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1.
Int J Infect Dis ; 139: 109-117, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37984763

ABSTRACT

OBJECTIVES: SARS-CoV-2 transmission and epidemic potential is related to the population's immunity levels. As such, assessing different regions' preexisting immune responses to SARS-CoV-2 is important to understand the transmission potential of emerging SARS-CoV-2 variants. DESIGN: In 975 serum samples from Vietnam (2014 to 2019), anti-SARS-CoV-2 Immunoglobulin G levels were determined by enzyme-linked immunosorbent assay. Plaque reduction neutralization test (PRNT) was performed using Wuhan strain and variants of concern (VOCs). Cross-reactivity was confirmed by analyzing B-cell receptor (BCR) repertoire sequences and identifying BCR repertoire sequences-derived T-cell epitopes. RESULTS: Overall, 20.9% (n = 76/364) and 9.2% (n = 7) demonstrated SARS-CoV-2 neutralizing activity (PRNT50) against the Wuhan and Alpha strain, respectively. Neutralizing activity against Beta, Gamma, and Delta strains was absent (PRNT50<5) in all samples. Cross-reactive epitopes against SARS-CoV-2 and other coronavirus spike proteins were detected in the N-terminal domain, S2, and receptor-binding domain regions. CONCLUSIONS: Following BCR and major histocompatibility complex analysis, T-cell receptor-recognized epitope motif (TREM) among pathogenic coronaviruses and coronaviruses spike proteins were the top TREM peptide, suggesting that pre-existing immunity against SARS-CoV-2 in Vietnam was due to exposure to common cold coronaviruses. With limited immunity against emerging VOCs, further monitoring, and control of the epidemic, along with COVID-19 vaccine programs against VOCs, are necessary.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/genetics , COVID-19/epidemiology , COVID-19 Vaccines , Vietnam/epidemiology , Pandemics , Seasons , Spike Glycoprotein, Coronavirus/genetics , Epitopes , Antibodies, Neutralizing , Antibodies, Viral
2.
Viruses ; 15(5)2023 05 17.
Article in English | MEDLINE | ID: mdl-37243272

ABSTRACT

T-cell recognition of antigen epitopes is a crucial step for the induction of adaptive immune responses, and the identification of such T-cell epitopes is, therefore, important for understanding diverse immune responses and controlling T-cell immunity. A number of bioinformatic tools exist that predict T-cell epitopes; however, many of these methods highly rely on evaluating conventional peptide presentation by major histocompatibility complex (MHC) molecules, but they ignore epitope sequences recognized by T-cell receptor (TCR). Immunogenic determinant idiotopes are present on the variable regions of immunoglobulin molecules expressed on and secreted by B-cells. In idiotope-driven T-cell/B-cell collaboration, B-cells present the idiotopes on MHC molecules for recognition by idiotope-specific T-cells. According to the idiotype network theory formulated by Niels Jerne, such idiotopes found on anti-idiotypic antibodies exhibit molecular mimicry of antigens. Here, by combining these concepts and defining the patterns of TCR-recognized epitope motifs (TREMs), we developed a T-cell epitope prediction method that identifies T-cell epitopes derived from antigen proteins by analyzing B-cell receptor (BCR) sequences. This method allowed us to identify T-cell epitopes that contain the same TREM patterns between BCR and viral antigen sequences in two different infectious diseases caused by dengue virus and SARS-CoV-2 infection. The identified epitopes were among the T-cell epitopes detected in previous studies, and T-cell stimulatory immunogenicity was confirmed. Thus, our data support this method as a powerful tool for the discovery of T-cell epitopes from BCR sequences.


