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Nutrients Mar 2024The goblet cells of the gastrointestinal tract (GIT) produce glycoproteins called mucins that form a protective barrier from digestive contents and external stimuli....
The goblet cells of the gastrointestinal tract (GIT) produce glycoproteins called mucins that form a protective barrier from digestive contents and external stimuli. Recent evidence suggests that the milk fat globule membrane (MFGM) and its milk phospholipid component (MPL) can benefit the GIT through improving barrier function. Our objective was to compare the effects of two digested MFGM ingredients with or without dextran sodium sulfate (DSS)-induced barrier stress on mucin proteins. Co-cultured Caco-2/HT29-MTX intestinal cells were treated with in vitro digests of 2%, 5%, and 10% (/) MFGM or MPL alone for 6 h or followed by challenge with 2.5% DSS (6 h). Transepithelial electrical resistance and fluorescein isothiocyanate (FITC)-dextran (FD4) permeability measurements were used to measure changes in barrier integrity. Mucin characterization was performed using a combination of slot blotting techniques for secreted (MUC5AC, MUC2) and transmembrane (MUC3A, MUC1) mucins, scanning electron microscopy (SEM), and periodic acid Schiff (PAS)/Alcian blue staining. Digested MFGM and MPL prevented a DSS-induced reduction in secreted mucins, which corresponded to the prevention of DSS-induced increases in FD4 permeability. SEM and PAS/Alcian blue staining showed similar visual trends for secreted mucin production. A predictive bioinformatic approach was also used to identify potential KEGG pathways involved in MFGM-mediated mucosal maintenance under colitis conditions. This preliminary in silico evidence, combined with our in vitro findings, suggests the role of MFGM in inducing repair and maintenance of the mucosal barrier.
Topics: Humans; Dextrans; Caco-2 Cells; Alcian Blue; Glycoproteins; Epithelial Cells; Mucins; Glycolipids; Fluorescein-5-isothiocyanate; Lipid Droplets
PubMed: 38612988
DOI: 10.3390/nu16070954 -
Journal of Chemical Theory and... Apr 2024The photochemistry of nitrophenols is a source of smog as nitrous acid is formed from their photolysis. Nevertheless, computational studies of the photochemistry of...
The photochemistry of nitrophenols is a source of smog as nitrous acid is formed from their photolysis. Nevertheless, computational studies of the photochemistry of these widespread toxic molecules are scarce. In this work, the initial photodeactivation of -nitrophenol and -nitrophenol is modeled, both in gas phase and in aqueous solution to simulate atmospheric and aerosol environments. A large number of excited states, six for -nitrophenol and 11 for -nitrophenol, have been included and were all populated during the decay. Moreover, periodic time-dependent density functional theory (TDDFT) is used for both the explicitly included solvent and the solute. A comparison to periodic QM/MM (TDDFT/MM), with electrostatic embedding, is made, showing notable differences between the decays of solvated nitrophenols simulated with QM/MM and full (TD)DFT. A reduced intersystem crossing in aqueous solution could be observed thanks to the surface hopping approach using explicit, periodic TDDFT solvation including spin-orbit couplings.
PubMed: 38606908
DOI: 10.1021/acs.jctc.3c01400 -
Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi... Apr 2024To investigate the mechanism of circadian clock protein Bmal1 (Bmal1) on renal injury with chronic periodontitis, we established an experimental rat periodontitis model.
OBJECTIVES
To investigate the mechanism of circadian clock protein Bmal1 (Bmal1) on renal injury with chronic periodontitis, we established an experimental rat periodontitis model.
METHODS
Twelve male Wistar rats were randomly divided into control and periodontitis groups (=6, each group). The first maxillary molars on both sides of the upper jaw of rats with periodontitis were ligated by using orthodontic ligature wires, whereas the control group received no intervention measures. After 8 weeks, clinical periodontal parameters, including probing depth, bleeding index, and tooth mobility, were evaluated in both groups. Micro-CT scanning and three-dimensional image reconstruction were performed on the maxillary bones of the rats for the assessment of alveolar bone resorption. Histopatholo-gical observations of periodontal and renal tissues were conducted using hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) staining. Renal function indicators, such as creatinine, albumin, and blood urea nitrogen levels, and oxidative stress markers, including superoxide dismutase, glutathione, and malondialdehyde levels, were measured using biochemical assay kits. MitoSOX red staining was used to detect reactive oxygen species (ROS) content in the kidneys. The gene and protein expression levels of Bmal1, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in rat renal tissues were assessed using real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical staining.
