Tetra-Quark Resonances in Lattice QCD

We study $qq \bar q \bar q$-type four-quark (4Q) systems in SU(3)$_c$ anisotropic quenched lattice QCD, using the $O(a)$-improved Wilson (clover) fermion at $\beta=5.75$ on $12^3 \times 96$ with renormalized anisotropy $a_s/a_t=4$.For comparison, we first investigate the lowest $q\bar q$ scalar meson from the connected diagram and find its large mass of about 1.32GeV after chiral extrapolation, and thus the lowest $q\bar q$ scalar meson corresponds to $f_0(1370)$.We investigate the lowest 4Q state in the spatially periodic boundary condition, and find that it is just a two-pion scattering state, as is expected. To examine spatially-localized 4Q resonances, we use the Hybrid Boundary Condition (HBC) method, where anti-periodic and periodic boundary conditions are imposed on quarks and antiquarks, respectively. By applying HBC on a finite-volume lattice, the threshold of the two-meson scattering state is raised up, while the mass of a compact 4Q resonance is almost unchanged.In HBC, the lowest 4Q state appears slightly below the two-meson threshold. To clarify the nature of the 4Q system, we apply the Maximum Entropy Method (MEM) for the 4Q correlator and obtain the spectral function of the 4Q system.From the combination analysis of MEM with HBC, we finally conclude that the 4Q system appears as a two-pion scattering state and there is no spatially-localized 4Q resonance in the quark-mass region of $m_s< m_q <2m_s$

The fungal metabolite (+)-terrein abrogates osteoclast differentiation via suppression of the RANKL signaling pathway through NFATc1

Pathophysiological bone resorption is commonly associated with periodontal disease and involves the excessive resorption of bone matrix by activated osteoclasts. Receptor activator of nuclear factor (NF)-κB ligand (RANKL) signaling pathways have been proposed as targets for inhibiting osteoclast differentiation and bone resorption. The fungal secondary metabolite (+)-terrein is a natural compound derived from Aspergillus terreus that has previously shown anti-interleukin-6 properties related to inflammatory bone resorption. However, its effects and molecular mechanism of action on osteoclastogenesis and bone resorption remain unclear. In the present study, we showed that 10 µM synthetic (+)-terrein inhibited RANKL-induced osteoclast formation and bone resorption in a dose-dependent manner and without cytotoxicity. RANKL-induced messenger RNA expression of osteoclast-specific markers including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), the master regulator of osteoclastogenesis, cathepsin K, tartrate-resistant acid phosphatase (Trap) was completely inhibited by synthetic (+)-terrein treatment. Furthermore, synthetic (+)-terrein decreased RANKL-induced NFATc1 protein expression. This study revealed that synthetic (+)-terrein attenuated osteoclast formation and bone resorption by mediating RANKL signaling pathways, especially NFATc1, and indicated the potential effect of (+)-terrein on inflammatory bone resorption including periodontal disease

The Fungal Metabolite (+)-Terrein Abrogates Ovariectomy-Induced Bone Loss and Receptor Activator of Nuclear Factor-kappa B Ligand-Induced Osteoclastogenesis by Suppressing Protein Kinase-C alpha/beta II Phosphorylation

