•Bletilla striata polysaccharide is a neutral heteropolysaccharide composed of mannose and glucose.•The molecular weight was evaluated by HPSEC-MALLS.•The surface morphology and conformation of BFPS ...was greatly different from BVPS by means of SEM and AFM measurements.•The solubility and moisture of BFPS were higher compared with BVPS.
The polysaccharide from Bletilla striata, a traditional Chinese herbal medicine, was obtained by different drying techniques: vacuum-drying (BVPS) or vacuum freeze-drying (BFPS). The effect of drying method on the physicochemical properties of the B striata polysaccharide was evaluated using high size exclusion chromatography coupled to multiangle laser light scattering (HPSEC-MALLS), FT-IR and UV spectroscopy, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM) and atomic force microscopy (AFM). The monosaccharide analysis and pH test revealed that the polysaccharide derived from B. striata was a neutral polysaccharide that is composed of glucose and mannose. The solubility and moisture content test's results demonstrated that BFPS was greater than BVPS. The number average molecular weight (Mn) and the computed average molecular weight (Mw) of 99.3% BFPS were 7.297×104g/mol and 9.545×104g/mol, respectively, whereas the Mn and Mw of 97.6% BVPS were 1.218×105g/mol and 1.472×105g/mol, respectively. The FT-IR and UV results indicated that drying technique has little effect on the structure of the polysaccharide. The thermal analysis showed that weight loss event was at 307.85°C and 305.50°C to BVPS and BFPS, respectively. Furthermore, the XRD confirmed that the polysaccharide was the amorphous nature. However, both SEM and AFM images exhibited that the drying technique had a significant impact on the morphology and conformation of the polysaccharide.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Pulmonary fibrosis, which influences lung function and exacerbates a patient's condition, is the ultimate stage of many lung diseases. Vitamin D deficiency is associated with pulmonary fibrosis and ...impaired lung function, but the underlying mechanism has not yet been fully elucidated. Moreover, vitamin D deficiency may cause over-activation of the renin-angiotensin system (RAS), which aggravates extracellular matrix (ECM) deposition and lung fibrosis. This study aims to investigate the effect of chronic vitamin D deficiency on lung fibrosis in otherwise healthy mice and to explore the role of RAS in this process. Mice were depleted of vitamin D through diet control and were compared with healthy subjects. Chronic vitamin D deficiency destructs lung structures, impairs lung development and stimulates ECM deposition. RAS components are also found to increase. These effects seem to worsen with prolonged vitamin D deficiency. By giving RAS blockers, these changes can be largely rescued. However, a smooth muscle relaxant whose regulatory effect on blood pressure is independent of RAS does not show similar effects. This study demonstrated that chronic vitamin D deficiency may induce RAS activation, which subsequently stimulates the expression of profibrotic factors and activates the fibrotic cascade. This profibrotic effect of RAS is independent of elevated blood pressure.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Crohn's disease (CD) and ulcerative colitis (UC) actually had different pathological mechanisms, as the former was mainly induced by Th1 and Th17 response and the latter by Th2 response. Our previous ...study found that oxazolone-induced Th2-mediated colitis could not be attenuated by vitamin D supplementation. This study investigated the influence of intestinal vitamin D receptor (VDR) knockout on oxazolone-induced colitis and explored the possible immunological mechanism. Intestinal VDR knockout mice had milder oxazolone-induced colitis than wildtype controls, as demonstrated by less body weight decrease and faster recovery, more intact local structure, reduced cell apoptosis, and better preserved barrier function. Th2-mediated inflammation was significantly inhibited by VDR deficiency. Meanwhile, the percentage of invariant natural killer T (iNKT) cells did not increase as much in intestinal VDR knockout mice as in wild-type controls, nor did the iNKT cells develop normally as in the controls. Intestinal VDR knockout protected against oxazolone-induced colitis in mice by blocking Th2 cell response and reducing the function of intestinal iNKT cells. Vitamin D status had no influence on the severity of colitis. This study may explain the diverse outcomes after vitamin D supplementation in literature and add some clue to the targeted therapy of IBD.
Brain injury, a common complication in preterm infants, includes the destruction of the key structural and functional connections of the brain and causes neurodevelopmental disorders; it has high ...morbidity and mortality rates. The exact mechanism underlying brain injury in preterm infants is unclear. Intestinal flora plays a vital role in brain development and the maturation of the immune system in infants; however, detailed understanding of the gut microbiota-metabolite-brain axis in preterm infants is lacking. In this review, we summarise the key mechanisms by which the intestinal microbiota contribute to neurodevelopment and brain injury in preterm infants, with special emphasis on the influence of microorganisms and their metabolites on the regulation of neurocognitive development and neurodevelopmental risks related to preterm birth, infection and neonatal necrotising enterocolitis (NEC). This review provides support for the development and application of novel therapeutic strategies, including probiotics, prebiotics, synbiotics, and faecal bacteria transplantation targeting at brain injury in preterm infants.