RESULTS
Micro-CT and HE staining results showed significant bone resorption and attachment loss in the maxillary first molar region of the periodontitis group. Histological examination through HE and PAS staining revealed substantial histopathological damage to the renal tissues of the rats in the periodontitis group. The findings of the assessment of renal function and oxidative stress markers indicated that the periodontitis group exhibited abnormal levels of oxidative stress, whereas the renal function levels showed abnormalities without statistical significance. MitoSOX Red staining results showed that the content of ROS in the renal tissue of the periodontitis group was significantly higher than that of the control group, and RT-qPCR and immunohistochemistry results showed that the expression levels of Bmal1, Nrf2, and HO-1 in the renal tissues of the rats in the periodontitis group showed a decreasing trend.
CONCLUSIONS
Circadian clock protein Bmal1 plays an important role in the oxidative damage process involved in the renal of rats with periodontitis.
Topics: Animals; Male; Rats; Bone Resorption; Circadian Clocks; Kidney; NF-E2-Related Factor 2; Organophosphorus Compounds; Oxidative Stress; Periodontitis; Phenanthridines; Rats, Wistar; Reactive Oxygen Species
PubMed: 38597076
DOI: 10.7518/hxkq.2024.2023245 -
Frontiers in Pharmacology 2024The Bushenyiqi decoction (BYD), a contemporary prescription of traditional Chinese medicine (TCM), has been observed to significantly ameliorate asthma symptoms in...
The Bushenyiqi decoction (BYD), a contemporary prescription of traditional Chinese medicine (TCM), has been observed to significantly ameliorate asthma symptoms in patients based on clinical observations. Although multi-component and multi-target characteristics are important attributes of BYD treatment, its pharmacological effect on asthma and the underlying mechanism of action remain unclear. Network pharmacology: the asthma-related genes were retrieved from the GeneCards and OMIM database. The active constituents of BYD and their corresponding target genes were collected from the TCMSP database. The underlying pathways associated with overlapping targets between BYD and asthma were identified through GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis. Experimental validation: pulmonary function tests, enzyme-linked immunosorbent assay (ELISA), Hematoxylin and eosin (HE), periodic acid-Schiff (PAS), and Masson's trichrome stainings were conducted to validate the efficacy of BYD in ameliorating airway inflammation in allergic asthma mice. Western blot (WB) and molecular docking were performed to confirm the involvement of the underlying pathway in BYD treatment of asthma. The results of animal experiments demonstrated that BYD may improve airway responsiveness and suppress airway inflammation in allergic asthma mice. The network pharmacological analysis revealed the involvement of 11 potentially key active components, 9 potential key targets, and the phosphatidylinositol3 kinase-RAC-α serine/threonine-protein kinase (PI3K/AKT) signaling pathway in the mechanism of action of BYD for asthma treatment. Our findings have confirmed that BYD effectively alleviated airway inflammation by targeting interleukin 6 (IL-6), epidermal growth factor receptor (EGFR), and hypoxia inducible factor 1 alpha (HIF1A), with quercetin, kaempferol, and luteolin performing as the pivotal active constituents. BYD may potentially reduce inflammatory cell infiltration in lung tissues by regulating the PI3K/AKT signaling pathway. In conclusion, the integration of network pharmacology and biological experiments has demonstrated that key constituents of BYD, such as quercetin, kaempferol, and luteolin, exhibit targeted effects on IL-6, EGFR, and HIF1A in combating asthma-related inflammation through inhibition of the PI3K/AKT signaling pathway. The findings of this investigation provide evidence supporting the effectiveness of TCM's "bushenyiqi" therapy in asthma management, as corroborated by contemporary medical technology.
PubMed: 38590639
DOI: 10.3389/fphar.2024.1361379 -
World Journal of Experimental Medicine Mar 2024Diabetes is known damage the liver and kidney, leading to hepatic dysfunction and kidney failure. Honey is believed to help in lowering the blood glucose levels of...
