Enhanced molecular recognition with longer chain crosslinkers in molecularly imprinted polymers for an efficient separation of TR active substances.

Molecular imprinting technology has been widely studied as a technique to obtain molecular recognition by artificial means. Selecting functional monomers or polymerization conditions plays a key role to optimize molecularly imprinted polymer (MIP) synthesis. To date, there have been few reports well exploiting the effect of crosslinkers. Here, in this study, we synthesized the MIPs using poly(ethyleneglycol) dimethacrylate with different units of ethylene oxide (n = 1 to 23) as crosslinkers to observe the molecular recognition abilities. The MIPs were attached to the surface of mono-dispersed polymer beads. The obtained spherical MIPs and non-imprinted polymers were filled in a column for high performance liquid chromatography. Then the retention selectivity toward TR active substances was evaluated. The result revealed that the recognition ability did not improve regardless of the amount of ethylene oxide. With the crosslinker (n = 9), extremely high retention selectivity was observed, which provides at most around ten times as large imprinting factors in comparison with other MIPs. Interestingly, we obtained the highest recognition ability at around polymerization temperature from the evaluation of the recognition ability toward temperature shift using the MIP (n = 9). In general, hydrogen bonding based on MIPs provides high recognition ability at low temperature, whereas, this study indicates that the use of flexible crosslinkers may enable the synthesis of MIPs that precisely memorize the conditions of polymerization. Lastly, we simultaneously analyzed the TR active substances using the column filled with MIPs (n = 9). The result showed relatively linear correlation between the retention strength of each substance and phycological activity toward TR obtained by yeast assay. Therefore, we can conclude that an induced fit like the receptor emerged by constructing the flexible molecular recognition field.

Pathology of Critical Limb Ischemia; Comparison of Plaque Characteristics Between Anterior and Posterior Tibial Arteries.

AIMS: Though the number of patients with peripheral arterial disease (PAD) and critical limb ischemia (CLI) is increasing, few histopathological studies of PAD, particularly that involving below-the-knee arteries, has been reported. We analyzed the pathology of anterior tibial artery (ATA) and posterior tibial artery (PTA) specimens obtained from patients who underwent lower extremity amputation due to CLIMethods: Dissected ATAs and PTAs were subjected to ex-vivo soft X-ray radiography, followed by pathological examination using 860 histological sections. This protocol was approved by the Ethics Review Board of Nihon University Itabashi Hospital (RK-190910-01) and Kyorin University Hospital (R02-179). RESULTS: The calcified area distribution was significantly larger in PTAs than in ATAs on soft X-ray radiographic images (ATAs, 48.3% ±19.2 versus PTAs, 61.6% ±23.9; p＜0.001). Eccentric plaque with necrotic core and macrophage infiltration were more prominent in ATAs than in PTAs (eccentric plaque: ATAs, 63.7% versus PTAs, 49.1%; p＜0.0001, macrophage: ATAs, 0.29% [0.095 - 1.1%] versus PTAs, 0.12% [0.029 - 0.36%]; p＜0.001), histopathologically. Thromboembolic lesions were more frequently identified in PTAs than in ATAs (ATAs, 11.1% versus PTAs 15.8%; p＜0.05). Moreover, post-balloon injury pathology differed between ATAs and PTAs. CONCLUSIONS: Histological features differed strikingly between ATAs and PTAs obtained from CLI patients. Clarifying the pathological features of CLI would contribute to establishing therapeutic strategies for PAD, particularly disease involving below-the knee-arteries.

Intravenous Semaphorin 3A Administration Maintains Cardiac Contractility and Improves Electrical Remodeling in a Mouse Model of Isoproterenol-Induced Heart Failure.

