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1.
Can J Cardiol ; 2024 Apr 29.
Article in English | MEDLINE | ID: mdl-38692430

ABSTRACT

BACKGROUND: Pulmonary hypertension leads to right ventricular failure, which is a major determinant of prognosis. Circulating biomarkers for right ventricular function are poorly explored in pulmonary hypertension. This study aimed to clarify the significance of collagen triple helix repeat-containing protein 1 (CTHRC1) as a biomarker of right ventricular failure in pulmonary hypertension. METHODS: A monocrotaline-induced pulmonary hypertension rat model was used to evaluate right ventricular CTHRC1 expression and its relationship with fibrosis. Next, human plasma CTHRC1 levels were measured in controls (n = 20), pulmonary arterial hypertension (n = 46), and chronic thromboembolic pulmonary hypertension (CTEPH) patients (n = 64) before the first and after the final balloon pulmonary angioplasty. RESULTS: CTHRC1 expression was higher in the right ventricles of rats with monocrotaline-induced pulmonary hypertension than in those of controls. CTHRC1 was co-localized with vimentin and associated with fibrosis in the right ventricles. Plasma CTHRC1 levels were higher in human pulmonary arterial hypertension (P = 0.006) and CTEPH patients (P = 0.011) than in controls. Plasma CTHRC levels were correlated with B-type natriuretic peptide (R = 0.355, P < 0.001), tricuspid lateral annular peak systolic velocity (R = -0.213, P = 0.029), and right ventricular fractional area change (R = -0.225, P = 0.017). Finally, plasma CTHRC1 levels were decreased after the final balloon pulmonary angioplasty (P < 0.001) in CTEPH. CONCLUSIONS: CTHRC1 can be a circulating biomarker associated with right ventricular function and fibrosis in pulmonary hypertension and might reflect the therapeutic efficacy of balloon pulmonary angioplasty in CTEPH.

2.
Allergol Int ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38670810

ABSTRACT

BACKGROUND: Basal cell hyperplasia is commonly observed in nasal polyp epithelium of eosinophilic chronic rhinosinusitis (eCRS). We examined the function and mechanisms of basal cell hyperplasia in the pathophysiology of eCRS. METHODS: We found that normal human bronchial epithelial (NHBE) cells obtained basal cell characteristics when cultured with PneumaCult™-Ex Plus Medium. Most of the cells passaged three times expressed basal cell surface markers CD49f and CD271 by flow cytometry, and basal cell nuclear marker p63 by immunohistochemical staining. We named these NHBE cells with basal cell characteristics cultured Basal-like cells (cBC), and NHBE cells cultured with BEGM™ cultured Epithelial cells (cEC). The characteristics of cBC and cEC were examined and compared by RNA sequencing, RT-PCR, ELISA, and cell proliferation studies. RESULTS: RNA sequencing revealed that cBC showed higher gene expression of thymic stromal lymphopoietin (TSLP), IL-8, TLR3, and TLR4, and lower expression of PAR-2 compared with cEC. The mRNA expression of TSLP, IL-8, TLR3, and TLR4 was significantly increased in cBC, and that of PAR-2 was significantly increased in cEC by RT-PCR. Poly(I:C)-induced TSLP production and LPS-induced IL-8 production were significantly increased in cBC. IL-4 and IL-13 stimulated the proliferation of cBC. Finally, the frequency of p63-positive basal cells was increased in nasal polyp epithelium of eCRS, and Ki67-positive proliferating cells were increased in p63-positive basal cells. CONCLUSIONS: Type 2 cytokines IL-4 and IL-13 induce basal cell hyperplasia, and basal cells exacerbate type 2 inflammation by producing TSLP in nasal polyp of eCRS.

