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Diterpenoid Phytoalexin Factor (DPF) is a key transcription factor involved in diterpenoid phytoalexin (DP) biosynthesis under non-stressed conditions in rice (Oryza sativa L.). Using clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9, DPF knockout rice lines were generated. Treatments with abiotic stresses (copper chloride, ultraviolet light, and jasmonic acid) and biotic stress (blast fungus infection) to the knockout lines revealed that the DPF positively regulates stress-induced DP biosynthesis., (© The Author(s) 2024. Published by Oxford University Press on behalf of Japan Society for Bioscience, Biotechnology, and Agrochemistry.)

Esophageal cancer, which is common among the elderly, has the poorest prognosis among gastrointestinal cancers. Previously, we demonstrated that ferrichrome, produced by the probiotic Lactobacillus casei , exhibited anti-tumor effects in various gastrointestinal cancers, including colorectal and gastric cancers, with minimal effects on non-cancerous intestinal cells. However, it remains unclear whether ferrichrome exerts anti-tumor effects in esophageal cancer. A sulforhodamine B assay revealed that ferrichrome suppressed esophageal adenocarcinoma (OE33, OE19) and squamous cell carcinoma (KYSE70) cells. Ki-67 staining indicated that ferrichrome inhibited the proliferation of esophageal cancer cells. Cell cycle analysis showed that ferrichrome inhibited the DNA synthesis. TUNEL staining revealed that ferrichrome-induced DNA fragmentation. We also confirmed the cleavage of caspase-9 and PARP in ferrichrome-treated cells. Reverse transcription polymerase chain reaction demonstrated an increase in the mRNA of DNA damage-inducible transcript 3 (DDIT-3), a key regulator of programmed cell death, in ferrichrome-treated OE33 cells. In an in vivo OE33 xenograft model, intraperitoneal administration of 5-mg/kg ferrichrome for 14 days resulted in an almost complete inhibition of tumor growth. However, 14 days of intraperitoneal administration of 20-mg/kg 5-fluorouracil (5-FU), but not 20-mg/kg ferrichrome, induced weight loss and myelosuppression in both young and aged mice. Our findings indicate that ferrichrome induces DNA damage-inducible transcript-3, thereby producing anti-tumor effects, including cell cycle arrest and apoptosis, with minimal adverse effects in esophageal cancer cells. This illustrates the high potential of ferrichrome as an anti-tumor drug against esophageal carcinoma., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Mikihiro Fujiya and Hiroaki Konishi have received financial support from Kamui Pharma Inc. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Several microorganisms inhabit the mammalian gastrointestinal tract and are associated with the pathogenesis of various diseases, including cancer. Recent studies have indicated that several probiotics produce antitumor molecules and inhibit host tumor progression. We demonstrated that heptelidic acid (HA), a sesquiterpene lactone derived from the probiotic Aspergillus oryzae, exerts antitumor effects against pancreatic cancer in vitro and in vivo. In this study, the antitumor effects of HA against extraintestinal melanoma were assessed in vitro and in vivo., Results: Sulforhodamine B (SRB) assay revealed that the growth of B16F10 cells was significantly inhibited by HA in a concentration-dependent manner. The enzymatic activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) decreased in proportion with the growth inhibition effect of HA. Moreover, oral HA administration significantly suppressed the growth of transplanted B16F10 tumors without any significant changes in biochemical test values. Moreover, GAPDH activity in the transplanted tumor tissues in the HA group significantly decreased compared with that in the PBS group., Conclusion: This study suggests that orally administered HA was absorbed in the gastrointestinal tract, reached the cancer cells transplanted in the skin, and inhibited GAPDH activity, thereby inhibiting the growth of extraintestinal melanoma cells. Thus, this study proposes a novel system for extraintestinal tumor regulation via gut bacteria-derived bioactive mediators., (© 2022. The Author(s).)

