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1.
Methods Mol Biol ; 2587: 455-464, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36401043

RESUMO

Duchenne muscular dystrophy (DMD) is a progressive myopathy caused by mutations in genes encoding dystrophin proteins that ultimately lead to depletion of myogenic progenitor cells (MPCs). Several approaches have been used to correctly express the dystrophin gene in induced pluripotent stem cells (iPSCs), including deletion of mutated exon 23 (ΔEx23) by clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated gene 9 (Cas9)-mediated gene editing technology. However, this approach is labor-intensive due to individual colony picking and genotyping to verify allelic modification. Here, we present a protocol to restore the function of the dystrophin gene by using homology-directed repair (HDR)-based CRISPR/Cas9 and inducing myogenic program of reprogrammed iPSCs from Mdx mice by inducible muscle-specific transcription factor MyoD.


Assuntos
Sistemas CRISPR-Cas , Distrofina , Camundongos , Animais , Distrofina/genética , Distrofina/metabolismo , Sistemas CRISPR-Cas/genética , Camundongos Endogâmicos mdx , Mioblastos/metabolismo , Músculos/metabolismo , Tecnologia
2.
BMC Womens Health ; 22(1): 488, 2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36460984

RESUMO

BACKGROUND: This study evaluated the prognostic value of the Silva pattern system for invasive endocervical adenocarcinoma (EAC) by analysing its association with clinical and pathological features to provide more appropriate clinical management. METHODS: A retrospective analysis including 63 patients with pathological diagnosis of invasive EAC was performed from March 2011 to December 2016 at our hospital. All pathological slides were reviewed by three senior pathologists, and cases were stratified into patterns A, B, or C by consensus according to the Silva pattern system criteria. Clinicopathological characteristics and follow-up of the three Silva subgroups were analysed. RESULTS: Silva A, B, and C EAC patients were compared based on tumour size, clinical stage, lymphovascular invasion (LVI), and depth of invasion (DOI). The differences were found to be statistically significant (p < 0.01). There was no statistically significant difference in the proportion of lymph node metastasis among the three groups (p > 0.05) or in the recurrence and mortality rates of patients with Silva A, B, and C EAC (p > 0.05). Single factor analysis showed that tumour size, clinical stage, lymph node metastasis, LVI, and DOI were related to postoperative recurrence, whereas age, Silva classification, and postoperative recurrence were not correlated. CONCLUSION: The Silva classification system can predict lymph node status and prognosis of invasive EAC, but it cannot be used as an independent indicator. Individualized treatment plans should be adopted for patients with EAC.

3.
BMC Immunol ; 23(1): 55, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36376784

RESUMO

BACKGROUND: Antineutrophil Cytoplasmic Antibodies (ANCA) associated glomerulonephritis (AGN) is a group of autoimmune diseases and mono-macrophages are involved in its glomerular injuries. In this study, we aim to investigate the role of CD206+ mono-macrophages in AGN. METHODS: 27 AGN patients (14 active AGN, 13 remissive AGN) together with healthy controls (n = 9), disease controls (n = 6) and kidney function adjusted controls (n = 9) from Department of Nephrology, Ruijin hospital were recruited. Flow cytometry was used to study proportion of CD206+ cells in peripheral blood. Immunohistochemistry for CD206 staining was performed and CD206 expression was scored in different kidney regions. Serum soluble CD206 (sCD206) was measured by enzyme-linked immunosorbent assay (ELISA). We also generated murine myeloperoxidase (MPO) (muMPO) ANCA by immunizing Mpo-/- mice. Mouse bone marrow-derived macrophages (BMDMs) from wild C57BL/6 mice and peripheral blood mononuclear cell (PBMC) derived macrophages from healthy donors were treated with MPO ANCA with or without its inhibitor AZD5904 to investigate the effects of MPO-ANCA on CD206 expression. RESULTS: The proportion of peripheral CD206+CD68+ cells in active AGN patients were significantly higher than that in remissive patients (p < 0.001), healthy controls (p < 0.001) and kidney function adjusted controls (p < 0.001). Serum sCD206 level in active AGN patients was higher than that in healthy controls (p < 0.05) and remissive patients (p < 0.01). Immunohistochemistry showed CD206 was highly expressed in different kidney regions including fibrinoid necrosis or crescent formation, glomeruli, periglomerular and tubulointerstitial compartment in active AGN patients in comparison with disease controls. Further studies showed MPO ANCA could induce CD206 expression in BMDMs and PBMC derived macrophages and such effects could be reversed by its inhibitor AZD5904. CONCLUSION: ANCA could induce CD206 expression on mono-macrophages and CD206+ mono-macrophages are activated in AGN. CD206 might be involved in the pathogenesis of AAV and may be a potential target for the disease.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos , Glomerulonefrite , Animais , Camundongos , Glomerulonefrite/metabolismo , Glomerulonefrite/patologia , Leucócitos Mononucleares/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Peroxidase/metabolismo
4.
Ying Yong Sheng Tai Xue Bao ; 33(10): 2769-2776, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36384613

