Search

The gastrointestinal (GI) system is affected in Alzheimer's disease (AD); however, it is currently unknown whether GI alterations arise as a consequence of central nervous system (CNS) pathology or play a causal role in the pathogenesis. GI mucus is a possible mediator of GI dyshomeostasis in neurological disorders as the CNS controls mucus production and secretion via the efferent arm of the brain-gut axis. The aim was to use a brain-first model of sporadic AD induced by intracerebroventricular streptozotocin (STZ-icv; 3 mg/kg) to dissect the efferent (i.e., brain-to-gut) effects of isolated central neuropathology on the GI mucus. Morphometric analysis of goblet cell mucigen granules revealed altered GI mucus secretion in the AD model, possibly mediated by the insensitivity of AD goblet cells to neurally evoked mucosal secretion confirmed by ex vivo cholinergic stimulation of isolated duodenal rings. The dysfunctional efferent control of the GI mucus secretion results in altered biochemical composition of the mucus associated with reduced mucin glycoprotein content, aggregation, and binding capacity in vitro. Finally, functional consequences of the reduced barrier-forming capacity of the mucin-deficient AD mucus are demonstrated using the in vitro two-compartment caffeine diffusion interference model. Isolated central AD-like neuropathology results in the loss of efferent control of GI homeostasis via the brain-gut axis and is characterized by the insensitivity to neurally evoked mucosal secretion, altered mucus constitution with reduced mucin content, and reduced barrier-forming capacity, potentially increasing the susceptibility of the STZ-icv rat model of AD to GI and systemic inflammation induced by intraluminal toxins, microorganisms, and drugs.

Objective To explore how alveolar macrophages from chronic obstructive pulmonary disease (COPD)-model rats affect proliferation and secretion of 16HBE human bronchial epithelial cells and investigate the associated mechanism. Methods Alveolar macrophages were extracted from COPD rats induced by cigarette smoke exposure and LPS instillation through bronchoalveolar lavage, then co-cultured with 16HBE cells in vitro. Exosomes were extracted from alveolar macrophages of rats with exosome isolation kit. The differentially expressed miRNA in exosomes derived from macrophages of rats in COPD group and control group was detected by PCR. miR-380 was overexpressed with miR-380 mimic while the expression of cystic fibrosis transmembrane transduction regulator (CFTR) was knocked down with siRNA in 16HBE cells. The proliferation of 16HBE cells was detected with CCK-8 assay. The migration ability of 16HBE cells was evaluated with Transwell TM migration assay. The levels of mucins (MUC5AC, MUC5B, MUC2) and CFTR expressed by 16HBE cells were detected with Western blot analysis. The expression of TNF-α and IL-6 in the supernatant of 16HBE cells was detected with ELISA. Results The alveolar macrophages from COPD rats enhanced the proliferation and migration of 16HBE cells. The production of mucins and TNF-α as well as IL-6 in 16HBE cells were increased by COPD macrophages. The expression of miR-380 was significantly elevated in exosomes derived from COPD alveolar macrophages. Both overexpression of miR-380 and inhibition of CFTR decreased the expression of CFTR, resulting in the significantly enhanced proliferation and migration of 16HBE cells as well as increased expression of MUC5AC, MUC5B, MUC2 and TNF-α, IL-6. Conclusion The alveolar macrophages from COPD rats can enhance the proliferation and mucin expression as well as inflammatory cytokine secretion of 16HBE cells. This process may be involved with abnormal expression of miR-380 in exosomes of COPD alveolar macrophages and down-regulation of CFTR in bronchial epithelial cells.

In the present study, the mechanism of ellagic acid (EA) in alleviated ulcerative colitis (UC) was investigated. Twenty-four SD rats were randomly distributed into three treatment groups: (1) control group, (2) UC group, and (3) UC + EA group. Samples were collected for analysis after a 15-day trial period. We found that EA mitigated the colitis symptoms in TNBS-treated rats. Besides, EA decreased the expression of cytokines by inhibiting NF-κB signalling. TNBS-induced reduction in tight junction proteins was restored by EA supplementation via regulating RhoA/ROCK/MLC signalling. Further, persistent colonic inflammation destroyed the activity of goblet cells by inhibiting the expression of KLF4 and TFF3. EA also enhanced the expression of MUC2, AGR2, ST6GAL1 and B3GNT6. In summary, our findings demonstrated that dietary supplementation with EA ameliorated TNBS-induced colitis by maintaining intestinal barrier function, which proves its potential role as a therapeutic agent in the attenuation of UC.

