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1.
bioRxiv ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38853845

RESUMO

Drosophila germ granules enrich mRNAs critical for fly development. Within germ granules, mRNAs form multi-transcript clusters marked by increased mRNA concentration, creating an elevated potential for intermolecular base pairing. However, the type and abundance of intermolecular base pairing in mRNA clusters is poorly characterized. Using single-molecule super-resolution microscopy, chemical probing for base accessibility, phase separation assays, and simulations, we demonstrated that mRNAs remain well-folded upon localization to germ granules. While most base pairing is intramolecular, mRNAs still display the ability for intermolecular base pairing, facilitating clustering without high sequence complementarity or significant melting of secondary structure. This base pairing among mRNAs is driven by scattered and discontinuous stretches of bases appearing on the surface of folded RNAs, providing multivalency to clustering but exhibits low probability for sustained interactions. Notably, engineered germ granule mRNAs with exposed GC-rich complementary sequences (CSs) presented within stable stem loops induce sustained base pairing in vitro and enhanced intermolecular interactions in vivo. However, the presence of these stem loops alone disrupts fly development, and the addition of GC-rich CSs exacerbates this phenotype. Although germ granule mRNAs contain numerous GC-rich CSs capable of stable intermolecular base pairing, they are primarily embedded by RNA folding. This study emphasizes the role of RNA folding in controlling the type and abundance of intermolecular base pairing, thereby preserving the functional integrity of mRNAs within the germ granules.

2.
Burns Trauma ; 12: tkae005, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716050

RESUMO

Background: Despite being a stable component of burn rehabilitation at later stages of recovery, exercise training is not commonly provided during the acute phase of burns. A lack of evidence surrounding its efficacy and safety in severely burned adults has hampered its implementation in acute burn care. The aim of this study was to investigate the capacity of early exercise training to modulate parameters of postburn muscle wasting and quality of life. Methods: Adults <65 years of age with burns ≥40% total burn surface area (TBSA) were randomly allocated to either receive early exercise (n = 29) in addition to standard care or standard care alone (n = 29). Early exercise involved resistance and aerobic training, which commenced as early as possible and lasted for a duration of 6 to 12 weeks, in line with burn center length of stay. Ultrasound-derived quadriceps muscle layer thickness (QMLT) and rectus femoris cross-sectional area (RF-CSA), lower limb muscle force, Eurocol Quality of Life-5 Dimensions and Burn Specific Health Scale Brief (BSHS-B) were assessed 6 and 12 weeks after baseline. Mixed models were fitted to compare between-group changes over time. Results: A total of 58 adults [42 (95% confidence interval 40-45) years old; 40-94% TBSA range, 86% previously mechanically ventilated] participated in this study. Exercise commenced 7 days [IQR (interquartile range) 5-9] after burn center admission with an attendance rate of 93%. Allocation to the exercise group had a protective effect on the loss of muscle size from baseline to 6 weeks of follow-up (QMLT: ß-coefficient: 0.05 cm, p = 0.010; RF-CSA: ß-coefficient: 0.05 cm2, p = 0.045), and resulted in an improved recovery from 6 to 12 weeks (QMLT: ß-coefficient: 0.04 cm, p = 0.01; RF-CSA: ß-coefficient: 0.06 cm2, p < 0.001). Muscle force increased significantly more in the exercise group than in the control group (ß-coefficient: 3.102 N, p < 0.001) between 6 and 12 weeks. Besides a marginally significant effect for the BSHS-B domains 'affect' and 'interpersonal relationships' between 6 and 12 weeks, no benefits were observed in the other assessed quality-of-life measures. No serious adverse events were reported in the exercise group. Conclusions: The results of this study support the use of early exercise training as a feasible and efficacious therapeutic strategy to manage burn-related changes in muscle size and strength in adults with acute severe burn injury.

