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Background Unlike other IL-17 family members, the Th2-derived cytokine IL-25 ( IL-17E) induces (promotes) Th2 responses. One or both of the two receptors for IL-25 ( IL-17 RA, IL-17 RB) is expressed on inflammatory cells and tissue structural cells, suggesting that in addition to promoting Th2-type inflammation IL-25 may also act on structural cells at sites of Th2-type inflammation such as in the asthmatic bronchial mucosa to promote remodelling changes. Objective Our previous studies showed elevated expression of IL-25 and IL-17RB immunoreactivity in asthmatic airways with co-localization of the latter to endothelial cells. We therefore hypothesized that IL-25 acts on endothelial cells through this receptor to induce production of the key angiogenic and remodelling cytokine basic fibroblast growth factor ( bFGF). Methods Polymerase chain reaction (PCR) immunocytochemistry/immunohistochemistry and ELISA were employed to detect expression of IL-17RB, IL-17RA and bFGF by human vascular endothelial cells (HUVEC) and immunoreactivity for IL-25 and bFGF in asthmatic bronchial biopsies. Receptor-blocking antibodies, PCR and an in vitro angiogenesis assay were used to investigate whether IL-25 acts on IL-17RB or IL-17RA to induce bFGF expression and angiogenesis. PCR was also employed to investigate the signalling pathways involved in IL-25-mediated bFGF expression. Results HUVEC constitutively expressed IL-17RB, IL-17RA and bFGF. Production of the latter was further increased by IL-25, but attenuated after blockade of the IL-17RB, but not the IL-17RA receptor. Neutralization of endogenous VEGF and bFGF completely abrogated IL-25-induced angiogenesis which was also inhibited by blocking IL-17RB, but not IL-17RA. The PI3K-specific inhibitor also completely attenuated IL-25-induced bFGF expression. Immunoreactivity for IL-25 and bFGF was elevated in the asthmatic bronchial mucosa and the expression of each correlated with the other. Conclusions and Clinical Relevance Our data support the hypothesis that IL-25 contributes to elevated bFGF in asthmatic airways by acting on the endothelial cell IL-17RB receptor through PI3K-signalling pathways. Targeting the pathways might benefit therapy of airways remodelling. [ABSTRACT FROM AUTHOR]

A rabbit endocarditis model was used to test the efficacy of oral linezolid and iv vancomycin. Twenty-four hours after catheter placement across the aortic valve, rabbits were infected with 3.5 x 10(6) cfu of Staphylococcus aureus (UC-9258). Two days after infection, control rabbits were killed, and treated rabbits were given 5 days of therapy with linezolid at 8 h intervals (tds) using either 25, 50 or 75 mg/kg/dose, or vancomycin at 12 h intervals (bd) using 25 mg/kg/dose. Linezolid at 75 and 50 mg/kg, and vancomycin significantly reduced S. aureus in aortic valve vegetations compared with the control. Linezolid at 25 mg/kg was ineffective. The efficacy of 75 and 50 mg/kg linezolid was related to maintenance of plasma drug levels near or above the linezolid MIC for UC-9258 (2 mg/L). [ABSTRACT FROM AUTHOR]

Acrokeratosis paraneoplastica is a rare disease and is uncommon even in patients with upper aerodigestive tract cancer. We report a 63-year-old man with a 1-month history of numerous pruritic lesions and vesicles on both feet. Although he had received local therapy, progressive dense scale formation involving both palms and both soles was found. Colonoscopy was performed because of hematochezia, and it revealed an early colon cancer. After the resection of the cancer, the skin lesions began to fall off dramatically. To the best of our knowledge, there is no report of acrokeratosis paraneoplastica associated with colon cancer in the literature. This is the first case report of acrokeratosis paraneoplastica associated with early colon cancer. [ABSTRACT FROM AUTHOR]

