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Decreased miR-155-5p in exosomes from human peripheral mononuclear cells preconditioned by oxygen-glucose deprivation
Get PDF新潟大学Niigata University博士（医学）近年，脳梗塞患者の機能回復を促進する方法として，細胞療法が注目されている．当研究室では，低酸素低糖刺激(OGD)を加えたラット末梢血単核球(OGD-PBMC)が組織保護的な極性に変化し，脳梗塞ラットに経頸動脈投与することで脳内の血管内皮増殖因子(VEGF)増加を介して脳梗塞治療効果を有することを示した．一方で，低酸素条件下では，低酸素誘導因子(HIF-1α)の増加によりVEGFが増加することも報告されているが，OGD刺激を加えたPBMCで同様の機序が働いているかは検証されていなかった．また，PBMCと脳内常在細胞との細胞間相互作用の機序は明確ではなかった．そこで，OGD-PBMCの脳梗塞に対する治療効果の機序について，細胞間相互作用にエクソソームが関与していると想定し，HIF-1α発現とVEGF分泌に関わるmiRNAに注目して検討した．ヒトOGD-PBMCを一過性局所脳梗塞モデルラットに経頸動脈投与して，脳内への生着を検証した．さらに，ミクログリアに対する極性変化の誘導の有無を，抗VEGF抗体を用いて蛍光免疫染色で検証した．次に，通常培養したPBMC(Normoxic-PBMC)，OGD-PBMCそれぞれのエクソソーム由来の200bp以下のRNAを濃縮し，HIF-1αの発現に関与するmiRNAを比較した．その結果を踏まえ，HIF-1αとVEGFを増加させる可能性のあるmiRNAに対するアンチセンスオリゴヌクレオチド投与による阻害を行い，Normoxic-PBMCとOGD-PBMCにおけるHIF-1αとVFGFの発現をウエスタンブロッティングとルミネックスアッセイで評価した．ヒトOGD-PBMCは，投与3日後には梗塞部位周囲で確認されたが，投与21日後には確認されなかった．一方，VEGFを発現しているミクログリアはNormoxic-PBMC投与群に比して，OGD-PBMC投与群で3.9倍に増加した(P<0.05)．HIF-1αまたはVEGFの発現増加に関わるmiRNAの中で，唯一miR-155-5pがNormoxic-PBMCと比して，OGD-PBMCでは0.37倍にダウンレギュレートしていた(P=0.01)．miR-155-5p阻害を行ったヒトOGD-PBMCでは，HIF-1αの発現が3倍に増加した(P<0.05)．また，VEGFの発現も1.36倍に増加した(P<0.05)．一方，Normoxic-PBMCではmiR-155-5p阻害にてHIF-1αの発現は検出されなかった．以上から，OGD-PBMCでは，miR-155-5pの減少によりHIF-1αの発現が増加しVEGFの分泌が増加する．さらに，OGD-PBMC投与による組織保護的極性の獲得にはエクソソームを介した細胞間情報伝達が関与している可能性が示唆された．新大院博(医)第1110
尿中A-,C-メガリンの糖尿病性腎臓病患者における腎予後予測性の検討 : 探索的後ろ向きコホート研究
Get PDF新潟大学Niigata University博士（医学）Aims: Megalin, a proximal tubular endocytosis receptor, is excreted in urine in two forms: ectodomain (A-megalin) and full-length (C-megalin). We explored whether urinary megalin levels can be used as independent prognostic biomarkers in the progression of diabetic kidney disease (DKD). Methods: The associations between baseline urinary A-megalin/creatinine (Cr) and/or C-megalin/Cr levels and the subsequent estimated glomerular filtration rate (eGFR) slope were analyzed using a generalized estimating equation. Patients were categorized into higher or lower groups based on the optimal cutoff values, obtained from a receiver operating characteristic curve, of the two forms of urinary megalin. Results: We retrospectively analyzed 188 patients with type 2 diabetes. The eGFR slopes of the higher A-megalin/Cr and higher C-megalin/Cr groups were - 0.904 and - 0.749 ml/min/1.73 m2/year steeper than those of the lower groups, respectively. Moreover, the eGFR slope was - 1.888 ml/min/1.73 m2/year steeper in the group with both higher A- and higher C-megalin/Cr than in the other group. These results remained significant when adjusted for known urinary biomarkers (albumin, α1-microglobulin, β2-microglobulin, and N-acetyl-β-D-glucosaminidase). Conclusions: Urinary A- and C-megalin/Cr levels are likely to be prognostic biomarkers in the progression of DKD independent of other urinary biomarkers.Journal of Diabetes and its Complications. 2022, 36(11), 108312.新大院博(医)第1119
硬膜下血腫における皮質動脈微小破裂の検出と形態解析 : CUBIC法による組織透明化を用いた3次元画像化
Get PDF新潟大学Niigata University博士（医学）One of the causes of bleeding in subdural hematoma is cortical artery rupture, which is difficult to detect at autopsy. Therefore, reports of autopsy cases with this condition are limited and hence, the pathogenesis of subdural hematoma remains unclear. Herein, for the detection and morphological analysis of cortical artery ruptures as the bleeding sources of subdural hematoma, we used the tissue-clearing CUBIC (clear, unobstructed, brain/body imaging cocktails and computational analysis) method with