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INTRODUCTION: Periostin, an extracellular matrix protein, plays an important role in osteogenesis and is also known to activate several signals that contribute to chondrogenesis. The absence of periostin in periostin knockout mice leads to several disorders such as craniosynostosis and periostitis. There are several splice variants with different roles in heart disease and myocardial infarction. However, little is known about each variant's role in chondrogenesis, followed by bone formation. Therefore, the aim of this study is to investigate the role of several variants in chondrogenesis differentiation and bone formation in the craniofacial region. Periostin splice variants included a full-length variant (Control), a variant lacking exon 17 (ΔEx17), a variant lacking exon 21 (ΔEx21), and another variant lacking both exon 17 and 21 ***(ΔEx17&21). MATERIALS AND METHODS: We used C56BL6/N mice (n = 6) for the wild type (Control)*** and the three variant type mice (n = 6 each) to identify the effect of each variant morphologically and histologically. Micro-computed tomography demonstrated a smaller craniofacial skeleton in ΔEx17s, ΔEx21s, and ΔEx17&21s compared to Controls, especially the mandibular bone. We, thus, focused on the mandibular condyle. RESULTS: The most distinctive histological observation was that each defected mouse appeared to have more hypertrophic chondrocytes than Controls. Real-time PCR demonstrated the differences among the group. Moreover, the lack of exon 17 or exon 21 in periostin leads to inadequate chondrocyte differentiation and presents in a diminutive craniofacial skeleton. DISCUSSION: Therefore, these findings suggested that each variant has a significant role in chondrocyte hypertrophy, leading to suppression of bone formation.
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Condrocitos , Condrogénesis , Animales , Ratones , Huesos , Diferenciación Celular/genética , Condrocitos/metabolismo , Condrogénesis/genética , Hipertrofia/genética , Hipertrofia/metabolismo , Hipertrofia/patología , Ratones Noqueados , Osteogénesis/genética , Microtomografía por Rayos XRESUMEN
The aim of this study was to review long-term clinical outcomes and valve performance after Epic Supra valve implantation in aortic position. From 2011 to 2022, 44 patients (mean age 75 ± 8 years) underwent surgical aortic valve replacement (SAVR) with an Epic Supra valve at our hospital. Survival, incidence of late complications, and echocardiographic date were retrospectively analyzed. During a mean follow-up period of 6.2 ± 3.5 years, the overall survival rate was 91 ± 4% at 2 and 88 ± 5% at 5 years, while rates of freedom from major adverse cardiovascular and cerebrovascular events (MACCE) were 86 ± 5% and 83 ± 6%, respectively. There was one case of reoperation for prosthetic valve endocarditis at 6 years after the initial surgery. Echocardiographic examinations showed 5-year rates of freedom from severe structural valve deterioration (SVD) and moderate SVD of 100 and 92%, respectively. There was no significant increase in mean pressure gradient or decrease in left ventricular ejection fraction from 1 week after surgery to the late follow-up period. Long-term clinical results and durability of the Epic Supra valve in aortic position were satisfactory.
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BACKGROUND: Medical film dressings have been used to obtain skin microbiota for skin microbiome studies, although their adhesive force may be so strong that the skin could be injured when applied to those who have fragile skin, such as older people. Several products with less adhesive force are available, although their applicability for skin microbiome studies remains unknown. This study aimed to test whether the dressings with less adhesive force could be used for amplicon-based skin microbiome studies. A set of three different film dressings, with acrylic, urethane, or silicone adhesive, was applied to the back skin of nine healthy young participants. The copy number of the 16S ribosomal RNA (rRNA) gene, microbial compositions, and alpha and beta diversity indices were analyzed by amplicon analysis of the 16S rRNA gene using next-generation sequencing and were compared among the three film dressings. RESULTS: The dressing with acrylic adhesive yielded the highest copy number of 16S rRNA genes, followed by that with urethane adhesive. The silicone-adhesive dressing yielded a significantly lower copy number of the 16S rRNA gene. The microbial composition of skin microbiota was similar among the three film dressings, although significant differences in the relative abundance of Pseudomonas species and alpha diversity indices were found in the silicone-adhesive dressing. The Bray-Curtis dissimilarity was significantly higher between the acrylic- and silicone-adhesive dressings than between the acrylic- and urethane-adhesive dressings. No adverse effects related to tape stripping were observed for any of the film dressings. CONCLUSION: We recommend dressings with acrylic or urethane adhesive for amplicon-based skin microbiome studies. An acrylic adhesive has an advantage in the yield of skin microbiota, and a urethane adhesive should be chosen when applied to fragile skin. The adhesive force of the dressing with silicone adhesive was too weak to be used for collecting skin microbiota.