3.
Materials (Basel) ; 17(3)2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38591987

ABSTRACT

Unsymmetrical disulfides, in which different organic groups are bonded to disulfide bonds, have been synthesized by cross-coupling reactions using thiols as substrates. However, due to the low-binding energy of unsymmetrical disulfides, its disproportionation occurs based on the side reactions with nucleophilic thiols, resulting in the impurity of symmetric disulfides. In this study, we developed a solvent-free synthesis method for unsymmetrical disulfides using thiosulfonates, thiols, and a base. This synthetic method enabled us to obtain highly pure diaryl-substituted unsymmetrical disulfides with particularly low-binding energy without control over the nucleophilicity and elimination properties of the substrate. Furthermore, it was observed that the disproportionation of unsymmetrical disulfides occurred in the solvent. This means that solvent-free condition is one of the factors to obtain unsymmetrical disulfides. As a new application of unsymmetrical disulfides, we applied unsymmetrical disulfides to cathode active materials of lithium batteries based on the reversible multi-electron redox activity of S-S bonds. The batteries using unsymmetrical disulfide cathode-active materials with a carbon nanotube exhibited initial capacities of 127 and 158 Ah/kg, equal to 42 and 53% of their theoretical ones. We demonstrated that unsymmetrical disulfides could be used as cathode-active materials for rechargeable batteries.

4.
Biochem Biophys Res Commun ; 714: 149967, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38669752

ABSTRACT

Butyrate and other Short-chain fatty acids (SCFAs) are microbial metabolites from Bacteroides and Clostridium species that may suppress type 2 inflammation. However, the mechanisms of SCFAs in the nasal sinuses are not fully understood. We aimed to clarify the in vitro and in vivo roles of SCFAs in eosinophilic chronic rhinosinusitis (ECRS) pathophysiology. We investigated whether SCFAs induced changes in type 2 cytokines, IgE, and apoptosis and the roles of GPR41, GPR43, and histone deacetylase. Analysis of the control subjects demonstrated that butyrate of SCFAs effectively inhibited type 2 cytokine production in PBMCs, ILC2s, and CD4+ T cells and IgE production in CD19+ B cells. In annexin V analysis, butyrate also induced late apoptosis of PBMCs. The butyrate-induced inhibition of type 2 cytokines appeared involved in histone deacetylase inhibition but not in GPR41 or GPR43. In an analysis of ECRS in humans, butyrate inhibited type 2 cytokine production in PBMCs and nasal polyp-derived cells. The butyrate concentration in nasal lavage fluid was significantly decreased in ECRS patients compared to controls and non-ECRS patients. Our findings confirm that butyrate can inhibit type 2 inflammation and may be a potential therapeutic target for ECRS.


Subject(s)
Butyrates , Cytokines , Receptors, Cell Surface , Receptors, G-Protein-Coupled , Rhinitis , Sinusitis , Humans , Sinusitis/drug therapy , Sinusitis/metabolism , Sinusitis/immunology , Sinusitis/pathology , Butyrates/pharmacology , Chronic Disease , Rhinitis/drug therapy , Rhinitis/metabolism , Rhinitis/immunology , Rhinitis/pathology , Cytokines/metabolism , Receptors, G-Protein-Coupled/metabolism , Male , Adult , Apoptosis/drug effects , Female , Middle Aged , Inflammation/drug therapy , Inflammation/metabolism , Immunoglobulin E/immunology , Eosinophilia/drug therapy , Eosinophilia/metabolism , Eosinophilia/pathology , Eosinophilia/immunology , Nasal Polyps/drug therapy , Nasal Polyps/metabolism , Nasal Polyps/pathology , Nasal Polyps/immunology , Cells, Cultured , Rhinosinusitis
5.
Cancer Med ; 13(2): e6957, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38379325