Intake of probiotics or fermented food produced by some probiotic bacteria is believed to exert anti-tumor functions in various cancers, including pancreatic cancer, because several studies have demonstrated the anti-tumor effects of probiotic bacteria in vitro and in vivo in animal carcinogenesis models. However, the mechanisms underlying the anticancer effects of probiotics on pancreatic cancer have not been clarified. In this study, we assessed the anti-tumor effects of probiotic bacteria against pancreatic cancer cells. Among the known probiotic bacteria, Aspergillus oryzae exhibited a strong pancreatic tumor suppression effect. The culture supernatant of A. oryzae was separated by HPLC. Heptelidic acid was identified as an anti-tumor molecule derived from A. oryzae by LC-MS and NMR analysis. The anti-tumor effect of heptelidic acid was exhibited in vitro and in vivo in a xenograft model of pancreatic cancer cells. The anti-tumor effect of heptelidic acid was exerted by the p38 MAPK signaling pathway. Heptelidic acid traverses the intestinal mucosa and exerts anti-tumor effects on pancreatic cancer cells. This is a novel anti-tumor mechanism induced by beneficial bacteria against pancreatic cancer in which bacterial molecules pass through the intestinal tract, reach the extra-intestinal organs, and then induce apoptosis via an inducible signaling pathway.

Background : The degree of difficulty of skills of paretic upper limbs in daily life has not been investigated. Objective : To determine the internal validity and level of difficulty of items of the Functional Skills Measure After Paralysis (FSMAP), which can be used to evaluate the functional skills of daily living for stroke patients. Method : A total of 105 first-stroke patients were assessed using the FSMAP. The evaluation system consists of 65 items in 15 categories. We examined the internal validity and level of difficulty of these items using Rasch analysis. In this study, an item with either infit or outfit of ≥1.5 was defined as underfit. Results : Rasch analysis showed that 8 items were underfit. The highest infit and outfit logits were 2.47 for "Trouser donning/doffing" and 8.44 for "Paper manipulation". "Shirt donning/doffing" was the easiest item and "Coin manipulation" was the most difficult, with difficulty logits of -35.8 and 41.5, respectively. Conclusion : The therapist can confirm items that the patient can or cannot perform. By understanding the level of difficulty of each item, the most appropriate functional skill to focus on acquiring next can be identified.

Rice (Oryza sativa) produces diterpenoid phytoalexins (DPs), momilactones and phytocassanes as major phytoalexins. Accumulation of DPs is induced in rice by blast fungus infection, copper chloride or UV light. Here, we describe a rice transcription factor named diterpenoid phytoalexin factor (DPF), which is a basic helix-loop-helix (bHLH) transcription factor. The gene encoding DPF is expressed mainly in roots and panicles, and is inducible in leaves by blast infection, copper chloride or UV. Expression of all DP biosynthetic genes and accumulation of momilactones and phytocassanes were remarkably increased and decreased in DPF over-expressing and DPF knockdown rice, respectively. These results clearly demonstrated that DPF positively regulates DP accumulation via transcriptional regulation of DP biosynthetic genes, and plays a central role in the biosynthesis of DPs in rice. Furthermore, DPF activated the promoters of COPALYL DIPHOSPHATE SYNTHASE2 (CPS2) and CYTOCHROME P450 MONOOXYGENASE 99A2 (CYP99A2), whose products are implicated in the biosynthesis of phytocassanes and momilactones, respectively. Mutations in the N-boxes in the CPS2 upstream region, to which several animal bHLH transcription factors bind, decreased CPS2 transcription, indicating that DPF positively regulates CPS2 transcription through the N-boxes. In addition, DPF partly regulates CYP99A2 through the N-box. This study demonstrates that DPF acts as a master transcription factor in DP biosynthesis., (© 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.)

A 69-year-old woman presented with periodic hypertension, edema, and hypokalemia that occurred within an interval of a few weeks. Her laboratory test values showed autonomously elevated plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations. The patient's Cushingoid features were not evident on first admission. Several weeks later, in spite of constant oral potassium supplementation, severe hypokalemia recurred with Cushingoid features and worsening symptoms of leg edema and pigmentation, which spontaneously disappeared within a few days. Her periodic symptoms occurred in parallel with fluctuations of plasma ACTH and cortisol concentrations. A series of endocrinological and pituitary imaging findings led to a tentative diagnosis of cyclic Cushing's syndrome caused by ectopic ACTH secretion. However, chest and abdominal computed tomography did not reveal any candidate lesion. The patient's periodic hypercortisolemia and symptoms were well controlled after treatment with metyrapone plus dexamethasone. This is a very rare case of periodic hypokalemia and hypertension caused by cyclic Cushing's syndrome.

