Probiotics are live microorganisms ingested for the purpose of conferring a health benefit on the host. Development of new probiotics includes the need for safety evaluations that should consider ...factors such as pathogenicity, infectivity, virulence factors, toxicity, and metabolic activity. Clostridium butyricum MIYAIRI 588® (CBM 588®), an anaerobic spore-forming bacterium, has been developed as a probiotic for use by humans and food animals. Safety studies of this probiotic strain have been conducted and include assessment of antimicrobial sensitivity, documentation of the lack of Clostridium toxin genes, and evaluation of CBM 588® on reproductive and developmental toxicity in a rodent model. With the exception of aminoglycosides, to which anaerobes are intrinsically resistant, CBM 588® showed sensitivity to all antibiotic classes important in human and animal therapeutics. In addition, analysis of the CBM 588® genome established the absence of genes for encoding for α, β, or ε toxins and botulin neurotoxins types A, B, E, or F. There were no deleterious reproductive and developmental effects observed in mice associated with the administration of CBM 588®. These data provide further support for the safety of CBM 588® for use as a probiotic in animals and humans.
Implantable devices have been investigated with great interest as communication tools. These implantable devices are embedded into the human or pet body. The vital information (such as temperature, ...blood pressure, cardiac beat, etc.) can be transmitted from implantable devices to the external equipment by use of a wireless communication link. Therefore, the research on the antenna for implantable devices (implanted antennas) is very important. This paper proposes an implanted H-shaped cavity slot antenna for short-range wireless communications. This type of antenna, which is designed to operate at the industrial-scientific-medical band (2.45 GHz), is investigated by using finite-difference time-domain calculation. We analyzed the performances of the proposed antenna which is embedded into the human body between the shoulder and the elbow. However, since the proposed antenna is too small to fabricate, a scale model is adopted for antenna measurements. Some characteristics of the scale model of the antenna are also calculated and measured by using the 2/3 muscle-equivalent phantom. The results show that the proposed antenna has promise for use in an implant.
Aims/hypothesis
Mutations in
BSCL
2/seipin cause Berardinelli–Seip congenital lipodystrophy (BSCL), a rare recessive disorder characterised by near absence of adipose tissue and severe insulin ...resistance. We aimed to determine how seipin deficiency alters glucose and lipid homeostasis and whether thiazolidinediones can rescue the phenotype.
Methods
Bscl2
−/−
mice were generated and phenotyped. Mouse embryonic fibroblasts (MEFs) were used as a model of adipocyte differentiation.
Results
As observed in humans,
Bscl2
−/−
mice displayed an early depletion of adipose tissue, with insulin resistance and severe hepatic steatosis. However,
Bscl2
−/−
mice exhibited an unexpected hypotriglyceridaemia due to increased clearance of triacylglycerol-rich lipoproteins (TRL) and uptake of fatty acids by the liver, with reduced basal energy expenditure. In vitro experiments with MEFs demonstrated that seipin deficiency led to impaired late adipocyte differentiation and increased basal lipolysis. Thiazolidinediones were able to rescue the adipogenesis impairment but not the alteration in lipolysis in
Bscl2
−/−
MEFs. In vivo treatment of
Bscl2
−/−
mice with pioglitazone for 9 weeks increased residual inguinal and mesenteric fat pads as well as plasma leptin and adiponectin concentrations. Pioglitazone treatment increased energy expenditure and improved insulin resistance, hypotriglyceridaemia and liver steatosis in these mice.
Conclusions/interpretation
Seipin plays a key role in the differentiation and storage capacity of adipocytes, and affects glucose and lipid homeostasis. The hypotriglyceridaemia observed in
Bscl2
−/−
mice is linked to increased uptake of TRL by the liver, offering a new model of liver steatosis. The demonstration that the metabolic complications associated with BSCL can be partially rescued with pioglitazone treatment opens an interesting therapeutic perspective for BSCL patients.
FSCN1 and matrix metalloproteinase 14 (MMP14) are both invadopodia-related proteins. We herein elucidate the tumourigenicity of these proteins and identify novel therapeutic agents in esophageal ...squamous cell carcinoma (ESCC).
FSCN1 and MMP14 were evaluated by immunohistochemistry and quantitative PCR, and microRNA (miR)-133a was also evaluated by PCR in surgical ESCC specimens. The roles of FSCN1, MMP14 and miR-133a were established in ESCC cells.
The expression of FSCN1 or MMP14 was an independent poor prognostic factor according to a multivariate analysis of immunohistochemistry, and their co-expression correlated with the poorest overall survival (OS) out of all the examined factors. Additionally, their mRNAs significantly correlated and both inversely correlated with miR-133a in surgical specimens. Transfection of a miR-133a mimic decreased the mRNA and protein levels of both FSCN1 and MMP14 in ESCC cells. The knockdown of FSCN1 or MMP14 and transfection of a miR-133a mimic inhibited the proliferation and invasion of ESCC cells. Patients with a lower miR-133a expression have a significantly poorer OS than those with a higher expression.
The combined expression of FSCN1 and MMP14 is associated with a poor prognosis, and miR-133a, which regulates their mRNAs, can serve as a strong tumour suppressor of ESCC.
1. The purpose of the present study was to examine whether zymosan, which is a component of fungi, affects feed passage through the digestive tract in chicks (Gallus gallus).
2. Intraperitoneal (IP) ...injection of 2.5 mg zymosan significantly reduced the crop-emptying rate and this effect was similar to that of 100 µg lipopolysaccharide (LPS). Zymosan affected phenol red transit from the proventriculus.
