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1.
J Control Release ; 371: 484-497, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38851537

ABSTRACT

The precise and targeted delivery of therapeutic agents to the lesion sites remains a major challenge in treating brain diseases represented by ischemic stroke. Herein, we modified liposomes with mesenchymal stem cells (MSC) membrane to construct biomimetic liposomes, termed MSCsome. MSCsome (115.99 ± 4.03 nm) exhibited concentrated accumulation in the cerebral infarcted hemisphere of mice with cerebral ischemia-reperfusion injury, while showing uniform distribution in the two cerebral hemispheres of normal mice. Moreover, MSCsome exhibited high colocalization with damaged nerve cells in the infarcted hemisphere, highlighting its advantageous precise targeting capabilities over liposomes at both the tissue and cellular levels. Leveraging its superior targeting properties, MSCsome effectively delivered Dl-3-n-butylphthalide (NBP) to the injured hemisphere, making a single-dose (15 mg/kg) intravenous injection of NBP-encapsulated MSCsome facilitate the recovery of motor functions in model mice by improving the damaged microenvironment and suppressing neuroinflammation. This study underscores that the modification of the MSC membrane notably enhances the capacity of liposomes for precisely targeting the injured hemisphere, which is particularly crucial in treating cerebral ischemia-reperfusion injury.


Subject(s)
Benzofurans , Drug Delivery Systems , Liposomes , Mesenchymal Stem Cells , Reperfusion Injury , Animals , Reperfusion Injury/therapy , Male , Benzofurans/administration & dosage , Brain Ischemia/therapy , Biomimetic Materials/chemistry , Biomimetic Materials/administration & dosage , Mice , Mice, Inbred C57BL , Mesenchymal Stem Cell Transplantation/methods
2.
Phytopathology ; : PHYTO01240006RVW, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38669603

ABSTRACT

Sclerotinia sclerotiorum is an economically damaging fungal pathogen that causes Sclerotinia stem rot in legumes, producing enormous yield losses. This pathogen is difficult to control due to its wide host spectrum and ability to produce sclerotia, which are resistant bodies that can remain active for long periods under harsh environmental conditions. Here, the biocontrol methods for the management of S. sclerotiorum in legumes are reviewed. Bacillus strains, which synthesized lipopeptides and volatile organic compounds, showed high efficacies in soybean plants, whereas the highest efficacies for the control of the pathogen in alfalfa and common bean were observed when using Coniothyrium minitans and Streptomyces spp., respectively. The biocontrol efficacies in fields were under 65%, highlighting the lack of strategies to achieve a complete control. Overall, although most studies involved extensive screenings using different biocontrol agent concentrations and application conditions, there is a lack of knowledge regarding the specific antifungal mechanisms, which limits the optimization of the reported methods.

3.
J Biol Chem ; 300(4): 107123, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38417796

ABSTRACT

Thiram is a toxic fungicide extensively used for the management of pathogens in fruits. Although it is known that thiram degrades in plant tissues, the key enzymes involved in this process remain unexplored. In this study, we report that a tau class glutathione S-transferase (GST) from Carica papaya can degrade thiram. This enzyme was easily obtained by heterologous expression in Escherichia coli, showed low promiscuity toward other thiuram disulfides, and catalyzed thiram degradation under physiological reaction conditions. Site-directed mutagenesis indicated that G-site residue S67 shows a key influence for the enzymatic activity toward thiram, while mutation of residue S13, which reduced the GSH oxidase activity, did not significantly affect the thiram-degrading activity. The formation of dimethyl dithiocarbamate, which was subsequently converted into carbon disulfide, and dimethyl dithiocarbamoylsulfenic acid as the thiram degradation products suggested that thiram undergoes an alkaline hydrolysis that involves the rupture of the disulfide bond. Application of the GST selective inhibitor 4-chloro-7-nitro-2,1,3-benzoxadiazole reduced papaya peel thiram-degrading activity by 95%, indicating that this is the main degradation route of thiram in papaya. GST from Carica papaya also catalyzed the degradation of the fungicides chlorothalonil and thiabendazole, with residue S67 showing again a key influence for the enzymatic activity. These results fill an important knowledge gap in understanding the catalytic promiscuity of plant GSTs and reveal new insights into the fate and degradation products of thiram in fruits.