Aim: Impaired mobility at the onset of dialysis is considered one of the most important risk factors for short-term mortality after initiation of dialysis in elderly patients. However, whether a decline in mobility after starting dialysis also affects mortality is unclear., Methods: A total of 202 patients (age, >75 years; mean, 80.4 ± 4.3) were enrolled in this retrospective cohort study in Yokosuka, Japan. They were divided into three subgroups by mobility: independent mobility at onset of dialysis and preservation of mobility after starting dialysis (group 1, n = 104); independent mobility at onset of dialysis and decline in mobility after starting dialysis (group 2, n = 48); and impaired mobility at onset of dialysis (group 3, n = 50). They were followed for 6 months after starting dialysis. A Cox proportional hazards model was used to evaluate the association between mobility and mortality., Results: A total of 24.8% of patients had impaired mobility at the start of dialysis, and 68.9% declined in mobility after starting dialysis. In multivariate Cox proportional hazards analysis, the adjusted hazard ratios of groups 2 and 3 compared with group 1 were 3.80 (95% confidence interval, 1.02-14.10) and 4.94 (95% confidence interval, 1.42-17.10), respectively., Conclusion: Not only impaired mobility at the start of dialysis but also a decline in mobility after starting dialysis is associated with short-term mortality after initiation of dialysis., (© 2014 Asian Pacific Society of Nephrology.)

A 76-year-old man with a history of type 2 diabetes mellitus was admitted with cholangitis caused by cholangiocarcinoma. Cholangitis with Escherichia coli (E. coli) bacteremia recurred due to the unstable bile drainage. At 1 month after recurrence, rapidly progressive glomerulonephritis with nephrotic syndrome was manifested. Renal biopsy findings were consistent with immunoglobulin A (IgA)-dominant postinfectious glomerulonephritis (PIGN). After ensuring that the recurrent cholangitis was controlled by drainage and antibiotic therapy, oral prednisolone was initiated, and the patient's renal function and proteinuria subsequently gradually improved. This is the first case report of IgA-dominant PIGN associated with cholangitis caused by E. coli infection.

A 76-year-old woman with a history of lumbar fracture and marked proteinuria, bilateral pitting edema, malaise and pruritus was referred for an evaluation of an impaired renal function. A renal biopsy led to a tentative diagnosis of acute interstitial nephritis (AIN) with minimal change disease caused by nonsteroidal anti-inflammatory drugs (NSAIDs). Following the discontinuation of oral NSAIDs, the patient's symptoms disappeared spontaneously. However, nephrotic-range proteinuria relapsed one month after discharge, following loxoprofen patch use. The withdrawal of the topical loxoprofen patches once again resulted in the disappearance of all symptoms. This is the first case report of nephrotic-range proteinuria and AIN secondary to topical NSAID patch use.

We established cell lines that stably express orphan GPCR GPR174 using CHO cells, and studied physiological and pharmacological features of the receptor. GPR174-expressing cells showed cell-cell adhesion with localization of actin filaments to cell membrane, and revealed significant delay of cell proliferation. Since the morphological changes of GPR174-cells were very similar to mock CHO cells treated with cholera toxin, we measured the concentration of intracellular cAMP. The results showed the concentration was significantly elevated in GPR174-cells. By measuring intracellular cAMP concentration in GPR174-cells, we screened lipids and nucleotides to identify ligands for GPR174. We found that lysophosphatidylserine (LysoPS) stimulated increase in intracellular cAMP in a dose-dependent manner. Moreover, phosphorylation of Erk was elevated by LysoPS in GPR174 cells. These LysoPS responses were inhibited by NF449, an inhibitor of Gα(s) protein. These results suggested that GPR174 was a putative LysoPS receptor conjugating with Gα(s), and its expression induced morphological changes in CHO cells by constitutively activating adenylyl cycles accompanied with cell conjunctions and delay of proliferation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Effects of sound generated by a dental turbine and a small stream (murmur) and the effects of no sound (null, control) on heart rate, systolic and diastolic blood pressure, and hemodynamic changes (oxygenated, deoxygenated, and total hemoglobin concentrations) in the frontal cortex were measured in 18 young volunteers. Questionnaires completed by the volunteers were also evaluated. Near-infrared spectroscopy and the Finapres technique were employed to measure hemodynamic and vascular responses, respectively. The subjects assessed the murmur, null, and turbine sounds as "pleasant," "natural," and "unpleasant," respectively. Blood pressures changed in response to the murmur, null, and turbine sound stimuli as expected: lower than the control level, unchanged, and higher than the control level, respectively. Mean blood pressure values tended to increase gradually over the recording time even during the null sound stimulation, possibly because of the recording environment. Oxygenated hemoglobin concentrations decreased drastically in response to the dental turbine sound, while deoxygenated hemoglobin concentrations remained unchanged and thus total hemoglobin concentrations decreased (due to the decreased oxygenated hemoglobin concentrations). Hemodynamic responses to the murmuring sound and the null sound were slight or unchanged, respectively. Surprisingly, heart rate measurements remained fairly stable in response to the stimulatory noises. In conclusion, we demonstrate here that sound generated by a dental turbine may affect cerebral blood flow and metabolism as well as autonomic responses., (Copyright 2004 The Society of the Nippon Dental University)

