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1.
Front Microbiol ; 15: 1386428, 2024.
Article in English | MEDLINE | ID: mdl-38784796

ABSTRACT

Allergic asthma (AA) is a common inflammatory airway disease characterized by increased airway hyper-responsiveness (AHR), inflammation, and remodeling. Akkermansia muciniphila is a strictly anaerobic bacterium residing in the gut and is a promising next-generation probiotic to improve metabolic inflammatory syndrome. A recent study suggested the beneficial effect of live A. muciniphila on allergic airway inflammation (AAI) in mice. However, whether the heat-killed form can improve AAI requires further investigation. Mice sensitized and challenged with house dust mites (HDM) develop AA hallmarks including inflammatory cell infiltration, goblet cell hyperplasia, and subepithelial collagen deposition in the lungs. These phenomena were reversed by oral administration of the heat-killed A. muciniphila strain EB-AMDK19 (AMDK19-HK) isolated from the feces of healthy Koreans. Furthermore, AMDK19-HK diminished the HDM-induced AHR to inhaled methacholine, lung mast cell accumulation, and serum HDM-specific IgE levels. It also led to the overall suppression of IL-4, IL-13, and eotaxin production in bronchoalveolar lavage fluids, and Il4, Il5, Il13, and Ccl17 gene expression in lung tissues. Moreover, AMDK19-HK suppressed Th2-associated cytokine production in the splenocytes of HDM-sensitized mice in vitro. Additionally, a combination of 16S rRNA gene sequencing and short-chain fatty acid (SCFA) analysis in cecal samples revealed that AMDK19-HK modulated the relative abundance of circulating SCFA-associated gut genera, including a positive correlation with Lachnospiraceae_ NK4A136_group and a negative correlation with Lachnoclostridium and significantly increased cecal SCFA concentrations. Finally, AMDK19-HK improved intestinal mucosal barrier function. These results suggest that the oral administration of AMDK19-HK ameliorates HDM-induced AAI in mice by suppressing Th2-mediated immune responses and could have a protective effect against AA development.

2.
FASEB Bioadv ; 5(12): 521-527, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38094156

ABSTRACT

The beneficial effects of Akkermansia muciniphila (Akk) on gut health and inflammation reduction have been demonstrated; however, scientific evidence of hair growth enhancement by Akk has not been reported. Therefore, this study was undertaken to investigate the effect of Akk on improving testosterone-mediated hair growth inhibition. Hair growth inhibition was induced through subcutaneous injection of testosterone into the shaved dorsal skin of C57BL/6 male mice. Live and pasteurized Akk were orally administered at a concentration of 1 × 108 colony-forming unit. After 5 weeks, hair length and skin tissues were analyzed. The live and pasteurized Akk significantly stimulated hair growth, countering the inhibitory effect of testosterone compared to the testosterone-alone group. Hematoxylin and eosin staining revealed a significant increase in hair follicle size in the Akk-treated group. An increase in ß-catenin levels, which are associated with hair growth and cell cycle progression, was also observed. Moreover, the Akk-treated group exhibited increased levels of fibroblast growth factors, including Fgf7, Igf1, Fgf7, Fgf10, and Fgf21. However, no significant difference was observed between the live and pasteurized Akk groups. These results underscore the potential of live and pasteurized Akk in improving testosterone-mediated hair growth inhibition.