The study was conducted to investigate the effects of dietary inclusion of fermented cottonseed meal (FCM) on the ileal and cecal bacterial microbiota of broiler chickens. A total of 300 newborn yellow-feathered broiler chickens were randomly divided into 2 treatments with 3 replicates each (50 birds per replicate): control and 80 g/kg of FCM group. The feeding trial lasted for 42 d. Ileal and cecal digesta samples were collected from 8 chicks per replicate at 21 and 42 d of age to determine the composition of bacterial microbiota using denaturing gradient gel electrophoresis, cloning, sequencing, and real-time quantitative PCR analysis. The results demonstrated that the microbial composition in the ileum and cecum were considerably affected by the diet. The similarity dendrogram of banding profiles showed a more rapid stabilization of intestinal bacterial microbiota in broilers fed diets supplemented with FCM, compared with that of the birds fed the control diet. No significant difference was observed in total number of bands and Shannon-Weaver index, indicating that FCM had no effects on bacterial diversity. However, enumeration of bacteria in the ileal and cecal contents by quantitative PCR showed an increased (P < 0.05) population of lactobacilli, as well as a decreased (P < 0.05) Escherichia coli number by the dietary inclusion of FCM. In summary, dietary inclusion of FCM did not affect the intestinal microbial diversity but shifted intestinal microbiota, with a more homogenous population and an increased colonization of lactobacilli. The results also support the concept that dietary FCM inclusion could promote the beneficial bacteria in the intestinal tract. [ABSTRACT FROM AUTHOR]

Background: Oligodendrocyte precursor cells (OPCs) are myelinated glial cells of the central nervous system (CNS), able to regenerate oligodendrocytes and myelin. This study aimed to elucidate the effect of A2B5-positive (A2B5+) OPC transplantation in rats with spinal cord contusion (SCC) and to investigate changes in expression of various factors involved in the Notch signaling pathway after OPC transplantation., Methods: OPCs were obtained from induced pluripotent stem cells (iPSCs) originating from mouse embryo fibroblasts (MEFs). After identification of iPSCs and iPSC-derived OPCs, A2B5+ OPCs were transplanted into the injured site of rats with SCC one week after SCC insult. Behavioral tests evaluated motor and sensory function 7 days after OPC transplantation. Real-time quantitative polymerase chain reaction (RT-qPCR) determined the expression of various cytokines related to the Notch signaling pathway after OPC transplantation., Results: IPSC-derived OPCs were successfully generated from MEFs, as indicated by positive immunostaining of A2B5, PDGFα and NG2. Further differentiation of OPCs was identified by immunostaining of Olig2, Sox10, Nkx2.2, O4, MBP and GFAP. Importantly, myelin formation was significantly enhanced in the SCC+ OPC group and SCI-induced motor and sensory dysfunction was largely alleviated by A2B5+ OPC transplantation. Expression of factors involved in the Notch signaling pathway (Notch-1, Numb, SHARP1 and NEDD4) was significantly increased after OPC transplantation., Conclusions: A2B5+ OPC transplantation attenuates motor and sensory dysfunction in SCC rats by promoting myelin formation, which may be associated with change in expression of factors involved in the Notch signaling pathway., (Copyright © 2021. Published by Elsevier Masson SAS.)

Objective: Osteosarcoma (OS) is a frequent bone malignancy. Long non-coding RNA myocardial infarction associated transcript (MIAT) has been reported to be involved in the development of human cancers, including OS. However, the mechanism underlying MIAT in OS progression remains largely unclear., Patients and Methods: The expression levels of MIAT and sineoculis homeobox homolog 1 (SIX1) in OS tissues and cells were detected by quantitative real-time polymerase chain reaction and Western blot. Cell viability, apoptosis, migration and invasion of OS cells were determined by MTT, flow cytometry and trans-well assays, respectively. The target interaction among MIAT, miR-141-3p and SIX1 was analyzed by bioinformatics analysis and luciferase reporter assay. Phosphatidylinositide 3-kinases (PI3K)/protein kinase B (AKT) pathway was evaluated by Western blot., Results: MIAT and SIX1 expression levels were enhanced in OS tissues and cells. Knockdown of MIAT or SIX1 repressed cell viability, migration and invasion but promoted apoptosis in OS cells. Moreover, overexpression of SIX1 reversed the inhibitive role of MIAT silence in OS progression. Furthermore, MIAT could increase SIX1 expression by competitively sponging miR-141-3p. Besides, inhibition of MIAT blocked PI3K/AKT pathway by decreasing SIX1 in OS cells., Conclusions: MIAT silence suppresses OS progression through inactivating PI3K/AKT signaling by sponging miR-141-3p to regulate SIX1, indicating a novel target for the treatment of OS.