Subject(s)
Carica , Glutathione Transferase , Thiram , Carica/enzymology , Carica/genetics , Fungicides, Industrial/metabolism , Glutathione Transferase/metabolism , Glutathione Transferase/genetics , Glutathione Transferase/chemistry , Mutagenesis, Site-Directed , Plant Proteins/chemistry , Plant Proteins/genetics , Plant Proteins/metabolism , Thiram/metabolism , Escherichia coli/genetics , Recombinant Proteins/genetics , Recombinant Proteins/metabolism
4.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-1012773

ABSTRACT

Objective To investigate the current status of radiation protection in non-medical radiation workplaces in Yantai, China, and to provide a scientific basis for occupational health management in non-medical radiation workplaces. Methods Non-medical radiation workplaces in Yantai were investigated using a questionnaire survey in 2022, including radiation source term, occupational health examination, personal dose monitoring, personal protective equipment, and radiation protection testing workplaces. Data were entered by a double-entry method and then analyzed. Results There were 56 non-medical radiation workplaces in Yantai, covering manufacturing, nonferrous metal ore mining, nuclear power plant, transportation, and technical services. There were 0 Class I radiation device, 150 Class II radiation devices, and 10 Class III radiation devices; there were 80 Class I radiation sources, 16 Class II radiation sources, 14 Class III radiation sources, 62 Class IV radiation sources, and 135 Class V radiation sources. There were 998 radiation workers, with an occupational health examination rate and personal dose monitoring rate of 98.3%. Among the 56 non-medical radiation workplaces, 47 (83.9%) were equipped with radiation protection monitoring instruments, 24 (51.1%) workplaces had verified the radiation protection monitoring instruments, with 2017 personal dose monitoring instruments and 2327 personal protective equipment in place, 42 (75%) workplaces carried out occupational health assessments, 44 (78.6%) workplaces carried out self-detection, and 53 (94.6%) workplaces carried out entrusting detections (monitoring pass rate: 100% [53/53]). The declaration rate of occupational hazard items was 87.5% (49/56). Conclusion There is still a gap between the current status and the requirements in the national regulations and standards regarding radiation protection in non-medical radiation workplaces. Therefore, the supervision and management of non-medical radiation workplaces should be further strengthened, especially the configuration and verification of radiation protection monitoring instruments.

5.
Phys Rev Lett ; 131(17): 176401, 2023 Oct 27.
Article in English | MEDLINE | ID: mdl-37955469

ABSTRACT

The disorder systems host three types of fundamental quantum states, known as the extended, localized, and critical states, of which the critical states remain being much less explored. Here we propose a class of exactly solvable models which host a novel type of exact mobility edges (MEs) separating localized states from robust critical states, and propose experimental realization. Here the robustness refers to the stability against both single-particle perturbation and interactions in the few-body regime. The exactly solvable one-dimensional models are featured by a quasiperiodic mosaic type of both hopping terms and on-site potentials. The analytic results enable us to unambiguously obtain the critical states which otherwise require arduous numerical verification including the careful finite size scalings. The critical states and new MEs are shown to be robust, illustrating a generic mechanism unveiled here that the critical states are protected by zeros of quasiperiodic hopping terms in the thermodynamic limit. Further, we propose a novel experimental scheme to realize the exactly solvable model and the new MEs in an incommensurate Rydberg Raman superarray. This Letter may pave a way to precisely explore the critical states and new ME physics with experimental feasibility.