3.
Dig Liver Dis ; 56(1): 50-54, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37925254

RESUMO

BACKGROUND: Very early onset inflammatory bowel disease (VEOIBD) is associated with a unique disease course and distinct endoscopic features. AIMS: This study aims to provide a comprehensive description of the endoscopic and histologic features observed in a large cohort of patients with VEOIBD from a tertiary medical center. METHODS: A retrospective review of medical records from 2011 to 2021 was conducted to analyze clinical data, including disease phenotypes, endoscopic and histologic findings. Next generation sequencing was performed. RESULTS: A total of 225 VEOIBD subjects were included in this study. Monogenic defects were identified in 161 patients. Monogenic IBD patients more commonly had CD-like disease. Colonic involvement was more prevalent among those with monogenic IBD (P<0.001). Pseudo-polyps were significantly more common in the monogenic IBD group (P<0.001), while ileal edema and ulcers were significantly more prevalent in non-monogenic IBD cases. IL10RA deficiency were characterized by colonic ulcers and pseudo-polyps without upper gastrointestinal tract lesions, while patients with TNFAIP3 mutations demonstrated both upper and lower gastrointestinal tract involvement. The non-monogenic IBD patients showed a higher incidence of chronic architectural changes of crypt, increased apoptosis and eosinophils infiltration. CONCLUSIONS: Endoscopic and histologic analysis of children with VEOIBD plays a crucial role in facilitating accurate diagnosis. Various forms of monogenic IBD exhibit distinct endoscopic and pathologic changes.


Assuntos
Doenças Inflamatórias Intestinais , Pólipos , Criança , Humanos , Doenças Inflamatórias Intestinais/complicações , Úlcera/patologia , Colo/patologia , Endoscopia , Fenótipo
4.
Nat Commun ; 14(1): 6124, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37777513

RESUMO

Van der Waals interactions with transition metal dichalcogenides were shown to induce strong spin-orbit coupling (SOC) in graphene, offering great promises to combine large experimental flexibility of graphene with unique tuning capabilities of the SOC. Here, we probe SOC-driven band splitting and electron dynamics in graphene on WSe2 by measuring ballistic transverse magnetic focusing. We found a clear splitting in the first focusing peak whose evolution in charge density and magnetic field is well reproduced by calculations using the SOC strength of ~ 13 meV, and no splitting in the second peak that indicates stronger Rashba SOC. Possible suppression of electron-electron scatterings was found in temperature dependence measurement. Further, we found that Shubnikov-de Haas oscillations exhibit a weaker band splitting, suggesting that it probes different electron dynamics, calling for a new theory. Our study demonstrates an interesting possibility to exploit ballistic electron motion pronounced in graphene for emerging spin-orbitronics.

5.
Curr Res Food Sci ; 7: 100547, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37522134

RESUMO

In this study, Tuna trimmings (Thunnas albacares) protein hydrolysate (TPA) was produced by alcalase. The anti-tumor synergistic effect and intestinal mucosa protective effect of TPA on S180 tumor-bearing mice treated with 5-fluorouracil (5-FU) chemotherapy were investigated. The results showed that TPA can enhance the anti-tumor effect of 5-FU chemotherapy, as evident by a significant reduction in tumor volume observed in the medium and high dose TPA+5-FU groups compared to the 5-FU group (p < 0.001). Moreover, TPA significantly elevated the content of total protein and albumin in all TPA dose groups (p < 0.01, p < 0.001), indicating its ability to regulate the nutritional status of the mice. Furthermore, histopathological studies revealed a significant increase in the height of small intestinal villi, crypt depth, mucosal thickness, and villi area in the TPA+5-FU groups compared to the 5-FU group (p < 0.05), suggesting that TPA has a protective effect on the intestinal mucosa. Amino acid analysis revealed that TPA had a total amino acid content of 66.30 g/100 g, with essential amino acids accounting for 30.36 g/100 g. Peptide molecular weight distribution analysis of TPA indicated that peptides ranging from 0.25 to 1 kDa constituted 64.54%. LC-MS/MS analysis identified 109 peptide sequences, which were predicted to possess anti-cancer and anti-inflammatory activities through database prediction. Therefore, TPA has the potential to enhance the antitumor effects of 5-FU, mitigate immune depression and intestinal mucosal damage induced by 5-FU. Thus, TPA could be serve as an adjuvant nutritional support for malnourished patients undergoing chemotherapy.

6.
Natl Sci Rev ; 10(4): nwac232, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37180357

RESUMO

The recently discovered nonlinear Hall effect (NHE) in a few non-interacting systems provides a novel mechanism for generating second-harmonic electrical Hall signals under time-reversal-symmetric conditions. Here, we introduce a new approach to engineering an NHE by using twisted moiré structures. We found that the twisted WSe2 bilayer exhibited an NHE when the Fermi level was tuned to the moiré flat bands. When the first moiré band was half-filled, the nonlinear Hall signal exhibited a sharp peak with a generation efficiency that was at least two orders of magnitude greater than those obtained in previous experiments. We discuss the possible origins of the diverging generation efficiency in twisted WSe2 based on resistivity measurements, such as moiré-interface-induced correlation effects and mass-diverging-type continuous Mott transition. This study demonstrates not only how interaction effects can combine with Berry curvature dipoles to produce novel quantum phenomena, but also the potential of NHE measurements as a new tool for studying quantum criticality.