Chondrogenic differentiation by mesenchymal progenitor cells (MPCs) is associated with cytokines such as transforming growth factor-beta 1 (TGF-beta1) and dexamethasone. Extracellular matrix (ECM) also regulates the differentiation by MPCs. To define whether ECM plays a functional role in regulation of the chondrogenic differentiation by MPCs, an in vitro model was used. That model exposed to dexamethasone, recombinant human TGF-beta1(rhTGF-beta1) and collagens. The results showed that MPCs incorporated with dexamethasone and rhTGF-beta1 increased proliferation and expression of glycosaminoglycan (GAG) after 14 days. Type II collagen enhanced the GAG synthesis, but did not increase alkaline phosphatase (ALP) activity. When adding dexamethasone and rhTGF-beta1 MPCs increased mRNA expression of Sox9. Incorporation with type II collagen, dexamethasone and rhTGF-beta1, MPCs induced mRNA expression of aggrecan and enhanced levels of type II collagen, and Sox9 mRNA. In contrast, incorporation with type I collagen, dexamethasone and rhTGF-beta1 MPCs reduced levels of aggrecan, and Sox9 mRNA, and showed no type II collagen mRNA. Altogether, these results indicate that type I and II collagen, in addition to the cytokine effect, may play a functional role in regulating of chondrogenic differentiation by MPCs.

Prognosis for patients with early gastric cancer who undergo gastric resection is far better than that for patients with advanced disease. However, patients with advanced liver cirrhosis may not be suitable for general anesthesia and major surgery. We used a less invasive endoscopic mucosal resection (EMR) with a cap-fitted endoscope to resect an early gastric cancer in a 58-year-old male with decompensated liver cirrhosis. Although postoperative pathology revealed that the tumor had focal invasion to the submucosa, the patient had an uneventful course and was well during 4 years' follow-up. This method may be effective for the treatment of early gastric cancer with focal submucosal invasion when patients are not suitable for major surgery.

An 81-year-old woman had an early carcinoma invading focally into the upper submucosa of the middle-transverse colon, which was accompanied by extensive lymph node metastases and resulted in a poor prognosis. Although her tumor was small and flat, a rim of pale yellow-speckled mucosa adjacent to the tumor enabled its earlier detection. To further study the exceptional lymph node metastases we studied the expression of intestinal trefoil factor and sialyl Tn antigen immunohistochemically on the resected specimen. Their simultaneous expression in lymph node metastasis further supports the aggressive nature of this tumor.

The efficacies of orally (p.o.) dosed linezolid and intravenously (i.v.) dosed vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) in rabbits with experimental aortic-valve endocarditis were investigated. After endocarditis was established with a recent clinical MRSA isolate, rabbits were dosed for 5 days with linezolid (p.o., three times a day) at either 25, 50, or 75 mg/kg of body weight or vancomycin (i.v., twice a day) at 25 mg/kg. The 25-mg/kg linezolid group had a high mortality rate and bacterial counts in the valve vegetations that were not different from those of the controls. Linezolid dosed p.o. at 50 and 75 mg/kg and i.v. vancomycin produced statistically significant reductions in bacterial counts compared to those of the untreated controls. The reduced bacterial counts and culture-negative valve rates for the animals treated with linezolid at 75 mg/kg were similar to those for the vancomycin-treated animals. Concentrations of linezolid in plasma were determined at several points in the dosing regimen. These results suggest that the efficacy of linezolid in this infection model is related to trough levels in plasma that remain above the MIC for this microorganism. At the ineffective dose of linezolid (25 mg/kg) the concentration at sacrifice was 0.045 times the MIC, whereas the concentrations of linezolid in plasma in the 50- and 75-mg/kg groups were 2 and 5 times the MIC at sacrifice, respectively. The results from this experimental model suggest that the oxazolidinone linezolid may be effective for the treatment of serious staphylococcal infections when resistance to other antimicrobials is present.