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Adhesivos/química , Bacterias/genética , Vendajes/microbiología , ADN Bacteriano/genética , Microbiota/genética , Piel/microbiología , Acrilatos , Adhesivos/clasificación , Bacterias/clasificación , Bacterias/aislamiento & purificación , Vendajes/clasificación , Femenino , Variación Genética , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Filogenia , ARN Ribosómico 16S/genética , Siliconas , Uretano , Adulto JovenRESUMEN
BACKGROUND: We report a rare case of concomitant inferior left ventricular aneurysm and ventricular septal rupture in a patient presenting with chronic heart failure. CASE PRESENTATION: An 81-year-old man suffered from congestive heart failure. His symptoms were alleviated by medical management; however, heart failure symptoms continued according to the New York Heart Association Functional Classification III. Ten months after presentation, ventricular septal rupture was diagnosed using echocardiography. The left ventricular aneurysm was also complicated. Surgical repair of the ventricular septal rupture and left ventricular aneurysm was successfully performed. The ventricular septal rupture consisted of multiple holes, and the infarcted myocardium had already progressed to firm, fibrotic scar tissue. We closed the ventricular septal rupture with a small bovine pericardial patch and performed an aneurysmectomy with a liner technique. CONCLUSIONS: Cases of ventricular septal rupture can have various clinical scenarios, and treatment should be optimized for each patient, especially with respect to the timing of surgery.
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Aneurisma Cardíaco/etiología , Insuficiencia Cardíaca/etiología , Infarto del Miocardio/complicaciones , Rotura Septal Ventricular/etiología , Anciano de 80 o más Años , Ecocardiografía , Aneurisma Cardíaco/diagnóstico por imagen , Aneurisma Cardíaco/cirugía , Humanos , Masculino , Tomografía Computarizada por Rayos X , Rotura Septal Ventricular/diagnóstico por imagen , Rotura Septal Ventricular/cirugíaRESUMEN
Water-soluble cationic and anionic cyclophanes (1a and 2a, respectively) having a dabsyl group with a cleavable disulfide linkage were synthesized as a host-guest conjugate covalently bound with both host and guest components. Self-inclusion phenomena but not self-aggregation behaviors were observed for each cyclophane in aqueous media. Each cyclophane includes its own dabsyl moiety (guest component) in its macrocyclic cavity (host component) through hydrophobic interaction. When 1 equiv. of cationic 1a was added to an aqueous solution of anionic 2a, however, supramolecular coaggregates formed spontaneously through host-guest complexation. As regard the supramolecular coaggregates, the existence of larger particles was confirmed by DLS measurements and TEM observation. The hydrophobic interaction between the dabsyl moiety and macrocyclic cavity and electrostatic interactions between 1a and 2a play important roles in the supramolecular coaggregate formation. Each cyclophane having a cleavable disulfide linkage was easily transformed to the corresponding thiols by reducing reagents such as DTT, which was confirmed by MALDI-TOF MS. Disaggregation of the supramolecular coaggregates composed of 1a and 2a was successfully performed upon addition of DTT, with release of the thiol derivative of dabsyl. Such disaggregation of the coaggregates was also conducted by other external stimuli such as salts and competitive guests.