BACKGROUND
Diabetes is known damage the liver and kidney, leading to hepatic dysfunction and kidney failure. Honey is believed to help in lowering the blood glucose levels of diabetic patients and reducing diabetic complications. However, the effect of stingless bee honey (SBH) administration in relieving liver and kidney damage in diabetes has not been well-studied.
AIM
To investigate the effect of SBH administration on the kidney and liver of streptozotocin-induced (STZ; 55 mg/kg) diabetic Sprague Dawley rats.
METHODS
The rats were grouped as follows ( = 6 per group): non-diabetic (ND), untreated diabetic (UNT), metformin-treated (MET), and SBH+metformin-treated (SBME) groups. After successful diabetic induction, ND and UNT rats were given normal saline, whereas the treatment groups received SBH (2.0 g/kg and/or metformin (250 mg/kg) for 12 d. Serum biochemical parameters and histological changes using hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining were evaluated.
RESULTS
On H&E and PAS staining, the ND group showed normal architecture and cellularity of Bowman's capsule and tubules, whereas the UNT and MET groups had an increased glomerular cellularity and thickened basement membrane. The SBH-treated group showed a decrease in hydropic changes and mild cellularity of the glomerulus the ND group based on H&E staining, but the two were similar on PAS staining. Likewise, the SBME-treated group had an increase in cellularity of the glomerulus on H&E staining, but it was comparable to the SBH and ND groups on PAS staining. UNT diabetic rats had tubular hydropic tubules, which were smaller than other groups. Reduced fatty vacuole formation and dilated blood sinusoids in liver tissue were seen in the SBH group. Conversely, the UNT group had high glucose levels, which subsequently increased MDA levels, ultimately leading to liver damage. SBH treatment reduced this damage, as evidenced by having the lowest fasting glucose, serum alanine transaminase, aspartate transaminase, and alkaline phosphatase levels compared to other groups, although the levels of liver enzymes were not statistically significant.
CONCLUSION
The cellularity of the Bowman's capsule, as well as histological alteration of kidney tubules, glomerular membranes, and liver tissues in diabetic rats after oral SBH resembled those of ND rats. Therefore, SBH exhibited a protective hepatorenal effect in a diabetic rat model.
PubMed: 38590306
DOI: 10.5493/wjem.v14.i1.91271 -
Laboratory Animal Research Apr 2024Gastrodia elata Blume (GEB), a traditional medicinal herb, has been reported to have pharmacological effect including protection against liver, neuron and kidney...
BACKGROUND
Gastrodia elata Blume (GEB), a traditional medicinal herb, has been reported to have pharmacological effect including protection against liver, neuron and kidney toxicity. However, explanation of its underlying mechanisms remains a great challenge. This study investigated the protective effects of GEB extract on vancomycin (VAN)-induced nephrotoxicity in rats and underlying mechanisms with emphasis on the anti-oxidative stress, anti-inflammation and anti-apoptosis. The male Sprague-Dawley rats were randomly divided three groups: control (CON) group, VAN group and GEB group with duration of 14 days.
RESULTS
The kidney weight and the serum levels of blood urea nitrogen and creatinine in the GEB group were lower than the VAN group. Histological analysis using hematoxylin & eosin and periodic acid Schiff staining revealed pathological changes of the VAN group. Immunohistochemical analysis revealed that the expression levels of N-acetyl-D-glucosaminidase, myeloperoxidase and tumor necrosis factor-alpha in the GEB group were decreased when compared with the VAN group. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells, phosphohistone and malondialdehyde levels were lower in the GEB group than VAN group. The levels of total glutathione in the GEB group were higher than the VAN group.
CONCLUSIONS
The findings of this study suggested that GEB extract prevents VAN-induced renal tissue damage through anti-oxidation, anti-inflammation and anti-apoptosis.
PubMed: 38589968
DOI: 10.1186/s42826-024-00200-y -
BMC Pulmonary Medicine Apr 2024Autoimmune pulmonary alveolar proteinosis (APAP) is a diffuse lung disease that causes abnormal accumulation of lipoproteins in the alveoli; however, its pathogenesis...
A case of autoimmune pulmonary alveolar proteinosis during the course of treatment of rapidly progressive interstitial pneumonia associated with anti-MDA5 antibody-positive dermatomyositis.