RESUMO

Ningxia is an important agriculture-pastoral area in China. Research on the temporal and spatial variations of net primary productivity (NPP) in this area and its driving factors would help understand the trends and leading factors of NPP variations, and reveal vegetation restoration status and causes. Based on the NPP data of MODIS, we used Theil-Sen Median trend analysis, correlation analysis, overlay analysis and other methods to analyze the spatiotemporal variations and driving factors of NPP in Ningxia. The results showed that NPP of Ningxia vegetation showed a fluctuating upward trend during 2000-2019, with a linear growth rate of 5.46 g C·m-2·a-1. The NPP presented a spatial characteristics of "two high and two low", with the highest in the southern mountain area, followed by the Yellow River irrigation area, and the lowest in the hilly area of the central arid zone and Helan Mountain. 84.2% of the NPP in the study area was under significant restoration, mainly distributed in the central and southern mountainous and hilly areas. The NPP varied significantly with altitude and was significantly affected by the terrain. NPP center of gravity had generally moved to the south, with the increase and growth rate of NPP of vegetation in the south being greater than that in the north. The annual precipitation in Ningxia had shown an increasing trend, while the average annual temperature had slightly decreased. The NPP was significantly affec-ted by precipitation (R2=0.291), whereas the correlation between mean annual temperature and NPP was weak. 96.9% of the study area was at a state of vegetation restoration, which was promoted by both climate change and human activities.


Assuntos
Ecossistema , Modelos Teóricos , Humanos , Mudança Climática , China , Temperatura
5.
Yi Chuan ; 44(10): 975-982, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36384733

RESUMO

Bardet-Biedl syndrome (BBS) is a rare autosomal recessive ciliopathy, which is caused by mutations mainly in genes encoding BBSome complex and IFT complex. Here, we reported a 21-year-old female with BBS characterized by three primary features including obesity, retinitis pigmentosa sine pigmento and bilateral renal cysts. She also had some secondary features such as diabetes mellitus, nonalcoholic fatty liver disease, subclinical hypothyroidism and mild conductive hearing damage. Whole exome sequencing revealed two compound heterozygous mutations in exon 2 of the BBS12 gene (c.188delC, p.T63fs and c.1993_1995del, p.665_665del) in this patient. Sanger sequencing showed that her father and mother carried c.188delC (p.T63fs) and c.1993_1995del (p.665_665del) variants, respectively, while her parents were free of BBS-related symptoms. In conclusion, this case reported two novel mutations (c.188delC, p.T63fs and c.1993_1995del, p.665_665del) of the BBS12 gene in a girl presented with BBS, which provides novel genetic resources for studies of the disease. Meanwhile, the BBS case shows the entire development progress from her birth to adulthood, which helps facilitate clinicians' understanding of BBS.