3. Zymosan significantly affected the gene expression of interleukin-1β (IL-1β), IL-6, IL-8 and histidine decarboxylase in various regions of the digestive tract.
4. The present study suggested that zymosan retarded feed passage through the digestive tract in chick and interleukins and histamine may be participating in this process.
Fluorouracil (5-FU), leucovorin (LV) and oxaliplatin (FOLFOX) plus panitumumab therapy is a commonly used first-line chemotherapy for metastatic colorectal cancer (mCRC). However, the long-term ...administration of oxaliplatin is associated with peripheral neuropathy (PN). We investigated whether the planned discontinuation of oxaliplatin after FOLFOX plus panitumumab therapy can maintain efficacy and reduce PN incidence.
Chemotherapy-naive patients with RAS wild-type mCRC, aged ≥20 years, were enrolled and received six cycles of modified FOLFOX6 (mFOLFOX6) plus panitumumab as induction therapy. Patients who completed induction therapy without progression were randomised to mFOLFOX6 plus panitumumab (group A) or to 5-FU/LV plus panitumumab (group B). The primary end-point was the progression-free survival (PFS) rate at 9 months after randomisation. The secondary end-points were PFS, overall survival (OS), time to treatment failure (TTF), response rate (RR) and safety.
In total, 164 patients were enrolled; of whom, 113 patients were then randomised (group A, n = 56; group B, n = 57). The median follow-up after randomisation was 19.6 months. The PFS rates at 9 months and median PFS were 46.4% (80% confidence interval CI, 38.1–54.9) and 9.1 months (95% CI, 8.6–11.1) in group A, compared with 47.4% (80% CI, 39.1–55.8) and 9.3 months (95% CI, 6.0–13.0) in group B, respectively. RR, OS and TTF were also similar in both groups. Grade ≥2 PN incidence was lower in group B (9.3%) than in group A (35.7%).
Planned discontinuation of oxaliplatin after six cycles of mFOLFOX6 plus panitumumab is a potential treatment option in patients with mCRC, achieving similar efficacy while reducing oxaliplatin-associated PN compared with mFOLFOX6 plus panitumumab.
NCT02337946
•Stopping oxaliplatin after six cycles of modified fluorouracil, leucovorin and oxaliplatin (mFOLFOX6) plus panitumumab is a potential treatment option.•Efficacy after stopping oxaliplatin is similar to mFOLFOX6 plus panitumumab.•Stopping oxaliplatin reduces peripheral neuropathy vs mFOLFOX6 plus panitumumab.
We report dissolution Dynamic Nuclear Polarization (d‐DNP) of 15N3metronidazole (15N3MNZ) for the first time. Metronidazole is a clinically approved antibiotic, which can be potentially employed as a ...hypoxia‐sensing molecular probe using 15N hyperpolarized (HP) nucleus. The DNP process is very efficient for 15N3MNZ with an exponential build‐up constant of 13.8 min using trityl radical. After dissolution and sample transfer to a nearby 4.7 T Magnetic Resonance Imaging scanner, HP 15N3MNZ lasted remarkably long with T1 values up to 343 s and 15N polarizations up to 6.4 %. A time series of HP 15N3MNZ images was acquired in vitro using a steady state free precession sequence on the 15NO2 peak. The signal lasted over 13 min with notably long T2 of 20.5 s. HP 15N3MNZ was injected in the tail vein of a healthy rat, and dynamic spectroscopy was performed over the rat brain. The in vivo HP 15N signals persisted over 70 s, demonstrating an unprecedented opportunity for in vivo studies.
15N3Metronidazole (MNZ) is an emerging hyperpolarized contrast agent. The dynamic nuclear polarization process of this clinically used antibiotic is very fast compared to many other 15N‐labeled molecules and has remarkably long T1 and T2. The hyperpolarized signal of MNZ lasted for over a minute in a rat brain. Future work on hyperpolarized MNZ will investigate its potential as an antibiotic or hypoxia‐sensing probe in disease models.
Cyclosporine (CyA) and atorvastatin (AT) are often administered concomitantly to treat dyslipidemia in renal transplant recipients. However, CyA greatly increases the plasma concentration of AT; ...therefore, concomitant use might increase the frequency of statin-induced adverse effects. The aim of this study was to investigate whether concomitant use of CyA and AT increases intolerance of the latter agent in Japanese renal transplantation recipients. We performed a retrospective cohort analysis of renal transplant recipients aged 18 years and older who had concomitantly received AT and CyA, or tacrolimus (Tac) therapy. We defined statin intolerance as a decrease in dose or discontinuation of AT due to adverse effects. We evaluated the incidence of statin intolerance in concomitant therapy with CyA for 100 days after the initial administration of AT in comparison with Tac. A total of 144 renal transplant recipients who received AT and CyA, or Tac between January 2013 and December 2019 were included. There was no statistical difference in the incidence of statin intolerance in both the CyA (1.8%; 1/57 patients) and Tac (3.4%; 3/87 patients) groups. Concomitant use of CyA and AT might not increase the incidence of statin intolerance in Japanese renal transplant recipients.
Highlights • TRG neurons innervate inflamed MM and projecting Vi/Vc region are labeled by FG and MB. • BDNF inhibits IA and IK currents in small-diameter FG/MB-labeled TRG neurons. • Inhibition ...magnitude of potassium currents by BDNF was greater in inflamed than in naïve rats. • BDNF inhibited IA to a significantly greater extent than IK and inhibition was blocked by k252a. • Potassium channel openers and tyrosine kinase inhibitors are therapeutic agents of hyperalgesia.
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