BACKGROUND
Autoimmune pulmonary alveolar proteinosis (APAP) is a diffuse lung disease that causes abnormal accumulation of lipoproteins in the alveoli; however, its pathogenesis remains unclear. Recently, APAP cases have been reported during the course of dermatomyositis. The combination of these two diseases may be coincidental; however, it may have been overlooked because differentiating APAP from a flare-up of interstitial pneumonia associated with dermatomyositis is challenging. This didactic case demonstrates the need for early APAP scrutiny.
CASE PRESENTATION
A 50-year-old woman was diagnosed with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatitis and interstitial pneumonia in April 2021. The patient was treated with corticosteroids, tacrolimus, and cyclophosphamide pulse therapy for interstitial pneumonia complicated by MDA5 antibody-positive dermatitis, which improved the symptoms and interstitial pneumonia. Eight months after the start of treatment, a new interstitial shadow appeared that worsened. Therefore, three additional courses of cyclophosphamide pulse therapy were administered; however, the respiratory symptoms and interstitial shadows did not improve. Respiratory failure progressed, and 14 months after treatment initiation, bronchoscopy revealed turbid alveolar lavage fluid, numerous foamy macrophages, and numerous periodic acid-Schiff-positive unstructured materials. Blood test results revealed high anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) antibody levels, leading to a diagnosis of APAP. The patient underwent whole-lung lavage, and the respiratory disturbance promptly improved. Anti-GM-CSF antibodies were measured from the cryopreserved serum samples collected at the time of diagnosis of anti-MDA5 antibody-positive dermatitis, and 10 months later, both values were significantly higher than normal.
CONCLUSIONS
This is the first report of anti-MDA5 antibody-positive dermatomyositis complicated by interstitial pneumonia with APAP, which may develop during immunosuppressive therapy and be misdiagnosed as a re-exacerbation of interstitial pneumonia. In anti-MDA5 antibody-positive dermatomyositis, APAP comorbidity may have been overlooked, and early evaluation with bronchoalveolar lavage fluid and anti-GM-CSF antibody measurements should be considered, keeping the development of APAP in mind.
Topics: Female; Humans; Middle Aged; Pulmonary Alveolar Proteinosis; Dermatomyositis; Autoantibodies; Lung Diseases, Interstitial; Cyclophosphamide; Dermatitis; Interferon-Induced Helicase, IFIH1; Autoimmune Diseases
PubMed: 38589870
DOI: 10.1186/s12890-024-02989-9 -
Nutrition Research and Practice Apr 2024Chronic renal failure (CRF) is a complex pathological condition that lacks a cure. Certain Chinese medicines, such as melittin, a major component in bee venom, have...
BACKGROUND/OBJECTIVES
Chronic renal failure (CRF) is a complex pathological condition that lacks a cure. Certain Chinese medicines, such as melittin, a major component in bee venom, have shown efficacy in treating CRF patients. On the other hand, the mechanisms underlying the therapeutic effects of melittin are unclear.
MATERIALS/METHODS
A 5/6 nephrectomy model (5/6 Nx) of renal failure was established on rats for assays, and mouse podocyte clone 5 (MPC5) mouse podocyte cells were treated with angiotensin II (AngII) to establish an podocyte damage model. The 24-h urine protein, serum creatinine, and blood urea nitrogen levels were evaluated after one, 2, and 4 weeks. Hematoxylin and eosin staining, Masson staining, and periodic acid-Schiff staining were used to examine the pathological changes in kidney tissues. A cell counting kit 8 assay was used to assess the cell viability. Reverse transcription polymerase chain reaction and Western blot were used to assess the mRNA and protein levels in the cells, respectively.
RESULTS
In the rat 5/6 Nx, melittin reduced the 24-h urinary protein excretion and the serum creatinine and blood urea nitrogen levels. Furthermore, the renal pathology was improved in the melittin-treated 5/6 Nx rats. Melittin promoted podocin, nephrin, Beclin 1, and the LC3II/LC3I ratio and inhibited phosphorylated mammalian target of rapamycin (mTOR)/mTOR in 5/6 Nx-induced rats and AngII-induced MPC5 mouse podocyte cells. Moreover, inhibiting autophagy with 3-MA weakened the effects of melittin on podocin, nephrin, and the LC3II/LC3I ratio in podocytes.