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Aggregation of 42-residue amyloid ß-protein (Aß42) can be prevented by ß-sheet breaker peptides (BSBps) homologous to LVFFA residues, which are included in a ß-sheet region of Aß42 aggregates. To enhance the affinity of BSBps to the Aß42 aggregates, we designed and synthesized ß-strand-fixed peptides (BSFps) whose side chains were cross-linked by ring closing metathesis. Conformation analysis verified that the designed peptides could be fixed in ß-strand conformation. Among the synthesized pentapeptides, 1 and 12, whose side chains of 2nd and 4th residues were cross-linked, significantly inhibited the aggregation of Aß42. This suggested that ß-strand-fixation of BSBps could enhance their inhibitory activity against the Aß42 aggregation. However, pentapeptides 1 and 12 had little effect on morphology of Aß42 aggregates (fibrils) and neurotoxicity of Aß42 against SH-SY5Y cells.
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Amiloide/química , Fármacos Neuroprotectores/química , Oligopéptidos/química , Agregado de Proteínas/efectos de los fármacos , Secuencia de Aminoácidos , Amiloide/metabolismo , Diseño de Fármacos , Humanos , Modelos Moleculares , Fármacos Neuroprotectores/metabolismo , Fármacos Neuroprotectores/farmacología , Oligopéptidos/metabolismo , Oligopéptidos/farmacología , Unión Proteica , Conformación Proteica , Conformación Proteica en Lámina beta , Relación Estructura-ActividadRESUMEN
Snakes contain three types of phospholipase A2 (PLA2)-inhibitory proteins in their blood, PLIα, ß, and γ, which protect them from their own venom, PLA2. PLIß is the snake ortholog of leucine-rich α2 glycoprotein (LRG). Since autologous cytochrome c (Cyt c) serves as an endogenous ligand for LRG, in this study, we purified snake LRGs from various snake serum samples using Cyt c affinity chromatography. All purified snake LRGs were found to be dimers linked by disulfide bonds. Laticauda semifasciata and Naja kaouthia LRGs showed no inhibitory activity against L. semifasciata PLA2 and weak inhibitory activity against Gloydius brevicauda basic PLA2. Elaphe climacophora PLIß had weaker inhibitory activity against G. brevicauda basic PLA2 than G. brevicauda and Elaphe quadrivirgata PLIs, which are abundant in blood and known to neutralize G. brevicauda basic PLA2. Protobothrops flavoviridis LRG showed no inhibitory activity against basic venom PLA2, PL-X, or G. brevicauda basic PLA2. Binding analysis of P. flavoviridis LRG using surface plasmon resonance showed very strong binding to snake Cyt c, followed by that to horse Cyt c, weak binding to yeast Cyt c, and no binding to P. flavoviridis PL-X or BPI/II. We also deduced the amino acid sequences of L. semifasciata and P. flavoviridis LRG by means of cDNA sequencing and compared them with those of other known sequences of PLIs and LRGs. This study concluded that snake LRG can potentially inhibit basic PLA2, but, whether it actually functions as a PLA2-inhibitory protein, PLIß, depends on the snake.
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Colubridae , Glicoproteínas , Animales , Caballos , Leucina , Cromatografía de Afinidad , Citocromos c , Fosfolipasas A2 , Saccharomyces cerevisiaeRESUMEN
OBJECTIVE: Aortic dilatation concurrent with aortic valve disease is a common condition. However, the incidence of aortic dissection after aortic valve replacement for tricuspid aortic valve has not been fully investigated. Therefore, we performed a risk factor analysis for the incidence of aortic dissection after aortic valve replacement in patients with tricuspid aortic valve. METHODS: We retrospectively reviewed 599 patients who underwent aortic valve replacement at our hospital between January 2000 and December 2020. We performed a risk factor analysis for the incidence of aortic dissection after aortic valve replacement in patients with tricuspid aortic valve. RESULTS: Seven patients developed late aortic dissections during the follow-up period. All patients with aortic dissection underwent aortic valve replacement for aortic regurgitation. Multivariable analysis revealed that aortic regurgitation was an independent predictor of aortic dissection (p < 0.0001). The mean ascending aortic diameter at aortic valve replacement for aortic regurgitation was significantly greater in patients with aortic dissection than in those without aortic dissection (46 [43.5-46] mm vs. 39 [36-42] mm, p < 0.001). The predictive cutoff value of ascending aortic diameter was indicated using receiver operating characteristic curve analysis; 46.0 mm (area under the curve: 0.8987). Freedom rates from aortic dissection in patients with aortic regurgitation and an ascending aortic diameter ≥ 46 mm were significantly lower than those in patients with an ascending aortic diameter < 46 mm (66.7% vs. 100% at 5 years, p < 0.0001). CONCLUSION: Aortic regurgitation combined with ascending aortic dilatation at aortic valve replacement could be a significant risk factor for late aortic dissection.