Subject(s)
COVID-19 , T-Lymphocytes , Humans , Epitopes, T-Lymphocyte , Epitopes, B-Lymphocyte , SARS-CoV-2 , Receptors, Antigen, T-Cell , Receptors, Antigen, B-Cell
3.
Int J Mol Sci ; 23(23)2022 Nov 23.
Article in English | MEDLINE | ID: mdl-36498952

ABSTRACT

This study evaluated the mid-term (12-month) biomechanical, biocompatibility, and biological performance of additive-manufactured bioabsorbable iron-based interference screws (ISs). Two bioabsorbable iron IS types-manufactured using pure iron powder (iron_IS) and using pure iron powder with 0.2 wt% tricalcium phosphate (TCP_IS)-were compared with conventional metallic IS (control) using in vitro biocompatibility and degradation analyses and an in vivo animal study. The in vitro ultimate failure strength was significantly higher for iron_IS and TCP_IS than for control ISs at 3 months post-operatively; however, the difference between groups were nonsignificant thereafter. Moreover, at 3 months after implantation, iron_IS and TCP_IS increased bone volume fraction, bone surface area fraction, and percent intersection surface; the changes thereafter were nonsignificant. Iron_IS and TCP_IS demonstrated degradation over time with increased implant surface, decreased implant volume, and structure thickness; nevertheless, the analyses of visceral organs and biochemistry demonstrated normal results, except for time-dependent iron deposition in the spleen. Therefore, compared with conventional ISs, bioabsorbable iron-based ISs exhibit higher initial mechanical strength. Although iron-based ISs demonstrate high biocompatibility 12 months after implantation, their corrosive iron products may accumulate in the spleen. Because they demonstrate mechanical superiority along with considerable absorption capability after implantation, iron-based ISs may have potential applications in implantable medical-device development in the future.


Subject(s)
Calcium Phosphates , Iron , Animals , Rabbits , Iron/chemistry , Porosity , Absorbable Implants
5.
Materials (Basel) ; 15(10)2022 May 20.
Article in English | MEDLINE | ID: mdl-35629694

ABSTRACT

Autogenous bone grafts are the gold standard for interbody fusion implant materials; however, they have several disadvantages. Tantalum (Ta) and titanium (Ti) are ideal materials for interbody cages because of their biocompatibility, particularly when they are incorporated into a three-dimensional (3D) porous structure. We conducted an in vitro investigation of the cell attachment and osteogenic markers of self-fabricated uniform porous Ti (20%, 40%, 60%, and 80%), nonporous Ti, and porous Ta cages (n = 6) in each group. Cell attachment, osteogenic markers, and alkaline phosphatase (ALP) were measured. An in vivo study was performed using a pig-posterior-instrumented anterior interbody fusion model to compare the porous Ti (60%), nonporous Ti, and porous Ta interbody cages in 12 pigs. Implant migration and subsidence, determined using plain radiographs, were recorded before surgery, immediately after surgery, and at 1, 3, and 6 months after surgery. Harvested implants were assessed for bone ingrowth and attachment. Relative to the 20% and 40% porous Ti cages, the 60% and 80% cages achieved superior cellular migration into cage pores. Among the cages, osteogenic marker and ALP activity levels were the highest in the 60% porous Ti cage, osteocalcin expression was the highest in the nonporous Ti cage, and the 60% porous Ti cage exhibited the lowest subsidence. In conclusion, the designed porous Ti cage is biocompatible and suitable for lumbar interbody fusion surgery and exhibits faster fusion with less subsidence compared with porous Ta and nonporous Ti cages.

6.
Materials (Basel) ; 15(8)2022 Apr 11.
Article in English | MEDLINE | ID: mdl-35454494

ABSTRACT

Suture anchors are extensively used in rotator cuff tear surgery. With the advancement of three-dimensional printing technology, biodegradable metal has been developed for orthopedic applications. This study adopted three-dimensional-printed biodegradable Fe suture anchors with double-helical threads and commercialized non-vented screw-type Ti suture anchors with a tapered tip in the experimental and control groups, respectively. The in vitro study showed that the Fe and Ti suture anchors exhibited a similar ultimate failure load in 20-pound-per-cubic-foot polyurethane foam blocks and rabbit bone. In static immersion tests, the corrosion rate of Fe suture anchors was 0.049 ± 0.002 mm/year. The in vivo study was performed on New Zealand white rabbits and SAs were employed to reattach the ruptured supraspinatus tendon. The in vivo ultimate failure load of the Fe suture anchors was superior to that of the Ti suture anchors at 6 weeks. Micro-computed tomography showed that the bone volume fraction and bone surface density in the Fe suture anchors group 2 and 6 weeks after surgery were superior, and the histology confirmed that the increased bone volume around the anchor was attributable to mineralized osteocytes. The three-dimensional-printed Fe suture anchors outperformed the currently used Ti suture anchors.