ABSTRACT

AIM: To investigate the current treatment for liver metastasis and clarify the indications for percutaneous thermal ablation for liver metastasis. METHODS: Ninety-two patients were enrolled and retrospectively analyzed. The patients underwent hepatectomy and/or percutaneous thermal ablation for liver metastases between January 2012 and December 2018. Twenty-six patients who underwent ablation treatment and seven patients who underwent both ablation and hepatectomy were included in the ablation treatment group (group A). We compared these patients with 59 patients who underwent hepatectomy only (group H). Subgroup analyses were performed between ablation (group AC) for colorectal liver metastasis and hepatectomy (group HC) for colorectal liver metastasis in 17 and 53 patients, respectively. RESULTS: The percentage of liver metastases other than colorectal cancer in group A was higher than that in the group H. Maximum tumor size in group A was significantly smaller than that in group H. Similarly, the patients in group AC were significantly older and demonstrated higher total bilirubin, lower serum albumin, and lower platelet counts than those in group HC. Overall survival was poorer in the AC group than that in the HC group. However, no differences were observed at metastasis ≤2 cm in size. CONCLUSIONS: Percutaneous thermal ablation was performed for many cancer types than hepatectomy. It is performed in elderly patients. We suggested that ablation for colorectal liver metastasis sized ≤2 cm is a suitable indication.


Subject(s)
Catheter Ablation , Colorectal Neoplasms , Liver Neoplasms , Humans , Aged , Hepatectomy , Retrospective Studies , Catheter Ablation/adverse effects , Colorectal Neoplasms/pathology , Treatment Outcome
6.
Neurol Med Chir (Tokyo) ; 64(4): 154-159, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38355130

ABSTRACT

Treatment strategies for unruptured intracranial aneurysms (UIAs) should be carefully considered with reference to rupture and complication rates. It is also important to minimize the length of hospital stay (LOS) and to ensure a high quality of medical care. In this study, we aim to clarify the factors that affect the LOS of patients treated for UIAs using the Inpatient Clinico-Occupational Database of the Rosai Hospital Group (ICOD-R). This was a nationwide-multicenter study based on ICOD-R data from 2000 to 2019. Patients diagnosed with UIAs who were treated with clipping or coiling were included in the study. Multivariate analysis was performed to identify the factors affecting LOS. LOS was also compared between groups classified by surgical procedure or treatment period. We identified 3294 patients on the database who underwent clipping or coiling of UIAs during the study period. Multivariate analysis revealed hospital admission during the early 2000s and the late 2010s, age, and treating institution to be significantly correlated with LOS (p < 0.05). There was a significant difference between the mean LOS of the clipping group (20.3 days) and the coiling group (9.65 days) (p < 0.001). Compared by treatment period, LOS significantly shortened over time. Our results suggest that the type of treatment, time of treatment, patient age, and the treating institution affect postoperative LOS for UIAs. Although coiling was found to lead to a lower average LOS than clipping, treatment selection should take the characteristics of each patient's aneurysm into consideration.


Subject(s)
Endovascular Procedures , Intracranial Aneurysm , Humans , Length of Stay , Intracranial Aneurysm/surgery , Intracranial Aneurysm/etiology , Japan/epidemiology , Endovascular Procedures/adverse effects , Treatment Outcome
7.
J Neuroimmunol ; 387: 578288, 2024 02 15.
Article in English | MEDLINE | ID: mdl-38237527

ABSTRACT

We examined the histopathological changes in the olfactory mucosa of cynomolgus and rhesus macaque models of SARS-CoV-2 infection. SARS-CoV-2 infection induced severe inflammatory changes in the olfactory mucosa. A major histocompatibility complex (MHC) class II molecule, HLA-DR was expressed in macrophage and supporting cells, and melanocytes were increased in olfactory mucosa. Supporting cells and olfactory neurons were infected, and SARS-CoV-2 N protein was detected in the axons of olfactory neurons and in olfactory bulbs. Viral RNA was detected in olfactory bulbs and brain tissues. The olfactory epithelium-olfactory bulb pathway may be important as a route for intracranial infection by SARS-CoV-2.