Assuntos
Síndrome de Bardet-Biedl , Humanos , Feminino , Adulto , Adulto Jovem , Síndrome de Bardet-Biedl/genética , Síndrome de Bardet-Biedl/diagnóstico , Testes Genéticos , Mutação , Éxons
6.
BMC Infect Dis ; 22(1): 850, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36376835

RESUMO

BACKGROUND: Despite a large amount of behavioral interventions to reduce human immunodeficiency virus (HIV)-related high-risk sexual behaviors, consistent condom use remains suboptimal among men who have sex with men (MSM). However, current databases are lack of synthesized evidence to explain why MSM practiced condomless sex. OBJECTIVE: Our study aims to conduct a systematic review and meta-synthesis of 39 eligible qualitative studies to explore the barriers to condom use among MSM. METHODS: A systematic review and meta-synthesis of qualitative studies (1994-2021). On March 4, 2021, a comprehensive search was conducted in 14 electronic databases. The study was conducted based on the Joanna Briggs Institute's recommendations. RESULTS: Thematic analysis produced six synthesized themes, which were classified into three levels according to the Social-ecology Model. Individual level barriers to condom use included physical discomfort, lack of HIV/STI-related knowledge and substance use; interpersonal-level barrier was mainly the condom stigma, namely regarding using condom as symbols of distrust or HIV/sexually transmitted infections (STIs) prevention, or as violating traditional cognition of sex, or as an embarrassing topic; environmental/structural-level barriers included situational unavailability, unaffordability of condoms and power imbalance in the sexual relationship. CONCLUSION: This meta-synthesis offered in-depth understanding of condom use barriers for MSM and could guide the development of multifactorial interventions according to the identified barriers, especially targeting to reduce condom stigma, which has not been focused and intervened previously.


Assuntos
Infecções por HIV , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Humanos , Masculino , Sexo sem Proteção , Homossexualidade Masculina , Infecções Sexualmente Transmissíveis/prevenção & controle , Infecções por HIV/prevenção & controle , Comportamento Sexual , Preservativos , Parceiros Sexuais
7.
Medicine (Baltimore) ; 101(45): e31370, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36397372

RESUMO

OBJECTIVE: This study aims to investigate the current situation of pelvic floor muscle (PFM) in the second trimester postpartum 42 days by detecting the electrophysiological indexes of PFM on pelvic floor rehabilitation after 2 months. METHODS: In total, 198 cases of second child puerpera were selected, who were delivered in our hospital between June 1, 2020, and December 10, 2020, and underwent outpatient reexamination 42 days after delivery. RESULTS: Except for the rest post-baseline stage values, the pelvic floor surface electromyography evaluation values significantly differed from each other at the considered time points in group A, P < .05; on day 72 in group B, no obvious improvement in the evaluation values was observed as than those on day 42 (P > .05) except for the endurance contractions stage values. However, on day 102, all values were markedly different at each considered time point (P < .05). On day 102 postpartum, the evaluation values of group A in the rest pre-baseline stage, the time before and after peak of phasic (flick) contractions stage, and the endurance contractions stage were significantly improved to those in group B with all P < .05. On day 42 after parturition, each index of the tonic contractions stage was higher after spontaneous labor than that after cesarean; the differences were all significant, P < .05, but on day 102 postpartum, all of the values exhibited no difference between the 2 modes. In only the phasic (flick) contractions stage at 42th, were the values of younger mothers obviously higher, P = .025; the other stage values for different ages of women during different time periods were not statistically significant, P > .05. CONCLUSIONS: In the short term, the effect of biofeedback plus electrical stimulation on the PFM function in second pregnant women was better than that of the Kegel exercise, but with time, there was no significant difference between the 2 training methods on the recovery of the PFM.