7.
J Hosp Infect ; 124: 1-8, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35307505

ABSTRACT

BACKGROUND: To reduce transmission of carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE), screening is recommended for patients sharing rooms with CP-CRE-detected patients and healthcare workers caring for them. AIM: The aim of this study was to investigate the transmission rate of CP-CRE among exposed people in a tertiary hospital using whole-genome sequencing. METHODS: This study was conducted in a 1751-bed tertiary teaching hospital from January 2017 to December 2019. Index patients were defined as those with positive results in CP-CRE tests during hospitalization. When an index patient was detected in a shared room, we performed CRE screening tests for patients whose stay overlapped with an index patient's stay for at least one day. Where a second case was found, healthcare worker contacts were also screened. CP-CRE were confirmed, and the carbapenemase type identified, by PCR. Whole-genome sequencing was used to compare isolates from index and exposed patients. RESULTS: During the study period, 47 index patients were identified, and they had been in contact with 152 patients in shared rooms and 54 healthcare workers. None of the healthcare workers had CRE. Among the 152 exposed patients, four patients had the same type of carbapenemases as their CP-CRE index patients and all of them were KPC. Whole-genome sequencing revealed that three of these four pairs showed genotypic accordance between the index and the exposed. CONCLUSION: The CP-CRE transmission rate among the exposed patients was calculated as 2.0% (= 3/152).


Subject(s)
Carbapenem-Resistant Enterobacteriaceae , Enterobacteriaceae Infections , Gammaproteobacteria , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins/genetics , Carbapenem-Resistant Enterobacteriaceae/genetics , Carbapenems/pharmacology , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae Infections/epidemiology , Humans , Tertiary Care Centers , beta-Lactamases/genetics
8.
Cell Immunol ; 367: 104410, 2021 09.
Article in English | MEDLINE | ID: mdl-34274730

ABSTRACT

Rapid immune reconstitution without developing graft-versus-host disease (GVHD) is required for the success of allogeneic hematopoietic stem cell transplantation. Here, we analyzed the effects of pharmacological MEK inhibition on human polyclonal T-cell reconstitution in a humanized mouse GVHD model utilizing deep sequencing-based T-cell receptor (TCR) repertoire analysis. GVHD mice exhibited a skewed TCR repertoire with a common clone within target organs. The MEK inhibitor trametinib ameliorated GVHD and enabled engraftment of diverse T-cell clones. Furthermore, trametinib also ameliorated GVHD sparing diverse T cell repertoire, even when it was given from day 15 through 28. Although tacrolimus also reduced development of GVHD, it disturbed diverse T cell reconstitution and resulted in skewed TCR repertoire. Thus, trametinib not only suppresses GVHD-inducing T cells but also promotes human T cell reconstitution in vivo, providing a novel rationale for translational studies targeting human GVHD.


Subject(s)
Graft vs Host Disease/prevention & control , Hematopoietic Stem Cell Transplantation , Immunosuppressive Agents/therapeutic use , Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors , Protein Kinase Inhibitors/therapeutic use , Pyridones/therapeutic use , Pyrimidinones/therapeutic use , T-Lymphocytes/immunology , Animals , Cells, Cultured , Clone Cells , Graft vs Host Disease/immunology , Humans , Janus Kinase 3/genetics , Mice , Mice, Knockout , Mice, SCID , Mitogen-Activated Protein Kinase Kinases/metabolism , Receptors, Antigen, T-Cell/metabolism , Tacrolimus/therapeutic use , Transplantation, Heterologous
9.
Int J Mol Sci ; 22(14)2021 Jul 08.
Article in English | MEDLINE | ID: mdl-34298988

