Antidepressant-Like Activity of 10-Hydroxy-Trans-2-Decenoic Acid, a Unique Unsaturated Fatty Acid of Royal Jelly, in Stress-Inducible Depression-Like Mouse Model

Symptoms of depression and anxiety appeared in mice after they had been subjected to a combination of forced swimming for 15 min followed by being kept in cages that were sequentially subjected to leaning, drenching, and rotation within 1-2 days for a total of 3 weeks. The animals were then evaluated by the tail-suspension test, elevated plus-maze test, and open-field test at 1 day after the end of stress exposure. Using these experimental systems, we found that 10-hydroxy-trans-2-decenoic acid (HDEA), an unsaturated fatty acid unique to royal jelly (RJ), protected against the depression and anxiety when intraperitoneally administered once a day for 3 weeks simultaneously with the stress loading. Intraperitoneally administered RJ, a rich source of HDEA, was also protective against the depression, but RJ given by the oral route was less effective. Our present results demonstrate that HDEA and RJ, a natural source of it, were effective in ameliorating the stress-inducible symptoms of depression and anxiety

プリアジャステッドアプライアンスで治療したClass I叢生患者における前歯の移動と安定性

プリアジャステッドアプライアンスで治療されたClass I不正咬合患者36例(17.70±7.80歳)を抜歯群24例(男児3例、女児21例、17.30±7.10歳)と非抜歯群12例(男児4例、女児8例、18.40±9.40歳)に分け、治療前後の上顎前歯および下顎前歯の移動を評価した。抜歯群では、上顎および下顎切歯が後方に移動し、舌側傾斜がみられたが、下顎中切歯の歯軸は適切であり、condylar incisal angleは約90°であった。非抜歯群では上顎中切歯が前方に移動したが、下顎切歯のlabial proclinationによりcondylar incisal angleは減少した。切歯～第2大臼歯までの歯の平均幅、アーチレングスディスクレパンシー、irregularity indexは抜歯群の方が有意に大きかった。以上から、プリアジャステッドアプライアンスで治療したClass I叢生は、両群において保定時に良好な閉塞を示したが、上顎および下顎中切歯の移動には群間差がみられるため、症例に応じて治療戦略を変えるべきであることが示された

The Effects of Inbreeding on the Egg Production Rate in Japanese Quail

本研究は,近交退化現象を明らかにする目的で,日本ウズラを用い,きょうだい交配によって近交世代を進めた場合の産卵率について近交群と無作為交配群とで比較検討した. 本研究に用いた日本ウズラは,当研究室において無作為交配によって維持した閉鎖集団を起源とする近交群と無作為交配群である. 産卵率は連続32日間にわたって検討した. 得られた結果は要約すると以下の通りである. 1.近交群と無作為交配群における産卵率について比較した結果,近交群では2世代目で急激な低下がみられ,4世代目まで低い値が維持された. 両群間には1世代目を除くすべての世代で有意差が認められた. 2.近交群と無作為交配群における産卵率の範囲と産卵率の範囲に含まれる維持家系数について検討した結果,近交群では無作為交配群に比較して,産卵率の高い家系数は少なくなり,一方,産卵率の低い家系数は多くなった. 3.産卵率の退化現象について回帰の面から検討した結果,産卵率は退化の傾向がみられた. 近交係数10%増加するごとに,3.80%低下することが示された. 4.以上の結果から,近交による産卵率の低下は,ホモ接合体の増加に伴う雌ウズラでの生殖機能の低下に起因したものと考えられる

The Effects of Inbreeding on Body Weight, Age at Sexual Maturity and Egg Weight in Japanese Quail

