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1.
Food Chem ; 306: 125613, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31610331

RESUMO

Reduction of bitter taste in protein hydrolysates is a challenging task. The aim of this study was to apply a simple two-step approach to prepare low bitter hydrolysates and investigate the influence of peptide modifications on taste characteristics. Protein hydrolysates were prepared from porcine muscle and plasma through simultaneous hydrolysis using endo- and exo-peptidases combined with peptide glycation by glucosamine (GlcN). Spectroscopic analysis and quantification of major alpha-dicarbonyl compounds (α-DCs) indicated the relatively low extent of Maillard reaction in GlcN-glycated protein hydrolysates. Thermal degradation of high MW peptides (>10 kDa) might play a major role in Maillard reaction, reflected by the formation of more Maillard reacted peptides (1-5 kDa), especially in plasma samples. Sensory evaluation indicated that glycation by GlcN can alter taste profiles of protein hydrolysates, which may be attributed to the formation of Maillard reacted peptides and peptide modifications revealed by LC-MS/MS analysis.

2.
J Ethnopharmacol ; 247: 112283, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31605736

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Bulbus Fritillaria cirrhosa D. Don (BFC) is a Chinese traditional herbal medicine that has long been used as an indispensable component in herbal prescriptions for bronchopulmonary diseases due to its well-established strong anti-inflammation and pulmonary harmonizing effects. Interestingly, there are few case reports in traditional Chinese medicine available where they found it to contribute in anti-tumor therapies. Imperialine is one of the most favored active substances extracted from BFC and has been widely recognized as an anti-inflammatory agent. AIM OF THE STUDY: The aim of the current work is to provide first-hand evidences both in vitro and in vivo showing that imperialine exerts anti-cancer effects against non-small cell lung cancer (NSCLC), and to explore the molecular mechanism of this anti-tumor activity. It is also necessary to examine its systemic toxicity, and to investigate how to develop strategies for feasible clinical translation of imperialine. MATERIALS AND METHODS: To investigate anti-NSCLC efficacy of imperialine using both in vitro and in vivo methods where A549 cell line were chosen as in vitro model NSCLC cells and A549 tumor-bearing mouse model was constructed for in vivo study. The detailed underlying anti-cancer mechanism has been systematically explored for the first time through a comprehensive set of molecular biology methods mainly including immunohistochemistry, western blot and enzyme-linked immunosorbent assays. The toxicity profile of imperialine treatments were evaluated using healthy nude mice by examining hemogram and histopathology. An imperialine-loaded liposomal drug delivery system was developed using thin film hydration method to evaluate target specific delivery. RESULTS: The results showed that imperialine could suppress both NSCLC tumor and associated inflammation through an inflammation-cancer feedback loop in which NF-κB activity was dramatically inhibited by imperialine. The NSCLC-targeting liposomal system was successfully developed for targeted drug delivery. The developed platform could favorably enhance imperialine cellular uptake and in vivo accumulation at tumor sites, thus improving overall anti-tumor effect. The toxicity assays revealed imperialine treatments did not significantly disturb blood cell counts in mice or exert any significant damage to the main organs. CONCLUSIONS: Imperialine exerts anti-cancer effects against NSCLC both in vitro and in vivo, and this previously unknown function is related to NF-κB centered inflammation-cancer feedback loop. Imperialine mediated anti-cancer activity is not through cytotoxicity and exhibit robust systemic safety. Furthermore, the liposome-based system we commenced would dramatically enhance therapeutic effects of imperialine while exhibiting extremely low side effects both on cellular and in NSCLC model. This work has identified imperialine as a promising novel anti-cancer compound and offered an efficient target-delivery solution that greatly facilitate practical use of imperialine.