The effects of recombinant semaphorin 3A (Sema3A) on myocardial contractility and electrical remodeling in mice with isoproterenol (ISP) -induced heart failure were investigated.C57BL/6J mice intraperitoneally received ISP (480 mg/kg/day, ISP group; n = 24) or saline (control group; n = 31) for 14 days. Twenty-one ISP-treated mice received 0.5 mg/kg Sema3A intravenously on days 7 and 11 (ISP+Sema3A group). The sympathetic nervous system was activated upon ISP treatment, but was reduced upon Sema3A administration. Greater myocardial tissue fibrosis was observed in the ISP group than in the control group. However, fibrosis was not significantly different between the ISP+Sema3A and control groups. Fractional shortening of the left ventricle was lower in the ISP group than in the control group and was restored in the ISP+Sema3A group (control, 53 ± 8%; ISP, 37 ± 7%; ISP+Sema3A, 48 ± 3%; P < 0.05). Monophasic action potential duration at 20% repolarization (MAPD20) was prolonged in the ISP group (compared to control group), but this was reversed upon Sema3A administration (control, 29 ± 3 ms; ISP, 35 ± 6 ms; ISP+Sema3A, 29 ± 3 ms; P < 0.05). qPCR revealed Kv4.3, KChIP2, and SERCA2 downregulation in the ISP group and upregulation in the ISP+Sema3A group; however, Western blotting revealed similar changes only for Kv4.3 (P < 0.05).Intravenous Sema3A may maintain myocardial contractility by suppressing the sympathetic innervation of the myocardium and reducing myocardial tissue damage, in addition to restoring MAPD via Kv4.3 upregulation.

Histopathological Evaluation of Pulmonary Thromboendarterectomy Specimens of Chronic Thromboembolic Pulmonary Hypertension.

AIMS: Chronic thromboembolic pulmonary hypertension (CTEPH) is a condition with a poor prognosis in which the pulmonary arteries are occluded by organized thrombi. Pulmonary thromboendarterectomy (PEA) is an effective treatment for CTEPH; however, the literature on its histopathological examination is lacking. This study aimed to investigate the histopathological findings and protein and gene expression in PEA specimens, establish an optimal histopathological evaluation method, and clarify the mechanisms of thrombus organization and disease progression in CTEPH. METHODS: In total, 50 patients with CTEPH who underwent PEA were analyzed. The patients were categorized according to their clinical data into two groups: good and poor postoperative courses. The relationship between their histopathological findings and the clinical course was examined. Immunohistochemical studies confirmed the expression of oxidants, antioxidants, and smooth muscle cell (SMC) differentiation markers and their changes during the progression of thrombus organization. The mRNA expression analysis of 102 samples from 27 cases included oxidants, antioxidants, and vasoconstrictor endothelin-1. RESULTS: In the PEA specimens, colander-like lesions (aggregations of recanalized blood vessels with well-differentiated SMCs) were significantly more common in the good postoperative course group than in the poor postoperative course group; analysis of proteins and genes proposed that oxidative and antioxidant mechanisms were involved. In the colander-like lesions, there was an increase in endothelin-1 mRNA and protein expression of endothelin receptor A. CONCLUSIONS: Colander-like lesions in PEA specimens must be identified. Additionally, SMC differentiation in recanalized vessels and the expression of vasoconstrictors and their receptors may contribute to the progression of CTEPH.

The Impact of Age- and Sex-Specific Reference Ranges for Serum Thyrotropin and Free Thyroxine on the Diagnosis of Subclinical Thyroid Dysfunction: A Multicenter Study from Japan.

Background: Reference ranges for serum thyrotropin (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) established without considering age- and sex-based differences are currently used to evaluate thyroid function. Therefore, we investigated age- and sex-based differences in serum TSH and thyroid hormone levels in euthyroid individuals. Methods: We performed cross-sectional analyses of retrospective data collected from two Japanese institutions. We estimated sex-specific 95% reference ranges for TSH and fT4 according to age strata. Results: We included data from 14,860 participants undergoing screening with a Siemens thyroid testing kit and 8,132 participants undergoing screening with an Abbott kit during annual health check-ups at Takasaki Hidaka Hospital. In addition, 515 participants visiting a specialized thyroid-focused hospital were evaluated using Tosoh kits. The median TSH level of women in their 30s was 1.5 mIU/L (2.5th percentile, 0.5; 97.5th percentile, 4.6) using the Siemens kit, while that of women in their 60s was 1.9 (0.7-7.8) mIU/L. The corresponding levels were lower in men; the age-associated increase was small. The median serum fT4 level of men in their 30s was 1.3 (1.0-1.7) ng/dL and that of men in their 60s was 1.2 (1.0-1.6) ng/dL. These levels gradually but significantly decreased with age. fT4 levels in women were lower than those in men and remained consistent with age. Serum fT3 levels were significantly higher in men than in women and gradually but significantly decreased with age. The Abbott and Tosoh kits showed similar results. When using the Siemens kit, ∼60% (216/358) of women diagnosed with subclinical hypothyroidism using manufacturer-recommended reference ranges had normal results when age- and sex-specific reference ranges were applied, demonstrating the high percentage of overdiagnosis, especially in those aged ≥60 years. Conversely, some middle-aged individuals with normal thyroid function were reassessed and classified as having subclinical hyperthyroidism by age- and sex-specific reference ranges. Conclusions: Age- and sex-specific reference ranges should be used to avoid over- and underdiagnosis of subclinical thyroid dysfunction and appropriate therapies.