本研究は,近親交配の継続によって発現する近交退化現象を明らかにする目的で,日本ウズラを用い,きょうだい交配によって近交世代を進めた場合の体重,性成熟日齢,卵重について近交群と無作為交配群とで比較検討した. なお,本研究に用いた日本ウズラは,岡山大学農学部家畜育種学教室で無作為交配によって維持してきた集団を基礎として得られた近交群と無作為交配群である. 体重は艀化時,艀北後2,4,6,10週齢時に,卵重は13週齢時に測定した. 得られた結果は以下の通りである. 1.近交に伴う系統数と家系数の推移について検討した結果,近交群では,1世代目16系統36家系で出発したが,4世代目では3系統14家系となり,近交に伴い系統数と家系数が急激に低下した. これに対して,近交群では,毎世代40家系を維持した. 2.近交群と無作為交配群における体重,性成熟日齢,卵重について比較検討した結果,近交群では,無作為交配群に比較していずれの形質も劣る傾向が認められた. 特に,雄と雌の4週齢と6週齢時体重は,いずれの世代においても両群間に有意な差が認められた. 3.体重,性成熟日齢,卵重の退化現象について回帰の面から検討した結果,いずれの形質も退化の傾向がみられた. 近交係数10%増加あたりの回帰係数に有意差が認められたのは雌の6週齢時体重であった. 近交係数10%増加するごとに,雌の6週齢時体重は3.27ｇ減少することが示された. 性成熟日齢は,雄では0.67日,雌では0.96日遅延し,卵重は0.21g減少することが示された. 4.以上の結果から,近交に伴う体重,性成熟日齢,卵重の退化は,ヘテロ接合体の減少に伴うホモ接合体の増加に起因したものと考えられた

PAX2 promoted prostate cancer cell invasion through transcriptional regulation of HGF in an in vitro model

AbstractElucidating the mechanism of prostate cancer cell invasion may lead to the identification of novel therapeutic strategies for its treatment. Paired box 2 (PAX2) and hepatocyte growth factor (HGF) proteins are promoters of prostate cancer cell invasion. We found that PAX2 protein activated the HGF gene promoter through histone H3 acetylation and upregulated HGF gene expression. Deletion analysis revealed that the region from −637 to −314 of the HGF gene was indispensable for HGF promoter activation by PAX2. This region contains consensus PAX2 binding sequences and mutations of the sequences attenuated HGF promoter activation. Using an in vitro invasion model, we found that PAX2 and HGF promoted prostate cancer cell invasion in the same pathway. Knockdown of HGF expression attenuated the cells' invasive capacity. Moreover, in tissue samples of human prostate cancers, HGF and PAX2 expression levels were positively correlated. These results suggested that upregulation of HGF gene expression by PAX2 enhanced the invasive properties of prostate cancer cells. The PAX2/HGF pathway in prostate cancer cells may be a novel therapeutic target in prostate cancer patients

The Influence of Chronic Cerebral Hypoperfusion on Cognitive Function and Amyloid β Metabolism in APP Overexpressing Mice

Cognitive impairment resulting from cerebrovascular insufficiency has been termed vascular cognitive impairment, and is generally accepted to be distinct from Alzheimer's disease resulting from a neurodegenerative process. However, it is clear that this simple dichotomy may need revision in light of the apparent occurrence of several shared features between Alzheimer's disease and vascular cognitive impairment. Nevertheless, it still remains largely unknown whether the burden of vascular- and Alzheimer-type neuropathology are independent or interdependent. Therefore, we investigated whether chronic cerebral hypoperfusion influences cognitive ability or amyloid β deposition in amyloid precursor protein (APP) overexpressing transgenic mice

Involvement of heterologous ubiquitination including linear ubiquitination in Alzheimer’s disease and amyotrophic lateral sclerosis