3.
Front Endocrinol (Lausanne) ; 14: 1220044, 2023.
Article in English | MEDLINE | ID: mdl-37711887

ABSTRACT

Introduction: Obesity and related metabolic issues are a growing global health concern. Recently, the discovery of new probiotics with anti-obesity properties has gained interest. Methods: In this study, four Faecalibacte-rium prausnitzii strains were isolated from healthy human feces and evaluated on a high-fat diet-induced mouse model for 12 weeks. Results: The F. prausnitzii strains reduced body weight gain, liver and fat weights, and calorie intake while improving lipid and glucose metabolism in the liver and adipose tissue, as evidenced by regulating lipid metabolism-associated gene expression, including ACC1, FAS, SREBP1c, leptin, and adiponectin. Moreover, the F. prausnitzii strains inhibited low-grade inflammation, restored gut integrity, and ameliorated hepatic function and insulin resistance. Interestingly, the F. prausnitzii strains modulated gut and neural hormone secretion and reduced appetite by affecting the gut-brain axis. Supplementation with F. prausnitzii strains noticeably changed the gut microbiota composition. Discussion: In summary, the novel isolated F. prausnitzii strains have therapeutic effects on obesity and associated metabolic disorders through modulation of the gut-brain axis. Additionally, the effectiveness of different strains might not be achieved through identical mechanisms. Therefore, the present findings provide a reliable clue for developing novel therapeutic probiotics against obesity and associated metabolic disorders.


Subject(s)
Faecalibacterium prausnitzii , Metabolic Diseases , Humans , Animals , Mice , Diet, High-Fat/adverse effects , Metabolic Diseases/etiology , Obesity/etiology , Pharmaceutical Preparations
4.
Front Microbiol ; 14: 1123547, 2023.
Article in English | MEDLINE | ID: mdl-37007480

ABSTRACT

Introduction: Nonalcoholic steatohepatitis (NASH) is an advanced nonalcoholic fatty liver disease characterized by chronic inflammation and fibrosis. A dysbiosis of the gut microbiota has been associated with the pathophysiology of NASH, and probiotics have proven helpful in its treatment and prevention. Although both traditional and next-generation probiotics have the potential to alleviate various diseases, studies that observe the therapeutic effect of next-generation probiotics on NASH are lacking. Therefore, we investigated whether a next-generation probiotic candidate, Faecalibacterium prausnitzii, contributed to the mitigation of NASH. Methods: In this study, we conducted 16S rRNA sequencing analyses in patients with NASH and healthy controls. To test F. prausnitzii could alleviate NASH symptoms, we isolated four F. prausnitzii strains (EB-FPDK3, EB-FPDK9, EB-FPDK11, and EB-FPYYK1) from fecal samples collected from four healthy individuals. Mice were maintained on a high-fructose high-fat diet for 16 weeks to induce a NASH model and received oral administration of the bacterial strains. Changes in characteristic NASH phenotypes were assessed via oral glucose tolerance tests, biochemical assays, and histological analyses. Results: 16S rRNA sequencing analyses confirmed that the relative abundance of F. prausnitzii reduced significantly in patients with NASH compared to healthy controls (p < 0.05). In the NASH mice, F. prausnitzii supplementation improved glucose homeostasis, prevented hepatic lipid accumulation, curbed liver damage and fibrosis, restored damaged gut barrier functions, and alleviated hepatic steatosis and liver inflammation. Furthermore, real-time PCR assays documented that the four F. prausnitzii strains regulated the expression of genes related to hepatic steatosis in these mice. Discussion: Our study, therefore, confirms that the administration of F. prausnitzii bacteria can alleviate NASH symptoms. We propose that F. prausnitzii has the potential to contribute to the next-generation probiotic treatment of NASH.