Subject(s)
COVID-19 , Olfactory Bulb , Animals , Olfactory Bulb/metabolism , Olfactory Bulb/pathology , SARS-CoV-2 , COVID-19/pathology , Macaca mulatta , Olfactory Mucosa/metabolism , Olfactory Mucosa/pathology , Inflammation/metabolism , Macaca fascicularis
8.
Int Heart J ; 65(1): 63-70, 2024.
Article in English | MEDLINE | ID: mdl-38296581

ABSTRACT

Paravalvular leakage (PVL) is a complication of transcatheter aortic valve implantation (TAVI) for aortic stenosis, leading to an adverse prognosis. We investigated whether aortic valve calcium volume (Ca-Vol) measured by preoperative cardiac computed tomography had a predictive value for PVL after TAVI using a third-generation self-expandable valve.We retrospectively analyzed 59 consecutive patients who underwent TAVI using a third-generation self-expandable valve. We measured Ca-Vol in the aortic valve and each cusp (non-coronary cusp [NCC], right-coronary cusp [RCC], and left-coronary cusp [LCC]). We divided the patients into 2 groups: a PVL group (32.2%) and a non-PVL group (67.8%). Total Ca-Vol was significantly higher in the PVL group than in the non-PVL group (P < 0.001). Ca-Vol in each cusp was also significantly higher in the PVL group ([NCC] P < 0.001, [RCC] P = 0.001, [LCC] P < 0.001). Univariate logistic regression analysis for PVL indicated that the total and per-cusp Ca-Vols were predictors for PVL (total, odds ratio [OR] 4.0, P < 0.001; NCC, OR 12.5, P = 0.002; RCC, OR 16.0, P = 0.008; LCC, OR 44.5, P < 0.001).Receiver operating characteristic curve analysis of Ca-Vol for predicting PVL revealed the optimal cut-off values of Ca-Vol were 2.4 cm3 for the total, 0.74 cm3 for NCC, 0.73 cm3 for RCC, and 0.56 cm3 for LCC (area under the curve, 0.85, 0.79, 0.76, and 0.83, respectively).Preoperative total, NCC, RCC, and LCC calcium volumes were significant predictors for PVL after TAVI using third-generation self-expandable valves.


Subject(s)
Aortic Valve Insufficiency , Aortic Valve Stenosis , Carcinoma, Renal Cell , Heart Valve Prosthesis , Kidney Neoplasms , Transcatheter Aortic Valve Replacement , Humans , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/methods , Calcium , Retrospective Studies , Carcinoma, Renal Cell/surgery , Aortic Valve Insufficiency/surgery , Risk Factors , Heart Valve Prosthesis/adverse effects , Aortic Valve Stenosis/surgery , Aortic Valve Stenosis/complications , Tomography, X-Ray Computed , Kidney Neoplasms/surgery , Treatment Outcome
9.
Int Forum Allergy Rhinol ; 14(1): 57-67, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37345377

ABSTRACT

BACKGROUND: Allergic rhinitis (AR) impairs quality of life and affects nearly 40% of the Japanese population. Sublingual immunotherapy (SLIT) is the disease-modifying treatment for AR, but requires the selection of a biomarker associate with clinical efficacy in patients with AR who are treated with SLIT. The present study sought to examine objective biomarkers used for assessing the clinical efficacy of SLIT. METHODS: The authors examined the effects of 1 year of SLIT treatment with house dust mites (HDMs) using peripheral blood mononuclear cells (PBMCs) and serum from patients with AR. The prevalences of follicular regulatory T (Tfr), type 2 follicular helper T (Tfh2), type 2 helper T (Th2), conventional regulatory T (Treg), and type 1 regulatory T (Tr1) cells were examined by flow cytometry. Serum concentrations of HDM-specific IgA, IgE, and IgG4 antibodies, and HDM-induced production of interleukin (IL) 5 and IL-10 from cultured PBMCs were evaluated by enzyme-linked immunosorbent assay. RESULTS: Following 1 year of SLIT, the prevalences of Tfr, conventional Treg, and Tr1 cells were significantly increased, whereas that of Th2 cells and Tfh2 cells were significantly decreased; the serum concentration of HDM-specific IgG4 was significantly increased; and HDM-induced production of IL-5 from PBMCs was significantly decreased, while that of IL-10 was significantly increased. The increase in the prevalence of Tfr cells after SLIT correlated positively with the improvement of clinical symptom scores. CONCLUSION: An increase in Tfr cells may play an important role in SLIT, and may be a useful indicator for the clinical efficacy of SLIT.


