Publications by authors named "Tomoya Nakanishi"

Background: Early response of the primary tumor (PT) to neoadjuvant chemotherapy (NAC) in patients with esophageal squamous cell carcinoma (ESCC) is considered a potential predictor of postoperative prognosis. However, the role of metastatic lymph nodes (LNs) remains poorly understood. This study aimed to compare the predictive value of early response in PT and LNs for postoperative prognosis.

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In vitro maturation (IVM) produces offspring from domestic animals; however, the blastocyst rate after IVM was low. We previously reported that the developmental competence of oocytes derived from follicles with blood vessels absent on the surface (non-vascularized follicles: NVF) is quite low compared to those derived from follicles with blood vessels present on the surface (vascularized follicles: VF). Thus, it is important to develop technique to improve the quality of NVF-derived oocyte by IVM.

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We aimed to determine the frequency and prognosis of supraclavicular (#104) lymph node (LN) metastasis compared with other LN stations in patients with advanced thoracic esophageal cancer and to identify risk factors for metastasis to delineate the indications for three-field lymphadenectomy (3FL). The study cohort of 567 eligible patients with esophageal cancer had undergone subtotal esophagectomy from 2003 to 2020. LN metastasis was defined as pathologically proven metastasis or positron emission tomography-positive LNs.

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Background: While a neoadjuvant chemotherapy regimen using docetaxel, cisplatin, and 5-fluorouracil (NAC-DCF) is considered the standard treatment for locally advanced esophageal cancer (EC) in Japan, a reliable marker for early prediction of treatment efficacy remains unclear. We investigated the utility of the tumor response after a first course of NAC-DCF as a post-surgery survival predictor in patients with EC.

Methods: We enrolled 150 consecutive patients who underwent NAC-DCF followed by surgery for EC between September 2009 and January 2019.

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Purpose: LH induces the expression of EGF-like factors and their shedding enzyme (ADAM17) in granulosa cells (GCs), which is essential for ovulation via activation of the ErbB-ERK1/2 pathway in cumulus cells (CCs). Neurotensin (NTS) is reported as a novel regulator of ovulation, whereas the NTS-induced maturation mechanism in oocytes remains unclear. In this study, we focused on the role of NTS in the expression of EGF-like factors and ErbBs, and ADAM17 activity, during oocyte maturation and ovulation in mice.

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Recent reports have described the practicality of laparoscopic intragastric surgery (l-IGS) as an alternative for resecting submucosal tumors (SMTs) near the esophagogastric junction (EGJ), where excision using an exogastric approach would be difficult. However, even using IGS to perform a full-thickness resection of SMTs that are in or extremely close to the EGJ is very difficult to do safely and avoid disrupting or causing stenosis of the EGJ, without advanced experience. This study retrospectively examined the usefulness of l-IGS for gastric SMTs located in or extremely close to the EGJ.

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Purpose: Since the developmental competence of oocytes cultured after in vitro maturation (IVM) is low, it is necessary to improve the IVM method for efficient offspring production. In this study, we revealed that transferrin (TF)-Fe was accumulated in follicular fluid with increasing the follicular diameter, and that TF receptor (TFR1) was localized in granulosa cells of pig. Thus, we hypothesized that TF-Fe would be a factor in the induction of developmental competence of porcine oocytes.

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Purpose: Gastric cancer patients with peritoneal metastasis (PM) are generally treated with systemic chemotherapy. When PM has disappeared because of chemotherapy, radical gastrectomy (so-called conversion surgery) is usually performed. We have previously reported the efficacy of conversion surgery, but there are no reports examining the efficacy of palliative gastrectomy for patients with residual PM after chemotherapy.

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Postpartum endometritis is known to be associated with ovarian dysfunction in cows. Lipopolysaccharide (LPS) generated by Gram-negative bacteria is recognized by toll-like receptor 4 (TLR4), which leads to an inflammatory response by the generation of cytokines such as tumor necrosis factor-α (TNF-α) and interleukins. In this study, we investigated the effect of endometrial LPS on granulosa cell functions during early follicular development in cows.

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Article Synopsis
  • - The study analyzed how long-term participation in para-sports affects brain reorganization in the primary motor cortex (M1) of lower limb amputees, building on previous findings from a single Paralympic athlete.
  • - Using functional MRI, researchers evaluated 30 lower limb amputees and found that those with more years of para-sports experience showed increased brain activity in areas related to motor control during muscle contractions of the amputated limb.
  • - Results suggest long-term engagement in para-sports leads to significant brain network reorganization, impacting not just M1 but also other areas like the frontal lobe and visual pathways, indicating a strong relationship between injury, activity, and brain plasticity.
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Unconscious state has been investigated in numerous studies so far, but pathophysiology of this state is not fully understood. Recently, combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been developed to allow for non-invasive assessment of neurophysiology in the cerebral cortex. We conducted a systematic literature search for TMS-EEG studies on human unconscious state using PubMed with cross-reference and manual searches.

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Functional electrical stimulation therapy (FEST) can improve motor function after neurological injuries. However, little is known about cortical changes after FEST and weather it can improve motor function after traumatic brain injury (TBI). Our study examined cortical changes and motor improvements in one male participant with chronic TBI suffering from mild motor impairment affecting the right upper-limb during 3-months of FEST and during 3-months follow-up.

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In the liver, the sterol response element binding protein (SREBP) and the SREBP cleavage-activated protein (SCAP) complex upregulate cholesterol biosynthesis by gene induction of de novo cholesterol synthetic enzymes (Hmgcr, Cyp51, and Dhcr7). Insulin induced gene 1 (INSIG1) negatively regulates cholesterol biosynthesis by the inhibition of de novo cholesterol biosynthetic gene expression. In the ovary, cholesterol is de novo synthesized; however, the roles of SREBP and its regulators (SCAP and INSIG1) are not well understood.