Role of Thyrotropin-Releasing Hormone in Regulating Fibroblast Growth Factor 21 in Mouse Pancreatic ß Cells.

Background: Thyrotropin-releasing hormone (TRH) is primarily produced in the hypothalamus and regulates the thyrotropin secretion from the pituitary. TRH is distributed ubiquitously in the extrahypothalamic region, especially in pancreatic islets, while its physiological role remains nebulous. We have previously established a TRH-deficient mouse model, and showed impaired glucose tolerance and downregulated expression of fibroblast growth factor 21 (FGF21) in islets. Recent studies have demonstrated the physiological roles of pancreatic FGF21. Therefore, in this study, we elucidate the direct functions of TRH in pancreatic islets via the regulation of FGF21. Methods: To explore the functions of TRH in pancreatic islets, a microarray analysis using isolated islets from TRH-knockout mice was conducted. The regulatory mechanism of TRH in pancreatic FGF21 was investigated using islet cell lines; reverse transcription-quantitative polymerase chain reaction and Western blotting were used to determine the mRNA and protein expression levels of FGF21 in pancreatic islets and islet cell lines. Induction of FGF21 expression by TRH treatment was examined in vitro. To identify the transcription factors binding to the region responsible for TRH-induced stimulation of the FGF21 promoter, electromobility shift assays were conducted. Results: Among the detected and considerably changed genes in microarray, FGF21 was the most consistently downregulated in TRH-deficient mice islets. FGF21 was strongly co-expressed with insulin in mouse islets, and TRH stimulated endogenous Fgf21 mRNA expression in the islet cell line ßHC9. The E-box site in the FGF21 promoter was responsible for TRH-induced stimulation via the extracellular signal-regulated kinase (ERK)1/2 signaling pathway. The transcription factor upstream stimulatory factor 1 (USF1) could specifically bind to the E-box site. Overexpression of USF1 increased FGF21 promoter activity. Conclusion: FGF21 was transcriptionally upregulated by TRH through the ERK1/2 and USF1 pathways in pancreatic ß cells.

Restriction of SARS-CoV-2 replication in the human placenta.

Although SARS-CoV-2 can infect human placental tissue, vertical transmission is rare. Therefore, the placenta may function as a barrier to inhibit viral transmission to the foetus, though the mechanisms remain unclear. In this study, we confirmed the presence of the SARS-CoV-2 genome in human placental tissue by in situ hybridization with antisense probes targeting the spike protein; tissue staining was much lower when using sense probes for the spike protein. To the best of our knowledge, this is the first evidence directly indicating inefficient viral replication in the SARS-CoV-2-infected placenta. Additional studies are required to reveal the detailed mechanisms.

Maternal hypothyroidism is associated with M-opsin developmental delay.

Thyroid hormones are critical for the development of opsins involved in color vision. Hypothyroid mice show delayed M-opsin development and expanded distribution of S-opsin on the retina. However, the effects of maternal hypothyroidism on opsin development remain unknown. This study investigates the effects of congenital central hypothyroidism and maternal hypothyroidism on opsin development in thyrotropin-releasing hormone knockout (TRH-/-) mice. We examined the mRNA expression and protein distribution of S/M-opsin on postnatal days (P)12 and 17, as well as mRNA expression of type 2 and 3 iodothyronine deiodinase (DIO2 and DIO3, respectively) in the retina and type 1 iodothyronine deiodinase (DIO1) in the liver at P12 in TRH+/- mice born to TRH+/- or TRH-/- dams, and conducted S/M-opsin analysis in TRH+/+ or TRH-/- mice born to TRH+/- dams at P12, P17, and P30. M-opsin expression was lower in TRH+/- mice born to TRH-/- dams than in those born to TRH+/- dams, whereas S-opsin expression did not significantly differ between them. DIO1, DIO2, and DIO3 mRNA expression levels were not significantly different between the two groups; therefore, thyroid function in peripheral tissues in the pups was similar. S/M-opsin expression did not significantly differ between the TRH+/+ and TRH-/- mice born to TRH+/- dams on any postnatal day. These results demonstrate that maternal hypothyroidism causes M-opsin developmental delay during the early developmental stages of neonatal mice, and TRH-/- mice, a model of congenital central hypothyroidism, born to a euthyroid dam do not have delayed opsin development.

