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1.
Ann Palliat Med ; 10(10): 11067-11073, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34763468

RESUMO

BACKGROUND: This study was to investigate the clinical effect of a sural nerve nutrition flap with peroneal artery perforator for repairing tophus wound of the heel. METHODS: Over a 5-year period, 7 elderly male patients with tophus ulceration of the heel were admitted with exposed Achilles' tendon, and a chronic unhealed wound. Debridement, expansion and vacuum sealing drainage (VSD) lavage were performed initially, with simultaneous uric acid-lowering treatment. A 4×6-8×10 cm sural nerve nutrition flap with peroneal artery perforator was the secondary repair after further debridement of the wound. Preoperative Doppler ultrasound located the penetrating point of the peroneal artery perforator as the rotation point of the flap, and the line between the midpoint of the Achilles' tendon and the lateral malleolus and the midpoint of the popliteal fossa 5° above the front of Achilles' tendon was the axis. The patients were treated postoperatively with anti-inflammatory, anticoagulant and spasmolytic drugs and other rehydration therapy, and allopurinol was continued to control uric acid. The blood supply and temperature of the flap and wound healing were monitored. RESULTS: All 7 flaps survived completely after operation, with 1 case of postoperative wound discharge that finally healed after dressing change and 1 case of skin flap redness and swelling, which improved after strengthening anti-infection treatment. All 7 patients were followed up for 6-12 months (average 10 months). The skin flaps were soft in texture, with good color and appearance, and no recurrence of ulceration. The dorsal extension and plantar flexion of the ankle joint were good, and function was satisfactory. CONCLUSIONS: The sural nerve nutrition flap with peroneal artery perforator has double blood supply, strong anti-infective ability, relatively fast tissue healing process, simple operation and high survival rate, making it ideal for repairing tophus wounds of the heel.


Assuntos
Retalho Perfurante , Procedimentos Cirúrgicos Reconstrutivos , Lesões dos Tecidos Moles , Idoso , Artérias , Calcanhar , Humanos , Masculino , Estudos Retrospectivos , Lesões dos Tecidos Moles/cirurgia , Nervo Sural , Resultado do Tratamento
2.
Clin Transl Med ; 11(11): e579, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34841705

RESUMO

Increasing evidence supports a central role of the immune system in lung diseases. Understanding how immunological alterations between lung diseases provide opportunities for immunotherapy. Exhausted T cells play a key role of immune suppression in lung cancer and chronic obstructive pulmonary disease was proved in our previous study. The present study aims to furthermore define molecular landscapes and heterogeneity of systemic immune cell target proteomic and transcriptomic profiles and interactions between circulating immune cells and lung residential cells in various lung diseases. We firstly measured target proteomic profiles of circulating immune cells from healthy volunteers and patients with stable pneumonia, stable asthma, acute asthma, acute exacerbation of chronic obstructive pulmonary disease, chronic obstructive pulmonary disease and lung cancer, using single-cell analysis by cytometry by time-of-flight with 42 antibodies. The nine immune cells landscape was mapped among those respiratory system diseases, including CD4+ T cells, CD8+ T cells, dendritic cells, B cells, eosinophil, γδT cells, monocytes, neutrophil and natural killer cells. The double-negative T cells and exhausted CD4+ central memory T cells subset were identified in patients with acute pneumonia. This T subset expressed higher levels of T-cell immunoglobulin and mucin domain-containing protein 3 (Tim3) and T-cell immunoreceptor with Ig and ITIM domains (TIGIT) in patients with acute pneumonia and stable pneumonia. Biological processes and pathways of immune cells including immune response activation, regulation of cell cycle and pathways in cancer in peripheral blood immune cells were defined by bulk RNA sequencing (RNA-seq). The heterogeneity among immune cells including CD4+ , CD8+ T cells and NK T cells by single immune cell RNA-seq with significant difference was found by single-cell sequencing. The effect of interstitial telocytes on the immune cell types and immune function was finally studied and the expressions of CD8a and chemokine C-C motif receptor 7 (CCR7) were increased significantly in co-cultured groups. Our data indicate that proteomic and transcriptomic profiles and heterogeneity of circulating immune cells provides new insights for understanding new molecular mechanisms of immune cell function, interaction and modulation as a source to identify and develop biomarkers and targets for lung diseases.

