mushrooms in cancer care conducted in the past 10 years. We searched Medline (Ovid), Embase (Ovid), Scopus (Wiley), and Cochrane Library to identify all mushroom studies conducted in humans published from January 2010 through December 2020. Two authors independently assessed papers for inclusion. RECENT FINDINGS: Of 136 clinical studies identified by screening 2349, 39 met inclusion criteria. The studies included 12 different mushroom preparations. A survival benefit was reported using Huaier granules (Trametes robiniophila Murr) in 2 hepatocellular carcinoma studies and 1 breast cancer study. A survival benefit was also found in 4 gastric cancer studies using polysaccharide-K (polysaccharide-Kureha; PSK) in the adjuvant setting. Eleven studies reported a positive immunological response. Quality-of-life (QoL) improvement and/or reduced symptom burden was reported in 14 studies using various mushroom supplements. Most studies reported adverse effects of grade 2 or lower, mainly nausea, vomiting, diarrhea, and muscle pain. Limitations included small sample size and not using randomized controlled trial design. Many of the reviewed studies were small and observational. Most showed favorable effects of mushroom supplements in reducing the toxicity of chemotherapy, improving QoL, favorable cytokine response, and possibly better clinical outcomes. Nevertheless, the evidence is inconclusive to recommend the routine use of mushrooms for cancer patients. More trials are needed to explore mushroom use during and after cancer treatment.

Antioxidant and antiproliferative potentials of phenolic-rich extracts from biotransformed grape pomace in colorectal Cancer.

BACKGROUND: Colorectal carcinoma is one of the most commonly diagnosed malignancies worldwide. Consumption of dietary supplements and nutraceuticals such as phenolic compounds may help combat colorectal carcinoma. The effect of two phenolic-rich extracts prepared from biotransformed grape pomace on the antioxidant properties and antiproliferative activity against two colorectal cancer cell lines (Caco-2 and SW620) were investigated. METHODS: A 15-day solid-state fermentation with the white-rot fungi Phanerochaete chrysosporium and Trametes gibbosa was used to biotransform grape pomace. Solid-liquid extraction was then performed to extract bioactive compounds. The extract was analyzed for the determination of phenolic compounds by ultra-high performance liquid chromatography and in vitro assays of biological activities (antioxidant activity, antiproliferative activity, cell cycle analysis). RESULTS: The 4 days of solid-state fermentation proved to be the optimal period to obtain the maximum yield of phenolic compounds. The tested extracts showed significant antioxidant and antiproliferative activities. Grape pomace treated with P. chrysosporium and T. gibbosa reduced cancer cell growth by more than 60% at concentrations (solid/liquid ratio) of 1.75 mg/mL and of 2.5 mg/mL, respectively. The cell cycle perturbations induced by the grape pomace extracts resulted in a significant increase in the number of cells in the S (9.8%) and G2/M (6.8%) phases of SW620 exposed to T. gibbosa after 48 hours, while P. chrysosporium increased the percentage of cells in the G1 phase by 7.7%. The effect of grape pomace extracts on Caco-2 was less pronounced. CONCLUSIONS: The obtained results suggest the presence of bioactive compounds in biotransformed grape pomace as a residue from winemaking, which could be used to prevent colon cancer.

The mycelium of the Trametes versicolor synn. Coriolus versicolor (Turkey tail mushroom) exhibit anti-melanoma activity in vitro.

Melanoma is one of the most aggressive forms of skin cancer and is characterized by high metastatic potential. Despite improvements in early diagnosis and treatment, the mortality rate among metastatic melanoma patients continues to represent a significant clinical challenge. Therefore, it is imperative that we search for new forms of treatment. Trametes versicolor is a mushroom commonly used in Chinese traditional medicine due to its numerous beneficial properties. In the present work, we demonstrate T. versicolor fruiting body and mycelium ethanol extracts exhibit potent cytotoxic activity towards A375 (IC50 = 663.3 and 114.5 µg/mL respectively) and SK-MEL-5 (IC50 = 358.4 and 88.6 µg/mL respectively) human melanoma cell lines. Further studies revealed that T. versicolor mycelium extract induced apoptotic cell death and poly (ADP-ribose) polymerase cleavage, upregulated the expression of autophagy-associated marker LC3-II, increased the presentation of major histocompatibility complex II and expression of programmed death-ligand receptor, and inhibited cell migration in SK-MEL-5 cells. Therefore, our present findings highlight the therapeutic potential of T. versicolor mycelium extract for the treatment of melanoma and merit further study.

Investigation of some endophytic fungi from five medicinal plants with growth promoting ability on maize (Zea mays L.).

AIMS: This study aimed to identify endophytic fungi from Anthemis altissima, Matricaria parthenium, Cichorium intybus, Achillea millefolium, and A. filipendulina with plant-promoting ability on the ZP684 maize hybrid-cultivar. METHODS AND RESULTS: Plants were collected from northeast-Iran and endophytic fungi were isolated and identified using partial large subunit nrDNA, internal transcribed spacer, translation elongation factor, and ß-tubulin genetic markers. Endophytic fungi that improved seed germination were studied under greenhouse conditions. Ninety-seven endophytic fungi were identified. Preussia africana, Bjerkandera adusta, Schizophyllum commune, Alternaria embellisia, Trichaptum biforme, Septoria malagutii, A. consortiale, Verticillium dahliae, Fusarium avenacearum, and Trametes versicolor significantly improved seed-germination. Alternaria consortiale produced the highest level of indole-3-acetic acid-like compounds and maize growth-promoting. CONCLUSIONS: Plant fungal colonization frequency increased with orthometric height. Sampling location Chahar Bagh at 2230 m contained the most endophytic fungi. Fusarium and Alternaria were the most frequently isolated endophytic genera. Therefore, medicinal plants are potential hosts for endophytic fungi that may be suitable biofertilizer agents in agriculture. SIGNIFICANCE AND IMPACT OF THE STUDY: This study helps to better understand the ecosystem functions by investigating of endophytic fungi distribution under different ecological conditions. Finding effective isolates among these microorganisms with a suitable plant-promoting ability on crops may help to reduce the use of chemical fertilizers in an agroecosystem.