Seasonal Variation in Thyroid Function in Over 7,000 Healthy Subjects in an Iodine-sufficient Area and Literature Review.

Context: Seasonal variation in thyroid function, especially serum free triiodothyronine (FT3) and free thyroxine (FT4) levels, in healthy subjects remains unclear. Methods: We examined thyroid function, including serum FT3 and FT4 levels, in healthy Japanese subjects using data of more than 7,000 health check-up participants and applied the analysis of means with transformed ranks (ANOMTR) to compare each month. In addition, we reviewed reports published in the last 2 decades. Results: The median serum thyrotropin (TSH) level was the highest in January (1.61 mIU/L), and the lowest in May (1.16 mIU/L). ANOMTR revealed that serum TSH levels are high in winter and low in summer. Conversely, the median serum FT3 level was higher in July than in other months, and the ANOMTR plot demonstrated serum FT3 levels to be significantly higher in summer and lower in winter. In contrast, serum FT4 levels were more consistent throughout the year, but statistically, those in February and March, October, and November were higher than those in other months. ANOMTR revealed variations in serum FT4 levels to be small through the year but biphasic. Conclusions: Taken together with previous reports, our study demonstrated seasonal changes in the serum TSH levels to be high in winter in the northern hemisphere; however, the serum FT3 differed among countries, and those of Japanese, an iodine-sufficient country, were high in summer. In contrast, FT4 levels were more consistent. These changes should be taken into account to precisely evaluate thyroid function.

Resolvin E3 ameliorates high-fat diet-induced insulin resistance via the phosphatidylinositol-3-kinase/Akt signaling pathway in adipocytes.

Obesity-associated type 2 diabetes mellitus is associated with the development of insulin resistance. Among several metabolites, resolvins that are metabolites of eicosapentaenoic acid have been shown to exert insulin-sensitizing effects; however, the role of resolvin E3 (RvE3) in glucose metabolism has not been studied. In this study, the effect of RvE3 on glucose metabolism in mice with high-fat diet-induced obesity and 3T3L1 adipocytes was studied. C57BL/6 mice fed a high-fat diet were administered RvE3, for which insulin tolerance, oral glucose tolerance tests, and the homeostasis model assessment of insulin resistance, were performed. RvE3 treatment significantly improved insulin sensitivity and glucose tolerance and regulated protein kinase B (Akt) phosphorylation in the adipose tissue. Moreover, RvE3 treatment enhanced the insulin-stimulated glucose transporter 4 (Glut4) translocation, glucose uptake, phosphatidylinositol-3-kinase (PI3K) activity, and Akt phosphorylation in 3T3L1 adipocytes, whereas a PI3K inhibitor inhibited the enhanced insulin-stimulated glucose uptake induced by RvE3. These findings indicate that RvE3 likely improves insulin sensitivity, resulting in the upregulation of glucose uptake in adipocytes by activating the PI3K/Akt signaling pathways. Collectively, the findings of this study show that RvE3 may play a role in glucose homeostasis and could be used as a potential therapeutic target for developing treatments for obesity-associated diabetes.

The Hypothalamic Paraventricular Nucleus Is the Center of the Hypothalamic-Pituitary-Thyroid Axis for Regulating Thyroid Hormone Levels.