ABSTRACT

This study evaluated the biocompatibility and biological performance of novel additive-manufactured bioabsorbable iron-based porous suture anchors (iron_SAs). Two types of bioabsorbable iron_SAs, with double- and triple-helical structures (iron_SA_2_helix and iron_SA_3_helix, respectively), were compared with the synthetic polymer-based bioabsorbable suture anchor (polymer_SAs). An in vitro mechanical test, MTT assay, and scanning electron microscope (SEM) analysis were performed. An in vivo animal study was also performed. The three types of suture anchors were randomly implanted in the outer cortex of the lateral femoral condyle. The ultimate in vitro pullout strength of the iron_SA_3_helix group was significantly higher than the iron_SA_2_helix and polymer_SA groups. The MTT assay findings demonstrated no significant cytotoxicity, and the SEM analysis showed cells attachment on implant surface. The ultimate failure load of the iron_SA_3_helix group was significantly higher than that of the polymer_SA group. The micro-CT analysis indicated the iron_SA_3_helix group showed a higher bone volume fraction (BV/TV) after surgery. Moreover, both iron SAs underwent degradation with time. Iron_SAs with triple-helical threads and a porous structure demonstrated better mechanical strength and high biocompatibility after short-term implantation. The combined advantages of the mechanical superiority of the iron metal and the possibility of absorption after implantation make the iron_SA a suitable candidate for further development.


Subject(s)
Absorbable Implants , Biocompatible Materials , Suture Anchors , Alanine Transaminase/blood , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/toxicity , Biomechanical Phenomena , Blood Urea Nitrogen , Calcium Phosphates/chemistry , Calcium Phosphates/toxicity , Calcium Sulfate/administration & dosage , Calcium Sulfate/chemistry , Calcium Sulfate/toxicity , Creatinine/blood , Equipment Design , Femur/diagnostic imaging , Femur/ultrastructure , Iron , Lasers , Materials Testing , Microscopy, Electron, Scanning , Molecular Structure , Osseointegration , Polymers/chemistry , Polymers/toxicity , Porosity , Rabbits , Random Allocation , Tensile Strength , Viscera , X-Ray Microtomography
10.
AJNR Am J Neuroradiol ; 42(5): 838-844, 2021 05.
Article in English | MEDLINE | ID: mdl-33737268

ABSTRACT

BACKGROUND AND PURPOSE: Differentiating glioblastoma from solitary brain metastasis preoperatively using conventional MR images is challenging. Deep learning models have shown promise in performing classification tasks. The diagnostic performance of a deep learning-based model in discriminating glioblastoma from solitary brain metastasis using preoperative conventional MR images was evaluated. MATERIALS AND METHODS: Records of 598 patients with histologically confirmed glioblastoma or solitary brain metastasis at our institution between February 2006 and December 2017 were retrospectively reviewed. Preoperative contrast-enhanced T1WI and T2WI were preprocessed and roughly segmented with rectangular regions of interest. A deep neural network was trained and validated using MR images from 498 patients. The MR images of the remaining 100 were used as an internal test set. An additional 143 patients from another tertiary hospital were used as an external test set. The classifications of ResNet-50 and 2 neuroradiologists were compared for their accuracy, precision, recall, F1 score, and area under the curve. RESULTS: The areas under the curve of ResNet-50 were 0.889 and 0.835 in the internal and external test sets, respectively. The area under the curve of neuroradiologists 1 and 2 were 0.889 and 0.768 in the internal test set and 0.857 and 0.708 in the external test set, respectively. CONCLUSIONS: A deep learning-based model may be a supportive tool for preoperative discrimination between glioblastoma and solitary brain metastasis using conventional MR images.