6.
Sci Adv ; 9(48): eadi7375, 2023 12.
Article in English | MEDLINE | ID: mdl-38019913

ABSTRACT

Myelodysplastic syndrome (MDS) is a group of clonal hematopoietic neoplasms originating from hematopoietic stem progenitor cells (HSPCs). We previously identified frequent roundabout guidance receptor 1 (ROBO1) mutations in patients with MDS, while the exact role of ROBO1 in hematopoiesis remains poorly delineated. Here, we report that ROBO1 deficiency confers MDS-like disease with anemia and multilineage dysplasia in mice and predicts poor prognosis in patients with MDS. More specifically, Robo1 deficiency impairs HSPC homeostasis and disrupts HSPC pool, especially the reduction of megakaryocyte erythroid progenitors, which causes a blockage in the early stages of erythropoiesis in mice. Mechanistically, transcriptional profiling indicates that Cdc42, a member of the Rho-guanosine triphosphatase family, acts as a downstream target gene for Robo1 in HSPCs. Overexpression of Cdc42 partially restores the self-renewal and erythropoiesis of HSPCs in Robo1-deficient mice. Collectively, our result implicates the essential role of ROBO1 in maintaining HSPC homeostasis and erythropoiesis via CDC42.


Subject(s)
Erythropoiesis , Myelodysplastic Syndromes , Animals , Humans , Mice , Erythropoiesis/genetics , Myelodysplastic Syndromes/genetics , Nerve Tissue Proteins/genetics , Prognosis , Receptors, Immunologic/genetics , Roundabout Proteins
7.
Food Res Int ; 173(Pt 1): 113331, 2023 11.
Article in English | MEDLINE | ID: mdl-37803641

ABSTRACT

Aspergillus flavus not only reduces kiwifruit production but also synthesizes carcinogenic aflatoxins, resulting in a relevant threat to human health. p-Hydroxybenzoic acid (pHBA) is one of the most abundant phenolics in kiwifruit. In this study, pHBA was found to reduce A. flavus mycelial growth by blocking the fungal mitotic exit network (MEN) and cytokinesis and to inhibit the biosynthesis of aflatoxins B1 and B2. The application of pHBA promoted the accumulation of endogenous pHBA and induced oxidative stress in A. flavus-infected kiwifruit, resulting in an increase in H2O2 content and catalase (CAT) and superoxide dismutase (SOD) activities. Preventive and curative treatments with 5 mM pHBA reduced A. flavus advancement by 46.1% and 68.0%, respectively. Collectively, the antifungal and elicitor properties of pHBA were examined for the first time, revealing new insights into the role of pHBA in the defense response of kiwifruit against A. flavus infection.


Subject(s)
Aflatoxins , Aspergillus flavus , Humans , Antifungal Agents/pharmacology , Hydrogen Peroxide
8.
MedComm (2020) ; 4(4): e313, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37533768

ABSTRACT

Mesenchymal stem cell (MSC)-based therapies are flourishing. MSCs could be used as potential therapeutic agents for regenerative medicine due to their own repair function. Meanwhile, the natural predisposition toward inflammation or injury sites makes them promising carriers for targeted drug delivery. Inorganic nanoparticles (INPs) are greatly favored for their unique properties and potential applications in biomedical fields. Current research has integrated INPs with MSCs to enhance their regenerative or antitumor functions. This model also allows the in vivo fate tracking of MSCs in multiple imaging modalities, as many INPs are also excellent contrast agents. Thus, INP-integrated MSCs would be a multifunctional biologic agent with great potential. In this review, the current roles performed by the integration of INPs with MSCs, including (i) enhancing their repair and regeneration capacity via the improvement of migration, survival, paracrine, or differentiation properties, (ii) empowering tumor-killing ability through agent loaded or hyperthermia, and (iii) conferring traceability are summarized. An introduction of INP-integrated MSCs for simultaneous treatment and tracking is also included. The promising applications of INP-integrated MSCs in future treatments are emphasized and the challenges to their clinical translation are discussed.