3.
Cell Death Discov ; 7(1): 271, 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34601500

RESUMO

Many self-renewal-promoting factors of embryonic stem cells (ESCs) have been implicated in carcinogenesis, while little known about the genes that direct ESCs exit from pluripotency and regulate tumor development. Here, we show that the transcripts of Gadd45 family genes, including Gadd45a, Gadd45b, and Gadd45g, are gradually increased upon mouse ESC differentiation. Upregulation of Gadd45 members decreases cell proliferation and induces endodermal and trophectodermal lineages. In contrast, knockdown of Gadd45 genes can delay mouse ESC differentiation. Mechanistic studies reveal that Gadd45g activates MAPK signaling by increasing expression levels of the positive modulators of this pathway, such as Csf1r, Igf2, and Fgfr3. Therefore, inhibition of MAPK signaling with a MEK specific inhibitor is capable of eliminating the differentiation phenotype caused by Gadd45g upregulation. Meanwhile, GADD45G functions as a suppressor in human breast cancers. Enforced expression of GADD45G significantly inhibits tumor formation and breast cancer metastasis in mice through limitation of the propagation and invasion of breast cancer cells. These results not only expand our understanding of the regulatory network of ESCs, but also help people better treatment of cancers by manipulating the prodifferentiation candidates.

4.
Nat Metab ; 3(10): 1400-1414, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34663975

RESUMO

5-diphosphoinositol pentakisphosphate (5-IP7) is a signalling metabolite linked to various cellular processes. How extracellular stimuli elicit 5-IP7 signalling remains unclear. Here we show that 5-IP7 in ß cells mediates parasympathetic stimulation of synaptotagmin-7 (Syt7)-dependent insulin release. Mechanistically, vagal stimulation and activation of muscarinic acetylcholine receptors triggers Gαq-PLC-PKC-PKD-dependent signalling and activates IP6K1, the 5-IP7 synthase. Whereas both 5-IP7 and its precursor IP6 compete with PIP2 for binding to Syt7, Ca2+ selectively binds 5-IP7 with high affinity, freeing Syt7 to enable fusion of insulin-containing vesicles with the cell membrane. ß-cell-specific IP6K1 deletion diminishes insulin secretion and glucose clearance elicited by muscarinic stimulation, whereas mice carrying a phosphorylation-mimicking, hyperactive IP6K1 mutant display augmented insulin release, congenital hyperinsulinaemia and obesity. These phenotypes are absent in mice lacking Syt7. Our study proposes a new conceptual framework for inositol pyrophosphate physiology in which 5-IP7 acts as a GPCR second messenger at the interface between peripheral nervous system and metabolic organs, transmitting Gq-coupled GPCR stimulation to unclamp Syt7-dependent, and perhaps other, exocytotic events.

5.
J Biol Chem ; 297(5): 101332, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34688658

RESUMO

Embryonic stem cells (ESCs) are progenitor cells that retain the ability to differentiate into various cell types and are necessary for tissue repair. Improving cell culture conditions to maintain the pluripotency of ESCs in vitro is an urgent problem in the field of regenerative medicine. Here, we reveal that Spautin-1, a specific small-molecule inhibitor of ubiquitin-specific protease (USP) family members USP10 and USP13, promotes the maintenance of self-renewal and pluripotency of mouse ESCs in vitro. Functional studies reveal that only knockdown of USP13, but not USP10, is capable of mimicking the function of Spautin-1. Mechanistically, we demonstrate that USP13 physically interacts with, deubiquitinates, and stabilizes serine/threonine kinase Raf1 and thereby sustains Raf1 protein at the posttranslational level to activate the FGF/MEK/ERK prodifferentiation signaling pathway in naïve mouse ESCs. In contrast, in primed mouse epiblast stem cells and human induced pluripotent stem cells, the addition of Spautin-1 had an inhibitory effect on Raf1 levels, but USP13 overexpression promoted self-renewal. The addition of an MEK inhibitor impaired the effect of USP13 upregulation in these cells. These findings provide new insights into the regulatory network of naïve and primed pluripotency.