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Aneurisma de la Aorta , Enfermedades de la Aorta , Disección Aórtica , Insuficiencia de la Válvula Aórtica , Humanos , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/diagnóstico por imagen , Insuficiencia de la Válvula Aórtica/etiología , Insuficiencia de la Válvula Aórtica/cirugía , Estudios Retrospectivos , Aneurisma de la Aorta/diagnóstico por imagen , Aneurisma de la Aorta/etiología , Aneurisma de la Aorta/cirugía , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/etiología , Disección Aórtica/cirugía , Factores de RiesgoRESUMEN
Tongue squamous cell carcinoma (TSCC) occurs frequently in the oral cavity, and because of its high proliferative and metastatic potential, it is necessary to develop a novel treatment for it. We have reported the importance of the inhibition of the periostin (POSTN) pathological splicing variant, including exon 21 (PN1-2), in various malignancies, but its influence is unclear in tongue cancer. In this study, we investigated the potential of POSTN exon 21-specific neutralizing antibody (PN21-Ab) as a novel treatment for TSCC. Human PN2 was transfected into the human TSCC (HSC-3) and cultured under stress, and PN2 was found to increase cell viability. PN2 induced chemotherapy resistance in HSC-3 via the phosphorylation of the cell survival signal Akt. In tissues from human TSCC and primary tumors of an HSC-3 xenograft model, PN1-2 was expressed in the tumor stroma, mainly from fibroblasts. The intensity of PN1-2 mRNA expression was positively correlated with malignancy. In the HSC-3 xenograft model, CDDP and PN21-Ab promoted CDPP's inhibition of tumor growth. These results suggest that POSTN exon 21 may be a biomarker for tongue cancer and that PN21-Ab may be a novel treatment for chemotherapy-resistant tongue cancer. The treatment points towards important innovations for TSCC, but many more studies are needed to extrapolate the results.
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Moléculas de Adhesión Celular , Resistencia a Antineoplásicos , Exones , Neoplasias de la Lengua , Humanos , Neoplasias de la Lengua/patología , Neoplasias de la Lengua/genética , Neoplasias de la Lengua/tratamiento farmacológico , Neoplasias de la Lengua/metabolismo , Moléculas de Adhesión Celular/metabolismo , Moléculas de Adhesión Celular/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Animales , Exones/genética , Línea Celular Tumoral , Ratones , Masculino , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto , Femenino , Cisplatino/farmacología , Cisplatino/uso terapéutico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Empalme Alternativo/genética , Empalme Alternativo/efectos de los fármacos , Persona de Mediana Edad , Ratones Endogámicos BALB C , Anticuerpos Neutralizantes/farmacología , Anticuerpos Neutralizantes/uso terapéutico , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , PeriostinaRESUMEN
Lipid nanoparticles (LNPs) are essential carrier particles in drug delivery systems, particularly in ribonucleic acid delivery. In preparing lipid-based nanoparticles, microfluidic-based ethanol injection may produce precisely size-controlled nanoparticles. Ethanol is critical in LNP formation and post-treatment processes and affects liposome size, structure, lamellarity, and drug-loading efficiency. However, the effects of time-dependent changes in the ethanol concentration on the structural dynamics of liposomes are not clearly understood. Herein, we investigated ethanol-induced lipid bilayer changes in liposomes on a time scale from microseconds to tens of seconds using a microfluidic-based small-angle X-ray scattering (SAXS) measurement system coupled with molecular dynamics (MD) simulations. The time-resolved SAXS measurement system revealed that single unilamellar liposomes were converted to multilamellar liposomes within 0.8 s of contact with ethanol, and the d-spacing was decreased from 6.1 (w/o ethanol) to 4.4 nm (80% ethanol) with increasing ethanol concentration. We conducted 1 µs MD simulations to understand the molecular-level structural changes in the liposomes. The MD simulations revealed that the changes in the lamellar structure caused by ethanol at the molecular level could explain the structural changes in the liposomes observed via time-resolved SAXS. Therefore, the post-treatment process to remove residual ethanol is critical in liposome formation.