9.
Blood ; 142(10): 903-917, 2023 09 07.
Article in English | MEDLINE | ID: mdl-37319434

ABSTRACT

The bone marrow microenvironment (BMM) can regulate leukemia stem cells (LSCs) via secreted factors. Increasing evidence suggests that dissecting the mechanisms by which the BMM maintains LSCs may lead to the development of effective therapies for the eradication of leukemia. Inhibitor of DNA binding 1 (ID1), a key transcriptional regulator in LSCs, previously identified by us, controls cytokine production in the BMM, but the role of ID1 in acute myeloid leukemia (AML) BMM remains obscure. Here, we report that ID1 is highly expressed in the BMM of patients with AML, especially in BM mesenchymal stem cells, and that the high expression of ID1 in the AML BMM is induced by BMP6, secreted from AML cells. Knocking out ID1 in mesenchymal cells significantly suppresses the proliferation of cocultured AML cells. Loss of Id1 in the BMM results in impaired AML progression in AML mouse models. Mechanistically, we found that Id1 deficiency significantly reduces SP1 protein levels in mesenchymal cells cocultured with AML cells. Using ID1-interactome analysis, we found that ID1 interacts with RNF4, an E3 ubiquitin ligase, and causes a decrease in SP1 ubiquitination. Disrupting the ID1-RNF4 interaction via truncation in mesenchymal cells significantly reduces SP1 protein levels and delays AML cell proliferation. We identify that the target of Sp1, Angptl7, is the primary differentially expression protein factor in Id1-deficient BM supernatant fluid to regulate AML progression in mice. Our study highlights the critical role of ID1 in the AML BMM and aids the development of therapeutic strategies for AML.


Subject(s)
Angiopoietin-Like Protein 7 , Inhibitor of Differentiation Protein 1 , Leukemia, Myeloid, Acute , Animals , Mice , Angiopoietin-Like Protein 7/genetics , Angiopoietin-Like Protein 7/metabolism , Bone Marrow/metabolism , Disease Models, Animal , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/pathology , Tumor Microenvironment , Humans , Inhibitor of Differentiation Protein 1/metabolism
10.
Pest Manag Sci ; 79(10): 4083-4093, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37291956

ABSTRACT

BACKGROUND: p-Aminobenzoic acid (pABA) is an environmentally friendly bioactive metabolite synthesized by Lysobacter antibioticus. This compound showed an unusual antifungal mode of action based on cytokinesis inhibition. However, the potential antibacterial properties of pABA remain unexplored. RESULTS: In this study, pABA showed antibacterial activity against Gram-negative bacteria. This metabolite inhibited growth (EC50 = 4.02 mM), and reduced swimming motility, extracellular protease activity, and biofilm formation in the soybean pathogen Xanthomonas axonopodis pv. glycines (Xag). Although pABA was previously reported to inhibit fungal cell division, no apparent effect was observed on Xag cell division genes. Instead, pABA reduced the expression of various membrane integrity-related genes, such as cirA, czcA, czcB, emrE, and tolC. Consistently, scanning electron microscopy observations revealed that pABA caused major alternations in Xag morphology and blocked the formation of bacterial consortiums. In addition, pABA reduced the content and profile of outer membrane proteins and lipopolysaccharides in Xag, which may explain the observed effects. Preventive and curative applications of 10 mM pABA reduced Xag symptoms in soybean plants by 52.1% and 75.2%, respectively. CONCLUSIONS: The antibacterial properties of pABA were studied for the first time, revealing new insights into its potential application for the management of bacterial pathogens. Although pABA was previously reported to show an antifungal mode of action based on cytokinesis inhibition, this compound inhibited Xag growth by altering the outer membrane's integrity. © 2023 Society of Chemical Industry.


Subject(s)
Fabaceae , Xanthomonas axonopodis , Xanthomonas , Glycine max/microbiology , Xanthomonas axonopodis/genetics , Xanthomonas axonopodis/metabolism , 4-Aminobenzoic Acid/pharmacology , 4-Aminobenzoic Acid/chemistry , 4-Aminobenzoic Acid/metabolism , Antifungal Agents/pharmacology , Antifungal Agents/metabolism , Glycine/metabolism , Anti-Bacterial Agents/pharmacology , Plant Diseases/microbiology , Xanthomonas/metabolism
11.
Anal Bioanal Chem ; 415(17): 3385-3398, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37140675