6.
J Sep Sci ; 44(22): 4082-4091, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34514725

RESUMO

Red and yellow pigments are the major ingredients of safflower, often used to color food and cosmetics. Carthamin was the main component of red pigment and hydroxysafflor yellow A and anhydrosafflower yellow B were representative components of yellow pigment. Plant metabolomics and semi-quantitative analysis were used to analyze the changes of pigment composition during the blooming period, especially these characteristic components. Carthamin, hydroxysafflor yellow A, anhydrosafflower yellow B, and other components were screened out as differential metabolites based on plant metabolomics. Then semi-quantitative analysis was used to quantify these three representative components of pigments. Experimental results showed that the content of pigments has dynamic changes along with flowering, in the early blooming period, yellow pigment accumulated much and red pigment was low in content. In the middle period, the accumulation rate of the yellow pigment slowed down and content was stabilized. In the next step, the content of yellow pigments gradually decreased, and the content of red pigments gradually increased. Later, the level of yellow pigment decreased significantly, and the accumulation rate of red pigment increased significantly. Last, the appearance color of safflower was red, with yellow parts barely visible, and accumulation of red pigment was the highest and of the yellow pigment was the lowest in content.

7.
PLoS One ; 16(9): e0257445, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34534244

RESUMO

TRIM59 is a protein that is highly expressed in a variety of tumors and promotes tumor development. However, the use of TRIM59 as tumor diagnosis and prognosis biomarker has not been fully explored. We collected datasets from the cancer genome atlas (TCGA) and gene expression omnibus (GEO) to investigate its potential as a biomarker for diagnosis and prognosis. A total of 46 studies, including 11,558 patients were included in this study. Here, we showed that TRIM59 was significantly upregulated in 15 type of human solid tumors in comparison to their adjacent tissues. Receiver operating characteristic curve (ROC) results provided further evidence for the use of TRIM59 as a potential tumor diagnosis biomarker. Overall survival (OS) was compared between TRIM59 high expression and low expression groups. High expression of TRIM59 indicated a poor prognosis in multiple solid tumors. Taken together, these analyses showed that TRIM59 was upregulated in various types of tumors and had the potential to be used as a diagnostic and prognostic biomarker in human solid tumors.


Assuntos
Biomarcadores Tumorais/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias/diagnóstico , Proteínas com Motivo Tripartido/metabolismo , Área Sob a Curva , Bases de Dados Factuais , Humanos , Neoplasias/mortalidade , Neoplasias/patologia , Prognóstico , Curva ROC , Análise de Sobrevida , Regulação para Cima
8.
Front Med (Lausanne) ; 8: 690995, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34336894

RESUMO

Background: Proton pump inhibitors (PPIs) are validated gastric acid suppressors and have been widely used to treat patients with active duodenal ulcers. Although existing PPIs have shown great efficacy, many scientists are still devoted to developing more effective PPIs with better safety profile. Herein, we aimed to compare the safety and efficacy of anaprazole in duodenal mucosal healing, a novel PPI, to that of rabeprazole. Methods: In this multicenter, randomized, positive-controlled, double-blinded, parallel-group phase II clinical trial, a total of 150 qualified patients with endoscopically confirmed active duodenal ulcers were randomized (1:1:1) to receive rabeprazole 10 mg, anaprazole 20 mg or anaprazole 40 mg for 4 weeks. The ulcer healing rates after 4 weeks of treatment were compared between groups by independent central review and investigator review. In addition, symptoms and safety were evaluated. Results: Based on the independent central review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole and 40 mg anaprazole groups were 88.0, 85.1, and 87.5%, respectively, in the FAS population and 88.9, 86.0, and 90.9%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is -2.9% (95% CI, -16.5-10.7%), and -0.5% (95% CI, -13.5-12.5%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Based on the investigator review, the ulcer healing rates of the 10 mg rabeprazole, 20 mg anaprazole, and 40 mg anaprazole groups were 72.0, 70.2, and 77.1%, respectively, in the FAS population and 75.6, 72.1, and 79.5%, respectively, in the PPS population. The ulcer healing rate difference between anaprazole 20 mg and Rabeprazole 10 mg is -1.8% (95% CI, -19.8-16.3%), and 5.1% (95% CI, -12.2-22.3%) between anaprazole 40 mg and Rabeprazole 10 mg, in the FAS population. Most patients (>90%) eventually achieved complete symptom relief. The incidence rates of adverse events were of no significant differences among the treatment groups. Potential possible better liver tolerance was observed in two anaprazole dose groups than rabeprazole 10 mg group. Conclusion: Both at a dosage of 20 and 40 mg daily, anaprazole, is effective with good safety profile in the treatment of active duodenal ulcers in this Phase 2 study, which allows anaprazole to be advanced to a phase III clinical trial. Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/results?cond=&term=NCT04503629&cntry=&state=&city=&dist=, Identifier: CTR20181464, NCT04503629.