Assuntos
Distúrbios do Assoalho Pélvico , Diafragma da Pelve , Feminino , Humanos , Gravidez , Biorretroalimentação Psicológica , Eletromiografia , Distúrbios do Assoalho Pélvico/etiologia , Distúrbios do Assoalho Pélvico/terapia , Gestantes
8.
Biology (Basel) ; 11(11)2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36421382

RESUMO

Serine-threonine kinase 10 (STK10) is a member of the STE20/p21-activated kinase (PAK) family and is predominantly expressed in immune organs. Our previous reports suggested that STK10 participates in the growth and metastasis of prostate cancer via in vitro and in vivo data. However, the correlation between STK10 and the tumor microenvironment (TME) remains unclear. In this study, we assessed the relationship between STK10 and the immune cells in the tumor microenvironment of prostate cancer through bioinformatic analysis, and investigated the role of Stk10 in tumor growth using an Stk10 knockout mouse model. The results showed that STK10 is significantly associated with the tumor-infiltrating immune cells including lymphocytes, neutrophils, macrophages and dendritic cells. The target deletion of host Stk10 results in increased tumor growth, due to decreased activated/effector cytotoxic T lymphocytes (CTLs) and increased vessel density in the TME. In conclusion, we demonstrate that host Stk10 is involved in the host anti-tumor response by modulating the activated tumor-infiltrated CTLs and angiogenesis.

9.
Pediatr Surg Int ; 39(1): 13, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36441295

RESUMO

PURPOSE: To present our experience of using the pediatric donor superior mesenteric artery (SMA) as the interpositioning vessel to reconstruct the hepatic artery in pediatric deceased donor liver transplantation. METHODS: Pediatric patients who received pediatric deceased donor livers from December 2019 to June 2021 were enrolled. RESULTS: A total of 43 pediatric recipients received pediatric deceased donor livers during the study period. Thirty-four (79.1%) pediatric donors had normal hepatic artery anatomy, while nine (20.9%) showed variant anatomies. The SMAs of the pediatric donors were interposed in the latter eight cases. The anastomosis between the donor distal SMA and the donor celiac trunk artery (CTA) was initially performed in the back-table period, after which the other anastomosis between the donor proximal SMA and recipient CHA was performed. Only one case showed HAT occurrence (incidence rate, 2.3%). However, no arterial complications occurred in pediatric recipients with donor grafts that showed the variation of RHA replacement from the SMA and had undergone usage of the donor's SMA as an interpositioning vessel. CONCLUSIONS: In pediatric deceased donor liver transplantation, the use of SMA as an interpositioning medium can solve the problems related to a tiny caliber and anatomical variations of the donor hepatic artery.


Assuntos
Artéria Hepática , Transplante de Fígado , Humanos , Criança , Artéria Hepática/cirurgia , Artéria Mesentérica Superior/cirurgia , Doadores Vivos , Cadáver
10.
Mol Biol Rep ; 2022 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-36435920

RESUMO

BACKGROUND: Lung cancer is the leading cause of cancer-related mortality worldwide. Dysregulation of mRNA translation can contribute to the development and progression of cancer whilst also having an impact on the prognosis of different types of malignancies. Eukaryotic translation initiation factors (eIFs) have been reported to serve a key role in the initiation of mRNA translation. However, little was known about the association between eIF6 and lung adenocarcinoma (LUAD) progression. We aimed to elucidate the roles of eIF6 in LUAD tumorigenesis. METHODS: Bioinformatic analysis was conducted to assess the clinical significance of eIF6 in LUAD. CCK-8, colony formation assays were used to evaluate the biological roles of eIF6. The subcutaneous model was used to assess the in vivo roles of eIF6. RESULTS: In the present study, it was found that eIF6 expression was significantly higher in LUAD samples compared with that in normal lung tissues. Higher expression levels of eIF6 were found to be associated with more advanced clinical stages of LUAD and poorer prognoses in patients with LUAD. Subsequently, overexpression of eIF6 was demonstrated to promote LUAD cell proliferation, migration and invasion, which are features of metastasis, in vitro. By contrast, inhibition of eIF6 induced cell cycle arrest and apoptosis in LUAD cells. Further bioinformatics analysis and experimental assays revealed that eIF6 expression positively correlated with the mRNA expression of stemness-associated genes in LUAD cells. Targeting eIF6 suppressed the sphere formation capacity of LUAD cells. In addition, data from the subcutaneous xenograft model in vivo also suggested that eIF6 deficiency could significantly delay tumor growth and improve the prognosis of mice. Targeting eIF6 rendered LUAD cells sensitive to arsenic trioxide treatment. CONCLUSION: The present study suggest that eIF6 can serve as a prognostic biomarker and a potential therapeutic target for patients with LUAD.