Subject(s)
Rhinitis, Allergic , Sublingual Immunotherapy , Animals , Humans , T-Lymphocytes, Regulatory , Interleukin-10 , Prevalence , Pyroglyphidae , Leukocytes, Mononuclear , Quality of Life , Allergens , Rhinitis, Allergic/epidemiology , Rhinitis, Allergic/therapy , Treatment Outcome , Biomarkers , Immunoglobulin G , Antigens, Dermatophagoides
10.
Arerugi ; 72(10): 1230-1239, 2023.
Article in Japanese | MEDLINE | ID: mdl-38092399

ABSTRACT

BACKGROUND: We investigated the effect of sublingual immunotherapy (SLIT) on Japanese cedar and cypress pollinosis in a mass scattering year of cedar pollen (total counts: 12353 grains/cm2, approximately four times the average). METHODS: SLIT patients of 84 in the first year, 107 in the second year and 67 in the third year treated with Cedarcure® were included. During the 2023 cedar and cypress pollen dispersal season, nasal and eye symptoms and general symptoms were examined using a visual analog scale (VAS). RESULTS: The VAS during the cedar season significantly decreased to improve with the number of years of SLIT, but the VAS during the cypress period slightly increased. A questionnaire survey before SLIT revealed that only 0.9% to 3.6% of patients had strong cypress symptoms. However, sneezing (p<0.01), rhinorrhea, itchy eyes and total symptoms (p<0.05) in the third year of SLIT were significantly stronger during the cypress period than during the cedar period. The VAS of total symptoms during the Japanese cedar pollen season were not affected by the pollen count, and the cure rate was affected by SLIT in the third year. CONCLUSION: The clinical efficacy of cedar SLIT on cedar pollinosis was high even in a mass scattering year, and the effect increased with the number of years of treatment. On the other hand, it was shown that the clinical efficacy on cypress pollinosis was insufficient.


Subject(s)
Cryptomeria , Cupressus , Rhinitis, Allergic, Seasonal , Sublingual Immunotherapy , Humans , Rhinitis, Allergic, Seasonal/therapy , Pollen , Treatment Outcome , Allergens
11.
J Cardiol Cases ; 28(6): 257-260, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38126047

ABSTRACT

A young female patient with Takayasu arteritis presented with unstable angina due to bilateral coronary artery involvement. Steroid pulse therapy and subsequent prednisolone administration were started, but early coronary artery bypass grafting was required because of the multiple angina attacks at rest, with a prednisolone dose of 22.5 mg (0.45 mg/kg/day). Since the left internal thoracic artery which was grafted to the left anterior descending artery resulted in graft failure a few days after the surgery, the immunosuppressive therapy was intensified with the addition of tocilizumab and methotrexate. After controlling the disease activity, coronary ostial angioplasty using external iliac artery grafts was successfully performed, with a prednisolone dose of 15 mg (0.3 mg/kg/day). Ten months after the operation, the patient has been free from chest pain. The present case demonstrated the importance of adequate preoperative immunosuppressive therapy, even when early surgical intervention is required. Learning objective: There are no established treatment regimens for immunosuppressive management in cases of Takayasu arteritis (TAK) requiring immediate surgical intervention. Even when early surgery is required, it is important to reduce disease activity with appropriate preoperative immunosuppressive therapy using steroids in addition to biological agents, such as tocilizumab. Coronary ostial angioplasty is the effective surgical revascularization technique for TAK with coronary artery involvement.