Osteoporosis is a common disease characterized by a systemic impairment of bone mass and microarchitecture that results in fragility fractures. Severe bone loss due to osteoporosis triggers pathological fractures and consequently decreases the daily life activity and quality of life. Therefore, prevention of osteoporosis has become an important issue to be addressed. We have reported that the fungal secondary metabolite (+)-terrein (TER), a natural compound derived from Aspergillus terreus, has shown receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclast differentiation by suppressing nuclear factor of activated T-cell 1 (NFATc1) expression, a master regulator of osteoclastogenesis. TER has been shown to possess extensive biological and pharmacological benefits; however, its effects on bone metabolism remain unclear. In this study, we investigated the effects of TER on the femoral bone metabolism using a mouse-ovariectomized osteoporosis model (OVX mice) and then on RANKL signal transduction using mouse bone marrow macrophages (mBMMs). In vivo administration of TER significantly improved bone density, bone mass, and trabecular number in OVX mice (p < 0.01). In addition, TER suppressed TRAP and cathepsin-K expression in the tissue sections of OVX mice (p < 0.01). In an in vitro study, TER suppressed RANKL-induced phosphorylation of PKC alpha/beta II, which is involved in the expression of NFATc1 (p < 0.05). The PKC inhibitor, GF109203X, also inhibited RANKL-induced osteoclastogenesis in mBMMs as well as TER. In addition, TER suppressed the expression of osteoclastogenesis-related genes, such as Ocstamp, Dcstamp, Calcr, Atp6v0d2, Oscar, and Itgb3 (p < 0.01). These results provide promising evidence for the potential therapeutic application of TER as a novel treatment compound against osteoporosis

Genetic analysis reveals a hierarchy of interactions between polycystin-encoding genes and genes controlling cilia function during left-right determination

During mammalian development, left-right (L-R) asymmetry is established by a cilia-driven leftward fluid flow within a midline embryonic cavity called the node. This ‘nodal flow’ is detected by peripherally-located crown cells that each assemble a primary cilium which contain the putative Ca2+ channel PKD2. The interaction of flow and crown cell cilia promotes left side-specific expression of Nodal in the lateral plate mesoderm (LPM). Whilst the PKD2-interacting protein PKD1L1 has also been implicated in L-R patterning, the underlying mechanism by which flow is detected and the genetic relationship between Polycystin function and asymmetric gene expression remains unknown. Here, we characterize a Pkd1l1 mutant line in which Nodal is activated bilaterally, suggesting that PKD1L1 is not required for LPM Nodal pathway activation per se, but rather to restrict Nodal to the left side downstream of nodal flow. Epistasis analysis shows that Pkd1l1 acts as an upstream genetic repressor of Pkd2. This study therefore provides a genetic pathway for the early stages of L-R determination. Moreover, using a system in which cultured cells are supplied artificial flow, we demonstrate that PKD1L1 is sufficient to mediate a Ca2+ signaling response after flow stimulation. Finally, we show that an extracellular PKD domain within PKD1L1 is crucial for PKD1L1 function; as such, destabilizing the domain causes L-R defects in the mouse. Our demonstration that PKD1L1 protein can mediate a response to flow coheres with a mechanosensation model of flow sensation in which the force of fluid flow drives asymmetric gene expression in the embryo