Subject(s)
Brain Neoplasms/diagnostic imaging , Brain Neoplasms/secondary , Deep Learning , Glioblastoma/diagnostic imaging , Image Processing, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Adult , Aged , Area Under Curve , Diagnosis, Differential , Female , Humans , Image Enhancement , Male , Middle Aged , Reproducibility of Results , Retrospective Studies
11.
Int J Mol Sci ; 21(10)2020 May 21.
Article in English | MEDLINE | ID: mdl-32455543

ABSTRACT

The interference screw fixation method is used to secure a graft in the tibial tunnel during anterior cruciate ligament reconstruction surgery. However, several complications have been reported, such as biodegradable screw breakage, inflammatory or foreign body reaction, tunnel enlargement, and delayed graft healing. Using additive manufacturing (AM) technology, we developed a titanium alloy (Ti6Al4V) interference screw with chemically calcium phosphate surface modification technology to improve bone integration in the tibial tunnel. After chemical and heat treatment, the titanium screw formed a dense apatite layer on the metal surface in simulated body fluid. Twenty-seven New Zealand white rabbits were randomly divided into control and additive manufactured (AMD) screw groups. The long digital extensor tendon was detached and translated into a tibial plateau tunnel (diameter: 2.0 mm) and transfixed with an interference screw while the paw was in dorsiflexion. Biomechanical analyses, histological analyses, and an imaging study were performed at 1, 3, and 6 months. The biomechanical test showed that the ultimate pull-out load failure was significantly higher in the AMD screw group in all tested periods. Micro-computed tomography analyses revealed early woven bone formation in the AMD screw group at 1 and 3 months. In conclusion, AMD screws with bioactive surface modification improved bone ingrowth and enhanced biomechanical performance in a rabbit model.


Subject(s)
Bone Screws/standards , Osseointegration , Printing, Three-Dimensional , Tendons/surgery , Tibia/surgery , Alloys/chemistry , Animals , Bone Screws/adverse effects , Bone-Implant Interface/surgery , Calcium Phosphates/chemistry , Porosity , Rabbits
12.
Sci Rep ; 9(1): 12372, 2019 08 26.
Article in English | MEDLINE | ID: mdl-31451757

ABSTRACT

The northern tree shrew (Tupaia belangeri) possesses high potential as an animal model of human diseases and biology, given its genetic similarity to primates. Although genetic information on the tree shrew has already been published, some of the entire coding sequences (CDSs) of tree shrew genes remained incomplete, and the reliability of these CDSs remained difficult to determine. To improve the determination of tree shrew CDSs, we performed sequencing of the whole-genome, mRNA, and total RNA and integrated the resulting data. Additionally, we established criteria for the selection of reliable CDSs and annotated these sequences by comparison to the human transcriptome, resulting in the identification of complete CDSs for 12,612 tree shrew genes and yielding a more accurate tree shrew genome database (TupaiaBase: http://tupaiabase.org ). Transcriptome profiles in hepatitis B virus infected tree shrew livers were analyzed for validation. Gene ontology analysis showed enriched transcriptional regulation at 1 day post-infection, namely in the "type I interferon signaling pathway". Moreover, a negative regulator of type I interferon, SOCS3, was induced. This work, which provides a tree shrew CDS database based on genomic DNA and RNA sequencing, is expected to serve as a powerful tool for further development of the tree shrew model.


Subject(s)
Databases, Genetic , Genome , Sequence Analysis, RNA , Transcriptome/genetics , Tupaia/genetics , Animals , Base Sequence , Gene Expression Regulation , Gene Ontology , Hepatitis B/genetics , Hepatitis B/pathology , Hepatitis B/virology , Hepatitis B virus/physiology , Interferon Type I/metabolism , Liver/metabolism , Male , Open Reading Frames/genetics , Organ Specificity/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reproducibility of Results , Signal Transduction , Tupaia/virology
13.
J Theor Biol ; 465: 7-16, 2019 03 21.
Article in English | MEDLINE | ID: mdl-30629963

ABSTRACT

A mathematical model of garden ants (Lasius japonicus) is introduced herein to investigate the relationship between the distribution of the degree of stochasticity in following pheromone trails and the group foraging efficiency. Numerical simulations of the model indicate that depending on the systematic change of the feeding environment, the optimal distribution of stochasticity shifts from a mixture of almost deterministic and mildly stochastic ants to a contrasted mixture of almost deterministic ants and highly stochastic ants. In addition, the interaction between the stochasticity and the pheromone path regulates the dynamics of the foraging efficiency optimization. Stochasticity could strengthen the collective efficiency when the variance in the sensitivity to pheromone for ants is introduced in the model.