Background: Thyrotropin-releasing hormone (TRH) was the first hypothalamic hormone isolated that stimulates pituitary thyrotropin (TSH) secretion. TRH was also later found to be a stimulator of pituitary prolactin and distributed throughout the brain, gastrointestinal tract, and pancreatic ß cells. We previously reported the development of TRH null mice (conventional TRHKO), which exhibit characteristic tertiary hypothyroidism and impaired glucose tolerance due to insufficient insulin secretion. Although in the past five decades many investigators, us included, have attempted to determine the hypothalamic nucleus responsible for the hypothalamic-pituitary-thyroid (HPT) axis, it remained obscure because of the broad expression of TRH. Methods: To determine the hypothalamic region functionally responsible for the HPT axis, we established paraventricular nucleus (PVN)-specific TRH knockout (PVN-TRHKO) mice by mating Trh floxed mice and single-minded homolog 1 (Sim1)-Cre transgenic mice. We originally confirmed that most Sim1 was expressed in the PVN using Sim1-Cre/tdTomato mice. Results: These PVN-TRHKO mice exhibited tertiary hypothyroidism similar to conventional TRHKO mice; however, they did not show the impaired glucose tolerance observed in the latter, suggesting that TRH from non-PVN sources is essential for glucose regulation. In addition, a severe reduction in prolactin expression was observed in the pituitary of PVN-TRHKO mice compared with that in TRHKO mice. Conclusions: These findings are conclusive evidence that the PVN is the center of the HPT axis for regulation of serum levels of thyroid hormones and that the serum TSH levels are not decreased in tertiary hypothyroidism. We also noted that TRH from the PVN regulated prolactin, whereas TRH from non-PVN sources regulated glucose metabolism.

Pathological findings after third- and second-generation everolimus-eluting stent implantations in coronary arteries from autopsy cases and an atherosclerotic porcine model.

Pathological changes after third-generation drug-eluting stent implantation remain unclear. We compared the tissue responses of coronary arteries after the implantation of third-generation abluminal biodegradable-polymer everolimus-eluting stent (3rd EES) and second-generation durable-polymer EES (2nd EES) using autopsy specimens and an atherosclerotic porcine model. We compared the histology of stented coronary arteries obtained by autopsy performed 1-10 months after 3rd EES (n (number of cases) = 4, stent-implanted period of 3-7 months) and 2nd EES (n (number of cases) = 9, stent-implanted period of 1-10 months) implantations. The ratio of covered stent struts was higher with 3rd EESs than with 2nd EESs (3rd; 0.824 ± 0.032 vs. 2nd; 0.736 ± 0.022, p = 0.035). Low-density lipoprotein receptor knockout minipigs were stented with 3rd or 2nd EES in the coronary arteries and the stented regions were investigated. The fibrin deposition around the 2nd EES was more prominent. Additionally, higher density of smooth muscle cells was confirmed after the 3rd EES implantation. Pathological examination after the 3rd EES demonstrated a combination of less fibrin deposition and more rapid acquisition of well-developed neointima as compared to the 2nd EES at autopsy and the atherosclerotic porcine model.

Exophytic cavernous hemangioma arising from the right ventricle: Report of a rare case.

Cardiac hemangioma is relatively rare, accounting for approximately 1-3% of all primary heart tumors. This benign tumor may be an incidental lesion, but can also cause arrhythmias, pericardial effusion, congestive heart failure or outflow obstruction. We report a rare case with exophytic cardiac hemangioma arising from the right ventricle. Echocardiography showed an approximately 40 mm round protruding mass on the anterior wall of the right ventricle. Cardiovascular magnetic resonance demonstrated isointense and hyperintense signals on T1- and T2-weighted images, respectively. These imaging studies suggested a pericardial cyst. Perioperative findings indicated a globular, exophytic mass, vascular in nature, arising from the right ventricle. The lesion was resected directly, and the space left by defect in the right ventricular wall was covered with a bovine pericardial patch. Cardiac hemangiomas are generally endoluminal tumors, but we must keep in mind that the differential diagnoses include various pericardial lesions by medical images.

The 89-kDa PARP1 cleavage fragment serves as a cytoplasmic PAR carrier to induce AIF-mediated apoptosis.