light-sheet fluorescence microscopy and reconstructed the two-dimensional and three-dimensional images. Using the CUBIC method, we could clearly visualize and detect cortical artery ruptures that were missed by conventional methods. Indeed, the CUBIC method enables three-dimensional morphological analysis of cortical arteries including the ruptured area, and the creation of cross-sectional two-dimensional images in any direction, which are similar to histopathological images. This highlights the effectiveness of the CUBIC method for subdural hematoma analysis.Diagnostics. 2022, 12(11), 2875.新大博(医)第1825
歯科診療所通院患者における不安の要因に関する研究 : Modified Dental Anxiety Scale日本語版(MDAS-J)を用いた分析
Get PDF新潟大学Niigata University博士（口腔保健福祉学）新大院博(口)第26
胃癌術後患者への超高濃度栄養食の投与が血糖変動および食事摂取量に対して及ぼす影響
Get PDF新潟大学Niigata University博士（医学）Abstract Purpose Adherence to oral nutritional supplements (ONS) to prevent weight loss after gastrectomy is problematic. The present study evaluated the impact of super energy-dense ONS (SED ONS; 4 kcal/mL) on glycemic change and energy intake after gastrectomy. Methods Gastrectomy patients were placed on continuous glucose monitoring for a 3-day observation period after food intake had been stabilized postoperatively. In addition, they were given 0, 200, and 400 kcal/day of SED ONS on Days 1, 2, and 3, respectively. The primary outcome was the area under the curve < glucose 70 mg/dL (AUC < 70). The secondary outcomes were other indices of glucose fluctuation and the amount of food and SED ONS intake. Results Seventeen patients were enrolled. The AUC < 70 did not differ significantly with or without SED ONS over the observation period. SED ONS did not cause postprandial hypoglycemia and prevented nocturnal hypoglycemia. The mean dietary intake did not change significantly during the observation period, and the total energy intake increased significantly according to the amount of SED ONS provided. Conclusion SED ONS after gastrectomy increased the total energy intake without dietary reduction and it did not result in hypoglycemia.Surgery Today. 2023, 53, 605-613.新大院博（医）第1141
哺乳瓶乳首を介して授乳する前後の搾乳母乳の細菌叢解析
Get PDF新潟大学Niigata University博士（保健学）Objectives: Breast milk is a valuable and useful source of nutrition; however, surplus milk is routinely discarded for hygiene reasons despite an unclear scientific basis. Here, we profiled the microbiota of expressed breast milk before and after feeding with an artificial nipple and examined the bacterial survival in breast milk stored at 4°C. Methods: Eleven mother-baby pairs were included in the study. Samples of expressed breast milk were collected before and after feeding with an artificial nipple and examined both immediately (0h) and after storage for 3 and 12 h at 4°C. Each sample was inoculated onto a blood agar plate and incubated anaerobically and aerobically at 37°C. Genomic DNA was extracted from individual bacterial colonies, which were identified by 16S rRNA gene sequencing. Results: Before feeding, the bacterial counts at 0 and 12 h were (1.4±1.6) × 105 colony-forming units (CFU)/mL and (1.4±0.6) × 105 CFU/mL, respectively. Staphylococcus (47.7% and 41.9%, respectively), Cutibacterium (20.7% and 36.0%, respectively), and Streptococcus (16.1% and 6.6%, respectively) were identified among the samples. In contrast, after feeding, the bacterial counts at 0 and 12 h were (2.7±1.7) × 105 CFU/mL and (2.1±2.5) × 105 CFU/mL, respectively. Staphylococcus (30.1% and 37.4%, respectively), Cutibacterium (11.7% and 31.7%, respectively), and Streptococcus (41.5% and 25.2%, respectively), were identified among the samples. Conclusions: Bacteria were present in the breast milk before feeding. Although the main component of the microbiota shifted from Staphylococcus to Streptococcus species after feeding, these results suggest that surplus expressed breast milk may be preserved safely in a refrigerator for at least 12 h after feeding with an artificial nipple.新大院博(保)第55