3.
Int Wound J ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31696637

RESUMO

Fistula formation in head and neck wounds is considered one of the most challenging complications that a head and neck reconstructive surgeon may encounter. The current mainstay of treatment is aggressive surgical debridement followed by vascularised soft tissue coverage. Negative pressure wound therapy (NPWT) has been successfully used for the closure of complicated wounds for decades. This study analysed the outcomes and complications of NPWT in the management of head and neck wounds with fistulas. A systematic search of studies published between January 1966 and September 2019 was conducted using the PubMed, MEDLINE, EMBASE, and SCOPUS databases and using the following key words: "negative pressure wound therapy," "head and neck," and "fistula." We included human studies with abstract and full text available. Analysed endpoints were rate of fistula closure, follow-up duration, and complications if present. Nine retrospective case series (Level IV evidence) that collectively included 122 head and neck wounds with orocutaneous fistulas, pharyngocutaneous fistulas, and salivary contamination were examined. The number of patients included in each study ranged from 5 to 64. The mode of NPWT varied among the included studies, with most adopting a continuous pressure of -125 mm Hg. Mean durations of NPWT ranged from 3.7 to 23 days, and the reported fistula closure rate ranged from 78% to 100%. To achieve complete wound healing, six studies used additional procedures after stopping NPWT, including conventional wound dressings and vascularised tissue transfer. Information regarding follow up was provided in only three of the nine studies, where patients were followed for 5, 10, and 18 months. No serious adverse events were reported. NPWT for head and neck wounds with fistulas may be considered a safe treatment method that yields beneficial outcomes with a low risk of complications. The current data originated mainly from studies with low levels of evidence characterised by heterogeneity. Therefore, definitive recommendations based on these data cannot be offered. Additional high-quality trials are warranted to corroborate the findings of this systematic review.

4.
Mikrochim Acta ; 186(12): 803, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31741092

RESUMO

A general approach is presented for synthesis of multicolored gold nanoparticles (GNPs) by Au(I)-mediated generation of interlocking rings in proteins and antibiotics. The Au(I) ions are shuttled from proteins to antibiotics, and this causes the formation of interlocking rings. The multicolored GNPs of different sizes were synthesized in the rings by using the rapid nucleation method. To take the unique colors of GNPs, a functional array was designed for the colorimetric determination and discrimination of antibiotics, specifically of amoxicillin, chlortetracycline, erythromycin, spiramycin, neomycin, thiamphenicol, gentamycin and lincomycin. The method is based on the "three color" (RGB) principle. The color response patterns are characteristic for each antibiotic and can be quantitatively differentiated by statistical techniques. The limits of detection (LOD, at S/N = 3) for spiramycin (Sp) have been calculated to be 0.18 µM and 0.10 µM in water and milk, respectively. The good linear range (from 0.3 to 3.5 µM) has been used for the quantitative assay of Sp in a certified reference material. Graphical abstractSchematic presentation of gold nanoparticles (GNPs) synthesis via formation of interlocking rings in protein and antibiotics. The Au(I) ions mediate protein and antibiotics to be interlocking rings, which are quickly fixed via microwave reaction. The GNPs are synthesized and assembled in the rings.

5.
BMC Immunol ; 20(1): 42, 2019 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-31718550

RESUMO

BACKGROUND: Myeloid cells, especially mononuclear phagocytes, which include monocytes, macrophages and dendritic cells (DC), play vital roles in innate immunity, and in the initiation and maintenance of adaptive immunity. While T cell-associated activation pathways and cytokines have been identified and evaluated in inflammatory bowel disease (IBD) patients (Neurath, Nat Rev Gastroenterol Hepatol 14:269-78, 1989), the role of mononuclear phagocytes are less understood. Recent reports support the crucial role of DC subsets in the development of acute colitis models (Arimura et al., Mucosal Immunol 10:957-70, 2017), and suggest they may contribute to the pathogenesis of ulcerative colitis (UC) by inducing Th1/Th2/Th17 responses (Matsuno et al., Inflamm Bowel Dis 23:1524-34, 2017). RESULTS: We performed in silico analysis and evaluated the enrichment of immune cells, with a focus on mononuclear phagocytes in IBD patient colonic biopsies. Samples were from different gut locations, with different levels of disease severity, and with treatment response to current therapies. We observe enrichment of monocytes, M1 macrophages, activated DCs (aDCs) and plasmacytoid dendritic cells (pDCs) in inflamed tissues from various gut locations. This enrichment correlates with disease severity. Additionally, the same mononuclear phagocytes subsets are among the top enriched cell types in both infliximab and vedolizumab treatment non-responder samples. We further investigated the enrichment of selected DC and monocyte subsets based on gene signatures derived from a DC- and monocyte-focused single cell RNA-seq (scRNA-seq) study (Villani et al., Science 356:eaah4573, 2017), and verified enrichment in both inflamed tissues and those with treatment resistance. Moreover, we validated an increased mononuclear phagocyte subset abundance in a Dextran Sulphate Sodium (DSS) induced colitis model in C57Bl/6 mice representative of chronic inflammation. CONCLUSIONS: We conducted an extensive analysis of immune cell populations in IBD patient colonic samples and identified enriched subsets of monocytes, macrophages and dendritic cells in inflamed tissues. Understanding how they interact with other immune cells and other cells in the colonic microenvironment such as epithelial and stromal cells will help us to delineate disease pathogenesis.