11.
Life (Basel) ; 12(11)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36362861

RESUMO

Coronavirus Disease 2019 (COVID-19) is a highly infectious and pathogenic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Early in this epidemic, the herbal formulas used in traditional Chinese medicine (TCM) were widely used for the treatment of COVID-19 in China. According to Venn diagram analysis, we found that Glycyrrhizae Radix et Rhizoma is a frequent herb in TCM formulas against COVID-19. The extract of Glycyrrhizae Radix et Rhizoma exhibits an anti-SARS-CoV-2 replication activity in vitro, but its pharmacological mechanism remains unclear. We here demonstrate that glycyrrhizin, the main active ingredient of Glycyrrhizae Radix et Rhizoma, prevents the coronavirus from entering cells by targeting angiotensin-converting enzyme 2 (ACE2). Glycyrrhizin inhibited the binding of the spike protein of the SARS-CoV-2 to ACE2 in our Western blot-based assay. The following bulk RNA-seq analysis showed that glycyrrhizin down-regulated ACE2 expression in vitro which was further confirmed by Western blot and quantitative PCR. Together, we believe that glycyrrhizin inhibits SARS-CoV-2 entry into cells by targeting ACE2.

12.
Drug Des Devel Ther ; 16: 3739-3776, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36324421

RESUMO

Background: Traditional Chinese medicine (TCM) has the advantage of multi-component and multi-target, which becomes a hot spot in the treatment of numerous diseases. Shaoyao decoction (SYD) is a TCM prescription, which is mainly used to treat damp-heat dysentery clinically, with small side effects and low cost. However, its mechanism remains elusive. The purpose of this study is to explore the mechanism of SYD in the treatment of mice with ulcerative colitis (UC) induced by dextran sulfate sodium (DSS) through metabolomics and network pharmacology, and verify through molecular docking and immunohistochemistry, so as to provide a scientific basis for the role of SYD in the treatment of UC. Materials and Methods: Firstly, DSS-induced UC models were established and then untargeted metabolomics analysis of feces, livers, serum and urine was performed to determine biomarkers and metabolic pathways closely related to the role of SYD. Besides, network pharmacology was applied to screen the active components and UC-related targets, which was verified by molecular docking. Finally, metabonomics and network pharmacology were combined to draw the metabolite-pathway-target network and verified by immunohistochemistry. Results: Metabolomics results showed that a total of 61 differential metabolites were discovered in SYD-treated UC with 3 main metabolic pathways containing glycerophospholipid metabolism, sphingolipid metabolism and biosynthesis of unsaturated fatty acids, as well as 8 core targets involving STAT3, IL1B, IL6, IL2, AKT1, IL4, ICAM1 and CCND1. Molecular docking demonstrated that the first five targets had strong affinity with quercetin, wogonin, kaempferol and baicalein. Combined with metabolomics and network pharmacology, sphingolipid signaling pathway, PI3K/AKT-mTOR signaling pathway and S1P3 pathway were identified as the main pathways. Conclusion: SYD can effectively ameliorate various symptoms and alleviate intestinal mucosal damage and metabolic disorder in DSS induced UC mice. Its effect is mainly related to sphingolipid metabolism, PI3K/AKT-mTOR signaling pathway and S1P3 pathway.