In neurodegenerative diseases such as Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS), the progressive accumulation of ubiquitin-positive cytoplasmic inclusions leads to proteinopathy and neurodegeneration. Along with the seven types of Lys-linked ubiquitin chains, the linear ubiquitin chain assembly complex (LUBAC)-mediated Met1-linked linear ubiquitin chain, which activates the canonical NF-κB pathway, is also involved in cytoplasmic inclusions of tau in AD and TAR DNA-binding protein 43 in ALS. Post-translational modifications, including heterologous ubiquitination, affect proteasomal and autophagic degradation, inflammatory responses, and neurodegeneration. Single nucleotide polymorphisms (SNPs) in SHARPIN and RBCK1 (which encodes HOIL-1L), components of LUBAC, were recently identified as genetic risk factors of AD. A structural biological simulation suggested that most of the SHARPIN SNPs that cause an amino acid replacement affect the structure and function of SHARPIN. Thus, the aberrant LUBAC activity is related to AD. Protein ubiquitination and ubiquitin-binding proteins, such as ubiquilin 2 and NEMO, facilitate liquid-liquid phase separation (LLPS), and linear ubiquitination seems to promote efficient LLPS. Therefore, the development of therapeutic approaches that target ubiquitination, such as proteolysis-targeting chimeras (PROTACs) and inhibitors of ubiquitin ligases, including LUBAC, is expected to be an additional effective strategy to treat neurodegenerative diseases

Hot cross bun" sign in multiple system atrophy with predominant cerebellar ataxia: a comparison between proton density-weighted imaging and T2-weighted imaging.

[Objective]: To investigate whether proton density-weighted imaging can detect the "hot cross bun" sign in the pons in multiple system atrophy with predominant cerebellar ataxia significantly better than T2-weighted imaging at 3T. [Methods]: Sixteen consecutive patients with multiple system atrophy with predominant cerebellar ataxia according to the Consensus Criteria were reviewed. Axial unenhanced proton density-weighted imaging and T2-weighted imaging were obtained using a dual-echo fast spin-echo sequence at 3T. Two neuroradiologists independently evaluated visualisation of the abnormal pontine signal using a 4-point visual grade from Grade 0 (no "hot cross bun" sign) to Grade 3 (prominent "hot cross bun" sign on two or more sequential slices). Differences in grade between proton density-weighted imaging and T2-weighted imaging were statistically analysed using the Wilcoxon signed-rank test. [Results]: In 11 patients (69%), a higher grade was given for proton density-weighted imaging than T2-weighted imaging. In 1 patient (6%), grades were the same (Grade 3) on both images. In the remaining 4 patients (25%), signal abnormalities were not detected on either image (Grade 0). The "hot cross bun" sign was thus observed significantly better on proton density-weighted imaging than on T2-weighted imaging (P = 0.001). [Conclusions]: The "hot cross bun" sign considered diagnostic for multiple system atrophy with predominant cerebellar ataxia is significantly better visualised on proton density-weighted imaging than on T2-weighted imaging at 3T

Amino acid polymorphisms in human histocompatibility leukocyte antigen class II and proinsulin epitope have impacts on type 1 diabetes mellitus induced by immune-checkpoint inhibitors

IntroductionImmune-checkpoint inhibitors are effective in various advanced cancers. Type 1 diabetes mellitus induced by them (ICI-T1DM) is a serious complication requiring prompt insulin treatment, but the immunological mechanism behind it is unclear.MethodsWe examined amino acid polymorphisms in human histocompatibility leukocyte antigen (HLA) molecules and investigated proinsulin epitope binding affinities to HLA molecules.Results and DiscussionTwelve patients with ICI-T1DM and 35 patients in a control group without ICI-T1DM were enrolled in the study. Allele and haplotype frequencies of HLA-DRB1*04:05, DQB1*04:01, and most importantly DPB1*05:01 were significantly increased in patients with ICI-T1DM. In addition, novel amino acid polymorphisms in HLA-DR (4 polymorphisms), in DQ (12 polymorphisms), and in DP molecules (9 polymorphisms) were identified. These amino acid polymorphisms might be associated with the development of ICI-T1DM. Moreover, novel human proinsulin epitope clusters in insulin A and B chains were discovered in silico and in vitro peptide binding assays to HLA-DP5. In conclusion, significant amino acid polymorphisms in HLA-class II molecules, and conformational alterations in the peptide-binding groove of the HLA-DP molecules were considered likely to influence the immunogenicity of proinsulin epitopes in ICI-T1DM. These amino acid polymorphisms and HLA-DP5 may be predictive genetic factors for ICI-T1DM