6.
Tuberculosis (Edinb) ; 119: 101862, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31733417

RESUMO

Nucleoid-associated proteins (NAPs) play an important role on chromosome condensation and organization. Mycobacterial integration host factor (mIHF) is one of the few mycobacterial NAPs identified so far. mIHF has the ability to stimulate mycobacteriophage L5 integration and compact DNA into nucleoid-like or higher order filamentous structures by atomic force microscopy observation. In this study, M. smegmatis IHF (MsIHF), which possesses the sequence essential for mIHF's functions, binds 30-bp dsDNA fragments in a sequence-independent manner and displays sensitivity to ion strength in bio-layer interferometry (BLI) experiments. The DNA compaction process of MsIHF was observed at the single-molecule level using the total internal reflection fluorescence microscopy (TIRFM). MsIHF efficiently compacted λ DNA into a highly condensed structure with the concentration of 0.25 and 1.0 µM, and the packing ratios were higher than 10. Further kinetic analysis revealed MsIHF compacts DNA in a three-step mechanism, which consists of two compaction steps with different compacting rates separated by a lag step. This study would help us better understand the mechanisms of chromosomal DNA organization in mycobacteria.

7.
Crit Rev Food Sci Nutr ; : 1-14, 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31738577

RESUMO

Food protein-derived peptides serve as food ingredients that can influence flavor and bioactivity of foods. The Maillard reaction plays a crucial role in food processing and storage, and generates a wide range of Maillard reaction products (MRPs) that contribute to flavor and bioactivity of foods. Even though the reactions between proteins and carbohydrates have been extensively investigated, the modifications of food protein-derived peptides and the subsequent impacts on flavor and bioactivity of foods have not been fully elucidated. In this review, the flavor and bioactive properties of food-derived peptides are reviewed. The formation mechanisms with respect to MRPs generated from food protein-derived peptides have been discussed. The state-of-the-art studies on impacts of the Maillard reaction on flavor and bioactivity of food protein-derived peptides are also discussed. In addition, some potential negative effects of MRPs are described.

8.
Inflammation ; 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31760526

RESUMO

C-reactive protein (CRP) is a major human acute-phase reactant that is composed of five identical subunits. CRP dissociates into subunits at inflammatory loci forming monomeric CRP (mCRP) with substantially enhanced activities, which can be further activated by reducing the intra-subunit disulfide bond. However, conformational changes underlying the activation process of CRP are less well understood. Conformational changes accompanying the conversion of CRP to mCRP with or without reduction were examined with circular dichroism spectroscopy, fluorescence spectroscopy, electron microscopy, size-exclusion chromatography, and neoepitope expression. The conversion of CRP to mCRP follows a two-stage process. In the first stage, CRP dissociates into molten globular subunits characterized by intact secondary structure elements with greatly impaired tertiary packing. In the second stage, these intermediates completely lose their native subunit conformation and assemble into high-order aggregates. The inclusion of reductant accelerates the formation of molten globular subunits in the first step and promotes the formation of more compact aggregates in the second stage. We further show a significant contribution of electrostatic interactions to the stabilization of native CRP. The conformational features of dissociated subunits and the aggregation of mCRP may have a key impact on their activities.

9.
Org Biomol Chem ; 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31748773

RESUMO

A hemin/H2O2 catalytic system for oxidative phenol-indole [3 + 2] coupling in aqueous solution has been developed, enabling benign synthesis of valuable benzofuroindolines under sustainable conditions. Mechanistic studies revealed the dual role of iron porphyrin responsible for both phenol oxidation and Lewis acid activation, which differs from the well-explored chemistry of hemin in carbene and nitrene insertion reactions. A preliminary experiment with cytochrome c showed that the turnover of iron porphyrin was amenable for a macromolecular setting with remarkable efficiency (ca. 13 300 TON).