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•The gut-microbiota-brain axis regulates vagus nerve, endocrine and immune pathways.•Preterm birth, dysbiosis and infection cause brain injury by acting on gut microbiota.•The activation of γδ T cells by the microbiome contributes to preterm brain injury.•Inflow of inflammatory cytokines across the blood-brain barrier leads to brain injury.•Metabolites of the gut microbiota may also serve as neuro-signal transmitters.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Dramatic intestinal epithelial cell death leading to barrier dysfunction is one of the mechanism of neonatal necrotizing enterocolitis (NEC), in which Toll-like receptor 4 (TLR4) plays a pivotal ...role. This study explored the role of necroptosis, a drastic way of cell death in NEC.
The expression of necroptotic proteins was tested in NEC intestinal tissue and compared with controls. NEC was induced in neonatal wild-type mice and a necroptosis inhibitor was given to investigate whether NEC could be relieved. The general condition, macroscopic scoring, and histological evaluations were performed. The expression of tight junction proteins, inflammatory cytokines, and necroptosis-related proteins was measured, and barrier function was examined. Then, NEC was induced in TLR4-knockout pups to confirm the role of TLR4 in necroptosis.
Necroptotic proteins were significantly upregulated in both NEC patient and animal models, together with the expression of TLR4. NEC could be relieved and inflammatory infiltration was decreased by necrostatin-1s. TLR4-knockout mice showed milder tissue degradation and less necroptosis after NEC induction.
Necroptosis is an essential pathological process of NEC. TLR4 may be one stimulator of necroptosis in NEC. Inhibiting the intestinal cell necroptosis might be a useful strategy in the treatment of NEC.
Necroptosis is a key pathological process in NEC, which appears to involve TLR4. Anti-necroptosis treatment is a promising strategy that could significantly relieve the symptoms of NEC.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Acute lung injury (ALI) is a hallmark of systemic inflammation associated with high mortality. Although the vitamin D receptor (VDR) is highly expressed in the lung, its role in lung physiology ...remains unclear. We investigated the effect of VDR deletion on ALI using a lipopolysaccharide (LPS)-induced sepsis model. After LPS challenge VDR-null mice exhibited more severe ALI and higher mortality compared with wild-type (WT) counterparts, manifested by increased pulmonary vascular leakiness, pulmonary edema, apoptosis, neutrophil infiltration, and pulmonary inflammation, which was accompanied by excessive induction of angiopoietin (Ang)-2 and myosin light chain (MLC) phosphorylation in the lung. 1,25-Dihydroxyvitamin D blocked LPS-induced Ang-2 expression by blocking nuclear factor-κB activation in human pulmonary artery endothelial cells. The severity of lung injury seen in VDR-null mice was ameliorated by pretreatment with L1–10, an antagonist of Ang-2, suggesting that VDR signaling protects the pulmonary vascular barrier by targeting the Ang-2-Tie-2-MLC kinase cascade. Severe ALI in VDR-null mice was also accompanied by an increase in pulmonary renin and angiotensin II levels, and pretreatment of VDR-null mice with angiotensin II type 1 receptor blocker losartan partially ameliorated the severity of LPS-induced lung injury. Taken together, these observations provide evidence that the vitamin D-VDR signaling prevents lung injury by blocking the Ang-2-Tie-2-MLC kinase cascade and the renin-angiotensin system.
A novel quasi orthogonal space-frequency block coding (QOSFBC) orthogonal frequency division multiplexing (QOSFBC-OFDM) scheme for doubly selective channels is proposed, which adopts the time ...difference of arrival (TDOA) parameter to calculate the complex phase rotation factor utilized in the pre-coding matrix. The novel QOSFBC employed in centralized cooperative scheme can obtain 3.056 diversity gain and full transmission rate at 15 dB SNR. Furthermore, the impact of TDOA on the performance of QOSFBC-OFDM system is investigated in the Rayleigh fading channels. Simulation results show that the proposed quasi-orthogonal recovering QOSFBC (QOR-QOSFBC) can achieve at most 12 dB more SNR gain after demodulation than the conventional QOSFBC.
The myosin light chain kinase (MLCK) pathway controls intestinal epithelial barrier permeability by regulating the tight junction. 1,25-dihydroxyvitamin D (1,25(OH)2D3)-vitamin D receptor (VDR) ...signaling protects the epithelial barrier, but the molecular mechanism is incompletely understood.
MLCK activation and barrier permeability were studied using monolayers of HCT116, Caco-2, and SW480 cells treated with tissue necrosis factor α with or without 1,25(OH)2D3. The MLCK pathway was analyzed in normal and inflamed colonic biopsies from patients with ulcerative colitis. Colonic mucosal barrier permeability and MLCK activation were also investigated using trinitrobenzene sulfonic acid-induced colitis models in vitamin D analog paricalcitol-treated wild-type mice and mice carrying VDR deletion in colonic epithelial cells.