7.
Development ; 150(10)2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-37139779

RESUMO

Defining pattern formation mechanisms during embryonic development is important for understanding the etiology of birth defects and to inform tissue engineering approaches. In this study, we used tricaine, a voltage-gated sodium channel (VGSC) inhibitor, to show that VGSC activity is required for normal skeletal patterning in Lytechinus variegatus sea urchin larvae. We demonstrate that tricaine-mediated patterning defects are rescued by an anesthetic-insensitive version of the VGSC LvScn5a. Expression of this channel is enriched in the ventrolateral ectoderm, where it spatially overlaps with posterolaterally expressed Wnt5. We show that VGSC activity is required to spatially restrict Wnt5 expression to this ectodermal region that is adjacent and instructive to clusters of primary mesenchymal cells that initiate secretion of the larval skeleton as triradiates. Tricaine-mediated Wnt5 spatial expansion correlates with the formation of ectopic PMC clusters and triradiates. These defects are rescued by Wnt5 knockdown, indicating that the spatial expansion of Wnt5 is responsible for the patterning defects induced by VGSC inhibition. These results demonstrate a previously unreported connection between bioelectrical status and the spatial control of patterning cue expression during embryonic pattern formation.


Assuntos
Lytechinus , Ouriços-do-Mar , Animais , Larva , Padronização Corporal/genética , Regulação da Expressão Gênica no Desenvolvimento , Embrião não Mamífero/metabolismo
8.
Artigo em Inglês | MEDLINE | ID: mdl-36643387

RESUMO

Objective: To investigate the clinical effectiveness of laser and secure wound-closure system (Tension reducer) in the treatment of postoperative scarring after tension incision. Methods: A retrospectively observational study was conducted. Twenty-six patients who underwent surgical treatment in our department between June 2017 and December 2021 were selected, and those treated with laser and tension reducer were treated as a combined treatment group, and those treated with laser were treated as a conventional treatment group. Fifteen patients in the conventional group were treated with the pulsed dye laser and CO2 fractional laser at 1-2 month intervals. Eleven people in the combined treatment group were treated with the laser in addition to a tension reducer for 3-6 months. The scar width, scar thickness, scar hardness, pruritus score, modified Vancouver scar scale and complication rates between the two treatment modalities were compared between the two groups at 6 months postoperatively. Results: The scar thickness, scar hardness and modified Vancouver scar scale of 1.25 (0.14, 1.90) mm, 31.80 (21.00, 37.20) HA, (6.00 ± 2.17) in patients in the combined treatment group were less than those of patients in the conventional treatment group of 5.50 (4.00, 11.50) mm, 42.60 (32.50, 47.00) HA, (8.25±1.91), (Z=2.883, 2.718, t=2.904, p<0.05). The scar width and pruritus score in the combined treatment group, were 8.00 (5.00, 18.00) mm and 0 (0, 1) respectively, while the scar score and pruritus score in the conventional treatment group, were 5.50 (4.00, 11.50) mm respectively, with no statistically significant difference between the two groups. The complication rate was 55% in the combined treatment group and no adverse reactions occurred in the control group. Conclusion: Sequential laser combined with tension reducer treatment can effectively inhibit the proliferation of postoperative tension incision scar.

10.
J Clin Immunol ; 43(2): 495-511, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36370291

RESUMO

Balancing natural selection is a process by which genetic variants arise in populations that are beneficial to heterozygous carriers, but pathogenic when homozygous. We systematically investigated the prevalence, structural, and functional consequences of pathogenic IL10RA variants that are associated with monogenic inflammatory bowel disease. We identify 36 non-synonymous and non-sense variants in the IL10RA gene. Since the majority of these IL10RA variants have not been functionally characterized, we performed a systematic screening of their impact on STAT3 phosphorylation upon IL-10 stimulation. Based on the geographic accumulation of confirmed pathogenic IL10RA variants in East Asia and in Northeast China, the distribution of infectious disorders worldwide, and the functional evidence of IL-10 signaling in the pathogenesis, we identify Schistosoma japonicum infection as plausible selection pressure driving variation in IL10RA. Consistent with this is a partially augmented IL-10 response in peripheral blood mononuclear cells from heterozygous variant carriers. A parasite-driven heterozygote advantage through reduced IL-10 signaling has implications for health care utilization in regions with high allele frequencies and potentially indicates pathogen eradication strategies that target IL-10 signaling.