SACCHACHITIN membrane, a weavable skin substitute made from the residual fruiting body of Ganoderma tsugae, has been demonstrated to promote skin wound healing. Prior to its clinical application, it is critical to learn more about any possible cytotoxicity, immunogenicity, or allergy response, and at least some of its mechanism(s) of action(s). In the present studies, it has been found that SACCHACHITIN suspension at less than 0.05% shows no cytotoxicity to the primary culture of rat fibroblasts. However, at higher concentrations (> or = 0.1%), it does reduce the growth of fibroblasts, based on MTT assays. This might be caused by positive charges on chitin molecules that are too strong, and may be harmful to the cell membrane. SACCHACHITIN showed no immunogenicity after it was inoculated into rats three times; however, the unmodified, purified rabbit type I and type II collagens did. Subcutaneous injection of SACCHACHITIN suspension into rats showed no gross allergic responses on skin. Nevertheless, it did cause local acute inflammation, as observed by histological investigation. This is similar to what occurred in the wound site covered with SACCHACHITIN membrane. The chemotactic effect of SACCHACHITIN was exhibited in both intact and wounded skin tissues. This may be one of the initial beneficial effects of SACCHACHITIN membrane to wound healing. The rapid acute inflammatory process was followed by the appearance of angiogenesis and granulation tissue formation, which occurred earlier than it normally would. Coverage of the wound area with SACCHACHITIN membrane also induced an earlier formation of scar tissue to replace the granulation tissue. A 1.5 x 1.5 cm(2) wound area covered by SACCHACHITIN completely healed by 21 days, while that covered with cotton gauze did not. Therefore, SACCHACHITIN is a safe biomaterial for use as a wound dressing for skin healing. Its promoting action for wound healing might be due to its chemotactic effect for inflammatory cells. This, in turn, may facilitate subsequent angiogenesis, granulation tissue formation, and faster new tissue formation, leading to faster wound healing.

Background and Purpose: This study investigated changes in the severity of gastric metaplasia (GM) of the duodenal mucosa before and after ulcer healing and Helicobacter pylori eradication. It also investigated whether deformity of the duodenal bulb affects the severity of GM and the likelihood of ulcer recurrence., Methods: Eleven patients were consecutively enrolled in this study. They all had duodenal ulcer(s) and H. pylori infection, for which they had received anti-H. pylori triple therapy during the active ulcer stage, and had all undergone serial endoscopic examinations during both the active ulcer and scarring ulcer stages, and at 1 year after ulcer healing. Duodenal biopsies were obtained at each endoscopy to identify the severity of GM. Duodenal ulcers were divided into three types by bulbar shape and GM was classified into four grades of severity., Results: All 11 patients had increased GM severity just after ulcer healing. The 1-year follow-up study revealed that the GM was unchanged in six of eight patients with grade 3 GM severity at the scarring stage, while in the other two it regressed to grade 1 or 2; these two patients suffered ulcer recurrence. A markedly deformed bulb (type III) was found in three patients, of whom two had ulcer recurrence., Conclusion: Two characteristic conditions were found in patients with duodenal ulcer recurrence after H. pylori eradication: a markedly deformed bulb with grade 3 GM at the scarring stage, and a change in GM from high to low grade at or around the previous ulcer site after ulcer healing.

The study was conducted in vitro to investigate the changes of indomethacin transdermal permeation pretreated by capsaicin and nonivamide, two compounds chemically similar to Azone. The combined effect of low frequency ultrasound (20 kHz) and enhancers on the indomethacin permeation was also evaluated. The experimental data demonstrated that capsaicin and nonivamide significantly enhanced the flux of indomethacin across nude mouse skin. Enhancement effects of both analogues were very similar and depended predominantly on the concentration tested. Histological examination coupled with visual scores indicated the safety of capsaicin and nonivamide on skin structure. Simultaneous application of ultrasound and enhancers significantly increased skin permeation of indomethacin compared with either ultrasound or enhancers alone. Better effect was obtained by the combination with capsaicin than nonivamide.

The major purpose of this work was to study the effect of various liposome formulations on the iontophoretic transport of enoxacin through excised rat skin. The electrochemical stability of these liposomes was also evaluated. The encapsulation percentage of enoxacin was significantly enhanced after 6 h incubation in an electric field; whereas the fusion of liposomes was inhibited by application of electric current. The results of iontophoretic drug transport showed that the permeability of enoxacin released from liposomes was higher compared with that of free drug. The iontophoretic permeability of enoxacin released from liposomes increased with a decrease in the fatty acid chain length of the phospholipid, which may be due to the different phase transition temperatures of the phospholipids. Incorporation of charged phospholipid resulted in an alteration of the transdermal behavior of enoxacin: the iontophoretic permeation as well as the amount of enoxacin partitioned in skin was greatly reduced after incorporation of stearylamine in liposomes, which can be attributed to the competitive ion effect. The enoxacin released from stratum corneum-based liposomes showed the highest amount of enoxacin partitioned into skin depot. The results of employing cathodal iontophoresis on negative charged liposomes suggested that the liposomal vesicles or phospholipids may carry enoxacin into deeper skin strata via the follicular route.