Assuntos
Colite Ulcerativa , Medicamentos de Ervas Chinesas , Camundongos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Metabolômica , Serina-Treonina Quinases TOR , Esfingolipídeos
13.
Ann Emerg Med ; 2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36328853

RESUMO

STUDY OBJECTIVE: Evaluate the utility of routine rescanning of older, mild head trauma patients with an initial negative brain computed tomography (CT), who is on a preinjury antithrombotic (AT) agent by assessing the rate of delayed intracranial hemorrhage (dICH), need for surgery, and attributable mortality. METHODS: Participating centers were trained and provided data collection instruments per institutional review board-approved protocols. Data were obtained from manual chart review and electronic medical record download. Adults ≥55 years seen at Level I/II Trauma Centers, between 2017 and 2019 with suspected head trauma, Glasgow Coma Scale 14 to 15, negative initial brain CT, and no other Abbreviated Injury Scale injuries >2 were identified, grouped by preinjury AT therapy (AT- or AT+) and compared on dICH rate, need for operative neurosurgical intervention, and attributable mortality using univariate analysis (α=.05). RESULTS: A total of 2,950 patients from 24 centers were enrolled; 280 (9.5%) had a repeat brain CT. In those rescanned, the dICH rate was 15/126 (11.9%) for AT- and 6/154 (3.9%) in AT+. Assuming nonrescanned patients did not suffer clinically meaningful dICH, the dICH rate would be 15/2001 (0.7%) for AT- and 6/949 (0.6%) for AT+. No surgical operations were done for dICH. All-cause mortality was 9/2950 (0.3%) and attributable mortality was 1/2950 (0.03%). The attributable death was an AT+, dICH patient whose family declined intervention. CONCLUSION: In older patients with an initial Glasgow Coma Scale of 14 to 15 and a negative initial brain CT scan, the dICH rate is low (<1%) and of minimal clinical consequence, regardless of AT use. In addition, no patient had operative neurosurgical intervention. Therefore, routine rescanning is not supported based on the results of this study.

14.
J Am Geriatr Soc ; 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36330687

RESUMO

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability in older adults. The aim of this study was to characterize the burden of TBI in older adults by describing demographics, care location, diagnoses, outcomes, and payments in this high-risk group. METHODS: Using 2016-2019 Centers for Medicare & Medicaid Services (CMS) Inpatient Standard Analytical Files (IPSAF), patients >65 years with TBI (>1 injury ICD-10 starting with "S06") were selected. Trauma center levels were linked to the IPSAF file via American Hospital Association Hospital Provider ID and fuzzy-string matching. Patient variables were compared across trauma center levels. RESULTS: Three hundred forty-eight thousand eight hundred inpatients (50.4% female; 87.1% white) from 2963 US hospitals were included. Level I/II trauma centers treated 66.9% of patients; non-trauma centers treated 21.5%. Overall inter-facility transfer rate was 19.2%; in Level I/II trauma centers transfers-in represented 23.3% of admissions. Significant TBI (Head AIS ≥3) was present in 70.0%. Most frequent diagnoses were subdural hemorrhage (56.6%) and subarachnoid hemorrhage (30.6%). Neurosurgical operations were performed in 10.9% of patients and operative rates were similar regardless of center level. Total unadjusted mortality for the sample was 13.9%, with a mortality of 8.1% for those who expired in-hospital, and an additional 5.8% for those discharged to hospice. Medicare payments totaled $4.91B, with the majority (73.4%) going to Level I/II trauma centers. CONCLUSIONS: This study fills a gap in TBI research by demonstrating that although the majority of older adult TBI patients in the United States receive care at Level I/II trauma centers, a substantial percentage are managed at other facilities, despite 1 in 10 requiring neurosurgical operation regardless of level of trauma center. This analysis provides preliminary data on the function of regionalized trauma care for older adult TBI care. Future studies assessing the efficacy of early care guidelines in this population are warranted.