Assuntos
Interleucina-10 , Leucócitos Mononucleares , Humanos , Receptores de Interleucina-10/genética , Interleucina-10/genética , Subunidade alfa de Receptor de Interleucina-10/genética , Seleção Genética
11.
Nanomaterials (Basel) ; 12(19)2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36234623

RESUMO

Metal halide perovskites have become a research highlight in the optoelectronic field due to their excellent properties. The perovskite light-emitting diodes (PeLEDs) have achieved great improvement in performance in recent years, and the construction of quasi-2D perovskites by incorporating large-size organic cations is an effective strategy for fabricating efficient PeLEDs. Here, we incorporate the fluorine meta-substituted phenethylammonium bromide (m-FPEABr) into CsPbBr3 to prepare quasi-2D perovskite films for efficient PeLEDs, and study the effect of fluorine substitution on regulating the crystallization kinetics and phase distribution of the quasi-2D perovskites. It is found that m-FPEABr allows the transformation of low-n phases to high-n phases during the annealing process, leading to the suppression of n = 1 phase and increasing higher-n phases with improved crystallinity. The rational phase distribution results in the formation of multiple quantum wells (MQWs) in the m-FPEABr based films. The carrier dynamics study reveals that the resultant MQWs enable rapid energy funneling from low-n phases to emission centers. As a result, the green PeLEDs achieve a peak external quantum efficiency of 16.66% at the luminance of 1279 cd m-2. Our study demonstrates that the fluorinated organic cations would provide a facile and effective approach to developing high-performance PeLEDs.

12.
Front Pediatr ; 10: 874425, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35664880

RESUMO

Aims: To explore the predictors of mucosal healing (MH) for short- and long-term after exclusive enteral nutrition (EEN) in pediatric Crohn's disease (CD) patients. Methods: A retrospective analysis was performed for newly diagnosed active CD patients admitted to our center from January 2017 to 30 December 2020, who were treated with EEN for induction therapy with a minimum of 12 months of follow-up post-EEN. According to the simple endoscopic score for CD (SES-CD), at 1-year post-EEN, 17 patients with an SES-CD < 3 were classified into the sustained MH group (sMH), and 33 patients with an SES-CD ≥ 3 were classified into the sustained non-MH group (sNMH). Statistical methods were used to compare the differences between the two groups and explore the predictors of MH at the end of EEN and 1-year post-EEN. Results: The SES-CD in the sMH group was lower than that in the sNMH group both at baseline and the end of EEN [sMH vs. sNMH: 8.7 ± 1.2 vs. 16.2 ± 1.0, respectively, p < 0.001 at baseline; 1.0 (3.5) vs. 4.0 (2.0), respectively, p < 0.01 at the end of EEN]. The weighted Pediatric Crohn's Disease Activity Index and erythrocyte sedimentation rate in the sMH group were lower than those in the sNMH group at baseline (both p < 0.05), but showed no difference at the end of EEN. From baseline to 1-year post-EEN, compared with patients in the sNMH group, there were more patients classified with L1 in the sMH group at each time point (all p < 0.001) and fewer patients classified with L3 in the sMH group at baseline and 1-year post-EEN. After EEN, fewer patients received infliximab and had a longer exposure time to infliximab in the sMH group than in the sNMH group. Only the SES-CD at baseline was negatively associated with MH at the end of EEN (OR = 1.40 95% CI = 1.12-1.67, p = 0.00) and 1-year post-EEN (OR = 1.33, 95% CI = 1.12-1.58, p = 0.001), and the cut off value was 11.5. Conclusion: The SES-CD could predict both short- and long-term MH for EEN. Patients with an SES-CD < 11.5 had a high probability of reaching MH by EEN-inducing therapy and maintaining sustained MH at 1-year post-EEN. Patients with an SES-CD greater than 11.5 at baseline should be treated more aggressively with biologics.