10.
BMC Pediatr ; 19(1): 443, 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31731890

RESUMO

BACKGROUND: Acute appendicitis (AA) is the most common surgical condition in children. Although a higher incidence of AA in summer has been reported, the reason for this observation remains unclear. The purpose of this study was to compare the clinical findings of AA patients who underwent appendectomies during the summer months with those who underwent the procedure during the non-summer months. METHODS: The clinical data of 171 patients who underwent appendectomy from January 2013 to December 2016 were reviewed. The patients were divided into a summer group (from May to October) and a non-summer group (from November to April) based on the month when appendectomy was performed. All patients were under 18 years of age at the time of surgery. The medical records including laboratory data, computed tomography scans, pathology reports and operative notes were reviewed. RESULTS: The number of patients with AA was higher in the summer group than in the non-summer group (101 vs. 70 patients). No significant differences in the laboratory results between the two groups of patients were observed. The percentage of AA patients who presented with a fecalith was significantly lower in the summer group (33.6%) than in the non-summer group (55.7%). No significant differences in the incidence of appendiceal perforations and abscesses, as well as postoperative complications were observed between the two groups. CONCLUSIONS: The percentage of AA patients with fecaliths in summer was lower than that in the non-summer months. The increase in the number of AA patients in summer may be due to the increased occurrence of lymphoid hyperplasia, which may be correlated with the yearly outbreak of enterovirus infection during this period.

11.
Mol Immunol ; 117: 122-130, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31765841

RESUMO

The acute phase reactant C-reactive protein (CRP) binds with high affinity to fibronectin (FN), but this binding occurs only at pH 6.5 or lower, and the binding is inhibited by calcium ions at physiological pH. Since CRP in the circulating blood exists in a calcium-binding form, the interaction between CRP and FN in vivo has been uncertain. CRP can undergo a conformational rearrangement in the absence of calcium or in the local microenvironment (e.g., acidic pH) of inflamed tissue to dissociate into monomeric CRP (mCRP). Therefore, we tested whether these discrepancies can be explained by the different isoforms and locations of CRP. Surface plasmon resonance and ELISA assays showed that mCRP binds with high affinity to FN, and the binding of mCRP to FN was unaffected by calcium or pH. Peptide competition assay, deletion mutant binding assay and protein docking analyse verified that the binding site of mCRP to FN is residues a.a.35-47. Furthermore, mCRP can significantly enhance the adhesion of monocytes to FN as well as upregulate the adhesion molecules expression on endothelial cell. Colocalization of mCRP with FN was observed in mice with DSS-induced colitis, whereas there was very little signal orcolocalization of CRP. These results provide in vitro and in vivo evidence that mCRP formed by local dissociation from circulating CRP is the major isoform that interacts with FN and regulates FN-mediated monocyte adhesion, which is involved in the pro-inflammatory process.

12.
Medicine (Baltimore) ; 98(48): e18203, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31770276

RESUMO

The aim of this study was to evaluate the safety and clinical effectiveness of endovascular stent repair of celiac arterial aneurysm (CAA).From January 2015 to December 2018, 11 patients (7 males, 4 females with a mean age of 52.2 ±â€Š7.9 years) underwent endovascular stent repair of CAA in our center. A covered stent was used to occlude the CAA neck. Follow-up was performed 2 weeks and 1, 3, 6, and 12 months following surgery and yearly thereafter. Rates of technical success, treatment-related complications, and long-term outcome were analyzed.Each patient was placed with 1 stent for repair of CAA. Stent was placed in the celiac and common hepatic arteries for 10 patients and was placed in the celiac artery for 1 patient. The duration of the procedure ranged from 50 to 75 minutes (mean 63.2 ±â€Š7.2 minutes). The rate of technical success of the endovascular stent repair was 100%. No patient experienced CAA rupture or instant endoleak during or after stent insertion. Abdominal pain was relieved progressively after stent insertion. All patients were followed-up for 6 to 48 months (mean 22.4 ±â€Š10.8 months). All patients were alive during the follow-up. No endoleaks were experienced during follow-up with 100% stent patency rate. No patient suffered splenic, hepatic, or bowel infarction during follow-up.Endovascular stent repair is a safe, simple, and effective treatment for patients with CAA.