Background/aim: Invasive stratified mucin-producing carcinoma (ISMC) of the uterine cervix has been reported to be more aggressive than other subtypes of endocervical adenocarcinoma. We investigated the clinicopathological and molecular characteristics of eight ISMCs., Patients and Methods: We reviewed the electronic medical records and pathology slides of eight patients with ISMC and conducted programmed death-ligand 1 (PD-L1) immunostaining and targeted sequencing., Results: The patients were between 31 and 54 years. Six tumors were pure ISMCs, and two showed co-existing squamous cell carcinoma and usual-type endocervical adenocarcinoma. Lymph node metastases were detected in three cases. Three patients developed distant metastases to the adnexa, lungs, inguinal lymph nodes, and small intestine. Two patients experienced disease progression, and three developed postoperative local recurrences. All tumors showed PD-L1 over-expression, with a mean combined positive score of 73.8 (range=30-100). One tumor harbored erb-b2 receptor tyrosine kinase 2 amplification., Conclusion: ISMC of the uterine cervix exhibits a high risk of recurrence, metastasis, and resistance to chemoradiation therapy. PD-L1 over-expression was consistently observed in all ISMCs. This finding raises the possibility that patients with ISMC may benefit from PD-L1 immunotherapy., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Xerostomia, known as dry mouth, is caused by decreased salivary flow. Treatment with lubricating oral rinses provides temporary relief of dry mouth discomfort; however, it remains unclear how their composition affects mineralized dental tissues. Therefore, the objective of this study was to analyze the effects of common components in xerostomia oral rinses on biomimetic apatite with varying carbonate contents. Carbonated apatite was synthesized and exposed to one of the following solutions for 72 hours at varying pHs: water-based, phosphorus-containing (PBS), mucin-like containing (MLC), or fluoride-containing (FC) solutions. Post-exposure results indicated that apatite mass decreased irrespective of pH and solution composition, while solution buffering was pH dependent. Raman and X-ray diffraction analysis showed that the addition of phosphorus, mucin-like molecules, and fluoride in solution decreases mineral carbonate levels and changed the lattice spacing and crystallinity of bioapatite, indicative of dissolution/recrystallization processes. The mineral recrystallized into a less-carbonated apatite in the PBS and MLC solutions, and into fluorapatite in FC. Tap water did not affect the apatite lattice structure suggesting formation of a labile carbonate surface layer on apatite. These results reveal that solution composition can have varied and complex effects on dental mineral beyond dissolution, which can have long term consequences on mineral solubility and mechanics. Therefore, clinicians should consider these factors when advising treatments for xerostomia patients., Competing Interests: The authors have declared that no competing interests exist.

Objective: Paraquat (PQ), a widely used toxic herbicide, induces lung inflammation through mechanisms that remain incompletely understood. In a previous study, we found that the plasma MUC5B mucin level was implicated in PQ poisoning in patients. Here, we hypothesize that MUC5B is a critical mediator in PQ-induced cell inflammation., Methods: A mouse model of PQ-induced lung injury was used to examine the MUC5B expression level. A549 cells (alveolar epithelial cells line) were exposed to PQ in dose-dependent and time-dependent manners. Cell viability was detected by CCK-8 assays. The expression levels of MUC5B were examined by dot blot enzyme-linked immunosorbent assay (ELISA) and RT-qPCR. Western blotting was used to detect the levels of proteins in the MAPK and NF- κ B pathways. Inflammatory factors in the cell culture medium were measured by ELISA. NF- κ B and MAPK pathway inhibitors and MUC5B siRNA (siMUC5B) were used to determine the function of MUC5B. Finally, N-acetyl-cysteine (NAC) was added and its regulatory effect on the MAPK-NF- κ B-MUC5B pathway was examined in PQ-induced cell inflammation., Results: MUC5B was significantly upregulated accompanying the increases in TNF- α and IL-6 secretion following PQ treatment in mouse and also in A549 cells after treatment with 50  μ M PQ at 24 hours. Furthermore, MAPK and NF- κ B pathway inhibitors could dramatically decrease the expression of MUC5B and the secretion of TNF- α and IL-6. Importantly, siMUC5B could significantly attenuate the secretion of TNF- α and IL-6 induced by PQ. As expected, the addition of NAC efficiently suppresses the TNF- α and IL-6 secretion stimulated from PQ and also downregulated ERK, JNK, and p65 phosphorylation (ERK/JNK MAPK and NF- κ B pathways) as well as MUC5B expression., Conclusion: Our findings suggest that MUC5B participates in the process of PQ-induced cell inflammation and is downstream of the NF- κ B and MAPK pathways. NAC can attenuate PQ-induced cell inflammation at least in part by suppressing the MAPK-NF- κ B-MUC5B pathway. These results nominate MUC5B as a new biomarker and therapeutic target for PQ-induced lung inflammation., Competing Interests: There was no conflict of interest declared., (Copyright © 2020 Hao Sun et al.)