13.
Molecules ; 27(9)2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35566036

RESUMO

Antioxidative peptides that inhibit myeloperoxidase (MPO) enzyme activity can effectively defend against oxidative stress damage. The antioxidant peptides from tuna protein were produced using alcalase hydrolysis and purified by ultrafiltration and Sephadex G-15, and the fractions with the highest free radicals scavenging ability and oxygen radical absorbance capacity (ORAC) values were sequenced using HPLC-MS/MS. Fifty-five peptide sequences were identified, 53 of which were successfully docked into MPO. The representative peptide ACGSDGK had better antioxidant activity and inhibition of MPO chlorination and peroxidation than the reference peptide hLF1-11. The docking model further showed intense molecular interactions between ACGSDGK and MPO, including hydrogen bonds, charge, and salt bridge interactions, which occluded the active site and blocked the catalytic activity of MPO. These results suggested that the antioxidant peptide ACGSDGK has the potential to inhibit oxidative stress and alleviate inflammation in vivo because of its inhibitory effect on the MPO enzyme.


Assuntos
Antioxidantes , Hidrolisados de Proteína , Animais , Antioxidantes/química , Hidrólise , Peptídeos/química , Peroxidase/metabolismo , Hidrolisados de Proteína/química , Espectrometria de Massas em Tandem , Atum/metabolismo
14.
Aliment Pharmacol Ther ; 55(11): 1414-1422, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35187668

RESUMO

BACKGROUND: Infantile-onset inflammatory bowel disease can be caused by defects in interleukin-10 signalling. The natural history and clinical outcomes of allogeneic haematopoietic stem cell transplantation, medical treatment and surgery have not been thoroughly described. AIMS: This study evaluates disease progression and clinical outcome in patients with interleukin-10 signalling deficiency. METHODS: One hundred and nine patients with interleukin-10 signalling deficiency were retrospectively reviewed from a single tertiary centre. The Kaplan-Meier method was applied to calculate probabilities of survival and interval between transplant and stoma closure. RESULTS: One hundred and nine patients were reviewed, and 102 patients were included in the survival analysis. One hundred and eight patients were identified with IL10RA mutations, and one patient harboured IL10RB mutation. Seventy-three patients received haematopoietic stem cell transplantation. The overall survival after transplantation was 64.2% (95% confidence interval, 52.8 to 75.6), and without transplantation, it was 47.5% (95% confidence interval, 14.8 to 80.2, P = 0.47). The median timeframe between transplant and stoma closure was 19.6 months. The probability of survival was significantly lower in patients with perforation (P < 0.001), ileus (P = 0.038) and without thalidomide treatment (P < 0.001) among patients who did not receive haematopoietic stem cell transplantation. The survival probability was not associated with timeframe between transplant and onset, graft source and genotypes. CONCLUSIONS: The survival probability was not significantly different between patients with transplantation and the non-transplanted patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/cirurgia , Interleucina-10/genética , Mutação , Estudos Retrospectivos , Resultado do Tratamento
15.
Nanoscale ; 14(3): 919-929, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34988562

RESUMO

Quasi-2D metal halide perovskites are promising candidates for light-emitting applications owing to their large exciton binding energy and strong quantum confinement effect. Usually, quasi-2D perovskites are composed of multiple phases with various numbers of layers (n) of metal halide octahedron sheets, enabling light emission from the lowest-bandgap phase by cascade energy transfer. However, the energy transfer processes are extremely sensitive to the phase distribution and trap density in the quasi-2D perovskite films, and the insufficient energy transfer between different-n phases and the defect-induced traps would result in nonradiative losses. Here, significantly reduced nonradiative losses in the quasi-2D perovskite films are achieved by tailoring the low-dimensional phase components and lowering the density of trap states. Butylammonium bromide (BABr) and potassium thiocyanate (KSCN) are employed to synergistically decrease the nonradiative recombination in the quasi-2D perovskite films of PEABr : CsPbBr3. The incorporation of BABr is found to suppress the formation of the n = 1 phase, while adding KSCN can further reduce the low-n phases, passivate the notorious defects and improve the alignment of the high-n phases. By incorporating appropriate contents of BABr and KSCN, the resultant quasi-2D perovskite films show high photoluminescence quantum yield (PLQY) and highly ordered crystal orientation, which enable not only the green light-emitting diodes (LEDs) with a high external quantum efficiency (EQE) of 16.3%, but also the amplified spontaneous emission (ASE) with a low threshold of 2.6 µJ cm-2. These findings provide a simple and effective strategy to develop high-quality quasi-2D perovskites for LED and laser applications.