9.
Front Bioeng Biotechnol ; 9: 673691, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34295880

RESUMO

Intestinal tuberculosis (ITB) and Crohn's disease (CD) are chronic inflammatory bowel disorders that are associated with dysregulated mucosal immunity. The gut microbiota plays an important role in the regulation of host immunity and inflammatory response. Although mounting evidence has linked CD with the dysbiosis of gut microbiota, the characteristic profiles of mucosal bacteria in ITB remain unclear. The aim of this study was to assess the alterations of the gut microbiota in ITB and compare the microbial structure of ITB with CD. A total of 71 mucosal samples were collected from patients with ITB, CD, and healthy controls (HC), and then, 16S rRNA gene sequencing was performed. The overall composition of gut microbiota in ITB was strikingly different from HC, with the dominance of Proteobacteria and reduction of Firmicutes. Of note, the short-chain fatty acids (SCFAs)-producing bacteria such as Faecalibacterium, Roseburia, and Ruminococcus were decreased in ITB relative to HC, while Klebsiella and Pseudomonas were enriched. Multiple predictive functional modules were altered in ITB, including the over-representation of lipopolysaccharide biosynthesis, bacterial invasion of epithelial cells, and pathogenic Escherichia coli infection that can promote inflammation. Additionally, the microbial structure in CD was distinctly different from ITB, characterized by lower alpha diversity and increased abundance of Bacteroides, Faecalibacterium, Collinsella, and Klebsiella. These four bacterial markers distinguished ITB from CD with an area under the curve of 97.6%. This study established the compositional and functional perturbation of the gut microbiome in ITB and suggested the potential for using gut microbiota as biomarkers to differentiate ITB from CD.

10.
Immunobiology ; 226(4): 152109, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34252840

RESUMO

Macrophages have a variety of functions, such as secreting cytokines, phagocytosis, et al. Tripartite motif containing 59 (TRIM59) protein is highly expressed in tumor cells. It can regulate proliferation of tumor cells and promote tumor progression. Recent studies shown that the expression of TRIM59 was different in macrophages when stimulated by different stimuli, however, the effects of TRIM59 on macrophage gene expression profiles and functions are still unknown. In our study, we constructed RAW264.7 macrophages with high and low expression of TRIM59, and used next generation sequencing to explore the effects of TRIM59 on macrophage gene expression profiles. Results showed that TRIM59 affected an abundant number of genes, and may affect phagocytosis and cell cycles. We also examined the expression of surface molecules, secretion of cytokines, phagocytosis, proliferation, and apoptosis of macrophages, and confirmed that TRIM59 increased the expression of FcγRs CD16/32, CD64 and the secretion of TNF-α and IL-10, promoted phagocytosis and proliferation of RAW264.7 cells, inhibited the expression of complement receptor CD11b and antigen presentation related receptors (MHCII, CD80), but TRIM59 had no significant effect on apoptosis. Our study explored the effect of TRIM59 on the gene expression and function of macrophages comprehensively.