ABSTRACT

Nanozyme, with enzyme-mimicking activity and excellent stability, has attracted extensive attention. However, some inherent disadvantages, including poor dispersion, low selectivity, and insufficient peroxidase-like activity, still limit its further development. Therefore, an innovative bioconjugation of a nanozyme and natural enzyme was conducted. In the presence of graphene oxide (GO), histidine magnetic nanoparticles (H-Fe3O4) were first synthesized by a solvothermal method. The GO-supported H-Fe3O4 (GO@H-Fe3O4) exhibited superior dispersity and biocompatibility because GO was the carrier and possessed outstanding peroxidase-like activity because of the introduction of histidine. Furthermore, the mechanism of the peroxidase-like activity of GO@H-Fe3O4 was the generation of •OH. Uric acid oxidase (UAO) was selected as the model natural enzyme and covalently linked to GO@H-Fe3O4 with hydrophilic poly(ethylene glycol) as a linker. UAO could specifically catalyze the oxidation of uric acid (UA) to generate H2O2, and subsequently, the newly produced H2O2 oxidized the colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue ox-TMB under the catalysis of GO@H-Fe3O4. Based on the above cascade reaction, the GO@H-Fe3O4-linked UAO (GHFU) and GO@H-Fe3O4-linked ChOx (GHFC) were used for the detection of UA in serum samples and cholesterol (CS) in milk, respectively. The method based on GHFU exhibited a wide detection range (5-800 µM) and a low detection limit (1.5 µM) for UA, and the method based on GHFC exhibited a wide detection range (4-400 µM) and a low detection limit (1.13 µM) for CS. These results demonstrated that the proposed strategy had great potential in the field of clinical detection and food safety.


Subject(s)
Hydrogen Peroxide , Uric Acid , Histidine , Peroxidase/metabolism , Colorimetry
12.
Pest Manag Sci ; 79(9): 3177-3189, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37024430

ABSTRACT

BACKGROUND: Kiwifruit is highly susceptible to fungal pathogens, such as Botrytis cinerea, which reduce crop production and quality. In this study, dipicolinic acid (DPA), which is one of the main components of Bacillus spores, was evaluated as a new elicitor to enhance kiwifruit resistance to B. cinerea. RESULTS: DPA enhances antioxidant capacity and induces the accumulation of phenolics in B. cinerea-infected 'Xuxiang' kiwifruit. The contents of the main antifungal phenolics in kiwifruit, including caffeic acid, chlorogenic acid and isoferulic acid, increased after DPA treatment. DPA enhanced H2 O2 levels after 0 and 1 days, which promoted catalase (CAT) and superoxide dismutase (SOD) activities, reducing long-term H2 O2 levels. DPA promoted the up-regulation of several kiwifruit defense genes, including CERK1, MPK3, PR1-1, PR1-2, PR5-1 and PR5-2. Furthermore, DPA at 5 mM inhibited B. cinerea symptoms in kiwifruit (95.1% lesion length inhibition) more effectively than the commercial fungicides carbendazim, difenoconazole, prochloraz and thiram. CONCLUSIONS: The antioxidant properties of DPA and the main antifungal phenolics of kiwifruit were examined for the first time. This study uncovers new insights regarding the potential mechanisms used by Bacillus species to induce disease resistance. © 2023 Society of Chemical Industry.


Subject(s)
Antifungal Agents , Antioxidants , Antifungal Agents/pharmacology , Botrytis , Plant Diseases/prevention & control , Plant Diseases/microbiology
13.
Compr Rev Food Sci Food Saf ; 22(3): 1722-1762, 2023 05.
Article in English | MEDLINE | ID: mdl-36856034

ABSTRACT

Chitosan is an interesting alternative material for packaging development due to its biodegradability. However, its poor mechanical properties and low permeability limit its actual applications. Chitosan nanoparticles (CHNPs) have emerged as a suitable solution to overcome these intrinsic limitations. In this review, all studies regarding the use of CHNPs to extend the shelf life and improve the quality of postharvest products are covered. The characteristics of CHNPs and their combinations with essential oils and metals, along with their effects on postharvest products, are compared and discussed throughout the manuscript. CHNPs enhanced postharvest antioxidant capacity, extended shelf life, increased nutritional quality, and promoted tolerance to chilling stress. Additionally, the CHNPs reduced the incidence of postharvest phytopathogens. In most instances, smaller CHNPs (<150 nm) conferred higher benefits than larger ones (>150 nm). This was likely a result of the greater plant tissue penetrability and surface area of the smaller CHNPs. The CHNPs were either applied after preparing an emulsion or incorporated into a film, with the latter often exhibiting greater antioxidant and antimicrobial activities. CHNPs were used to encapsulate essential oils, which could be released over time and may enhance the antioxidant and antimicrobial properties of the CHNPs. Even though most applications were performed after harvest, preharvest application had longer lasting effects.