Background: This study evaluated the efficacy, safety, and acceptability of a new ferrous sulfate oral solution (Tardyferon® 20 mg/mL) in young children with mild or moderate iron deficiency anemia (IDA)., Methods: This was a multicenter, national, single-arm, open-label study. Children aged 6-53 months presenting with mild or moderate IDA (i.e., blood hemoglobin (Hb) ranging from 7.0 to 10.9 g/dL and serum ferritin <12 ng/mL) were eligible for inclusion. The ferrous sulfate heptahydrate solution (2 mg/kg/day) was administered orally for 3 months. If normalization of either Hb or ferritin was not achieved at month 3 the treatment was continued for another 3 months., Results: Of the 100 children screened, 21 aged 6-17 months were included and received the study treatment, and 19 were analyzed for hematologic outcomes at month 3. Only one patient continued treatment for the additional 3 months. At month 3, mean ± SD Hb and ferritin levels were 12.0 ± 0.7 g/dL and 31.5 ± 19.4 ng/mL, respectively. Hemoglobin and ferritin levels were normalized in 95% (18/19) and 84% (16/19) of the patients, respectively. Treatment compliance and levels of satisfaction of both the parents and the investigators were high. Overall, 33.3% of patients (7/21) experienced at least one adverse event. Only one patient (4.8%) experienced a drug-related adverse event (upper abdominal pain)., Conclusions: A 2 mg/kg daily dose of the new oral ferrous sulfate heptahydrate solution provides substantial therapeutic benefit with high levels of tolerability in young children who have mild or moderate IDA., (© 2020 The Authors. Pediatrics International published by John Wiley & Sons Australia, Ltd on behalf of Japan Pediatric Society.)

Osteonecrosis of the jaw (ONJ), a rare side effect of bisphosphonate therapy, is a debilitating disorder with a poorly understood etiology. FDA's Adverse Event Reporting System (FAERS) provides the opportunity to investigate this disease. Our goals were to analyze FAERS data to discover possible relationships between ONJ and specific conditions and drugs and then to consult the scientific literature to deduce biological explanations. Our methodology revealed a very strong association between gastroesophageal reflux and bisphosphonate-induced ONJ, suggesting acidosis as a key factor. Overgrowth of acidophilic species, particularly Streptococcus mutans , in the oral microbiome in the context of insufficient acid buffering due to impaired salivary glands maintains the low pH that sustains damage to the mucosa. Significant associations between ONJ and adrenal insufficiency, vitamin C deficiency, and Sjögren's syndrome were found. Glucose 6 phosphate dehydrogenase (G6PD) deficiency can explain much of the pathology. An inability to maintain vitamin C and other antioxidants in the reduced form leads to vascular oxidative damage and impaired adrenal function. Thus, pathogen-induced acidosis, hypoxia, and insufficient antioxidant defenses together induce ONJ. G6PD deficiency and adrenal insufficiency are underlying factors. Impaired supply of adrenal-derived sulfated sterols such as DHEA sulfate may drive the disease process.

Objectives: To report the case of a 24 year old female undergraduate who presented with bowel obstruction, three weeks following the excision of a mucinous ovarian cyst., Patient and Methods: The records of the patients past and recent medical history laboratory and imaging studies were reviewed., Results: Clinical findings of a distended and a plain abdominal radiogram showing distended loops of bowel(Figure 2) were in keeping with acute bowel obstruction. This was confirmed by the intraoperative finding of fibrous encasement of small bowel. This was excised ,and 12months thereafter, patient has remain in good health. Figure 2Preoperative A-P abdominal X-ray in erect position showing small distension., Conclusion: Early and absolute adhesional bowel obstruction from abdominal surgery is failing conservative management rate. We attributed this to the ruptured mucinous cyst in our earlier operation. We therefore suggest that should a rupture cyst of this type occurs during a surgical procedure, any of the preventive methods discussed should be tried as a prophylactic measure.