5.
Allergy ; 78(7): 1866-1877, 2023 07.
Article in English | MEDLINE | ID: mdl-36883528

ABSTRACT

BACKGROUND: Allergic inflammation affects the epithelial cell populations resulting in goblet cell hyperplasia and decreased ciliated cells. Recent advances in single-cell RNA sequencing (scRNAseq) have enabled the identification of new cell subtypes and genomic features of single cells. In this study, we aimed to investigate the effect of allergic inflammation in nasal epithelial cell transcriptomes at the single-cell level. METHODS: We performed scRNAseq in cultured primary human nasal epithelial (HNE) cells and in vivo nasal epithelium. The transcriptomic features and epithelial cell subtypes were determined under IL-4 stimulation, and cell-specific marker genes and proteins were identified. RESULTS: We confirmed that cultured HNE cells were similar to in vivo epithelial cells through scRNAseq. Cell-specific marker genes were utilized to cluster the cell subtypes, and FOXJ1+ -ciliated cells were sub-classified into multiciliated and deuterosomal cells. PLK4 and CDC20B were specific for deuterosomal cells, and SNTN, CPASL, and GSTA2 were specific for multiciliated cells. IL-4 altered the proportions of cell subtypes, resulting in a decrease in multiciliated cells and loss of deuterosomal cells. The trajectory analysis revealed deuterosomal cells as precursor cells of multiciliated cells and deuterosomal cells function as a bridge between club and multiciliated cells. A decrease in deuterosomal cell marker genes was observed in nasal tissue samples with type 2 inflammation. CONCLUSION: The effects of IL-4 appear to be mediated through the loss of the deuterosomal population, resulting in the reduction in multiciliated cells. This study also newly suggests cell-specific markers that might be pivotal for investigating respiratory inflammatory diseases.


Subject(s)
Epithelial Cells , Interleukin-4 , Humans , Cell Differentiation/genetics , Cells, Cultured , Epithelial Cells/metabolism , Inflammation/metabolism , Interleukin-4/metabolism , Nasal Mucosa , Protein Serine-Threonine Kinases/metabolism
6.
Nat Nanotechnol ; 18(4): 390-402, 2023 04.
Article in English | MEDLINE | ID: mdl-36635335

ABSTRACT

Although conventional innate immune stimuli contribute to immune activation, they induce exhausted immune cells, resulting in suboptimal cancer immunotherapy. Here we suggest a kinetically activating nanoadjuvant (K-nanoadjuvant) that can dynamically integrate two waves of innate immune stimuli, resulting in effective antitumour immunity without immune cell exhaustion. The combinatorial code of K-nanoadjuvant is optimized in terms of the order, duration and time window between spatiotemporally activating Toll-like receptor 7/8 agonist and other Toll-like receptor agonists. K-nanoadjuvant induces effector/non-exhausted dendritic cells that programme the magnitude and persistence of interleukin-12 secretion, generate effector/non-exhausted CD8+ T cells, and activate natural killer cells. Treatment with K-nanoadjuvant as a monotherapy or in combination therapy with anti-PD-L1 or liposomes (doxorubicin) results in strong antitumour immunity in murine models, with minimal systemic toxicity, providing a strategy for synchronous and dynamic tailoring of innate immunity for enhanced cancer immunotherapy.


Subject(s)
CD8-Positive T-Lymphocytes , Neoplasms , Animals , Mice , Immunotherapy/methods , Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/therapeutic use , Immunity, Innate , Neoplasms/therapy
7.
Am J Respir Cell Mol Biol ; 67(3): 360-374, 2022 09.
Article in English | MEDLINE | ID: mdl-35679095

ABSTRACT

Allergic rhinitis (AR) is a multifactorial airway disease characterized by basal and goblet cell hyperplasia. Hyaluronic acid (HA) is a major component of extracellular matrix and a critical contributor to tissue repair and remodeling after injury. We previously demonstrated that the intermediate progenitor cell (IPC) surface marker CD44v3 is upregulated in the basal and suprabasal layers of well-differentiated primary human nasal epithelial (HNE) cells after stimulation with the Th2 (T-helper cell type 2) cytokine IL-4, and an antibody blocking the CD44v3-HA interaction suppressed IL-4-induced goblet cell hyperplasia. We now show that the expression of HA and two HA synthases, HAS2 and HAS3, was upregulated in both the nasal surface epithelium of subjects with AR and IL-4-stimulated HNE cells. Inhibition of HA synthesis by 4-methylumbelliferone suppressed IL-4-induced goblet cell hyperplasia. Moreover, HAS2 and HAS3 were expressed in IPCs depending on the differentiation events, as follows: the rapid, transient upregulation of HAS2 induced basal IPC proliferation and basal-to-suprabasal transition, whereas the delayed upregulation of HAS3 promoted the transition of suprabasal IPCs to a goblet cell fate. 4-methylumbelliferone treatment in a house dust mite-induced murine AR model attenuated goblet cell metaplasia. Last, HA concentrations in nasal epithelial lining fluids from patients with AR positively correlated with the concentrations of mediators causing allergic inflammation. These data suggest that HA produced after the sequential upregulation of HAS2 and HAS3 contributes to goblet cell hyperplasia in allergic airway inflammation and modulates disease progression.


