The C. elegans insulin-like peptides (ILPs)

Insulin and insulin-like peptides (ILPs) are conserved in living organisms to modulate homeostasis by functioning as ligands. For understanding of molecular mechanisms regulated by the ligands, the nematode Caenorhabditis elegans is a good model since: 1) the C. elegans genome size is small with over 40% homology to the human genome, 2) numerous genetic methods are available, and 3) the worms are transparent throughout the life cycle, so that the secretion of peptide hormones can be followed at cellular level in living preparations by GFP-tagged peptides. In this review, we describe the general appearance of the insulin/insulin-like growth factor (IGF)-1 signaling (IIS), and then focus on physiological functions, secretion, and transcriptional regulation of the C. elegans ILPs

The leech excitatory peptide, a member of the GGNG peptide family: isolation and comparison with the earthworm GGNG peptides

AbstractA member of the GGNG peptide family was isolated from Hirudo nipponia (leech). GGNG peptides had only been isolated previously from earthworms. The C-terminus structure of the leech peptide, LEP (leech excitatory peptide), was –Gly–Gly–Asn–amide, while that of the earthworm peptides, EEP (earthworm excitatory peptide), was –Gly–Gly–Asn–Gly. LEP exerted 1000-fold more potent activities on leech gut than did EEP-2. On the other hand, EEP-2 was 1000-fold more potent than LEP on the crop-gizzard of the earthworm. Analog peptides of LEP and EEP-2 were synthesized, and the myoactive potency of each analog on the leech and earthworm tissues was compared

Reduction of Postoperative Pain by Addition of Intravenous Acetaminophen after Total Hip Arthroplasty: A Retrospective Cohort Study

We evaluated the analgesic effects of multimodal pain control in which intravenous acetaminophen (IV APAP) was added to the standard protocol for Japanese patients who had undergone a total hip arthroplasty (THA). We performed a retrospective cohort study of 180 patients aged 66.4±10.5 years (30% male) who had undergone a THA (Oct. 2014 to Feb. 2015) at our hospital. The control patients were administered the standard analgesic protocol: flurbiprofen axetil as a continuous intravenous infusion and oral celecoxib (NAPAP; n=109). The patients in the new analgesic protocol group received IV APAP in addition to the standard analgesic protocol (APAP; n=71). The primary outcome was the maximum value of postoperative pain the patients reported on a numerical rating scale (NRS) during the first 24 h post-surgery. A univariate analysis and multivariate analyses adjusted for age, sex, the stage of hip osteoarthritis, preoperative pain, and surgical time showed that the maximum postoperative pain NRS scores during the first 24 h after surgery was significantly lower when the APAP protocol was used. The addition of IV APAP to the current standard multimodal analgesia protocol for Japanese patients who have undergone a THA may decrease the patients’ postoperative pain

Dersimelagon, a novel oral melanocortin 1 receptor agonist, demonstrates disease-modifying effects in preclinical models of systemic sclerosis

BACKGROUND Activation of melanocortin 1 receptor (MC1R) is known to exert broad anti-inflammatory and anti-fibrotic effects. The purpose of this study is to investigate the potential of dersimelagon, a novel oral MC1R agonist, as a therapeutic agent for systemic sclerosis (SSc). METHODS The effects of dersimelagon phosphoric acid (MT-7117) on skin fibrosis and lung inflammation were evaluated in bleomycin (BLM)-induced SSc murine models that were optimized for prophylactic and therapeutic evaluation. Microarray-based gene expression analysis and serum protein profiling were performed in the BLM-induced SSc models. The effect of MT-7117 on transforming growth factor-β (TGF-β)-induced activation of human dermal fibroblasts was evaluated in vitro. Immunohistochemical analyses of MC1R expression in the skin of SSc patients were performed. RESULTS Prophylactic treatment with MT-7117 (≥ 0.3 mg/kg/day p.o.) significantly inhibited skin fibrosis and lung inflammation, and therapeutic treatment with MT-7117 (≥ 3 mg/kg/day p.o.) significantly suppressed the development of skin fibrosis in the BLM-induced SSc models. Gene array analysis demonstrated that MT-7117 exerts an anti-inflammatory effect via suppression of the activation of inflammatory cells and inflammation-related signals; additionally, vascular dysfunction was extracted as the pathology targeted by MT-7117. Serum protein profiling revealed that multiple SSc-related biomarkers including P-selectin, osteoprotegerin, cystatin C, growth and differentiation factor-15, and S100A9 were suppressed by MT-7117. MT-7117 inhibited the activation of human dermal fibroblasts by suppressing TGF-β-induced ACTA2 (encoding α-smooth muscle actin) mRNA elevation. MC1R was expressed by monocytes/macrophages, neutrophils, blood vessels (endothelial cells), fibroblasts, and epidermis (keratinocytes) in the skin of SSc patients, suggesting that these MC1R-positive cells could be targets for MT-7117. CONCLUSIONS MT-7117 demonstrates disease-modifying effects in preclinical models of SSc. Investigations of its mechanism of action and target expression analyses indicate that MT-7117 exerts its positive effect by affecting inflammation, vascular dysfunction, and fibrosis, which are all key pathologies of SSc. The results of the present study suggest that MT-7117 is a potential therapeutic agent for SSc. A phase 2 clinical trial investigating the efficacy and tolerability of MT-7117 in patients with early, progressive diffuse cutaneous SSc is currently in progress