16.
Front Pediatr ; 9: 744599, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34966700

RESUMO

Background: Infliximab is an effective therapy for Crohn's disease (CD). Early non-invasive predictors of disease remission allow for modification of treatments. The aim of this study was to investigate the associations between genetic variants, pharmacokinetics, and infliximab efficacy in pediatric patients with CD. Methods: This retrospective observational study included CD patients under infliximab therapy between August 2015 and December 2020. Information on demographics, laboratory tests, medication data, and disease activity index was collected. The trough levels of infliximab (TLI) and antibodies to infliximab (ATI) were measured at week 14, and reactive drug monitoring was performed during follow-up. Ten single-nucleotide polymorphisms involved in the NF-κB-mediated inflammatory response, pharmacokinetics, and therapeutic response to infliximab were genotyped. Results: A total of 62 pediatric CD patients were enrolled. The clinical remission (CR) rate was 69.4 and 63.2% at week 14 and week 30, respectively. TLI at week 14 was significantly independently associated with CR at week 14 and mucosal healing (MH) at week 30 (p = 0.007 and p = 0.025, respectively). The optimal TLI threshold level capable of distinguishing between the CR and non-CR groups was 2.62 µg/ml (p < 0.001, area under the curve = 0.79, sensitivity = 69.2%, specificity = 78.9%), while that capable of distinguishing between the MH and non-MH groups was 3.34 µg/ml (p < 0.001, area under the curve = 0.85, sensitivity = 78.6%, specificity = 79.4%). Rs3397 in TNFRSF1B was associated with time to ATI production in CD patients (p < 0.001). Conclusions: Higher TLI contributed to achieving MH. Genotyping rs3397 in TNFRSF1B may identify patients who are prone to generating immunogenicity to drugs.

17.
World J Clin Cases ; 9(21): 5873-5888, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34368306

RESUMO

BACKGROUND: Patients with lipopolysaccharide (LPS)-responsive beige-like anchor protein (LRBA) deficiency have a variety of clinical symptoms, but there is no apparent genotype-phenotype correlation, and patients carrying the same mutations may have different phenotypes. Therefore, it is not easy for doctors to make a decision regarding hematopoietic stem cell transplantation (HSCT) for LRBA-deficient patients. We hypothesized that there may be a protein-phenotype correlation to indicate HSCT for LRBA-deficient patients. AIM: To report on three Chinese LRBA-deficient patients and determine the correlation between residual protein expression and disease phenotypes. METHODS: Clinical data of three Chinese LRBA-deficient patients were collected, and protein levels were detected by Western blot analysis. In addition, LRBA mutation information of another 83 previously reported patients was summarized. RESULTS: All the major clinical findings indicated enteropathy, but patients 1 and 3 presented with more severe symptoms than patient 2. Endoscopy and histology indicated nonspecific colitis for patients 1 and 3 but Crohn's disease-like colitis for patient 2. Compound heterozygous mutations in LRBA were found in patient 1, and homozygous mutations in LRBA were found in patient 2 and patient 3. Only patient 2 responded well to traditional immunosuppressive treatment. Residual expression of the LRBA protein in patients 1 and 3 was very low, but in patient 2, a more than 0.5-fold in expression of the LRBA protein was found compared to that in the control. After HSCT, patient 1 had increased LRBA protein expression. We summarized the genetic information of 86 patients, and the mutations in patients 1 and 3 were novel mutations. CONCLUSION: We described three Chinese LRBA-deficient patients, two of whom carried novel mutations. These patients had no genotype-phenotype correlations, but their residual LRBA protein expression might be associated with disease outcome and could be an indicator for HSCT.

18.
Food Sci Nutr ; 9(8): 4473-4483, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34401095

RESUMO

This study was aimed to assess the effects of bromelain on the eating quality of smoked salted duck. Whole ducks were marinated with different doses of bromelain (300 U/g, 600 U/g, 900 U/g, 1,200 U/g and 1,500 U/g), while the group without bromelain was considered as control (CK). After the production of smoked salted duck was completed, the pH, color, texture, electronic tongue detection, thiobarbituric acid reactive substances (TBARS), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and mass spectrometry analysis were determined. The results showed that, compared to CK, the pH, TBARS and hardness values in 900, 1,200 and 1,500 U/g groups were reduced. The cohesiveness and the springiness were increased while the values of b* were decreased in all bromelain treatments (p < .05). The SDS-PAGE and mass spectrometry analysis indicated that myosin and actin were further hydrolyzed into small-molecule proteins by bromelain. Electronic tongue detection showed that the umami, the saltiness and the richness of smoked salted duck were enhanced, while the bitterness was reduced at the dose of 900 U/g. Thus, bromelain improved the eating quality of smoked salted duck in particular at the level of 900 U/g.