Subject(s)
Goblet Cells , Hyaluronan Synthases , Rhinitis, Allergic , Animals , Goblet Cells/drug effects , Goblet Cells/enzymology , Goblet Cells/pathology , Humans , Hyaluronan Synthases/metabolism , Hyaluronic Acid/metabolism , Hymecromone/pharmacology , Hymecromone/therapeutic use , Hyperplasia/genetics , Hyperplasia/pathology , Interleukin-4/metabolism , Mice , Rhinitis, Allergic/drug therapy , Rhinitis, Allergic/enzymology , Rhinitis, Allergic/pathology
8.
Mol Cells ; 45(6): 353-361, 2022 Jun 30.
Article in English | MEDLINE | ID: mdl-35611689

ABSTRACT

Chronic rhinosinusitis (CRS) is a multifactorial, heterogeneous disease characterized by persistent inflammation of the sinonasal mucosa and tissue remodeling, which can include basal/progenitor cell hyperplasia, goblet cell hyperplasia, squamous cell metaplasia, loss or dysfunction of ciliated cells, and increased matrix deposition. Repeated injuries can stimulate airway epithelial cells to produce inflammatory mediators that activate epithelial cells, immune cells, or the epithelial-mesenchymal trophic unit. This persistent inflammation can consequently induce aberrant tissue remodeling. However, the molecular mechanisms driving disease within the different molecular CRS subtypes remain inadequately characterized. Numerous secreted and cell surface proteins relevant to airway inflammation and remodeling are initially synthesized as inactive precursor proteins, including growth/differentiation factors and their associated receptors, enzymes, adhesion molecules, neuropeptides, and peptide hormones. Therefore, these precursor proteins require post-translational cleavage by proprotein convertases (PCs) to become fully functional. In this review, we summarize the roles of PCs in CRS-associated tissue remodeling and discuss the therapeutic potential of targeting PCs for CRS treatment.


Subject(s)
Nasal Polyps , Sinusitis , Airway Remodeling , Chronic Disease , Humans , Hyperplasia/metabolism , Inflammation/metabolism , Nasal Mucosa , Proprotein Convertases/metabolism
9.
Small Methods ; 6(8): e2200127, 2022 08.
Article in English | MEDLINE | ID: mdl-35595685

ABSTRACT

There have been several studies for demonstration of 2D neural network using living cells or organic/inorganic molecules, but to date, there is no report of development of a 3D neural network in vitro. Based on developed bionanohybrid composed of protein, DNA, molybdenum disulfide nanoparticles, and peptides for controlling electrophysiological states of living cells, here, the in vitro 3D neural network composed of the bionanohybrid, 3D neurospheroid and the microelectrode array (MEA) is developed. After production of the 3D neurospheroid derived from human neural stem cells, the bionanohybrid developed on the MEA successfully semi-penetrates the neurites of the 3D neurospheroid and forms the 3D neural network. The developed 3D neural network successfully exhibited the electrophysiological output signals of the 3D neurospheroid by transmitting the input signal applied by the bionanohybrid. Moreover, by using the selectively immobilized bionanohybrid on the MEA, the spatial input signal recognition in the neurospheroid of 3D neural network is realized for the first time. This newly developed in vitro 3D neural network provides a promising strategy to be applied in brain-on-a-chip, brain disease-related drug efficacy evaluation, bioelectronics, and bioelectronic medicine.