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A 58-year-old female who underwent renal transplantation and closure of arteriovenous fistula (AVF) for hemodialysis at age 24 was presented with left forearm pain and cyanosis. Computed tomography revealed an obstructed true brachial aneurysm at the anterior aspect of the elbow joint. Under a diagnosis of true brachial aneurysm associated with AVF, aneurysm resection and brachial to ulnar artery bypass grafting using a reversed great saphenous vein were performed. To prevent graft occlusion due to elbow flexion, it was routed through the ulnar side of the elbow joint. One year after surgery, the patient was asymptomatic with a patent graft.
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A 74-year-old woman with no past medical history showed cardiac tamponade caused by rupture of a coronary-pulmonary artery fistula-related aneurysm. Preoperative pericardial puncture and multidetector computed tomography imaging enabled patient condition optimization and accurate morphologic evaluation of fistula and aneurysm, leading to complete surgical resection of the aneurysm. (Level of Difficulty: Advanced.).
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BACKGROUND: Rhabdomyolysis is the collapse of damaged skeletal muscle and the leakage of muscle-cell contents, such as electrolytes, myoglobin, and other sarcoplasmic proteins, into the circulation. The glomeruli filtered these products, leading to acute kidney injury (AKI) through several mechanisms, such as intratubular obstruction secondary to protein precipitation. The prognosis is highly mutable and depends on the underlying complications and etiologies. New therapeutic plans to reduce AKI are now needed. Up to now, several cellular pathways, with the nuclear factor kappa beta (NF-kB), as well as the proinflammatory effects on epithelial and tubular epithelial cells, have been recognized as the major pathway for the initiation of the matrix-producing cells in AKI. Recently, it has been mentioned that periostin (POSTN), an extracellular matrix protein, is involved in the development of inflammation through the modulation of the NF-kB pathway. However, how POSTN develops the inflammation protection in AKI by rhabdomyolysis is uncertain. This study aimed to investigate the role of POSTN in a rhabdomyolysis mice model of AKI induced by an intramuscular injection of 50% glycerol. METHODS: In vivo, we performed an intramuscular injection of 50% glycerol (5 mg/kg body weight) to make rhabdomyolysis-induced AKI. We examined the expression level of POSTN through the progression of AKI after glycerol intramuscular injection for C57BL/6J wildtype (WT) mice. We sacrificed mice at 72 h after glycerol injection. We made periostin-null mice to examine the role of POSTN in acute renal failure. The role of periostin was further examined through in vitro methods. The development of renal inflammation is linked with the NF-kB pathway. To examine the POSTN function, we administrated hemin (100 µM) on NIH-3T3 fibroblast cells, and the following signaling pathways were examined. RESULTS: The expression of periostin was highly increased, peaking at about 72 h after glycerol injection. The expression of inflammation-associated mRNAs such as monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-a) and IL-6, and tubular injury score in H-E staining were more reduced in POSTN-null mice than WT mice at 72 h after glycerol injection. CONCLUSION: POSTN was highly expressed in the kidney through rhabdomyolysis and was a positive regulator of AKI. Targeting POSTN might propose a new therapeutic strategy against the development of acute renal failure.