Poly(ADP-ribose) polymerase 1 (PARP1) is a nuclear protein that is activated by binding to DNA lesions and catalyzes poly(ADP-ribosyl)ation of nuclear acceptor proteins, including PARP1 itself, to recruit DNA repair machinery to DNA lesions. When excessive DNA damage occurs, poly(ADP-ribose) (PAR) produced by PARP1 is translocated to the cytoplasm, changing the activity and localization of cytoplasmic proteins, e.g., apoptosis-inducing factor (AIF), hexokinase, and resulting in cell death. This cascade, termed parthanatos, is a caspase-independent programmed cell death distinct from necrosis and apoptosis. In contrast, PARP1 is a substrate of activated caspases 3 and 7 in caspase-dependent apoptosis. Once cleaved, PARP1 loses its activity, thereby suppressing DNA repair. Caspase cleavage of PARP1 occurs within a nuclear localization signal near the DNA-binding domain, resulting in the formation of 24-kDa and 89-kDa fragments. In the present study, we found that caspase activation by staurosporine- and actinomycin D-induced PARP1 autopoly(ADP-ribosyl)ation and fragmentation, generating poly(ADP-ribosyl)ated 89-kDa and 24-kDa PARP1 fragments. The 89-kDa PARP1 fragments with covalently attached PAR polymers were translocated to the cytoplasm, whereas 24-kDa fragments remained associated with DNA lesions. In the cytoplasm, AIF binding to PAR attached to the 89-kDa PARP1 fragment facilitated its translocation to the nucleus. Thus, the 89-kDa PARP1 fragment is a PAR carrier to the cytoplasm, inducing AIF release from mitochondria. Elucidation of the caspase-mediated interaction between apoptosis and parthanatos pathways extend the current knowledge on mechanisms underlying programmed cell death and may lead to new therapeutic targets.

Promising advances in clinical trials of dental tissue-derived cell-based regenerative medicine.

BACKGROUND: Advances in regenerative medicine with stem cells have led to clinical trials. Dental/oral tissues are emerging as promising cellular sources of human mesenchymal stem cells. Recently, dental tissue-derived cells have been used clinically due to their great potential, easy accessibility, and ability to be obtained via methods with low invasiveness. The aim of this study is to systematically assess the clinical effectiveness of dental cell-mediated therapies compared to current evidence-based methods in human patients. METHODS: The electronic databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were searched up to December 2019 for clinical trials. Clinical trials with any intervention using stem cells/cells derived from dental tissue were included. RESULTS: A total of 815 studies were identified by the electronic search, and 38 articles qualified for full-text evaluation. Finally, 20 studies (10 clinical trials using dental pulp-derived cells, 3 clinical trials using periodontal ligament-derived cells, and 7 studies using gingiva-derived cells) were included in this review. No clinical trials using dental follicle- or apical papilla-derived cells were selected in this review. Dental pulp-derived cells were used in clinical trials for bone regeneration, periodontitis, and dental pulp regeneration. All clinical trials using periodontal ligament-derived cells and gingiva-derived cells were conducted for periodontal disease treatment and gingival augmentation, respectively. Among the 20 selected studies, 16 showed clinical benefits of cell transplantation therapies. In addition, no study reported adverse events that may have been associated with cell transplantation. CONCLUSIONS: These findings indicate that dental tissue-derived cells would be useful for cell-based regenerative medicine for various diseases.

Diagnostic Cytokines and Comparative Analysis Secreted from Exfoliated Deciduous Teeth, Dental Pulp, and Bone Marrow Derived Mesenchymal Stem Cells for Functional Cell-Based Therapy.

The aim of the study was to clarify the distinctive features of stem cells for effective cell-based therapy strategies in regenerative medicine. The expression levels of cytokines secreted from stem cells from exfoliated deciduous teeth (SHED), dental pulp stem cells (DPSCs), and bone marrow derived mesenchymal stem cells (BMMSCs) were examined to identify the details of their characteristics. A total of 174 cytokines were analyzed using cytokine antibody array, and their expression levels were confirmed by an enzyme-linked immunosorbent assay. These results indicated that 11 cytokines that were related to tissue regeneration, including growth factors, chemokines, and inflammatory cytokines, were identical in SHED, DPSCs, and BMMSCs. The comparative analyses between SHED and BMMSCs revealed that hepatocyte growth factor (HGF), matrix metalloproteinase-3, and stromal cell derived factor 1 (SDF-1) were expressed 6.7-, 2.5-, and 2.1-fold higher, respectively, in SHEDs. HGF was also expressed 3.4-fold higher in DPSCs than BMMSCs. Monocyte chemoattractant protein-1, and-3 were expressed more strongly in BMMSCs. SHED contained significantly higher SDF-1 levels than DPSCs. The distinct cytokine secretion indicated that they had different character besides basic MSC features. This knowledge of diagnostic cytokines analysis secreted from SHED, DPSCs, and BMMSCs extends our understanding, and can provide a novel therapeutic paradigm shift for functional cell-based therapy.