Subject(s)
Neural Stem Cells , Brain , Electrophysiological Phenomena , Humans , Microelectrodes , Neural Networks, Computer
10.
J Pharmacopuncture ; 25(1): 15-23, 2022 Mar 31.
Article in English | MEDLINE | ID: mdl-35371583

ABSTRACT

Objectives: This study aims to develop a community care model in traditional Korean medicine (TKM) by developing a community care participation model for the health of the elderly and deriving tasks to implement it. Methods: This study implemented a group interview with experts. A fact-finding survey was conducted targeting 16 local governments that are implementing a leading project to identify the status of TKM service provision and welfare service linkage in all regions. An expert group interview (FGI) targeted public and private sector experts for each job role, the former represented by those in charge of the central government's health care policy and administrative delivery system, and the latter by professors majoring in social welfare, professors majoring in health, and local TKM societies. After forming the expert groups, three expert group interviews were conducted. Results: Through collective interviews with experts, a model for providing TKM and welfare services in community integrated care was derived by dividing it into local and central government levels. The strategies and tasks for promoting TKM-oriented health welfare services were derived from 3 strategies, 8 tasks, and 20 detailed tasks. Conclusion: The core direction of the TKM health care model is the region-centered provision of TKM and welfare services. To this end, policy support for the use and linkage of health care service resources is required at the central government level, and linkage and provision of health welfare services centered on TKM are necessary through linkage and convergence between service subjects and between government health care projects.

11.
ACS Sens ; 7(2): 409-414, 2022 02 25.
Article in English | MEDLINE | ID: mdl-35044765

ABSTRACT

Combining human brain organoids holds great potential in recapitulating the human brain's histological features and modeling neural disorders. However, current combined-brain organoid models focus on the internal interactions between different brain regions. In this study, we develop an engineered brain-spinal cord assembloid (eBSA) by coculturing cerebral organoids (COs) and motor neuron spheroids (MNSs). By connecting COs and MNSs, we generate a terminal for signal transfer from the brain to the whole body by mimicking the brain-spinal cord connection. After the formation of COs from human induced pluripotent stem cells and MNSs from human neural stem cells, MNSs are prepatterned into specific CO regions and assembled to form an eBSA. Caffeine serves as a neurochemical model to demonstrate neural signal transmission. When the MNSs in the eBSA contact the multielectrode array, the eBSA successfully shows an increased neural spiking speed on the motor neuron region by caffeine treatment, which means that neural stimulation signals transfer from the COs to MNSs. The neural stimulation effects of caffeine are tested on the MNSs only to prove the eBSA system's neural signal transmission, and there were no stimulus effects. Our results demonstrate that the eBSA system can monitor a caffeine-mediated excitatory signal as an output signal from the brain to the spinal cord. We believe that the eBSA system can be utilized as a screening platform to validate the stimulus signal transfer by neurochemicals. In addition, the accumulation of understanding of the neural signal transfer from CNS to PNS will provide better knowledge for controlling muscle actuators with the nervous system.


Subject(s)
Caffeine , Induced Pluripotent Stem Cells , Brain , Caffeine/pharmacology , Electrophysiological Phenomena , Humans , Spinal Cord
12.
J Control Release ; 342: 228-240, 2022 02.
Article in English | MEDLINE | ID: mdl-35016917

ABSTRACT

RNA interference (RNAi) is being extensively investigated as a potential therapeutic strategy for cancer treatment. However, RNAi-based therapeutics have not yet been used to treat cancer because of their instability and the difficulty of microRNA (miRNA) delivery. Plasmonic nanoparticle-based RNAi nanotherapeutics have been developed for accurate and sensitive diagnosis and a strong therapeutic effect on cancers by leveraging their ease-of-use and specific properties such as photothermal conversion. In this review, recent strategies and advances in plasmonic nanoparticle-based miRNA delivery are briefly presented to facilitate the detection and treatment of several cancers. The challenges and potential opportunities afforded by the RNAi-based theragnosis field are discussed. We expect that the RNAi-integrated plasmonic nanotherapeutics discussed in this review can provide insights for the early diagnosis and effective treatment of cancer.