Subject(s)
Anti-Infective Agents , Chitosan , Nanoparticles , Oils, Volatile , Fruit , Vegetables , Antioxidants , Anti-Infective Agents/pharmacology , Oils, Volatile/pharmacology
14.
Stem Cells Transl Med ; 12(3): 154-168, 2023 03 17.
Article in English | MEDLINE | ID: mdl-36893290

ABSTRACT

Intrauterine adhesions (IUA), which is characterized by endometrial fibrosis, continue to be the most common cause of uterine infertility globally. Our work revealed that 3 fibrotic progression markers (Vimentin, COL5A2, and COL1A1) were significantly increased in the endometrium of IUA patients. Mesenchymal stem cell-derived exosomes (EXOs) have been recently revealed as a cell-free therapy for fibrosis diseases. Nevertheless, the application of EXOs is restricted by the short residency duration in the target tissue. To overcome this limitation, herein, we reported an exosome-based regimen (EXOs-HP) that thermosensitive poloxamer hydrogel possessed the ability to efficiently promote the residency duration of EXOs in the uterine cavity. By downregulating fibrotic progression markers (Vimentin, COL5A2, and COL1A1), EXOs-HP could significantly restore the function and structure of the injured endometrium in the IUA model. Our work provides the theoretical and experimental foundation of EXOs-HP in treating IUA, highlighting the clinical potential of topical EXOs-HP delivery system in IUA patients.


Subject(s)
Exosomes , Uterine Diseases , Female , Humans , Biomarkers , Collagen , Endometrium , Exosomes/transplantation , Fibrosis , Tissue Adhesions/drug therapy , Tissue Adhesions/pathology , Uterine Diseases/therapy , Uterine Diseases/pathology , Vimentin/therapeutic use
15.
Water Res ; 232: 119703, 2023 Apr 01.
Article in English | MEDLINE | ID: mdl-36758357

ABSTRACT

Aflatoxins are highly carcinogenic metabolites produced by some Aspergillus species and are the most prevalent mycotoxins. Although aflatoxins are commonly synthesized during fungal colonization in preharvest maize, cereals, and nuts, they can be transported by rainfall to surface water and are a common toxin found in wastewater from some food industries. Here, the occurrence of aflatoxins in bodies of water is reviewed for the first time, along with the decontamination methods. Aflatoxins have been detected in surface, wastewater and drinking water, including tap and bottled water. The specific sources of water contamination remain unclear, which is an important gap that must be addressed in future research. Two main kinds of decontamination methods have been reported, including degradation and adsorption. The best degradation rates were observed using gamma and UV irradiations, oxidoreductases and ozone, while the best adsorption abilities were observed with minerals, polyvinyl alcohol, durian peel and activated carbon. Synthetic polymers could be used as membranes in pipes to remove aflatoxins in water flows. Although most decontamination methods were screened using AFB1, the other commonly found aflatoxins were not used in the screenings. Overall, the occurrence of aflatoxins in water could be a significant emerging public health concern largely ignored by local and international legislation. Numerous advances have been reported for the decontamination of aflatoxins in water; however, there is still a long way to go to put them into practice.