Tissue necrosis factor α increased cell monolayer permeability and induced long isoform of MLCK expression and myosin II regulatory light chain (MLC) phosphorylation, and 1,25(OH)2D3 blocked tissue necrosis factor α-induced increases in monolayer permeability and MLCK-MLC pathway activation by a VDR-dependent fashion. 1,25(OH)2D3 directly suppressed long MLCK expression by attenuating NF-κB activation, and chromatin immunoprecipitation assays confirmed that 1,25(OH)2D3 disrupted p65 binding to 3 κB sites in long MLCK gene promoter. In human ulcerative colitis biopsies, VDR reduction was associated with increases in long MLCK expression and MLC phosphorylation. In trinitrobenzene sulfonic acid colitis models, paricalcitol ameliorated colitis, attenuated the increase in mucosal barrier permeability, and inhibited long MLCK induction and MLC phosphorylation. In contrast, mice with colonic epithelial VDR deletion exhibited more robust increases in mucosal barrier permeability and MLCK activation compared with wild-type mice.
These data demonstrate that 1,25(OH)2D3-VDR signaling preserves the mucosal barrier integrity by abrogating MLCK-dependent tight junction dysregulation during colonic inflammation.
Abstract
Objective
The incidence of open reduction and internal fixation (ORIF) in flexion-type supracondylar humerus fractures (SCHF) in children is significantly higher than that of extension-type ...fractures. This study aimed to identify risk factors for ORIF in flexion-type SCHF.
Methods
One hundred seventy-one patients with Wilkins type III flexion-type SCHF from January 2012 to December 2021 were retrospectively enrolled in a tertiary paediatric hospital. Patients were divided into ORIF group versus closed reduction and internal fixation (CRIF) group. Then, patients data of age, sex, injury side, obesity, deviation of displacement, fracture level, rotation, nerve injury, and delay from injury to surgery were reviewed. Univariate analysis and multivariate logistic regression were used to identify independent risk factors and odds ratios (OR) of ORIF.
Results
Overall, 171 children with type III flexion-type SCHF were analyzed (average aged 7.9 ± 2.8 years). Displacement was lateral in 151 cases, medial in 20. 20 cases had combined ulnar nerve injury. The failed closed reduction rate was 20%. Univariate analysis indicated age, distal fracture fragment rotation, and ulnar nerve injury were significantly associated with ORIF. (
P
= 0.047,
P
= 0.009, and
P
= 0.001, respectively). Multivariate logistic regression analysis showed that distal fracture fragment rotation (OR, 3.3; 95%CI:1.1–9.5;
P
= 0.028) and ulnar nerve injury (OR, 6.4; 95%CI:2.3–18.3;
P
= 0.001) were independent risk factors; however, the age was not an independent one (OR, 1.5; 95%CI:0.6–3.5;
P
= 0.397) for ORIF in the Wilkins type III flexion-type SCHF.
Conclusion
Distal fracture fragment malrotation on initial x-rays and ulnar nerve injury were significant risk factors for ORIF in Wilkins type III flexion-type SCHF. Surgeons should prepare tourniquets or other open reduction instruments when treating these types of fractures.
Level of evidence
Level IV
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Management of distal humerus metaphyseal-diaphyseal junction (MDJ) region fractures can be very challenging mainly because of the higher location and characteristics of the fracture lines. Loss of ...reduction is relatively higher in MDJ fractures treated with classical supracondylar humerus fractures (SHFs) fixation techniques.
Three different fracture patterns including transverse, medial oblique and lateral oblique fractures were computationally simulated in the coronal plane in the distal MDJ region of a pediatric humerus and fixated with Kirschner Wires (K-wires), elastic stable intramedullary nails (ESIN), and lateral external fixation system (EF). Stiffness values in flexion, extension, valgus, varus, internal, and external rotations for each fixation technique were calculated.
In the transverse fracture model, 3C (1-medial, 2-lateral K-wires) had the best stiffness in flexion, varus, internal, and external rotations, while 3L (3-divergent lateral K-wires) was the most stable in extension and valgus. In the medial oblique fracture model, EF had the best stiffness in flexion, extension, valgus, and varus loadings, while the best stiffness in internal and external rotations was generated by 3MC (2-medial, 1-lateral K-wires). In the lateral oblique fracture model, 3C (1-medial, 2-lateral K-wires) had the best stiffness in flexion and internal and external rotations, while ESIN had the best stiffness in extension and valgus and varus loadings.
The best stability against translational forces in lateral oblique, medial oblique, and transverse MDJ fractures would be provided by ESIN, EF, and K-wires, respectively. K-wires are however superior to both ESIN and EF in stabilizing all three fracture types against torsional forces, with both 2-crossed and 3-crossed K-wires having comparable stability. Depending on the fracture pattern, a 3-crossed configuration with either 2-divergent lateral and 1-medial K-wires or 2-medial and 1-lateral K-wires may offer the best stability.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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