Influence of Smoking on Thyroid Function in Japanese Subjects: Longitudinal Study for One Year of On-Off Smoking.

CONTEXT: We previously identified factors affecting thyroid status, including sex, age, and smoking. OBJECTIVE: In the current study, we increased the number of subjects examined and investigated the effects of these factors, particularly smoking and the thyroid peroxidase antibody (TPO-Ab), in Japanese patients with euthyroxinemia and serum free T4 levels within the normal range. PARTICIPANTS: A total of 12,289 subjects who underwent health checkups were analyzed in a cross-sectional and longitudinal study. RESULTS: The mean age of subjects was 50 ± 10 years (age range: 21 to 88 years). Serum TSH levels and the prevalence of positivity for TPO-Ab increased with age in Japanese subjects with euthyroxinemia. Mean serum TSH levels were significantly lower in the smoking group than in the nonsmoking group except for women older than 50 years. Serum TSH levels were significantly higher in subjects with positivity for TPO-Ab than in those with negativity at all ages and in both sexes; however, smoking did not affect free T4 levels or positivity for TPO-Ab. Among men, the rate of smokers was significantly higher in patients with subclinical hyperthyroidism (25%) than in those with subclinical hypothyroidism (10%; P < 0.05). Furthermore, the results of the longitudinal study revealed a significant decrease in serum TSH levels 1 year after the start of smoking in men (P < 0.05). CONCLUSION: Because smoking appeared to lower serum TSH levels in Japanese subjects with euthyroxinemia, their smoking status warrants careful consideration when evaluating subclinical thyroid function.

Clinical Potential and Current Progress of Dental Pulp Stem Cells for Various Systemic Diseases in Regenerative Medicine: A Concise Review.

Dental pulp stem cells (DPSCs) are mesenchymal stem cells (MSCs) that have multipotent differentiation and a self-renewal ability. They have been useful not only for dental diseases, but also for systemic diseases. Extensive studies have suggested that DPSCs are effective for various diseases, such as spinal cord injuries, Parkinson's disease, Alzheimer's disease, cerebral ischemia, myocardial infarction, muscular dystrophy, diabetes, liver diseases, eye diseases, immune diseases, and oral diseases. DPSCs have the potential for use in a cell-therapeutic paradigm shift to treat these diseases. It has also been reported that DPSCs have higher regenerative potential than the bone marrow-derived mesenchymal stem cells known as representative MSCs. Therefore, DPSCs have recently gathered much attention. In this review, the therapeutic potential of DPSCs, the latest progress in the pre-clinical study for treatment of these various systemic diseases, and the clinical applications of DPSCs in regenerative medicine, are all summarized. Although challenges, including mechanisms of the effects and establishment of cell processing and transplantation methods for clinical use, still remain, DPSCs could be promising stem cells sources for various clinical applications, because of their easy isolation by a noninvasive procedure without ethical concerns.

Social cognition and prefrontal hemodynamic responses during a working memory task in schizophrenia.

Social cognition is an important determinant of functional impairment in schizophrenia, but its relationship with the prefrontal functional abnormalities associated with the condition is still unclear. The present study aimed to explore the relationship between social cognition and prefrontal function in patients with schizophrenia using 52-channel near-infrared spectroscopy (NIRS). Twenty-six patients with schizophrenia and 26 age-, gender-, and intelligence quotient-matched healthy controls (HCs) participated in the study. Hemodynamic responses in the prefrontal and superior temporal cortical regions were assessed during a working memory task using NIRS. Social cognition was assessed using the Social Cognition Screening Questionnaire (SCSQ). The observed hemodynamic responses were significantly reduced in the lateral prefrontal cortex (PFC), the frontopolar cortex, and temporal regions in subjects with schizophrenia compared to HCs. Additionally, lateral PFC hemodynamic responses assessed during the working memory task demonstrated a strong positive correlation with the SCSQ theory of mind (ToM) subscale score even after controlling for working memory performance. These results suggest that ToM integrity is closely related to lateral PFC functional abnormalities found in patients with schizophrenia. In addition, this study provides evidence to suggest that NIRS could be used to identify biomarkers of social cognition function in subjects with schizophrenia.