The objective of this study was to evaluate the in vitro and in vivo transdermal iontophoresis of various diclofenac sodium polymer formulations. The excised rat skin, human skin as well as cellulose membrane were used to examine the in vitro drug permeation whereas the microdialysis technique was used to monitor the drug concentration in vivo. Polymer solutions based on polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose (HPMC) binary system showed higher drug permeability than that of single polymer vehicle. The effect of formulations on drug permeation through cellulose membrane was quite different from those through rat skin and human skin, which can be explained by the different permeation pathways between them. It appeared to be a membrane-controlled mechanism but not the vehicle matrix-controlled mechanism for diclofenac hydrogels when using skin as the diffusion barrier. The recovery of diclofenac sodium in the in vivo microdialysis was approximately 80-90%, indicating this technique can be used in the intradermal drug monitoring. For all the polymer formulations tested, there was a good relationship between the in vitro and in vivo drug permeation. A synergistic effect on drug permeation was observed when transdermal iontophoresis combined with the pretreatment of cardamom oil as a permeation enhancer.

Microscopic epididymal sperm aspiration (MESA) for sperm retrieval and intracytoplasmic sperm injection (ICSI) is currently our routine treatment for selected male patients with obstructive azoospermia. In order to refine the surgical technique and obtain better quality sperm for our assisted reproductive technology program, we observed the epididymal tubules in 40 sessions of surgical exploration of the epididymis for sperm aspiration. Epididymal tubules with long-term obstruction could be divided into three groups on the basis of clinical observations and pathology findings: markedly dilated, mildly dilated, and nondilated. All of the markedly dilated epididymal tubules (grade III, n = 10) were azoospermic and ICSI could not be done. Epididymal sperm obtained from the mildly dilated tubules (grade II, n = 9) resulted in poorer fertilization (49%) and pregnancy (33%) rates than sperm obtained from nondilated epididymal tubules (grade I, n = 21, fertilization rate 72%, pregnancy rate 57%). These findings demonstrate that nondilated epididymal tubules are best for sperm retrieval and successful ICSI. We believe this observation will be a good surgical parameter for urologic surgeons performing MESA.

A case of spontaneous isolated mesenteric fibromatosis presenting as megaduodenum is reported. The lesion was small, only 2 cm in its greatest diameter. However, because of its location near the ligament of Treitz and because of its characteristic infiltrative growth pattern, the tumour involved the distal duodenum and resulted in acute angulation and obstruction early in its course. We successfully resected the mass and the patient is in fair physical condition 6 months after operation.

Primary linitis plastica carcinoma of the colon is rare. Most lesions are located on the left side of the colon and these tumors often involve the lymph nodes, peritoneum, and ovaries. We report a case of primary linitis plastica of the sigmoid colon in a 32-year-old Chinese woman who presented with a 7-month history of constipation and associated abdominal pain and tenesmus. Colonoscopy and barium-enema studies showed a stricture at the sigmoid colon. The patient underwent radical surgical resection and received adjuvant radiation therapy and chemotherapy. She died 12 months after the initial diagnosis. The poor prognosis seen with this tumor is due largely to a delay in diagnosis. With increasing familiarity with this tumor, it is hoped that earlier diagnosis and curative surgery will be possible, leading to improvement in survival.

To evaluate group differences in coronary risk which could be attributed to the modality of habitual exercise, selected physiologic and lipid indices of coronary artery disease (CAD) were measured in 57 endurance trained (ET), strength trained (ST), or sedentary (SED) men (19 per group, aged 21 to 44 yr). Initial data reduction accomplished with principle component analysis identified three factors with eigenvalues greater than one. Orthogonal rotation of the preliminary solution demonstrated that low density lipoprotein cholesterol (LDL-C), percent body fat (%BF) and VO2max, and high density lipoprotein cholesterol (HDL-C) could be used to represent Factors 1, 2, and 3, respectively. The subsequent MANOVA using these variables proved significant. Post hoc analysis via simultaneous confidence intervals indicated that LDL-C group differences were not significant. Values for %BF and HCL-C in the ST group (14.0% and 1.17 mmol.l-1, respectively) were between but did not differ significantly from respective values in the ET (11.8% and 1.34 mmol.l-1) and SED (18.7% and 1.13 mmol.l-1) groups. However, %BF and HDL-C differences between the ET and SED groups were significant. The VO2max of the ET subjects (63.2 ml.kg-1.min-1) was significantly higher than that of either the ST or SED subjects (49.5 and 46.7 ml.kg-1.min-1, respectively). These results suggest that ET is the most effective modality of exercise for CAD risk reduction while benefits derived from ST are minimal.