12.
J Clin Med ; 12(19)2023 Oct 04.
Article in English | MEDLINE | ID: mdl-37835003

ABSTRACT

Idiopathic pulmonary arterial hypertension is a progressive and life-threatening disease with pulmonary vasculature remodeling, leading to right-sided heart failure. Epoprostenol (prostaglandin I2) is highly recommended for patients with severe pulmonary arterial hypertension (PAH) categorized by the World Health Organization as functional class III or IV. It has been reported that prostaglandin I2 analogs can cause thyroid gland swelling and abnormal thyroid function. A 34-year-old woman was diagnosed with idiopathic pulmonary arterial hypertension and started receiving continuous intravenous epoprostenol. Three years after starting epoprostenol, she began complaining of neck swelling and was diagnosed with Graves' disease. The patient's thyroid function was controlled by thiamazole and levothyroxine; nevertheless, her thyroid gland enlargement worsened as the epoprostenol dose was titrated. After 20 years, she developed respiratory failure with a giant goiter leading to airway stenosis, and she passed away. The pathological autopsy confirmed a massive goiter associated with hyperthyroidism and airway stenosis. We experienced a case of idiopathic pulmonary hypertension with a giant goiter and airway stenosis after long-term intravenous epoprostenol therapy.

13.
NMC Case Rep J ; 10: 241-245, 2023.
Article in English | MEDLINE | ID: mdl-37869376

ABSTRACT

A 54-year-old man with no medical history presented to our hospital with vomiting, left hemiplegia, and seizures. On arrival, he was experiencing generalized tonic-clonic seizures, which required him to be intubated and deeply sedated. Contrast-enhanced computed tomography revealed extensive venous sinus obstruction from the superior sagittal sinus to the bilateral sigmoid sinus and cerebral edema with intracranial hemorrhage. An intracranial pressure (ICP) monitor was immediately placed intracranially, and mechanical thrombectomy (MT) was performed under ICP monitoring. MT was immediately terminated when the venous sinus was partially recanalized enough to decrease the ICP; then, anticoagulation therapy was initiated. Postoperative follow-up angiography revealed that venous sinus obstruction and intracranial venous perfusion improved over time. Although he had intracranial hemorrhage-induced left hemiplegia and sensory deficits, his condition improved with rehabilitation, and the patient was eventually discharged home. The indication criteria and techniques for MT for cerebral venous sinus thrombosis are yet to be established. As in this case, in patients with impaired consciousness due to intracranial hemorrhage or epilepsy, preoperative ICP monitor placement is deemed useful to evaluate venous perfusion during MT and decide the treatment goal.

14.
Materials (Basel) ; 16(20)2023 Oct 11.
Article in English | MEDLINE | ID: mdl-37895636

ABSTRACT

Dye-sensitized solar cells (DSSCs) have been one of the most promising technologies to convert sunlight into electricity repeatedly based on the mechanism that dyes inject/accept electron into the metal oxides/from redox mediator. Specifically, N719 ([RuL2(NCS)2], L: 4,4'-dicarboxy-2,2'-bipyridine), immobilized on TiO2 through the interaction between its ligands (-COO- and -NCS) and the oxygen on the TiO2 surface, has been used as a conventional DSSC dye with high voltage. Nevertheless, -NCS ligands have been removed from Ru2+ in N719 due to UV irradiation and exchanged with H2O or OH- in electrolyte, resulting in voltage drop. In this work, we developed the first DSSC using the N719-adsorbed Eggshell (ESM)-TiO2 composite to maintain the immobilization of N719 on TiO2 through electrostatic interaction between the protein of ESM and N719. The DSSC using the composite maintained the voltage even after 12 h light irradiation, although the voltage of DSSC without ESM dropped drastically. It means that the ESM contributed to stable photovoltaic performances of DSSCs through the protection of NCS ligands of N719.