In comparison with the energy expenditure determined by a whole-body indirect human calorimeter, which provides 24-h energy expenditure (TEE) with high precision and accuracy, the accuracy of predicting energy expenditure (EE) using an activity diary (AD) method was evaluated. Observed and predicted basal metabolic rate (BMR) as well as literature values for typical physical activities were used for TEE prediction. The effect of the number of recorded items in the activity diary on the accuracy of TEE was also examined. Additionally, predicted EE was divided into sleeping, exercise, and sedentary EE to evaluate the estimation errors in the AD method. Subjects were 20- to 69-y-old Japanese women (n = 20) and men (n= 21). Predicted TEE based on the AD was derived by applying the observed or predicted BMR to literature values for physical activities; i.e., relative metabolic rate (R.M.R.), physical activity ratio (PAR), and metabolic equivalent (MET). The BMR value observed for each subject was obtained by indirect calorimetry using a Douglas bag. The BMR for the subject was also estimated from the predictive equations in the 6th revision of the Recommended Dietary Allowances for the Japanese (1999). The correlations between observed and predicted TEE appeared stronger when using observed BMR than those using predicted BMR. Although the difference of mean values between the predicted and observed TEE was small, the limits of agreement between the predicted and observed TEE were around +/- 400 kcal. Predicted EE, excluding the time periods for exercise and rest laying down when determining BMR, showed similar results to those of TEE. Furthermore, the number of recorded items in the AD was not significantly correlated to the accuracy of the predicted TEE (r = -0.03). These findings indicate that the predicted TEE of the AD using observed or predicted BMR and literature values is favorably comparable to observed TEE using a whole-body human calorimeter on a group basis; however, its use as a proxy measure of TEE or EE on an individual basis may be limited.

Patterns of jaw reflexes induced by periodontal stimulation were examined in ten adults. Surface electromyograms (EMGs) from the masseter and anterior temporal muscles were recorded when pressure stimulation was applied to either an incisor or a molar. Reflex responses to periodontal pressure stimulation varied, depending on the background levels of jaw-clenching force that preceded stimulation (background clenching force, BCF). At low BCF, excitatory reflexes were elicited from the jaw-closing muscles and jaw-clenching force. However, the magnitude of excitatory reflexes varied with the location of the stimulated tooth along the dentition. While excitatory reflexes were induced equally in the masseter and temporal muscles during incisal stimulation, stronger excitatory reflexes were induced in the temporal muscle than in the masseter muscle during molar stimulation. At high BCF, inhibitory reflexes in the jaw-closing muscles and jaw-clenching force were elicited in eight subjects (group A) during periodontal stimulation. However, excitatory reflexes in the muscles and force were elicited in the remaining two subjects (group B). In the subjects of group A, stronger inhibitory reflexes were elicited in the temporal muscle than in the masseter muscle, and jaw-clenching force also decreased during both incisal and molar stimulation. In the subjects of group B, the magnitude of excitatory reflexes decreased with increases in BCF.

The periodontal mechanism that controls the jaw reflexes was examined in lightly anesthetized rats. Motor-unit activity in the masseter and temporal muscles was recorded electromyographically and pressure stimulation was applied to either an upper incisor or an upper molar. Reflex effects of dental stimulation varied depending on the level of ongoing activity (background activity, BGA) in each motor unit. Incisal or molar stimulation elicited excitatory reflexes in both the masseter and temporal motor units at a low BGA, but inhibitory reflexes in both types of motor unit at a higher BGA. In contrast to these synergistic reflex actions, the reciprocal reflex actions of the two motor units that belonged to the respective muscles occurred when the BGA was intermediate. The results suggest that different patterns of periodontal jaw reflexes may be elicited, depending on the different levels of BGAs. Furthermore, the present reflexes were modified with the site of a stimulated tooth within the dentition. Incisal stimulation produced greater excitation in the masseter motor unit than in the temporal one, and the opposite type of response occurred during molar stimulation. Moreover, smaller-amplitude motor units with a low reflex threshold and larger-amplitude motor units with a higher reflex threshold tended to exhibit excitatory and inhibitory reflexes, respectively.