Subject(s)
Algorithms , Ants/physiology , Feeding Behavior/physiology , Models, Biological , Social Behavior , Animals , Ants/metabolism , Pheromones/metabolism , Pheromones/physiology , Stochastic Processes
14.
J Dent Sci ; 14(4): 419-425, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31890132

ABSTRACT

BACKGROUND/PURPOSE: Electrolyzed water has been identified as an effective disinfectant that could represent as an alternative to sodium hypochlorite. Unfortunately, it remains unclear whether the texture or physical properties of dentin are affected by the application of electrolyzed water of different acidities. This study was aimed to assess the influence of electrolyzed waters with differing pHs on the demineralizing of inner dentin. MATERIALS AND METHODS: The coronal superficial dentin of 20 human molars was exposed and further bisected into two pieces perpendicular to the dentin surface. The samples were immersed in strongly acidic electrolyzed water (AW group), neutral electrolyzed water (NW group), 5% sodium hypochlorite (positive control, NL group), or deionized water (negative control, DW group). Microhardness of the inner layer dentin was measured at a depth of 25 and 50 µm beneath the superficial surface layer every 5 up to 60 min. RESULTS: At a depth of 25 µm, microhardness decreased with increasing immersion time in all but the DW group. The AW group exhibited a decreasing trend from the first 5 min that became significant after 35 min of immersion and was the most rapid decrease in the four groups. The rate of decline in the NW group was low and similar to that of the NL group. Both NW and NL groups exhibited significantly less demineralization than the AW group after 15 min of immersion. No significant microhardness change was found at a depth of 50 µm in any of the samples. CONCLUSION: AW produces a more pronounced softening of dentin than NW at a depth of 25 µm.

15.
Int J Hematol ; 109(2): 221-227, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30368656

ABSTRACT

Adult T-cell leukemia (ATL) is an aggressive mature T-cell malignancy with a poor prognosis. The anti-C-C motif chemokine receptor 4 (CCR4) antibody mogamulizumab (moga) reduces ATL cells and induces reconstitution of polyclonal T cells; however, ATL cases often remain resistant and moga sometimes causes fatal immunopathology. Epstein-Barr virus (EBV)-related B-cell lymphoma develops in severely immunocompromised subjects, and is particularly associated with impaired T-cell immunity. Here, we report an ATL patient who had received conventional chemotherapy plus moga, and subsequently developed EBV-related diffuse large B-cell lymphoma (DLBCL) of the central nervous system. Next-generation sequencing-based T-cell receptor repertoire analyses identified residual abnormal clones and revealed that reconstitution of polyclonal T cells was incomplete, even after moga treatment. Furthermore, a skin rash that developed after moga treatment was found to contain ATL clones. This case suggests that the limited therapeutic effects of moga and incomplete T-cell reconstitution are associated with severely impaired T-cell immunity and subsequent development of EBV-related DLBCL.


Subject(s)
Herpesvirus 4, Human , Lymphoma, Large B-Cell, Diffuse/etiology , Adult , Antibodies, Monoclonal, Humanized/therapeutic use , Central Nervous System Neoplasms , Child , Clone Cells/pathology , Humans , Leukemia-Lymphoma, Adult T-Cell/complications , Leukemia-Lymphoma, Adult T-Cell/drug therapy , Lymphoma, Large B-Cell, Diffuse/virology , T-Lymphocytes/immunology , T-Lymphocytes/pathology
16.
Obes Rev ; 19(11): 1585-1596, 2018 11.
Article in English | MEDLINE | ID: mdl-30180304