Ultraflexible Wireless Imager Integrated with Organic Circuits for Broadband Infrared Thermal Analysis

Kawabata R., Li K., Araki T., et al. Ultraflexible Wireless Imager Integrated with Organic Circuits for Broadband Infrared Thermal Analysis. Advanced Materials 36, 2309864 (2024); https://doi.org/10.1002/adma.202309864.Flexible imagers are currently under intensive development as versatile optical sensor arrays, designed to capture images of surfaces and internals, irrespective of their shape. A significant challenge in developing flexible imagers is extending their detection capabilities to encompass a broad spectrum of infrared light, particularly terahertz (THz) light at room temperature. This advancement is crucial for thermal and biochemical applications. In this study, a flexible infrared imager is designed using uncooled carbon nanotube (CNT) sensors and organic circuits. The CNT sensors, fabricated on ultrathin 2.4 µm substrates, demonstrate enhanced sensitivity across a wide infrared range, spanning from near-infrared to THz wavelengths. Moreover, they retain their characteristics under bending and crumpling. The design incorporates light-shielded organic transistors and circuits, functioning reliably under light irradiation, and amplifies THz detection signals by a factor of 10. The integration of both CNT sensors and shielded organic transistors into an 8 × 8 active-sensor matrix within the imager enables sequential infrared imaging and nondestructive assessment for heat sources and in-liquid chemicals through wireless communication systems. The proposed imager, offering unique functionality, shows promise for applications in biochemical analysis and soft robotics

Successful Treatment of Hepatocellular Carcinoma with Transcatheter Arterial Chemoembolization followed by Radical Liver Transplantation in a Patient with Severe Liver Damage

Introduction: Liver transplantation for hepatocellular carcinoma (HCC) has been established as a curative therapy of underlying liver disease and cancer. However, the role of liver transplantation remains controversial for patients with HCC beyond Milan criteria. Case Presentation: A man in his 50s who was diagnosed as having two foci of HCC and advanced liver cirrhosis was referred to our hospital for further examination and treatment. Both foci of HCC were located in segment 8 of the liver and measured 39 and 9 mm. Endoscopy showed esophageal varices that had a high risk of bleeding. After endoscopic ligation of the esophageal varices, he underwent transcatheter arterial chemoembolization (TACE) for downstaging of the advanced HCCs. No further liver deterioration was observed after TACE, and HCC staging was successfully downstaged to within the Milan criteria. One hundred ten days after TACE, he underwent liver transplantation; at 2.5 years after transplantation, he remains alive without HCC recurrence. Discussion/Conclusion: There are only a few treatment options available for patients with advanced HCC and severe liver damage. Multidisciplinary treatment such as locoregional treatments and prophylaxis of variceal bleeding may result in tumor downstaging, enabling radical liver transplantation without further exacerbation of liver damage

A nationwide survey on unilateral moyamoya disease in Japan

Objective Moyamoya disease (MMD) is a unique occlusive disease of the bilateral internal carotid arteries; compensation for occlusion results in rich arterial collaterals at the base of the brain. The clinical features of unilateral MMD, confirmed by typical angiographic evidence of MMD unilaterally and normal or equivocal contralateral findings, are not well known. To identify the clinical features of unilateral MMD in Japan, a nationwide survey was conducted. Patients and methods The questionnaire was directly mailed to 241 departments that reported treating unilateral MMD patients in a primary survey. We ascertained the sex, age, family history, clinical manifestation, radiological findings, treatments, course of the disease, and daily activity of unilateral MMD patients. Results A total of 114 departments replied to the questionnaire. The data of 203 patients (118 female and 85 male; female to male ratio 1.4:1) were registered and analyzed. The mean age was 40.2 years old with a peak occurring in the fifties. Twenty-one patients (10.7%) exhibited familial MMD. The clinical symptoms are motor weakness 57 (26.8%), headache 37 (17.4%), transient ischemic attack 35 (16.4%), and no symptom 30 (14.1%). The MMD types determined by imaging included ischemic type in 64 patients (32.5%), bleeding type in 51 (25.9%), and normal in 82 (41.6%). The development of moyamoya vessels was mild in 78 patients (43.9%) and most patients (81.1%) were accompanied with cerebral hypoperfusion. Medical treatment or vascular reconstruction was employed for more than half of the patients. Conclusion The clinical feature of unilateral MMD was revealed in this nationwide study. Unilateral MMD was predominant in adults and the development of moyamoya vessel was relatively less prevalent