16.
J Cardiol Cases ; 28(4): 172-175, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37818432

ABSTRACT

A 40-year-old female with a history of steroid therapy for juvenile rheumatoid arthritis was brought to our hospital because of chest pain. A diagnosis of non-ST elevation myocardial infarction was made, and emergency coronary angiography revealed stenotic lesions with severe calcification in the left anterior descending artery and the right coronary artery. Percutaneous coronary intervention with rotational atherectomy followed by a drug-coated balloon was performed to the lesion in the left anterior descending artery. The patient had characteristic physical findings including short stature, a round face, and 'knuckle-dimple sign'. Whole-body computed tomography showed many ectopic calcifications, indicating Albright's hereditary osteodystrophy. Ellsworth-Howard test revealed that urinary cyclic adenosine monophosphate response was positive, thus a diagnosis of pseudo-pseudohypoparathyroidism (PPHP) was made. Here, we describe a rare case of PPHP complicated by acute coronary syndrome with severely calcified coronary arteries. Learning objective: Pseudo-pseudohypoparathyroidism (PPHP) presents with several characteristic physical findings and ectopic calcifications. Since PPHP involves coronary artery calcification as in the present case, it may be considered as a cause of coronary artery disease.

17.
Oncol Res ; 31(6): 833-844, 2023.
Article in English | MEDLINE | ID: mdl-37744270

ABSTRACT

Dihydroorotate dehydrogenase (DHODH) is a central enzyme of the de novo pyrimidine biosynthesis pathway and is a promising drug target for the treatment of cancer and autoimmune diseases. This study presents the identification of a potent DHODH inhibitor by proteomic profiling. Cell-based screening revealed that NPD723, which is reduced to H-006 in cells, strongly induces myeloid differentiation and inhibits cell growth in HL-60 cells. H-006 also suppressed the growth of various cancer cells. Proteomic profiling of NPD723-treated cells in ChemProteoBase showed that NPD723 was clustered with DHODH inhibitors. H-006 potently inhibited human DHODH activity in vitro, whereas NPD723 was approximately 400 times less active than H-006. H-006-induced cell death was rescued by the addition of the DHODH product orotic acid. Moreover, metabolome analysis revealed that H-006 treatment promotes marked accumulation of the DHODH substrate dihydroorotic acid. These results suggest that NPD723 is reduced in cells to its active metabolite H-006, which then targets DHODH and suppresses cancer cell growth. Thus, H-006-related drugs represent a potentially powerful treatment for cancer and other diseases.


Subject(s)
Dihydroorotate Dehydrogenase , Proteomics , Humans , Cell Transformation, Neoplastic , Cell Cycle , Cell Death
18.
J Nucl Cardiol ; 30(6): 2773-2789, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37758961

ABSTRACT

BACKGROUND: Absolute quantitative myocardial perfusion SPECT requires addressing of aleatory and epistemic uncertainties in conjunction with providing image quality sufficient for lesion detection and characterization. Iterative reconstruction methods enable the mitigation of the root causes of image degradation. This study aimed to determine the feasibility of a new SPECT/CT method with integrated corrections attempting to enable absolute quantitative cardiac imaging (xSPECT Cardiac; xSC). METHODS: We compared images of prototype xSC and conventional SPECT (Flash3DTM) acquired at rest from 56 patients aged 71 ± 12 y with suspected coronary heart disease. The xSC prototype comprised list-mode acquisitions with continuous rotation and subsequent iterative reconstructions with retrospective electrocardiography (ECG) gating. Besides accurate image formation modeling, patient-specific CT-based attenuation and energy window-based scatter correction, additionally we applied mitigation for patient and organ motion between views (inter-view), and within views (intra-view) for both the gated and ungated reconstruction. We then assessed image quality, semiquantitative regional values, and left ventricular function in the images. RESULTS: The quality of all xSC images was acceptable for clinical purposes. A polar map showed more uniform distribution for xSC compared with Flash3D, while lower apical count and higher defect contrast of myocardial infarction (p = 0.0004) were observed on xSC images. Wall motion, 16-gate volume curve, and ejection fraction were at least acceptable, with indication of improvements. The clinical prospectively gated method rejected beats ≥20% in 6 patients, whereas retrospective gating used an average of 98% beats, excluding 2% of beats. We used the list-mode data to create a product equivalent prospectively gated dataset. The dataset showed that the xSC method generated 18% higher count data and images with less noise, with comparable functional variables of volume and LVEF (p = ns). CONCLUSIONS: Quantitative myocardial perfusion imaging with the list-mode-based prototype xSPECT Cardiac is feasible, resulting in images of at least acceptable image quality.