Subject(s)
Aflatoxins , Drinking Water , Aflatoxins/analysis , Aflatoxins/metabolism , Food Contamination/analysis , Decontamination/methods , Wastewater
16.
Drug Deliv Transl Res ; 13(3): 716-737, 2023 03.
Article in English | MEDLINE | ID: mdl-36417162

ABSTRACT

Recently, nanoparticle-based drug delivery systems have been widely used for the treatment, prevention, and detection of diseases. Improving the targeted delivery ability of nanoparticles has emerged as a critical issue that must be addressed as soon as possible. The bionic cell membrane coating technology has become a novel concept for the design of nanoparticles. The diverse biological roles of cell membrane surface proteins endow nanoparticles with several functions, such as immune escape, long circulation time, and targeted delivery; therefore, these proteins are being extensively studied in the fields of drug delivery, detoxification, and cancer treatment. Furthermore, hybrid cell membrane-coated nanoparticles enhance the beneficial effects of monotypic cell membranes, resulting in multifunctional and efficient delivery carriers. This review focuses on the synthesis, development, and application of the cell membrane coating technology and discusses the function and mechanism of monotypic/hybrid cell membrane-modified nanoparticles in detail. Moreover, it summarizes the applications of cell membranes from different sources and discusses the challenges that may be faced during the clinical application of bionic carriers, including their production, mechanism, and quality control. We hope this review will attract more scholars toward bionic cell membrane carriers and provide certain ideas and directions for solving the existing problems.


Subject(s)
Biomimetic Materials , Nanoparticles , Biomimetics , Cell Membrane/metabolism , Drug Delivery Systems
17.
Leukemia ; 37(1): 164-177, 2023 01.
Article in English | MEDLINE | ID: mdl-36352191

ABSTRACT

The patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL) have poor prognosis, and a novel and effective therapeutic strategy for these patients is urgently needed. Although ubiquitin-specific protease 1 (USP1) plays a key role in cancer, the carcinogenic effect of USP1 in B-cell lymphoma remains elusive. Here we found that USP1 is highly expressed in DLBCL patients, and high expression of USP1 predicts poor prognosis. Knocking down USP1 or a specific inhibitor of USP1, pimozide, induced cell growth inhibition, cell cycle arrest and autophagy in DLBCL cells. Targeting USP1 by shRNA or pimozide significantly reduced tumor burden of a mouse model established with engraftment of rituximab/chemotherapy resistant DLBCL cells. Pimozide significantly retarded the growth of lymphoma in a DLBCL patient-derived xenograft (PDX) model. USP1 directly interacted with MAX, a MYC binding protein, and maintained the stability of MAX through deubiquitination, which promoted the transcription of MYC target genes. Moreover, pimozide showed a synergetic effect with etoposide, a chemotherapy drug, in cell and mouse models of rituximab/chemotherapy resistant DLBCL. Our study highlights the critical role of USP1 in the rituximab/chemotherapy resistance of DLBCL through deubiquitylating MAX, and provides a novel therapeutic strategy for rituximab/chemotherapy resistant DLBCL.


Subject(s)
Lymphoma, Large B-Cell, Diffuse , Lymphoma, Non-Hodgkin , Animals , Mice , Humans , Rituximab/therapeutic use , Pimozide/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/genetics , Lymphoma, Large B-Cell, Diffuse/pathology , Lymphoma, Non-Hodgkin/drug therapy , Ubiquitin-Specific Proteases/genetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
18.
Article in English | WPRIM (Western Pacific) | ID: wpr-1010295