Unlabelled: In the human gastrointestinal tract, trypsin and mucin may affect the absorption of heme iron. However, these interactions have not been well-established. We determined the effect of trypsin and mucin on heme iron absorption in humans., Design: Twenty-eight apparently healthy females participated in two studies (14 per study). Study A evaluated the effect of trypsin on iron bioavailability. Subjects ingested 100 mg trypsin and 1.7 g mucin on 5 mg heme iron bioavailability on days 1, 2, 14, and 15, respectively. In study B, which assessed the effect of mucin on heme iron bioavailability, the subjects ingested hemin, hemin plus mucin, hemoglobin (Hb), and Hb plus mucin, on days 1, 2, 14, and 15, respectively., Results: In study A, the geometric means ± 1 SD of heme iron absorption were 5.1 % (3.1-8.3), 2.9 % (1.6-5.1), 7.3 % (4.1-13.1), and 6 % (2.7-13) for hemin, hemin plus trypsin, Hb plus trypsin, and Hb plus mucin plus trypsin, respectively. In study B, the geometric means ± 1 SD of heme iron absorption were 16.4 % (10.5-25.7), 13.1 % (9.0-18.9), 13.7 % (9.0-20.7), and 11.8 % (7.6-18.3) for hemin, hemin plus mucin, Hb, and Hb plus mucin, respectively. The ratio increased when Hb plus trypsin was ingested and decreased when hemin plus trypsin was ingested. There were no differences in other ratios with respect to the ratio on day 1 (P < 0.05)., Conclusion: Trypsin is the only human gastrointestinal protein that evaluated the affects of heme iron absorption. However, this effect depends on how heme iron is ingested.

The objective was to measure the combined effect of mucin, chlorhexidine and tea solution on the staining of four dental resin composites, and to determine the effect of surface sealant on staining. One side of cured resin composite specimens of 10 mm in diameter and 2 mm in thickness were polished with 600-grit silicon carbide paper. One group of specimens (n = 5) was treated with a surface sealant [BisCover, Bisco, USA; SS (surface sealant) group], and the other group was not (NO group; control). Specimens were sequentially immersed in the following substances: Mucin in phosphate buffered saline (PBS); chlorhexidine; tea solution; and ultrasonic cleaning and then immersion in PBS. Color was measured on a reflection spectrophotometer. Changes in color (DeltaE (*) (ab)) and color parameters, such as hue, chroma and value, after immersion in tea solution and subsequent cleaning were analyzed by repeated measures, analysis of variance at the 0.05 level of significance. The range of DeltaE (*) (ab) values after immersion in tea solution was 11.4-21.1 for NO group and 10.5-19.6 for SS group, and that after cleaning was 2.4-10.0 for NO group and 2.7-8.3 for SS group. After staining, CIE L (*) value (lightness) decreased, and CIE a (*) and b (*) values increased. Color changes of resin composites were not acceptable after sequential immersion treatment (DeltaE (*) ( ab ) > 3.3). The changes in color and color parameters of sealant applied group were not significantly different from those of control group except for a few combinations of color parameters and resin composites.

Background: The most frequent complications of oral administration of medicinal iron are gastrointestinal complaints the incidence of which correlates with the iron content of the preparation. The objective of the present work was to compare the effectiveness and tolerance of two ferrous sulphate preparations, Aktiferrin capsules and Tardyferon dragées which differ as to the elemental iron content., Methods and Results: To two groups of patients with sideropenic anaemia selected at random (39 women and 1 men, age 14-61 years, median 28 years) Aktiferrin or Tardyferon was administered. Administration of the preparations which have a more than double different elemental iron content had a comparable effect on the investigated haematological parameters. In the group treated with Akiferrin no GIT intolerance was observed, in the group with Tardyferon it was observed in four patients., Conclusions: Aktiferrin has a comparable therapeutic effect although it contains 2.5 times less elemental iron, as compared with Tardyferon.