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Lesión Renal Aguda , Moléculas de Adhesión Celular , Animales , Ratones , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/patología , Modelos Animales de Enfermedad , Glicerol/farmacología , Inflamación/tratamiento farmacológico , Inflamación/patología , Ratones Endogámicos C57BL , Ratones Noqueados , FN-kappa B/metabolismo , Rabdomiólisis/complicaciones , Rabdomiólisis/inducido químicamente , Rabdomiólisis/patología , Moléculas de Adhesión Celular/efectos de los fármacos , Moléculas de Adhesión Celular/metabolismoRESUMEN
Staphylococcus spp. colonize commensally on the human skin. Some commensal coagulase-negative staphylococci and Staphylococcus aureus are also involved in nosocomial infections. Bacteria were collected from skin healed from pressure injury (PI). After the collection time points, some patients suffered from recurrent PI (RPI). This study analyzed the characteristics of Staphylococcus spp. on healed skin before recurrence between healed skin that suffered from RPI within 6 weeks (RPI group) and healed skin that did not suffer within the duration (non-RPI group) by Staphylococcus spp.-specific sequencing. Of the seven patients in the RPI group, two were dominated by S. aureus and four by Staphylococcus caprae, coagulase-negative human commensal staphylococci in the RPI group. Using mouse models, both S. caprae and S. aureus, but not Staphylococcus epidermidis, colonized on skin healed from injury at significantly higher rates than normal skin. Although subcutaneous injection of S. caprae did not induce lesion formation, the bacterium exhibited high hemolytic activity on human red blood cells. Lesion formation by subcutaneous injection of S. aureus was significantly suppressed in the presence of S. caprae. The hemolytic activity of rabbit blood cells of S. aureus was suppressed by S. caprae, whereas the hemolytic activity of S. caprae was dramatically suppressed by S. aureus. Data indicated that each of the two Staphylococcus spp. suppresses the pathogenicity of the other and that the imbalance between the two is associated with RPI.
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BACKGROUND: Periostin (POSTN) is a 93 kDa matrix protein that helps to regulate collagen gene expression in the extracellular matrix. POSTN overexpression is a prognostic factor in malignant cancers; however, some researchers have observed it in the stroma, whereas others have reported it on tumors. OBJECTIVE: This study aimed to investigate the function of POSTN on tumors. METHODS AND RESULTS: We found that POSTN in cancer cells can be detected by using an antibody against the POSTN C-terminal region exon 17 (Ex17 antibody), but not with an antibody against the POSTN N-terminal region exon 12 (Ex12 antibody) in patients with breast cancer. In a fraction secreted from fibroblasts, LC-MS/MS analysis revealed a short fragment of POSTN of approximately 40 kDa with exon 17. In addition, molecular interaction analysis showed that POSTN with exon 17, but not POSTN without exon 17, bound specifically to wnt3a, and the Ex17 antibody inhibited the binding. CONCLUSION: A short fragment of POSTN with exon 17, which originates in the fibroblasts, is transported to cancer cells, whereas POSTN fragments without exon 17 are retained in the stroma. The Ex17 antibody inhibits the binding between POSTN exon 17 and wnt3a.
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Empalme Alternativo/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Moléculas de Adhesión Celular/genética , Exones/genética , Secuencia de Aminoácidos , Animales , Moléculas de Adhesión Celular/química , Moléculas de Adhesión Celular/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Humanos , Ratones Endogámicos C57BL , Modelos Biológicos , Metástasis de la Neoplasia , Unión Proteica , Proteómica , Proteína Wnt3A/metabolismoRESUMEN
BACKGROUND: Preventing recurrent pressure injuries (RPIs) is one of the important challenges faced in healthcare, but the risk factors of RPIs have not been fully revealed. This study aims to explore factors associated with RPIs, by focusing on skin physiology and its microbiome as local factors crucial for the health of healed tissue after pressure injury healing. METHODS: This prospective observational study was conducted in a long-term care facility in Japan with patients whose PIs had healed within 1 month. Skin physiology was evaluated by stratum corneum (SC) hydration, pH, and transepidermal water loss. Skin bacteria was collected by tape stripping, followed by 16S ribosomal RNA-based metagenomics analysis. These parameters were evaluated every two weeks over a period of six weeks. RESULTS: A total of 30 patients were included in this study, and 8 patients (26.7%) had an RPI within 6 weeks. In this study, significantly lower SC hydration and a higher rate of Staphylococcus species on the healed site were found in the RPI group. DISCUSSION: A high rate of RPIs (about one in four) points out the necessity of a further care strategy on the healed PIs. Lower skin hydration and/or the increase in Staphylococcus bacteria may have a potential to be used as a biomarker for the prediction of RPIs, or may be an intervention point for the prevention of RPIs by, for example, skin cleansing with moisturizing care.