19.
Helicobacter ; 26(4): e12809, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33899288

RESUMO

BACKGROUND: We previously reported that the administration of 14-day standard triple therapy (TT), sequential therapy (ST), bismuth-based quadruple therapy (BT), and concomitant therapy (CT) as the first-line therapy for Helicobacter pylori infection in Chinese children achieved eradication rates of 74.1%, 69.5%, 89.8%, and 84.6%, respectively. In this follow-up study, we further evaluated the short- and long-term effects of the four regimens on the gut microbiota in these children. METHODS: We prospectively recruited treatment-naïve children with H. pylori infection. Fecal samples were collected at week 0, 2, 6, and 52, and alterations in the gut microbiota were analyzed by 16S rRNA gene sequencing. RESULTS: Sixty-three patients participated in this study (16 with TT, 15 with ST, 16 with BT and 16 with CT). At week 2, the alpha diversity (Shannon and Chao 1 index) was significantly reduced in the TT (p = 0.008, p < 0.001), ST (p < 0.001, p < 0.001), BT (p < 0.001, p < 0.001) and CT groups (p < 0.001, p < 0.001). Some changes persisted in the ST, BT, and CT groups at week 6, and all were restored (expect p = 0.02 with Chao 1 index in the CT group) at week 52. The beta diversity was significantly changed in the BT (p = 0.001) and CT groups (p = 0.001) 2 weeks post-eradication and restored 1 year after therapy. Immediately after therapy, the relative abundance of Proteobacteria was strikingly increased in the ST (p = 0.005), BT (p < 0.001) and CT groups (p < 0.001), and the genus-level analysis showed that the abundances of 23.1%, 43.3%, 78.6%, and 78% of the bacterial genera in the TT, ST, BT, and CT groups were significantly changed. All these changes returned to almost the pre-eradication level 1 year post-eradication. CONCLUSION: Eradication of H. pylori infection can lead to transient dysbiosis of gut microbiota, and these changes almost recovered 1 year post-eradication, which indicates the long-term safety of H. pylori therapy.


Assuntos
Microbioma Gastrointestinal , Infecções por Helicobacter , Helicobacter pylori , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Bismuto/uso terapêutico , Criança , China , Quimioterapia Combinada , Seguimentos , Infecções por Helicobacter/tratamento farmacológico , Humanos , Inibidores da Bomba de Prótons/uso terapêutico , RNA Ribossômico 16S/genética
20.
Transl Pediatr ; 10(2): 344-349, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33708520

RESUMO

BACKGROUND: The complete examination rate of video capsule endoscopy can be increased by reduced gastric transit time (GTT) and or small bowel transit time (SBTT). This study aims to examine whether the prokinetic domperidone reduces GTT and/or SBTT in pediatric patients undergoing video capsule endoscopy (VCE). METHODS: We performed a single-center randomized controlled trial (n=200) to evaluate the effect of domperidone on GTT and SBTT among pediatric patients in a tertiary university-affiliated hospital for children. We explored whether patients randomized to domperidone had increased GTT, SBTT (primary outcomes) or higher complete examination rate (secondary outcome). The safety outcomes were the adverse effects in the domperidone group. This study was registered on ClinicalTrials.gov (NCT03662113). RESULTS: Demographic features including gender and age were similar between the 100 patients of the domperidone group and the 100 patients of the control group. The median GTT was 67.5 minutes (44.8-117.5) in the domperidone group and 80.0 minutes (42.0-128.0) in the control group, while the median SBTT was 317 minutes (231-436) and 323 minutes (225-426), respectively. There were no significant differences in GTT (P=0.49) and SBTT (P=0.52) between the two groups. The complete examination rate was 97% and 98% in the domperidone and control groups, respectively (P=1.00). CONCLUSIONS: Domperidone shows no effect on GTT, SBTT and complete examination rate in pediatric patients receiving VCE.

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