11.
Immunopharmacol Immunotoxicol ; 43(4): 461-470, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34142927

RESUMO

AIM: High-mobility group box 1 (HMGB1) protein has been noticed particularly for its pivotal role in several pathologies. However, the relevance between HMGB1 and pathological progress in lung toxicity still remains unclear. In the study, we evaluated the effect of glycyrrhizic acid as an HMGB1 inhibitor on the early inflammation and late fibrosis in bleomycin-induced pulmonary toxicity in mice. METHODS: We established a bleomycin-induced pulmonary toxicity model to detect the relevance between HMGB1 and pathological changes in the early inflammatory and late fibrotic stages. RESULTS: We found that bleomycin-induced increase in inflammatory cytokines interleukin (IL)-ß1, tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, and inflammatory lesions in lung tissue in the early stage of the model. However, markers of fibrosis such as transforming growth factor (TGF)-ß1 and α-smooth muscle actin (α-SMA) were significantly elevated on day 7 after bleomycin instillation. Interestingly, HMGB1 also began to rise on day 7, rather than in the early inflammatory phase. However, early (from day 0 to 14 after bleomycin instillation) or late (from day 14 to 28) intervention with HMGB1 neutralizing antibody or glycyrrhizic acid alleviated inflammation and fibrosis through down-regulating the inflammatory signaling mitogen-activated protein kinase (MAPK) and fibrotic signaling Smad3 pathway. CONCLUSION: Our results suggested that HMGB1 mediates both inflammation and fibrosis in this model. The development of high-potency and low-toxicity HMGB1 inhibitors may be a class of potential drugs for the treatment of pulmonary fibrosis.

12.
J Am Chem Soc ; 143(27): 10077-10082, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34181405

RESUMO

Design and synthesis of air-stable and easily tailored high-performance single-molecule magnets (SMMs) are of great significance toward the implementation of SMMs in molecular-based magneto-electronic devices. Here, by introducing electron-withdrawing fluorinated substituents on equatorial ligand, two chiral Dy(III) macrocyclic complexes, RRRR-Dy-D6hF12 (1) and SSSS-Dy-D6hF12 (2), with a record anisotropy barrier exceeding 1800 K and the longest relaxation time approaching 2500 s at 2.0 K for all known air-stable SMMs, were obtained. The nearly perfect axiality of the ground Kramers doublet (KD) enables the open hysteresis loops up to 20 K in the magnetically diluted sample. It is notable that they are structurally rigid with high thermal stability and the apical ligand can be tailored to carry proper surface-binding groups. This finding not only improves the magnetic properties for air-stable SMMs but also provides a new avenue for deposition of SMMs on surfaces.

13.
Medicine (Baltimore) ; 100(25): e26504, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160468

RESUMO

ABSTRACT: Abnormal glucose metabolism brings out joint inflammation and destruction in rheumatoid arthritis (RA). The aim of this study was to evaluate the potential of circulating hexokinase-2 (HK2) in peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients.PBMCs were obtained from patients with RA or osteoarthritis (OA) and healthy controls (HCs). The expression of HK2 was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), Calprotectin, rheumatoid factor (RF), anti-cyclic citrullinated peptides (anti-CCP) antibody level and 28-joint Disease Activity Score (DAS28), Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) were measured. Spearman's analysis was performed to determine the association between the level of HK2 and clinical characteristics. A receiver operating characteristic (ROC) curve was employed to evaluate the diagnostic value of HK2 in PBMCs. Logistic regression was used to identify risk factors. Sixty-five RA patients, 35 OA patients, and 40 HCs were included in the study.HK2 was upregulated in RA and OA patients compared with that in HCs (P < .05). The area under the ROC of HK2 for diagnosing RA and OA was 0.808 and 0.640, respectively. In addition, HK2 levels were increased in active RA compared with those in remittent RA (P = .03). Furthermore, HK2 correlated positively with the DAS28-ESR (P < .001), CDAI (P = .02) and SDAI scores (P = .02). Moreover, HK2 was independently associated with an increased risk of disease activity (DAS28-ESR>3.2, P = .02; CDAI score>10, P = .03; SDAI score>11, P = .04). Additionally, HK2 positivity was more frequently detected in patients treated with biologic disease-modifying antirheumatic drugs (bDMARDs) than in those not treated with bDMARDs.HK2 levels in PBMCs can be considered an ideal biomarker for diagnosing RA and involved in disease activity in RA. Dysregulation of HK2 may participate in the molecular mechanism of RA and could be an attractive selective metabolic target for RA treatment.