ABSTRACT

This study aimed to evaluate the effect of acupuncture and intervention types on weight loss. We searched electronic databases, including Embase, PubMed, CENTRAL, RISS, KISS and CNKI, for randomized controlled trials that used acupuncture to treat obesity before June 2017. We found 27 trials involving 32 intervention arms and 2,219 patients. Acupuncture plus lifestyle modification (LM) was more effective than LM alone (Hedges' g = 1.104, 95% CI = 0.531-1.678) and sham acupuncture plus LM (Hedges' g = 0.324, 95% CI = 0.177-0.471), whereas acupuncture alone was not more effective than sham acupuncture alone and no treatment. Auricular acupuncture (Hedges' g = 0.522, 95% CI = 0.152-0.893), manual acupuncture (Hedges' g = 0445, 95% CI = 0.044-0.846) and pharmacopuncture (Hedges' g = 0.411, 95% CI = 0.026-0.796) favoured weight loss. Finally, acupuncture treatment was effective only in subjects with overweight (25 ≤ body mass index < 30, Hedges' g = 0.528, 95% CI = 0.279-0.776), not in subjects with obesity (body mass index ≥30). Our study suggests that the effect of acupuncture on weight loss may be maximized when auricular and manual acupuncture or pharmacopuncture treatment is combined with LM in patients with overweight.


Subject(s)
Acupuncture Therapy , Life Style , Obesity/therapy , Weight Loss , Body Mass Index , Humans , Treatment Outcome
17.
Molecules ; 23(5)2018 Apr 28.
Article in English | MEDLINE | ID: mdl-29710774

ABSTRACT

The synthesis and anti-inflammatory effects of certain pyrazolo[4,3-c]quinoline derivatives 2a⁻2r are described. The anti-inflammatory activities of these derivatives were evaluated by means of inhibiting nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Among them, 3-amino-4-(4-hydroxyphenylamino)-1H-pyrazolo[4,3-c]-quinoline (2i) and 4-(3-amino-1H-pyrazolo[4,3-c]quinolin-4-ylamino)benzoic acid (2m) exhibited significant inhibition of LPS-stimulated NO production with a potency approximately equal to that of the positive control, 1400 W. Important structure features were analyzed by quantitative structure⁻activity relationship (QSAR) analysis to give better insights into the structure determinants for predicting the inhibitory effects on the accumulation of nitric oxide for RAW 264.7 cells in response to LPS. In addition, our results indicated that their anti-inflammatory effects involve the inhibition of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expression. Further studies on the structural optimization are ongoing.


Subject(s)
Anti-Inflammatory Agents/chemical synthesis , Macrophages/cytology , Pyrazoles/chemical synthesis , Quinolines/chemical synthesis , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Cyclooxygenase 2/chemistry , Cyclooxygenase 2/metabolism , Down-Regulation , Gene Expression Regulation, Enzymologic/drug effects , Lipopolysaccharides/adverse effects , Macrophages/drug effects , Macrophages/metabolism , Mice , Models, Molecular , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/chemistry , Nitric Oxide Synthase Type II/metabolism , Pyrazoles/chemistry , Pyrazoles/pharmacology , Quantitative Structure-Activity Relationship , Quinolines/chemistry , Quinolines/pharmacology , RAW 264.7 Cells
18.
Front Immunol ; 9: 668, 2018.
Article in English | MEDLINE | ID: mdl-29666626

ABSTRACT

The human immune system is a fine network consisted of the innumerable numbers of functional cells that balance the immunity and tolerance against various endogenous and environmental challenges. Although advances in modern immunology have revealed a role of many unique immune cell subsets, technologies that enable us to capture the whole landscape of immune responses against specific antigens have been not available to date. Acquired immunity against various microorganisms including host microbiome is principally founded on T cell and B cell populations, each of which expresses antigen-specific receptors that define a unique clonotype. Over the past several years, high-throughput next-generation sequencing has been developed as a powerful tool to profile T- and B-cell receptor repertoires in a given individual at the single-cell level. Sophisticated immuno-bioinformatic analyses by use of this innovative methodology have been already implemented in clinical development of antibody engineering, vaccine design, and cellular immunotherapy. In this article, we aim to discuss the possible application of high-throughput immune receptor sequencing in the field of nutritional and intestinal immunology. Although there are still unsolved caveats, this emerging technology combined with single-cell transcriptomics/proteomics provides a critical tool to unveil the previously unrecognized principle of host-microbiome immune homeostasis. Accumulation of such knowledge will lead to the development of effective ways for personalized immune modulation through deeper understanding of the mechanisms by which the intestinal environment affects our immune ecosystem.