CONCLUSION
Melittin may offer protection against kidney injury, probably by regulating podocyte autophagy. These results provide the theoretical basis for applying melittin in CRF therapy.
PubMed: 38584815
DOI: 10.4162/nrp.2024.18.2.210 -
Acta Crystallographica. Section E,... Mar 2024Treatment of 3-(3,4-di-hydroxy-phen-yl)propenoic acid (caffeic acid or 3,4-di-hydroxy-cinnamic acid) with the alkali hydroxides OH ( = Li, Na) in aqueous solution led to...
Treatment of 3-(3,4-di-hydroxy-phen-yl)propenoic acid (caffeic acid or 3,4-di-hydroxy-cinnamic acid) with the alkali hydroxides OH ( = Li, Na) in aqueous solution led to the formation of poly[aqua-[μ-3-(3,4-di-hydroxy-phen-yl)propenoato]lithium], [Li(CHO)(HO)], , and poly[aqua-[μ-3-(3,4-di-hydroxy-phen-yl)propenoato]sodium], [Na(CHO)(HO)], . The crystal structure of consists of a lithium cation that is coordinated nearly tetra-hedrally by three carboxyl-ate oxygen atoms and a water mol-ecule. The carboxyl-ate groups adopt a μ-κ :':' coordination mode that leads to a chain-like catenation of Li cations and carboxyl-ate units parallel to the axis. Moreover, the lithium carboxyl-ate chains are connected by hydrogen bonds between water mol-ecules attached to lithium and catechol OH groups. The crystal structure of shows a sevenfold coordination of the sodium cation by one water mol-ecule, two monodentately binding carboxyl-ate groups and four oxygen atoms from two catechol groups. The coordination polyhedra are linked by face- and edge-sharing into chains extending parallel to the axis. The chains are inter-linked by the bridging 3-(3,4-di-hydroxy-phen-yl)propenoate units and by inter-molecular hydrogen bonds to form the tri-periodic network.
PubMed: 38584729
DOI: 10.1107/S2056989024002494 -
World Journal of Gastrointestinal... Mar 2024The Alcian blue (AB) and periodic acid Schiff (PAS) stains are representative mucus markers in gastric signet ring cell carcinoma (SRCC). They are low-cost special...
BACKGROUND
The Alcian blue (AB) and periodic acid Schiff (PAS) stains are representative mucus markers in gastric signet ring cell carcinoma (SRCC). They are low-cost special staining methods used to detect acidic mucus and neutral mucus, respectively. However, the clinical importance of the special combined AB and PAS stain is unclear.
AIM
To investigate AB expression, PAS expression and the AB-to-PAS (A/P) ratio in gastric SRCC patients and to assess patient prognosis.
METHODS
Paraffin-embedded sections from 83 patients with gastric SRCC were stained with AB and PAS, and signet ring cell positivity was assessed quantitatively. Immunohistochemical staining for Ki67, protein 53 (P53) and human epidermal growth factor receptor 2 (HER2) was performed simultaneously. The cancer-specific survival (CSS) rate was estimated Kaplan-Meier analysis. Cox proportional hazards models were used for univariate and multivariate survival analyses.
RESULTS
Kaplan-Meier survival analysis revealed that the 3-year CSS rate was significantly greater in the high-PAS-expression subgroup than in the low-PAS-expression subgroup ( < 0.001). The 3-year CSS rate in the A/P ≤ 0.5 group was significantly greater than that in the A/P > 0.5 group ( = 0.042). Univariate Cox regression analysis revealed that the factors affecting prognosis included tumor diameter, lymph node metastasis, vessel carcinoma embolus, tumor stage, the A/P ratio and the expression of Ki67, P53 and the PAS. Cox multivariate regression analysis confirmed that low PAS expression [hazard ratio (HR) = 3.809, 95% confidence interval (CI): 1.563-9.283, = 0.003] and large tumor diameter (HR = 2.761, 95%CI: 1.086-7.020, = 0.033) were independent risk factors for poor prognosis.
CONCLUSION
A/P > 0.5 is potentially a risk factor for prognosis, and low PAS expression is an independent risk factor in the prognosis of gastric SRCC. PAS expression and the A/P ratio could help in predicting the clinical prognosis of patients with SRCC.
PubMed: 38577442
DOI: 10.4251/wjgo.v16.i3.687