Assuntos
Artrite Reumatoide/diagnóstico , Hexoquinase/análise , Leucócitos Mononucleares/enzimologia , Adulto , Idoso , Artrite Reumatoide/sangue , Biomarcadores/análise , Biomarcadores/metabolismo , Hexoquinase/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Índice de Gravidade de Doença
14.
Int Immunopharmacol ; 98: 107813, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34126340

RESUMO

Pattern recognition receptors (PRRs) are a kind of recognition molecules mainly expressed on innate immune cells. PRRs recognize one or more kinds of pathogen-associated molecular patterns (PAMPs), inducing the production of interleukin (IL), tumor necrosis factor (TNF), interferon (IFN) and other related cytokines to aggravate immune-related diseases. PPR signaling pathways play an important role in both innate and adaptive immune system, and they are easy to be activated or regulated. Tripartite motif (TRIM) proteins are a group of highly conserved proteins in structure. Most of TRIM proteins contain RING domain, which is thought to play a role in ubiquitination. TRIM proteins are involved in viral immunity, inflammatory response, autophagy, and tumor growth. In this review, we focus on the regulation of TRIM proteins on PRR signaling pathways and their roles in immune-related diseases.

15.
Int J Clin Pract ; 75(9): e14462, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34107113

RESUMO

BACKGROUND AND PURPOSE: Studies have shown that some cytokines in COVID-19 patients were elevated. This study aims to assess whether IL-10, IL-1ß, IL-6, MCP-1, TNF-α, IP-10 and IL-4 serve as potential diagnostic biomarkers of COVID-19. METHODS: The above serum cytokines in COVID-19 patients and non-COVID-19 patients were detected by ELISA and SARS-CoV-2 IgM and IgG were detected by the chemiluminescence method. The independent-sample Mann-Whitney U test was utilised to compare cytokine levels in different groups and courses, the Levene T-test and T'-test were utilised to compare they in different genders and the Spearman correlation test was utilised to analyse the correlation between the cytokine levels with ages and SARS-CoV-2 IgG and IgM. RESULTS: Serum levels of IL-10, IL-1ß, MCP-1, TNF-α and IL-4 in COVID-19 patients were significantly higher than those in non-COVID-19 patients, while IL-6 were only significantly higher than in healthy people, IP-10 were significantly lower than in other diseases patients. AUCs of COVID-19 diagnosed by IL-10, IL-1ß, IL-6, MCP-1, TNF-α, IP-10 and IL-4 were 0.735, 0.775, 0.595, 0.821, 0.848, 0.38 and 0.682, respectively. In the COVID-19 patients' serum, the levels of IL-10 and MCP-1 of male were noticeably higher than those of female, and all cytokines were significantly positively correlated with age, IL-1ß and IL-4 were significantly negatively correlated with SARS-CoV-2 IgM, while IL-10, IL-1ß, IL-6, TNF- and IP-10 were significantly negatively correlated with SARS-CoV-2 IgG. IL-10 on 43-56 days was significantly lower than at 29-42 days, TNF-α at 15-42 days was significantly higher than at 0-14 days, IP-10 at 0-14 days was the highest and IL-4 at 29-42 days was significantly higher than at 0-14 days. CONCLUSIONS: The detection of IL-10, IL-1 ß, IL-6, MCP-1, TNF-α and IL-4 would assist the clinical study of COVID-19, and IP-10 may be the cytokine of early elevation in COVID-19 patients.


Assuntos
COVID-19 , Fator de Necrose Tumoral alfa , Quimiocina CXCL10 , Citocinas , Feminino , Humanos , Interleucina-10 , Interleucina-1beta , Interleucina-4 , Interleucina-6 , Masculino , SARS-CoV-2
16.
Chin J Nat Med ; 19(6): 422-431, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34092293