含糖酸化鉄注射液の長期投与でFGF23関連低リン血症性骨軟化症を来たしたクローン病の１例

症例は50歳代，男性．クローン病で２年前に右半結腸切除術，小腸部分切除を施行．術後に他院にてアダリムマブを導入され，クローン病は臨床的寛解の状態であった．４か月前より下肢を中心とした疼痛が出現した．アダリムマブによる薬剤起因性ループスあるいは腸炎性関節炎を疑い，２か月前よりアダリムマブ投与を中止し，プレドニゾロンの内服を開始するも改善を認めなかった．血液検査にて，低リン血症と高アルカリフォスファターゼ血症を認め，精査治療目的で当院に紹介入院となった．骨塩定量検査にて骨密度の低下を，骨シンチグラフィーで疼痛を認める骨への多発取り込みを認め，骨軟化症と診断した．血清のfibroblast growth factor 23（FGF23）が175pg/ml と高値であり，入院前まで定期的に使用されていた含糖酸化鉄注射液による，FGF23関連低リン血症性骨軟化症と診断した．含糖酸化鉄注射液投与を中止し，リン製剤とビタミンD 製剤の投与を開始したところ，徐々に低リン血症と高アルカリフォスファターゼ血症の改善を認めた．その後の経過は良好で，FGF23値は徐々に低下を示し，下肢を中心とした疼痛は軽快し，退院した．長期的に含糖酸化鉄注射液を投与する場合は，FGF23関連低リン血症の早期発見のため，血中リン濃度を定期的に測定する必要がある．The case is a man in his 50s. He underwent operations of right half colon resection and small intestine segmental resection due to Crohn’s disease two years ago. After surgery, Adalimumab was introduced in other hospital, and he was a state of the clinical remission in Crohn’s disease. The sharp pain mainly on lower limbs develops from four months ago. We doubted drug origin-related lupus with Adalimumab or enteritis-related joint pain. Therefore, we stopped Adalimumab injection and started internal use of the prednisolone, however the symptoms did not improve and had continued for two months.Laboratory test showed hypophosphatemia and hyperphosphatasemia and then he was transported to our hospital. Bone mineral quantity showed bone salt decrease and bone scan showed increased uptakes in multiple bones. Fibroblast growth factor23 (FGF23) of the serum was high (175pg/ml), and we diagnosed him FGF23-mediated hypophosphatemic osteomalasia induced by prolonged administration of saccharated ferric acid.Saccharated ferric acid has regularly been used until hospitalization. After stopping the ferric acid injection, and taking phosphorus and vitamin D, hypophosphatemia and hyperphosphatasemia was gradually improved. FGF23 level gradually reduced, and the sharp pain mainly on lower limbs was relieved, and it became a discharge. Regular measurement of serum phosphorus concentration is necessary for early detection of the FGF23-related hypophosphatemia in patients with long term use of saccharated ferric acid

内視鏡的ドレナージが有効であった胃壁膿瘍を合併した胃迷入膵の１例

　症例は30歳代女性．３日前から心窩部痛が出現し，徐々に増悪してきたため当院を受診した．血液検査でWBC 15,120/μl，CRP 2.95mg/dl と炎症反応上昇を認め，腹部超音波検査で胃幽門前庭部前壁に約3.5cm の粘膜下腫瘍様隆起を認めた．腫瘍内部はechogenic particles の混在する液体の貯留を認めた．腹部造影CT 検査では，胃前庭部から胃体部前壁にリング状の造影効果を伴う著明な壁肥厚を認めた．以上より胃壁膿瘍と診断した．胃前庭部前壁の弾性硬のやや発赤した粘膜下腫瘍様隆起に対して，超音波内視鏡下穿刺術（EUS-FNA）を行った．粘稠な白色液体の流出を認め，膿瘍を示唆する所見であった．絶食・点滴・抗生剤投与による保存的加療を施行後，速やかに腹部症状は消失し，EUS-FNA 施行後５日目に退院した．４か月後，病変は上部内視鏡検査で頂部に陥凹を有する腫瘍に形態変化を認め，さらに縮小傾向であった．また，腹部超音波検査では粘膜下層内に約５mm 大の嚢胞性領域とそれに接する約４mm 大の境界不明瞭な低エコー域，不整な固有筋層の肥厚を認め，胃迷入膵の所見であった．以上より，胃壁膿瘍を合併した胃迷入膵と診断した．現在，再発なく当科で経過観察中である．胃壁膿瘍を合併した胃迷入膵の報告は非常に稀であり，貴重な症例と考えられた．　Here, we report a case of gastric wall abscess in aberrant pancreas. A 30-yearold woman visited our hospital for epigastric pain. Routine hematological examination showed increased white blood cell count and biochemical tests revealed elevated C reactive protein levels. Abdominal ultrasound revealed a submucosal tumor that appeared as a hypoechoic heterogenous mass in the stomach. Abdominal computed tomography revealed a thickened gastric wall with a low-density area. This mass was diagnosed as a gastric wall abscess, which was treated with endoscopic ultrasound-guided fine needle aspiration and conservative therapy with antibiotics. The patient’s pain resolved after the treatment. Four months after the episode, follow-up examinations showed that the submucosal tumor had changed to a small submucosal mass with depression. This lesion was diagnosed as an aberrant pancreas. Thus, the final diagnosis was a gastric wall abscess in the aberrant pancreas. This patient was followed up for one year following this episode with no incidence of recurrence