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Microbiota , Úlcera por Presión/microbiología , Úlcera por Presión/patología , Fenómenos Fisiológicos de la Piel , Piel/microbiología , Anciano , Anciano de 80 o más Años , Epidermis/fisiología , Femenino , Humanos , Japón/epidemiología , Cuidados a Largo Plazo/estadística & datos numéricos , Masculino , Úlcera por Presión/enfermería , Estudios Prospectivos , Recurrencia , Piel/patologíaRESUMEN
Periostin (Pn) is involved in multiple processes of cancer progression. Previously, we reported that Pn expression is correlated with mesenchymal tumor markers and poor prognosis in triple-negative breast cancer (TNBC). In the TNBC xenograft model, chemotherapy increased expression of a Pn alternative splicing variant (ASV) with exon 21, and administration of the neutralizing antibody against Pn with exon 21 (Pn-21 Ab) overcame chemoresistance with a reduction in the mesenchymal cancer cell fraction. In the present study, the role of Pn ASV with exon 21 in TNBC progression has been addressed. We first established a stable cell line carrying a fluorescence-based splicing reporter. Pn-positive TNBC has higher expression of genes related to tumor-associated macrophage (TAM) recruitment and ECM-receptor interaction than Pn-negative cells. In a xenograft model, only Pn-positive cells initiated tumor formation, and the Pn-21 Ab suppressed tumor cell growth, accompanied by decreased M2 TAM polarization and the number of tumor vessels. These data suggest that cancer cell-derived Pn ASV educates TAMs and regulates angiogenesis, which in turn establishes a microenvironmental niche that is supportive of TNBC.
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Hepatocyte growth factor (HGF) is secreted from stromal and mesenchymal cells, and its receptor cMet is expressed on various types of cells such as smooth muscle cells, fibroblast, and endothelial cells. HGF stimulates epithelial and endothelial cell proliferation, motility, and morphogenesis in a paracrine and autocrine manner, organizing multistep of angiogenesis in many organs. In addition, HGF is recognized as a potent anti-inflammatory and anti-fibrotic growth factor, which has been proved in several animal studies, including neointimal hyperplasia and acute myocardial infarction model in rodent. Thus, as compared to other angiogenic growth factors, HGF exerts multiple effects on ischemic tissues, accompanied by the regression of tissue inflammation and fibrosis. These data suggest the therapeutic potential of the HGF for peripheral artery disease as it being accompanied with chronic tissue inflammation and fibrosis. In the present narrative review, the pleiotropic action of the HGF that differentiates it from other angiogenic growth factors is discussed first, and later, outcomes of the human clinical study with gene therapy are overviewed.
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With the increase in the older populations, the number of bedridden older patients is becoming a matter of concern. Skin microbiome and skin physiological functions are known to change according to lifestyle and community; however, such changes in case of movement- and cleaning-restricted bedridden older patients have not yet been revealed. To address this issue, we analyzed skin microbiome and skin physiological functions, including pH, hydration, sebum level, and transepidermal water loss (TEWL), of bedridden older patients, compared with those of ambulatory older and young individuals. For this analysis, we enrolled 19 healthy young and 18 ambulatory older individuals from the community and 31 bedridden older patients from a single, long-term care hospital in Japan. The area of interest was set to the sacral (lower back) skin, where pressure injuries (PIs) and subsequent infection frequently occurs in bedridden older patients. We observed a higher number of gut-related bacteria, fewer commensals, higher skin pH, and lower TEWL on the sacral skin of bedridden older patients than on that of young or ambulatory older individuals. In addition, we observed that 4 of the 31 bedridden older patients developed PIs during the research period; a higher abundance of pathogenic skin bacteria were also observed inside the PI wounds. These findings imply distinct skin microbiome and skin physiological functions in bedridden older patients in comparison with healthy individuals and may suggest the need for more stringent cleaning of the skin of bedridden older patients in light of the closeness of skin and wound microbiome.