RESUMO

Colon cancer-related anemia (CCRA) is mainly caused by systemic inflammation, intestinal bleeding, iron deficiency and chemotherapy-induced myelosuppression in colon cancer. However, the best therapeutic schedule and related mechanism on CCRA were still uncertain. Studies on blood enrichment and anti-tumor effects of combined Danggui Buxue Decoction (DBD), Fe and rhEPO based on CCRA and gut microbiota modulation were conducted in this paper. Here, CCRA model was successfully induced by subcutaneous inoculation of CT-26 and i.p. oxaliplatin, rhEPO + DBD high dosage + Fe (EDF) and rhEPO + DBD high dosage (ED) groups had the best blood enrichment effect. Attractively, EDF group also showed antitumor activity. The sequencing results of gut microbiota showed that compared to P group, the relative abundances of Lachnospiraceae and opportunistic pathogen (Odoribacter) in ED and EDF groups were decreased. Interestingly, EDF also decreased the relative abundances of cancer-related bacteria (Helicobacter, Lactococcus, Alloprevotella) and imbalance-inducing bacteria (Escherichia-Shigella and Parabacteroides) and increased the relative abundances of butyrate-producing bacteria (Ruminococcaceae_UCG-014), however, ED showed the opposite effects to EDF, this might be the reason of the smaller tumor volume in EDF group. Our findings proposed the best treatment combination of DBD, rhEPO and Fe in CCRA and provided theoretical basis and literature reference for CCRA-induced intestinal flora disorder and the regulatory mechanism of EDF.


Assuntos
Anemia , Neoplasias do Colo , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Anemia/tratamento farmacológico , Anemia/etiologia , Animais , Neoplasias do Colo/complicações , Neoplasias do Colo/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia
17.
Mol Genet Genomic Med ; 9(5): e1632, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33834621

RESUMO

BACKGROUND: Classical Ehlers-Danlos syndrome (cEDS) is a heterogeneous connective tissue disorder that mainly results from the germline mutation of COL5A1 and COL5A2. The majority of the COL5A2 mutations reported to date represent structural mutations, including missense or in-frame exon-skipping splice mutations. The only reported synonymous mutation was expected to affect on splicing of exon 29 by prediction programs which should be further confirmed. METHODS: Whole exome sequencing was performed to identify the genetic variants of a Chinese boy who was characterized by skin hyperextensibility, abnormal scarring, hypermobile joints and scoliosis. Sanger sequencing was used to validate the variants in his parents. Reverse transcription polymerase chain reaction (RT-PCR) was performed to analyze the functional effects of the variant. RESULTS: A de novo heterozygous synonymous variant (NM_000393.5:c.1977 G>A) of COL5A2 gene was identified in the patient. The results of RT-PCR revealed that the synonymous variant led to skipping of exon 29 in the RNA transcript. CONCLUSIONS: Our study supplies further supporting evidence that the synonymous COL5A2 mutation c.1977 G>A can cause skipping of exon 29 in the RNA transcript, thus resulting in the production of mutant α2(V)-chains and clinical phenotype of cEDS. This result highlights the need to include splicing-altering synonymous mutations into the screening for cEDS.

18.
J Cell Mol Med ; 25(10): 4765-4775, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33769664

RESUMO

Intestinal fibrosis is the most common complication of Crohn's disease (CD) that is one major disorder of inflammatory bowel disease (IBD), but the precise mechanism remains unclear. MiR-155 has been involved in fibrotic diseases. Here, we determined the role of miR-155 in regulating intestinal fibrosis. MiR-155 levels were significantly up-regulated in CD patients with intestinal stricture CD. The overexpression of miR-155 significantly aggravated TNBS-induced CD-associated intestinal fibrosis. Mechanistically, we identified that HBP1, a negative regulator of the Wnt/ß-catenin signalling pathway, is a direct target of miR-155. Moreover, in vitro and in vivo experiments suggested that the miR-155/HBP1 axis activates Wnt/ß-catenin signalling pathway to induce intestinal fibrosis. Taken together, we demonstrated that miR-155 directly targets HBP1 to induce CD-associated intestinal fibrosis via Wnt/ß-catenin signalling pathway.