13.
Eur Radiol ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31776740

RESUMO

OBJECTIVES: To assess the relative diagnostic utility of low- and standard-dose computed tomography (CT)-guided lung biopsy. METHODS: In this single-center, single-blind, prospective, randomized controlled trial, patients were enrolled between November 2016 and June 2017. Enrolled study participants were randomly selected to undergo either low- or standard-dose CT-guided lung biopsy. Diagnostic accuracy was the primary study endpoint, whereas technical success, radiation dose, and associated complications were secondary study endpoints. RESULTS: In total, 280 patients underwent study enrollment and randomization, with 271 (low-dose group, 135; standard-dose group, 136) receiving the assigned interventions. Both groups had a 100% technical success rate for CT-guided lung biopsy, and complication rates were similar between groups (p > 0.05). The mean dose-length product (36.0 ± 14.1 mGy cm vs. 361.8 ± 108.0 mGy cm, p < 0.001) and effective dose (0.5 ± 0.2 mSv vs. 5.1 ± 1.5 mSv, p < 0.001) were significantly reduced in the low-dose group participants. Sensitivity, specificity, and overall diagnostic accuracy rates in the low-dose group were 91.8%, 100%, and 94.6%, respectively, whereas in the standard-dose group, the corresponding values were 89.6%, 100%, and 92.4%, respectively. These results indicated that diagnostic performance did not differ significantly between the 2 groups. Using univariate and multivariate analyses, we found larger lesion size (p = 0.038) and procedure-related pneumothorax (p = 0.033) to both be independent predictors of diagnostic failure. CONCLUSIONS: Our results demonstrate that low-dose CT-guided lung biopsy can yield comparable diagnostic accuracy to standard-dose CT guidance, while significantly reducing the radiation dose delivered to patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02971176 KEY POINTS: • Low-dose CT-guided lung biopsy is a safe and simple method for diagnosis of lung lesions. • Low-dose CT-guided lung biopsy can yield comparable diagnostic accuracy to standard-dose CT guidance. • Low-dose CT-guided lung biopsy can achieve a 90% reduction in radiation exposure when compared with standard-dose CT guidance.

14.
J Cell Physiol ; 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31621909

RESUMO

It has been widely accepted that long-noncoding RNA (lncRNA) HOX transcript antisense intergenic RNA (HOTAIR) emerges as a crucial mediator in inflammation. Here, we first detected HOTAIR in lipopolysaccharide (LPS)-treated normal human liver cell line (L02) and hepatocellular carcinoma cell lines (C3A, HepG2, and SMMC-7721). Further, we explored the biological function of HOTAIR in LPS-induced hepatocytes (L02 and C3A) lesions and investigated the molecular mechanisms. Besides, we focused on inflammatory signaling crosstalk. The inflammatory insults were assayed by cell counting kit-8 (CCK-8), cell cycle and apoptosis analysis kit, and immunoblotting assay. HOTAIR level was examined by reverse-transcription polymerase chain reaction. To determine the effect of HOTAIR silence or overexpression in inflammation, we applied quantitative reverse-transcription polymerase chain reaction, immunoblotting assay, and enzyme-linked immuno sorbent assay. Regulator inhibitors of Janus kinase/signal transducer and activator of transcription (JAK2/STAT3; AG490) and nuclear factor κB (NF-κB; BAY-11-7082) were applied to treat cells. Our results suggested that LPS induced the overexpression of HOTAIR in L02, C3A, HepG2, and SMMC-7721 cells. LPS repressed viability, induced apoptosis, and facilitated the expression of interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in L02 and C3A cells. IL-1ß, IL-6, and TNF-α were upregulated by HOTAIR overexpression while downregulated by HOTAIR knockdown in LPS-treated cells. We further observed that HOTAIR overexpression accelerated LPS-induced phosphorylation whereas HOTAIR silence blocked this progress. Inhibition of JAK/STAT and NF-κB contributed to the suppression of cytokines which was evoked by LPS. Collectively, our findings indicated that HOTAIR exerted a crucial role in cytokines expression by activating JAK/STAT and NF-κB.