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During follicular development, a few dominant follicles develop to large antral dominant follicles, whereas the remaining follicles undergo atretic degeneration. Because vascularization on the follicular surface is a morphological feature of dominant follicles, we previously classified these follicles as vascularized follicles (VFs) and non-VFs (NVFs). In NVFs, progesterone producing genes were expressed similarly to that in VFs; however, the progesterone concentration in follicular fluid was low in large NVFs.

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Article Synopsis
  • Individuals with complete spinal cord injury (SCI) have better grip force control in their intact upper limbs compared to able-bodied people, but the reasons behind this are unclear.
  • The study used functional MRI to analyze brain activity and structure in SCI subjects and able-bodied subjects while performing grip force tasks.
  • Results indicated that SCI subjects had greater grip force steadiness, less activation in the primary motor cortex, more connectivity in specific brain areas, and increased gray matter volume, suggesting structural and functional changes that enhance grip control after SCI.
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Although successful fertilization is completed by only 150 sperm in the pig oviduct, more than 50,000 sperms are required to achieve a fertilization rate of more than 70% by pig in vitro fertilization (IVF). In this study, to improve the efficiency of pig IVF, the effects of hypoxic conditions and treatment with creatine and methyl-beta cyclodextrin (MβCD) on the glycolytic pathway were investigated. Under low O conditions, zig-zag motility was strongly induced within 30 min; however, the induction disappeared at 60 min.

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Article Synopsis
  • Iron is crucial for cellular processes like energy production and cell growth, and a lack of it in the diet can lead to iron deficiency anemia (IDA).
  • A study using mice on a low iron diet showed that iron deficiency disrupted their reproductive cycles, preventing proper follicle development and ultimately leading to infertility.
  • However, when these mice were switched back to a normal diet rich in iron for three weeks, their reproductive functions and estrous cycles were completely restored, indicating that the negative effects of iron deficiency are reversible.
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Despite their disabilities, top Paralympic athletes have better motor skills than able-bodied athletes. However, the neural underpinnings of these better motor skills remain unclear. We investigated the reorganization of the primary motor cortex (M1) in a Paralympic athlete with congenital amputation of both arms who holds the world record for the farthest accurate shot in archery (Amputee Archer: AA).

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Article Synopsis
  • Spinal cord injury leads to reorganization in the sensorimotor cortex, which may improve motor function in upper limbs, despite no damage to the brain itself.
  • An experiment involving individuals with complete spinal cord injury showed that they had significantly better handgrip force steadiness compared to control groups, and this steadiness was correlated with years of sports activity.
  • The study suggests that this brain reorganization could enhance fine motor skills, which has important implications for rehabilitation and occupations that require precision, like manufacturing and crafts.
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By utilizing features of the hemiacetal ester (HAE) bond: easy formation from vinyl ether and carboxylic acid and easy cleavage into different functional groups (-COOH and -OH), we achieved control of the alternating sequence of two functional pendant groups of a vinyl copolymer. Methacrylate- and acrylate-based vinyl groups were connected through HAE bonds to prepare a cleavable divinyl monomer, which was cyclo-polymerized under optimized conditions in a ruthenium-catalyzed living radical polymerization. Subsequent cleavage of the HAE bonds in the resultant cyclo-pendant led to a copolymer consisting of alternating methacrylic acid and 2-hydroxyethyl acrylate units as analyzed by C NMR spectroscopy.

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Herein we propose a new concept to control sequence for vinyl polymers. A tertiary alkyl methacrylate monomer carrying both adamantyl and isopropyl groups (IPAMA) is very unique to allow control of single unit addition with an alkyl halide initiator for metal-catalyzed living radical polymerization due to the exceptional bulkiness. After control of the single unit addition, the bulkiness can be removed via acidolysis to further convert into the ester pendant with less bulky and nontertiary alcohol.

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We have previously reported potent substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. While these inhibitors exhibited potent activities in enzymatic and cellular assays (KMI-429 in particular inhibited Aβ production in vivo), these inhibitors contained some natural amino acids that seemed to be required to improve enzymatic stability in vivo and permeability across the blood-brain barrier, so as to be practical drug. Recently, we synthesized non-peptidic and small-sized BACE1 inhibitors possessing a heterocyclic scaffold at the P2 position.

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Inhibition of amyloid β peptide (Aβ) aggregation is a potential therapeutic approach to treat Alzheimer's disease. We report that an O-acyl isopeptide of Aβ1-42 (1) containing an ester bond at the Gly(25)-Ser(26) moiety inhibits Aβ1-42 fibril formation at equimolar ratio. Inhibitory activity was retained by an N-Me-β-Ala(26) derivative (2), in which the ester of 1 was replaced with N-methyl amide to improve chemical stability at physiological pH.

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Recently, we reported substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. These inhibitors showed potent inhibitory activities in enzymatic and cell assays. We also designed and synthesized non-peptidic and small-sized inhibitors possessing a heterocyclic scaffold at the P(2) position.

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Recently, we reported potent substrate-based pentapeptidic BACE1 inhibitors possessing a hydroxymethylcarbonyl isostere as a substrate transition-state mimic. Because these inhibitors contained some natural amino acids, we would need to improve their enzymatic stability in vivo and permeability across the blood-brain barrier, so that they become practically useful. Subsequently, non-peptidic and small-sized BACE1 inhibitors possessing a heterocyclic scaffold, 2,6-pyridenedicarboxylic, chelidamic or chelidonic moiety, at the P(2) position were reported.

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