Subject(s)
Myocardial Perfusion Imaging , Humans , Retrospective Studies , Heart/diagnostic imaging , Tomography, Emission-Computed, Single-Photon , Respiration , Arrhythmias, Cardiac , Image Processing, Computer-Assisted
19.
Neurol Med Chir (Tokyo) ; 63(12): 542-547, 2023 Dec 15.
Article in English | MEDLINE | ID: mdl-37743507

ABSTRACT

There have been a number of anastomosis methods of bypass techniques reported for moyamoya disease. However, there are yet no randomized controlled trials conducted on the anastomosis method. Retrograde blood flow of the superficial temporal artery (STA) may be used as one of the donor options. Here, we examined the tolerability of retrograde bypass using a distal stump of the parietal STA (dsPSTA). Anastomosis between the dsPSTA and middle cerebral artery (MCA) was performed for consecutive patients with moyamoya disease whose parietal STA was visualized to be longer than 10 cm using contrast-enhanced computed tomography preoperatively. Retrospectively, we have examined its patency and clinical outcome. Retrograde dsPSTA-MCA bypass was performed in 22 hemispheres of 17 patients. The patency of retrograde dsPSTA-MCA bypass in all 22 anastomoses could be confirmed during follow-up periods (mean: 5.5, range: 2-15 years). No recurrence of ischemic events was observed. The dsPSTA-MCA bypass using retrograde blood flow has been determined as one of the many promising anastomosis methods, and long-term patency was achieved in moyamoya disease.


Subject(s)
Cerebral Revascularization , Moyamoya Disease , Humans , Moyamoya Disease/diagnostic imaging , Moyamoya Disease/surgery , Temporal Arteries/diagnostic imaging , Temporal Arteries/surgery , Retrospective Studies , Middle Cerebral Artery/diagnostic imaging , Middle Cerebral Artery/surgery , Cerebral Revascularization/methods
20.
Neuroscience ; 531: 117-129, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37678588

ABSTRACT

A positive affective response modulates the effects of aerobic exercise on prefrontal executive function (EF). Groove rhythm (GR), eliciting the feeling of wanting to move to music, is useful for inducing positive affective response during exercise. Three minutes of listening to GR activated the left dorsolateral prefrontal cortex (l-DLPFC) and enhanced EF in participants who had higher psychological responses to GR. This finding prompted us to test the hypothesis that the combination of GR and exercise (GREX) induces positive psychological responses that enhance PFC function through entrainment of body movements and musical beats. 41 participants were administered two experimental conditions: three min of very light-intensity (30% V̇ O2peak) exercise combined with GR and combined with a white-noise metronome (WMEX). Before and after exercise, participants performed a Stroop task and were monitored for l-DLPFC activity with functional near-infrared spectroscopy. GREX enhanced EF and l-DLPFC activity in participants who experienced greater subjective feelings of audiomotor entrainment and increased excitement with GREX. These psychological responses were predictive of the impact of GREX on l-DLPFC activity and EF. These findings, together with previous results, support the hypothesis that GR allows us to boost the cognitive benefits of exercise via l-DLPFC activity only in those who enjoy groove, and suggest that subjective audiomotor entrainment is a key mechanism of this boosting effect.


Subject(s)
Prefrontal Cortex , Spectroscopy, Near-Infrared , Humans , Spectroscopy, Near-Infrared/methods , Prefrontal Cortex/physiology , Executive Function/physiology , Exercise/physiology , Stroop Test , Cognition
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