15.
Sci Rep ; 9(1): 14945, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31628361

RESUMO

Acute ischemic stroke (AIS) has a high risk of recurrence, particularly in the early stage. The purpose of this study was to assess the frequency and risk factors of in-hospital recurrence in patients with AIS in China. A retrospective analysis was performed of all of the patients with new-onset AIS who were hospitalized in the past three years. Recurrence was defined as a new stroke event, with an interval between the primary and recurrent events greater than 24 hours; other potential causes of neurological deterioration were excluded. The risk factors for recurrence were analyzed using univariate and logistic regression analyses. A total of 1,021 patients were included in this study with a median length of stay of 14 days (interquartile range,11-18). In-hospital recurrence occurred in 58 cases (5.68%), primarily during the first five days of hospitalization. In-hospital recurrence significantly prolonged the hospital stay (P < 0.001), and the in-hospital mortality was also significantly increased (P = 0.006). The independent risk factors for in-hospital recurrence included large artery atherosclerosis, urinary or respiratory infection and abnormal blood glucose, whereas recurrence was less likely to occur in the patients with aphasia. Our study showed that the patients with AIS had a high rate of in-hospital recurrence, and the recurrence mainly occurred in the first five days of the hospital stay. In-hospital recurrence resulted in a prolonged hospital stay and a higher in-hospital mortality rate.

16.
ACS Appl Mater Interfaces ; 11(44): 41668-41675, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31623430

RESUMO

Dynamic color-changing nanomaterials have been widely investigated for applications in fields like optical sensors, wearable activity monitors, smart electronic devices, and anticounterfeiting materials due to the excellent ability to change their optical properties with external variation. Here, a simple metal-insulator-metal (MIM) trilayer Fabry-Perot resonance cavity with a poly(N-isopropylacrylamide) (PNIPAm) brush layer as a responsive element is reported as a thermal-induced colorimetric response platform. The dynamic changes of conformation and physical properties of PNIPAm brush layer in response to external signals give rise to a significant color change of the MIM Fabry-Perot resonance cavity. This MIM Fabry-Perot resonance cavity shows the advantages of dynamic color change, rapid response, good repeatability, and simple construction. Additionally, the as-prepared MIM cavity shows great potential in various applications such as color printing, multicolor indicator, and information anticounterfeiting.

17.
Chem Commun (Camb) ; 55(83): 12567-12570, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31577281

RESUMO

Amorphous bimetallic coordination polymers have been prepared by a mild room temperature solution phase method and utilized as an OER electrocatalyst. Their excellent performance with an overpotential of 228 mV at 10 mA cm-2 and a Tafel slope of 30.3 mV dec-1 exhibits their great potential in the field of the OER.

18.
Int J Med Sci ; 16(9): 1313-1319, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588198

RESUMO

Background: Preimplantation genetic testing for monogenic disease (PGT-M) has become an effective method for providing couples with the opportunity of a pregnancy with a baby free of spinal muscular atrophy (SMA). Multiple displacement amplification (MDA) overcomes the innate dilemma of very limited genetic material available for PGT-M. Objective: To evaluate the use of MDA, combined with haplotype analysis and mutation amplification, in PGT-M for families with SMA. Methods: MDA was used to amplify the whole genome from single blastomeres or trophectoderm (TE) cells. Exon 7 of the survival motor neuron gene 1 (SMN1) and eleven STRs markers flanking the SMN1 gene were incorporated into singleplex polymerase chain reaction (PCR) assays on MDA products. Results: Sixteen cycles (19 ovum pick-up cycles) of PGT-M were initiated in 12 couples. A total of 141 embryos were tested: 90 embryos were biopsied at the cleavage stage and 51 embryos were biopsied at the blastocyst stage. MDA was successful on 94.44% (85/90) of the single blastomeres and on 92.16% (47/51) of the TE cells. And the PCR efficiency were 98.4% (561/570) and 100% (182/182), respectively. In addition, the average allele drop-out (ADO) rates were 13.3% (60/392) and 9.8% (11/112), respectively. The results for SMN1 exon 7 were all matched with haplotype analysis, which allowed an accurate diagnosis of 93.62% (132/141) embryos. Twelve families had unaffected embryos available for transfer and a total of 38 embryos were transferred in 20 embryo transfer cycles. Eight transfers were successful, resulting in a clinical pregnancy rate of 40% (8/20) and an implantation rate of 28.95% (11/38). Finally, 11 healthy babies were born. Among them, 5 SMA carriers were singleton live births and 3 SMA carriers had twin births. Conclusion: Careful handling during the MDA procedure can improve subsequent PCR efficiency and reduce the ADO rate. We suggest that this protocol is reliable for increasing the accuracy of the PGT-M for SMA.