Subject(s)
Gastrointestinal Microbiome/immunology , High-Throughput Nucleotide Sequencing , Adaptive Immunity , Animals , Homeostasis , Humans
19.
Oncoimmunology ; 7(3): e1405204, 2018.
Article in English | MEDLINE | ID: mdl-29399406

ABSTRACT

Although the anti-CCR4 antibody mogamulizumab (moga) shows striking antitumor activity against adult T cell leukemia (ATL), it can also cause fatal immunological pathology such as severe skin rash and graft-versus-host disease, which might be attributed to depletion of CCR4+ regulatory T cells. We previously showed that next generation sequencing enables precise analysis of the T cell receptor (TCR) repertoire, and we here used the technique to reveal the immunological dynamics in moga-treated ATL patients. Treatment with moga resulted in remarkable reduction or elimination of clonal cells, and enhanced reconstitution of non-tumor polyclonal CD4+ T cells and oligoclonal CD8+ T cells. Interestingly, cutaneous T cells infiltrating moga-related skin rashes did not share the same major clones in peripheral blood, which minimizes the possibility of cross-reaction. Thus, deep sequencing of the TCR can reveal the immune reconstitution of moga-treated ATL and provides powerful insights into its mode of action.

20.
Curr Oncol ; 25(6): e507-e515, 2018 12.
Article in English | MEDLINE | ID: mdl-30607117

ABSTRACT

Background: Reducing inflammatory factors in wound exudate is a promising treatment approach for healing wounds in postsurgical breast cancer patients. Traditional Chinese Medicine (tcm) treatments have been shown to be beneficial and safe for optimal regulation of oxidative stress during the postoperative period. In the present clinical trial, we evaluated the effectiveness of a promising Chinese herbal formula, San Huang decoction [shd (Radix astragali, Radix et rhizoma rhei, and Rhizoma curcuma longa, 3:1:1; supplemental Table 1)], on wound inflammatory response after mastectomy. Methods: The study randomized 30 patients with breast cancer who fulfilled the inclusion and exclusion criteria to either a treatment (n = 15) or a control group (n = 15). Patients in the treatment group received liquid shd, taken twice daily with or without food. Treatment was given for 1 day before surgery and for 7 days postoperatively. Participants in the control group received a placebo on the same schedule as the treatment group. Outcomes measured in every subject included clinical tcm and wound inflammation symptom scores, daily and total amounts of drainage fluid, and levels of inflammatory factors in the exudate [tumour necrosis factor α (tnf-α), interleukins 6 (il-6), 8 (il-8), and 2R (il-2R), human C-reactive protein (crp)] at 2 hours and on days 1, 3, and 7 postoperatively. Results: The total amount of drainage fluid over 7 days was significantly lower in the treatment group (572.20 ± 93.95 mL) than in the control group (700.40 ± 107.38 mL). The tcm symptom score was also lower in treatment group (day 7: 1.87 ± 0.83 vs. 4.80 ± 3.61, p = 0.049), as was the inflammatory symptom score (day 7: 0.67 ± 0.72 vs. 3.67 ± 2.50, p = 0.001). Levels of tnf-α, il-6, il-8, il-2R, and crp in drainage fluid were significantly lower with shd treatment. Conclusions: Perioperative treatment with shd effectively lessened postoperative exudate and ameliorated inflammatory symptoms in patients who underwent surgery for breast cancer.


Subject(s)
Breast Neoplasms/complications , Drugs, Chinese Herbal/therapeutic use , Exudates and Transudates/drug effects , Inflammation/drug therapy , Inflammation/etiology , Postoperative Complications/drug therapy , Postoperative Complications/etiology , Adult , Aged , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Biomarkers , Breast Neoplasms/diagnosis , Breast Neoplasms/surgery , Case-Control Studies , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Female , Humans , Mastectomy/adverse effects , Mastectomy/methods , Medicine, Chinese Traditional , Middle Aged , Treatment Outcome
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