Assuntos
Colite/complicações , Fibrose/patologia , Proteínas de Grupo de Alta Mobilidade/metabolismo , Enteropatias/patologia , MicroRNAs/genética , Proteínas Repressoras/metabolismo , Proteína Wnt1/metabolismo , beta Catenina/metabolismo , Animais , Apoptose , Estudos de Casos e Controles , Proliferação de Células , Células Cultivadas , Fibrose/etiologia , Fibrose/metabolismo , Regulação da Expressão Gênica , Proteínas de Grupo de Alta Mobilidade/genética , Humanos , Enteropatias/etiologia , Enteropatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Prognóstico , Proteínas Repressoras/genética , Proteína Wnt1/genética , beta Catenina/genética
19.
J Orthop Surg Res ; 16(1): 224, 2021 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-33773575

RESUMO

BACKGROUND: The treatment for displaced Salter-Harris II (S-H II) distal tibia fractures remains controversial. The purpose of this study was to review S-H II distal tibia fractures and evaluate the rate of premature physeal closure (PPC) treated by open reduction and internal fixation (ORIF). METHODS: We reviewed the charts and radiographs of S-H II fractures of the distal tibia with displacement > 3 mm between 2012 and 2019 treated by ORIF. Patients were followed up for a minimum of 6 months. CT scans of injured side or contralateral ankle radiograph were obtained if there was any evidence of PPC. Any angular deformity or shortening of the involved leg was documented. Multivariable logistic regression was performed to identify risk factors for the occurrence of PPC. RESULTS: A total of 65 patients with a mean age of 11.8 years were included in this study. The mean initial displacement was 8.0 mm. All patients but one were treated within 7 days after injury and the mean interval was 3.7 days. Supination-external rotation injuries occurred in 50 patients, pronation-eversion external rotation in 13, and supination-plantar flexion in two. The residual gap was less than 1 mm in all patients following ORIF and all fractures healed within 4-6 weeks. Superficial skin infection developed in one patient. Ten patients complained of the cosmetic scar. The rate of PPC was 29.2% and two patients with PPC developed a varus deformity of the ankle. Patients with associated fibular fracture had 7 times greater odds of developing PPC. Age, gender, injured side, mechanism of injury, amount of initial displacement, interval from injury to surgery, or energy of injury did not significantly affect the rate of PPC. CONCLUSIONS: ORIF was an effective choice of treatment for S-H II distal tibia fractures with displacement > 3 mm to obtain a satisfactory reduction. PPC is a common complication following ORIF. The presence of concomitant fibula fracture was associated with PPC.


Assuntos
Tornozelo/anormalidades , Fixação Interna de Fraturas/métodos , Redução Aberta/métodos , Fraturas Salter-Harris/cirurgia , Fraturas da Tíbia/cirurgia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Deformidades Adquiridas do Pé/etiologia , Fixação Interna de Fraturas/efeitos adversos , Humanos , Modelos Logísticos , Masculino , Redução Aberta/efeitos adversos , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Fraturas Salter-Harris/classificação , Fraturas da Tíbia/classificação , Fraturas da Tíbia/diagnóstico por imagem , Tomografia Computadorizada por Raios X
20.
BMC Gastroenterol ; 21(1): 64, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579207

RESUMO

BACKGROUND: Endoscopic submucosal dissection (ESD) and endoscopic submucosal excavation (ESE) have been widely used and have gradually become the main endoscopic treatment for gastrointestinal mucosal and submucosal lesions. Whether antibiotics are necessary for fever after gastric ESD and ESE remain unclear. The aim of this study was to analyse the value of using antibiotics in patients without perforation after ESD or ESE with fever. METHODS: In this retrospective study, patients with fever without perforation after ESD or ESE from January 2014 to January 2019 were included and divided into 2 groups: the antibiotic group and the non-antibiotic group. Fever and hospitalization time were compared between the 2 groups after propensity score matching. RESULTS: Overall, 253 patients meeting the inclusion criteria were enrolled in the present study, with 186 patients in the non-antibiotic group and 67 patients in the antibiotic group before matching, 55 patients in the non-antibiotic group and 55 patients in the antibiotic group after matching with all baseline characteristics balanced (p > 0.05). The duration of fever was not significantly different between the 2 groups (p = 0.12). However, the median hospitalization stay in the antibiotic group was longer than that in the non-antibiotic group (8 vs 7, p = 0.007). CONCLUSIONS: Antibiotics may be unnecessary for fever in patients without perforation and without serious co-morbidities after gastric ESD or ESE.


Assuntos
Ressecção Endoscópica de Mucosa , Neoplasias Gástricas , Antibacterianos/uso terapêutico , Ressecção Endoscópica de Mucosa/efeitos adversos , Humanos , Pontuação de Propensão , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
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