ABSTRACT

OBJECTIVE@#To analyze the efficacy of Biejiajian Pill (BJJP) on intestinal microbiota in patients with hepatitis B cirrhosis/liver fibrosis, and explore its relationship with liver fibrosis.@*METHODS@#This was a prospective, randomized double-blind controlled trial. Using the stratified block randomization method, 35 patients with hepatitis B liver cirrhosis/liver fibrosis were randomly assigned (1:1) to receive entecavir (0.5 mg/d) combined with BJJP (3 g/time, 3 times a day) or placebo (simulator as control, SC group, simulator 3 g/time, 3 times a day) for 48 weeks. Blood and stool samples were collected from patients at baseline and week 48 of treatment, respectively. Liver and renal functions as well as hematological indices were detected. Fecal samples were analyzed by 16S rDNA V3-V4 high-throughput sequencing, and intestinal microbiota changes in both groups before and after treatment were compared, and their correlations with liver fibrosis were analyzed.@*RESULTS@#Compared with the SC group, there was no significant difference in liver function, renal function and hematology indices in the BJJP group, however, the improvement rate of liver fibrosis was higher in the BJJP group (94.4% vs. 64.7%, P=0.041). Principal coordinate analysis (PCoA) based on weighted Unifrac distance showed significant differences in intestinal microbiota community diversity before and after BJJP treatment (P<0.01 and P=0.003), respectively. After 48 weeks' treatment, the abundance levels of beneficial bacteria (Bifidobacteria, Lactobacillus, Faecalibacterium and Blautia) increased, whereas the abundance levels of potential pathogenic bacteria, including Escherichia coli, Bacteroides, Ruminococcus, Parabacteroides and Prevotella decreased, among which Ruminococcus and Parabacteroides were significantly positively correlated with degree of liver fibrosis (r=0.34, P=0.04; r=0.38, P=0.02), respectively. The microbiota in the SC group did not change significantly throughout the whole process of treatment.@*CONCLUSION@#BJJP had a certain regulatory effect on intestinal microbiota of patients with hepatitis B cirrhosis/liver fibrosis (ChiCTR1800016801).


Subject(s)
Humans , Gastrointestinal Microbiome , Prospective Studies , Liver Cirrhosis/drug therapy , Hepatitis B/drug therapy
19.
Article in English | MEDLINE | ID: mdl-36078255

ABSTRACT

Soybean plants are highly susceptible to Fusarium species, which significantly reduce soybean production and quality. Several Fusarium species have been reported to synthesize mycotoxins, such as trichothecene, which have been related to major human diseases. In November 2021, soybean pods in Nantong municipality, China, showed black necrotic lesions during the harvest stage. The disease incidence reached 69%. The pathogen was identified as Fusarium sulawense via morphological analysis and sequencing of ITS, EF1-α and RPB2 genes. A PCR assay with primers targeting the trichothecene biosynthesis genes suggested that the three isolates could synthesize trichothecenes. The effectiveness of fungicide carbendazim and natural metabolites dipicolinic acid and kojic acid was screened for the management of F. sulawense on postharvest soybean pods. The highest efficacy was obtained when combining 3.8 mg/mL carbendazim and 0.84 mg/mL dipicolinic acid (curative efficacy: 49.1% lesion length inhibition; preventive efficacy: 82.7% lesion length inhibition), or 1.9 mg/mL carbendazim and 0.71 mg/mL kojic acid (preventive efficacy: 84.9% lesion length inhibition). Collectively, this report will lead to a better understanding of the safety hazards found in soybean products in China and reveals the application of dipicolinic and kojic acids to reduce the use of carbendazim.


Subject(s)
Fusarium , Benzimidazoles , Carbamates , Fusarium/genetics , Humans , Picolinic Acids , Pyrones , Glycine max , Triticum
20.
J Fungi (Basel) ; 8(5)2022 May 23.
Article in English | MEDLINE | ID: mdl-35628802

ABSTRACT

Fungal pathogens can invade not only the fruit peel but also the outer part of the fruit mesocarp, limiting the efficacy of fungicides. In this study, the relationships between fungicide structure, diffusion capacity and in vivo efficacy were evaluated for the first time. The diffusion capacity from pear peel to mesocarp of 11 antifungal compounds, including p-aminobenzoic acid, carbendazim, difenoconazole, dipicolinic acid, flusilazole, gentamicin, kojic acid, prochloraz, quinolinic acid, thiophanate methyl and thiram was screened. The obtained results indicated that size and especially polarity were negatively correlated with the diffusion capacity. Although some antifungal compounds, such as prochloraz and carbendazim, were completely degraded after a few days in peel and mesocarp, other compounds, such as p-aminobenzoic acid and kojic acid, showed high stability. When applying the antifungal compounds at the EC50 concentrations, it was observed that the compounds with high diffusion capacity showed higher in vivo antifungal activity against Alternaria alternata than compounds with low diffusion capacity. In contrast, there was no relationship between stability and in vivo efficacy. Collectively, the obtained results indicated that the diffusion capacity plays an important role in the efficacy of fungicides for the control of pear fruit diseases.

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