Subject(s)
MicroRNAs , Nanoparticles , Neoplasms , Drug Delivery Systems , Humans , MicroRNAs/genetics , MicroRNAs/therapeutic use , Neoplasms/diagnosis , Neoplasms/genetics , Neoplasms/therapy , RNA Interference , RNA, Small Interfering/genetics , RNA, Small Interfering/therapeutic use
13.
Anal Bioanal Chem ; 414(10): 3219-3230, 2022 Apr.
Article in English | MEDLINE | ID: mdl-34767053

ABSTRACT

Microfluidic-based biosensors have been developed for their precise automatic reaction control. However, these biosensors require external devices that are difficult to transport and use. To overcome this disadvantage, our group made an easy-to-use, cheap, and light pumpless three-dimensional photo paper-based microfluidic analytical device (3D-µPAD; weight: 1.5 g). Unlike conventional paper-based microfluidic analytical devices, the 3D-µPAD can be used to control fluid flow in a 3D manner, thus allowing sophisticated multi-step reaction control. This device can control fluid flow speed and direction accurately using only the capillary-driven flow without an external device like a pump. The flow speed is controlled by the width of the microfluidic channel and its surface property. In addition, fluid speed control and 3D-bridge structure enable the control of fluid flow direction. Using these methods, multi-step enzyme-linked immunosorbent assay (ELISA) can be done automatically in sequence by injecting solutions (sample, washing, and enzyme's substrate) at the same time in the 3D-µPAD. All the steps can be performed in 14 min, and data can be analyzed immediately. To test this device, thioredoxin-1 (Trx-1), a biomarker of breast cancer, is used as the target. In the 3D-µPAD, it can detect 0-200 ng/mL of Trx-1, and the prepared 3D-µPAD Trx-1 sensor displays excellent selectivity. Moreover, by analyzing the concentration of Trx-1 in real patients and healthy individuals' blood serum samples using the 3D-µPAD, and comparing results to ELISA, it can be confirmed that the 3D-µPAD is a good tool for cancer diagnosis.


Subject(s)
Microfluidic Analytical Techniques , Microfluidics , Enzyme-Linked Immunosorbent Assay , Humans , Paper , Thioredoxins
14.
Nano Converg ; 8(1): 40, 2021 Dec 04.
Article in English | MEDLINE | ID: mdl-34862954

ABSTRACT

The degeneration or loss of skeletal muscles, which can be caused by traumatic injury or disease, impacts most aspects of human activity. Among various techniques reported to regenerate skeletal muscle tissue, controlling the external cellular environment has been proven effective in guiding muscle differentiation. In this study, we report a nano-sized graphene oxide (sGO)-modified nanopillars on microgroove hybrid polymer array (NMPA) that effectively controls skeletal muscle cell differentiation. sGO-coated NMPA (sG-NMPA) were first fabricated by sequential laser interference lithography and microcontact printing methods. To compensate for the low adhesion property of polydimethylsiloxane (PDMS) used in this study, graphene oxide (GO), a proven cytophilic nanomaterial, was further modified. Among various sizes of GO, sGO (< 10 nm) was found to be the most effective not only for coating the surface of the NM structure but also for enhancing the cell adhesion and spreading on the fabricated substrates. Remarkably, owing to the micro-sized line patterns that guide cellular morphology to an elongated shape and because of the presence of sGO-modified nanostructures, mouse myoblast cells (C2C12) were efficiently differentiated into skeletal muscle cells on the hybrid patterns, based on the myosin heavy chain expression levels. Therefore, the developed sGO coated polymeric hybrid pattern arrays can serve as a potential platform for rapid and highly efficient in vitro muscle cell generation.