19.
Theranostics ; 9(22): 6646-6664, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588241

RESUMO

Pulmonary fibrosis (PF) is a progressive and irreversible condition with various causes, and no effective treatment has been found to rescue fibrotic lungs. Successful recovery from PF requires inhibiting inflammation, promoting collagen degradation and stimulating alveolar regeneration. Human umbilical mesenchymal stem cells (HUMSCs) not only regulate immune responses but also synthesize and release hyaluronan to improve lung regeneration. This study investigated the feasibility of HUMSC engraftment into rats with bleomycin (BLM)-induced PF to explore HUMSC therapeutic effects/outcomes. Methods: A unique BLM-induced left-lung-dominated PF animal model was established. Rats were transplanted with low-dose (5×106) or high-dose (2.5×107) HUMSCs on Day 21 after BLM injection. Combinations in co-culture of pulmonary macrophages, fibroblasts, HUMSCs treated with BLM and the same conditions on alveolar epithelia versus HUMSCs were evaluated. Results: Rats with high-dose HUMSC engraftment displayed significant recovery, including improved blood oxygen saturation levels and respiratory rates. High-dose HUMSC transplantation reversed alveolar injury, reduced cell infiltration and ameliorated collagen deposition. One month posttransplantation, HUMSCs in the rats' lungs remained viable and secreted cytokines without differentiating into alveolar or vascular epithelial cells. Moreover, HUMSCs decreased epithelial-mesenchymal transition in pulmonary inflammation, enhanced macrophage matrix-metallopeptidase-9 (MMP-9) expression for collagen degradation, and promoted toll-like receptor-4 (TLR-4) expression in the lung for alveolar regeneration. In coculture studies, HUMSCs elevated the MMP-9 level in pulmonary macrophages, released hyaluronan into the medium and stimulated the TLR-4 quantity in the alveolar epithelium. Principal Conclusions: Transplanted HUMSCs exhibit long-term viability in rat lungs and can effectively reverse rat PF.

20.
ANZ J Surg ; 89(11): E514-E518, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31578777

RESUMO

BACKGROUND: Wedge resection via video-assisted thoracoscopic surgery (VATS) is the best choice for the diagnosis of sub-solid lung nodules. Preoperative localization is utilized to increase the success rate of this procedure. We aimed to evaluate the effectiveness of preoperative coil localization in VATS wedge resection for sub-solid lung nodules. METHODS: From October 2015 to August 2018, 42 patients with 55 sub-solid lung nodules underwent computed tomography-guided coil localization with subsequent VATS wedge resection in our centre. Data regarding visible coil rates, technical success of the wedge resection and pathological results were collected and analysed retrospectively. RESULTS: A total of 55 sub-solid lung nodules were localized in 42 patients. Thirty-three patients had one nodule and nine patients had multiple nodules. Fifty-two coils (52/55, 94.5%) were visible during the VATS. The mean duration of each coil localization was 14.3 ± 4.8 min (range 7-40 min). Three patients (7%) experienced pneumothorax after coil localization. VATS wedge resection was successfully performed for 53 nodules (53/55, 96.4%). The remaining two nodules were treated directly with lobectomy. The nine patients who had multiple nodules underwent one-stage VATS wedge resection of all nodules. The mean duration of the VATS in the 42 patients was 159.3 ± 83.4 min (range 60-360 min) while the mean blood loss was 119.3 ± 115.3 mL (range 10-700 mL). CONCLUSION: Preoperative computed tomography-guided coil localization is a safe and effective method to facilitate high success rates for diagnostic VATS wedge resection for sub-solid nodules.

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