Enzymatic Potential of Filamentous Fungi as a Biological Pretreatment for Acidogenic Fermentation of Coffee Waste.

Spent coffee grounds (SCGs) are a promising substrate that can be valorized by biotechnological processes, such as for short-chain organic acid (SCOA) production, but their complex structure implies the application of a pretreatment step to increase their biodegradability. Physicochemical pretreatments are widely studied but have multiple drawbacks. An alternative is the application of biological pretreatments that include using fungi Trametes versicolor and Paecilomyces variotii that naturally can degrade complex substrates such as SCGs. This study intended to compare acidic and basic hydrolysis and supercritical CO2 extraction with the application of these fungi. The highest concentration of SCOAs, 2.52 gCOD/L, was achieved after the acidification of SCGs pretreated with acid hydrolysis, but a very similar result, 2.44 gCOD/L, was obtained after submerged fermentation of SCGs by T. versicolor. This pretreatment also resulted in the best acidification degree, 48%, a very promising result compared to the 13% obtained with the control, untreated SCGs, highlighting the potential of biological pretreatments.

Polysaccharides Produced by the Mushroom Trametes robiniophila Murr Boosts the Sensitivity of Hepatoma Cells to Oxaliplatin via the miR-224-5p/ABCB1/P-gp Axis.

AIM: To investigate the mechanisms employed by PS-T (polysaccharides of Trametes, PS-T), the main active ingredient of Huaier granules, to improve the susceptibility of hepatoma cells to oxaliplatin (OXA). METHODS: Cell proliferation in response to PS-T was determined both in vitro and in vivo. The effects of PS-T on miRNAs were analyzed with the use of a microarray. MiRNAs were screened under specific conditions (P < .05, logFoldChange > ABS [1.5]) and further silenced or overexpressed by liposome transfection. Levels of ABCB1 mRNA and P-gp were detected by qRT-PCR and western blot analysis, respectively. A dual fluorescence assay was performed to determine whether miRNA directly targets ABCB1. RESULTS: PS-T enhanced the inhibitory effect of OXA in human hepatoma cells and xenografts. Among 5 up-regulated miRNAs, overexpression of only miR-224-5p inhibited the expression of ABCB1 mRNA and P-gp, while silencing of miR-224-5p had an opposite effect. Moreover, miR-224-5p can directly target the 3'-UTR of ABCB1. CONCLUSION: PS-T increases the sensitivity of human hepatoma cells to OXA via the miR-224-5p/ABCB1/P-gp axis.

An extraction from Trametes robiniophila Murr. (Huaier) inhibits non-small cell lung cancer proliferation via targeting to epidermal growth factor receptor.

An extraction from Trametes robiniophila Murr. (Huaier) is a kind of natural fungus growing from the sophora japonica tree. Huaier is widely applied to cure the hepatocellular cancer (HCC). However, the medicinal fungus' curative result on non-small-cell lung cancer (NSCLC) is not well elaborated. In this study, we applied in vitro experiments to study Huaier's curative result on NSCLC. The potential Huaier targets were predicted using bioinformatics and validated by western blotting. We further elucidated the mechanism of Huaier targeting by molecular docking, kinase activity assay, CEllular Thermal Shift Assays (CETSAs). At last, in vivo curative result was verified further. Huaier weakened proliferation and promoted apoptosis of the NSCLC cell lines. According to bioinformatics, Epidermal Growth Factor Receptor (EGFR) may be the target of Huaier. Western blotting showed that Huaier can attenuate the activation of EGFR and we found that Huaier can dock to EGFR. Huaier significantly inhibited the tumor growth by weakening the expression of p-EGFR in vivo. This study offers a new idea for further understanding of Huaier and shows its potential as a therapeutic agent.

Efficacy and Safety of Huaier Granule as an Adjuvant Therapy for Cancer: An Overview of Systematic Reviews and Meta-Analyses.

INTRODUCTION: In China, Huaier granule (HG) is widely applied to tumor adjuvant therapy. However, systematic reviews (SRs) or meta-analyses (MAs) published continuously failed to reach a consensus, without convincing evidence. An overview should be conducted to summarize the evidence-based progress and try to provide some value references for relative research and clinical practice in the future. METHODS: From inception to October 2021, 8 databases in English and Chinese were searched. SRs/MAs meeting the inclusion and exclusion criteria were included. Relevant criteria were used to evaluate SRs/MAs including methodological quality, reporting quality, risk of bias, and evidence quality of effect and safety. RESULTS: The short-term effect, long-term effect, and safety in 6 included SRs/MAs were assessed in this overview according to quantitative synthesis. Results assessed by AMSTAR-2, PRISMA, and ROBIS were generally unsatisfactory with the main problems on registration or protocol, a search of grey literature, a list of excluded studies, bias of each synthetic result, and inadequate report of search strategy and synthesis methods. Additionally, 28 items were assessed as moderate quality while 12 items were low-quality and 6 items were very low-quality in GRADE. Risk of bias was the main downgrading factor. CONCLUSION: HG may be a promising adjuvant therapy for cancer. However, high-quality SRs/MAs and RCTs should be conducted to provide sufficient evidence so as to draw a definitive conclusion.