15.
ACS Nano ; 15(8): 13475-13485, 2021 08 24.
Article in English | MEDLINE | ID: mdl-34369760

ABSTRACT

Nucleic acid biomarkers have been widely used to detect various viral-associated diseases, including the recent pandemic COVID-19. The CRISPR-Cas-based trans-activating phenomenon has shown excellent potential for developing sensitive and selective detection of nucleic acids. However, the nucleic acid amplification steps are typically required when sensitive and selective monitoring of the target nucleic acid is needed. To overcome the aforementioned challenges, we developed a CRISPR-Cas12a-based nucleic acid amplification-free biosensor by a surface-enhanced Raman spectroscopy (SERS)-assisted ultrasensitive detection system. We integrated the activated CRISPR-Cas12a by viral DNA with a Raman-sensitive system composed of ssDNA-immobilized Raman probe-functionalized Au nanoparticles (RAuNPs) on the graphene oxide (GO)/triangle Au nanoflower array. Using this CRISPR-based Raman-sensitive system improved the detection sensitivity of the multiviral DNAs such as hepatitis B virus (HBV), human papillomavirus 16 (HPV-16), and HPV-18 with an extremely low detection limit and vast detection range from 1 aM to 100 pM without the amplification steps. We suggest that this ultrasensitive amplification-free detection system for nucleic acids can be widely applied to the precise and early diagnosis of viral infections, cancers, and several genetic diseases.


Subject(s)
Biosensing Techniques , COVID-19 , Metal Nanoparticles , Nucleic Acids , Humans , Spectrum Analysis, Raman/methods , DNA, Viral/genetics , Gold/chemistry , Nucleic Acid Amplification Techniques/methods , Biosensing Techniques/methods
16.
Adv Sci (Weinh) ; 8(19): e2102043, 2021 10.
Article in English | MEDLINE | ID: mdl-34363349

ABSTRACT

The deficiency of antigen-specific T cells and the induction of various treatment-induced immunosuppressions still limits the clinical benefit of cancer immunotherapy. Although the chemo-immunotherapy adjuvanted with Toll-like receptor 7/8 agonist (TLR 7/8a) induces immunogenic cell death (ICD) and in situ vaccination effect, indoleamine 2,3-dioxygenase (IDO) is also significantly increased in the tumor microenvironment (TME) and tumor-draining lymph node (TDLN), which offsets the activated antitumor immunity. To address the treatment-induced immunosuppression, an assemblable immune modulating suspension (AIMS) containing ICD inducer (paclitaxel) and supra-adjuvant (immune booster; R848 as a TLR 7/8a, immunosuppression reliever; epacadostat as an IDO inhibitor) is suggested and shows that it increases cytotoxic T lymphocytes and relieves the IDO-related immunosuppression (TGF-ß, IL-10, myeloid-derived suppressor cells, and regulatory T cells) in both TME and TDLN, by the formation of in situ depot in tumor bed as well as by the efficient migration into TDLN. Local administration of AIMS increases T cell infiltration in both local and distant tumors and significantly inhibits the metastasis of tumors to the lung. Reverting treatment-induced secondary immunosuppression and reshaping "cold tumor" into "hot tumor" by AIMS also increases the response rate of immune checkpoint blockade therapy, which promises a new nanotheranostic strategy in cancer immunotherapy.


Subject(s)
Breast Neoplasms/drug therapy , Breast Neoplasms/immunology , Immunosuppression Therapy/methods , Immunotherapy/methods , Nanomedicine/methods , Animals , Disease Models, Animal , Immunotherapy/adverse effects
17.
Biomedicines ; 9(8)2021 Jul 31.
Article in English | MEDLINE | ID: mdl-34440132

ABSTRACT

Nucleic acids, including DNA and RNA, have received prodigious attention as potential biomarkers for precise and early diagnosis of cancers. However, due to their small quantity and instability in body fluids, precise and sensitive detection is highly important. Taking advantage of the ease-to-functionality and plasmonic effect of nanomaterials, fluorescence resonance energy transfer (FRET) and metal-enhanced fluorescence (MEF)-based biosensors have been developed for accurate and sensitive quantitation of cancer-related nucleic acids. This review summarizes the recent strategies and advances in recently developed nanomaterial-based FRET and MEF for biosensors for the detection of nucleic acids in cancer diagnosis. Challenges and opportunities in this field are also discussed. We anticipate that the FRET and MEF-based biosensors discussed in this review will provide valuable information for the sensitive detection of nucleic acids and early diagnosis of cancers.