Origin of feldspar veins and genesis of vesiculation in dolerite sills of the Shimokawa ophiolite in the northern Hidaka belt, Hokkaido
Get PDF新潟大学Niigata University博士（理学）Studies of the interaction of magma with sediments during shallow intrusion are scarce. This study will provide insight into the processes by which volatile components were added to the magma which intruded into shallow soft-sediment. Basalt and dolerite with N-MORB chemical features of the Shimokawa ophiolite in the northern Hidaka belt, Hokkaido, generally show poor vesiculation. However, some of dolerites are vesiculated up to 10 %, and these vesiculated rocks are exclusively found within sills thicker than 10 m, which intruded into clastic sediments. Non-vesiculated chilled margins suggest the vesiculation occurred after the magmatic emplacement. The vesiculated dolerite is richer in bulk-rock Na2O, K2O and Rb contents than poorly vesiculated basalt and dolerites. These observations suggest secondary enrichments of vapor and selective elements, and this paper tested this hypothesis by petrographic and petrochemical approaches. While looking for carriers of enriched components, I focused on plagioclase - K-feldspar veins 2 mm thick found in a vesiculated dolerite sill. The veins are irregularly bounded, and partly contain amygdules. Therefore, it is considered that the veins were formed before the solidification of the intruded magma. The examined vein shows trachytic bulk-rock major element composition and petrographically classified as monzonite. The multi-element patterns of the trace element composition shows that the incompatible elements are not enriched unlike trachytes from plume-related oceanic settings. The LREE-poor chemical feature is similar to that of normal to transitional MORBs. Both textures and chemical composition suggest that the veins originated from a trachytic melt. To seek the origin of the melt, the chemical compositions of the veins are compared with those of interstitial melt parts of the dolerite. The HREE-rich feature of the veins cannot be explained by the crystallization differentiation of the dolerite magma. Therefore, it is considered that the melt of the veins were not the residue of the host doleritemagma, and of an exotic origin. Although occurrences directly showing the vein melt have not been found yet, I assumed that the vein melt originated from mudstone to which the dolerite intruded. If mudstones are incorporated into dolerite magma and partially fused, the generated melt probably has a granitic composition on the three-phase eutectic point of quartz, albite, and K-feldspar, because the host mudstones are rich in these components. It is also considered that this granitic magma immediately loses silica, because it is surrounded by olivine tholeiite magma undersaturated in quartz. Losing silica, the granitic magma could thus transformed to monzonitic magma. The soft-sediment inclusions can provide water fluid and increase the volatile components in the dolerite magma. This mechanism can consistently explain the petrology of feldspar veins and vesiculation of the host magma together.新大院博(理)第487