18.
Nanomedicine ; 37: 102415, 2021 10.
Article in English | MEDLINE | ID: mdl-34174421

ABSTRACT

Although immune checkpoint inhibitors have significantly improved clinical outcomes in various malignant cancers, only a small proportion of patients reap benefits, likely due to the low number of T cells and high number of immunosuppressive cells in the tumor microenvironment (TME) of patients with advanced disease. We developed a cancer vaccine adjuvanted with nanoemulsion (NE) loaded with TLR7/8 agonist (R848) and analyzed its therapeutic effect alone or in combination with immune checkpoint inhibitors, on antitumor immune responses and the reprogramming of suppressive immune cells in the TME. NE (R848) demonstrated robust local and systemic antitumor immune responses in both subcutaneous and orthotopic mouse lung cancer models, inducing tumor-specific T cell activation and mitigating T cell exhaustion. Combination with anti-PD-1 antibodies showed synergistic effects with respect to therapeutic efficacy and survival rate. Thus, NE (R848)-based cancer vaccines could prevent tumor recurrence and prolong survival by activating antitumor immunity and reprogramming immunosuppression.


Subject(s)
Cancer Vaccines/pharmacology , Lung Neoplasms/therapy , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Toll-Like Receptor 7/genetics , Toll-Like Receptor 8/genetics , Adjuvants, Immunologic/pharmacology , Animals , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , Cancer Vaccines/chemistry , Cancer Vaccines/immunology , Cell Line, Tumor , Disease Models, Animal , Drug Synergism , Emulsions/chemistry , Emulsions/pharmacology , Humans , Imidazoles/pharmacology , Immune Checkpoint Inhibitors/pharmacology , Lung Neoplasms/genetics , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Lymphocyte Activation/drug effects , Mice , Programmed Cell Death 1 Receptor/immunology , Toll-Like Receptor 7/agonists , Toll-Like Receptor 8/agonists , Tumor Microenvironment/drug effects
19.
Front Chem ; 9: 672739, 2021.
Article in English | MEDLINE | ID: mdl-34055741

ABSTRACT

Noble metal nanomaterials, such as gold, silver, and platinum, have been studied extensively in broad scientific fields because of their unique properties, including superior conductivity, plasmonic property, and biocompatibility. Due to their unique properties, researchers have used them to fabricate biosensors. Recently, biosensors for detecting respiratory illness-inducing viruses have gained attention after the global outbreak of coronavirus disease (COVID-19). In this mini-review, we discuss noble metal nanomaterials and associated biosensors for detecting respiratory illness-causing viruses, including SARS-CoV-2, using electrochemical and optical detection techniques. this review will provide interdisciplinary knowledge about the application of noble metal nanomaterials to the biomedical field.

20.
Front Chem ; 9: 671922, 2021.
Article in English | MEDLINE | ID: mdl-34026732

ABSTRACT

The electrochemical technique is one of the most accurate, rapid, and sensitive analytical assays, which becomes promising techniques for biological assays at a single-cell scale. Nanometals have been widely used for modification of the traditional electrodes to develop highly sensitive electrochemical cell chips. The electrochemical cell chips based on the nanostructured surface have been used as label-free, simple, and non-destructive techniques for in vitro monitoring of the effects of different anticancer drugs at the cellular level. Here, we will provide the recent progress in fabrication of nanopatterned surface and cell-based nanoarray, and discuss their applications based on electrochemical techniques such as detection of cellular states and chemicals, and non-destructive monitoring of stem cell differentiation.

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