15.
ACS Infect Dis ; 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36378028

RESUMO

As antimicrobial resistance poses an increasing threat to public health, it is urgent to develop new antimicrobial agents. In this paper, we identify a novel 30-residue peptide (Nv-CATH, NCNFLCKVKQRLRSVSSTSHIGMAIPRPRG) from the skin of the frog Nanorana ventripunctata, which belongs to the cathelicidin family. Nv-CATH exhibited broad-spectrum antimicrobial activity against Gram-positive and Gram-negative bacteria. Nv-CATH significantly protected mice from lethal infections caused by Staphylococcus aureus. Furthermore, the peptide suppressed excessive and harmful inflammatory responses by repressing the production of NO, IL-6, TNF-α, and IL-1ß. The NF-κB-NLRP3 and MAPK inflammatory signaling pathways were involved in the protection in vitro and in vivo. Nv-CATH also modulated macrophage/monocyte and neutrophil trafficking to the infection site by stimulating CXCL1, CXCL2, and CCL2 production in macrophages. Nv-CATH augmented immunocyte-mediated bacterial killing by modestly promoting neutrophils' phagocytosis and PMA-induced NET formation. Thus, Nv-CATH protects mice against bacterial infection by antimicrobial-immunomodulatory duality. The combination of these two characteristics makes Nv-CATH a promising molecule template for the development of novel antimicrobial and antibiotic-resistant agents.

16.
Contrast Media Mol Imaging ; 2022: 7146978, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36237582

RESUMO

Pneumonia is a major research core topic in the medical field, and clinical trials of pneumonia and respiratory tract infection have been ongoing. The purpose of this study was to investigate the clinical efficacy and safety of Shuanghuanghua granules in the treatment of pneumonia and respiratory tract infection based on NMR molecular imaging, and to lay a foundation for the development of new drugs. In this paper, 126 patients were randomly divided into the control group, the treatment group 1, the and treatment group 2, and were given Fengreganmao granules, Shuanghuanghua granules (ultrafine preparation), and Shuanghuanghua granules (extract preparation), respectively. The main symptom scores, sign scores, antipyretic time, and virus content before and after treatment were recorded. Statistical analysis was carried out on this basis. The experiment showed that the body temperature of the subjects in the three groups before treatment was: control group (37.59 ± 0.78), treatment group 1 (37.8 ± 0.81), and treatment group 2 (37.6 ± 0.76). After treatment, the body temperature of subjects in the three groups was: control group (36.67 ± 0.71), treatment group 1 (36.49 ± 0.43), and treatment group 2 (36.19 ± 0.25). Experiments show that Shuanghuanghua granules can significantly reduce the nasal virus, adenovirus, parainfluenza virus, etc. in the patient's body. And it can shorten the antipyretic time of patients and has good clinical application. In addition, this study gave full play to the role of MRI molecular imaging and provided ideas and references for the clinical treatment of pneumonia and respiratory tract infection.


Assuntos
Antipiréticos , Pneumonia , Infecções Respiratórias , Antipiréticos/uso terapêutico , Humanos , Imageamento por Ressonância Magnética , Imagem Molecular , Pneumonia/diagnóstico por imagem , Pneumonia/tratamento farmacológico , Infecções Respiratórias/diagnóstico por imagem , Infecções Respiratórias/tratamento farmacológico
17.
Mol Biol Rep ; 49(12): 12055-12061, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36309610

RESUMO

BACKGROUND: Watercore is a common physiological disorder in pear and is closely related to the excessive accumulation of sorbitol and sucrose. Our previous research found that the incidence of watercore in 'Akibae' (Pyrus pyrifolia cv. Akibae) fruit significantly decreased after boron application (BA). Moreover, the foliar spray of boric acid also significantly improved fruit quality. However, the mechanisms underlying the pear fruit response to BA was still limited. METHODS AND RESULTS: A comprehensive transcriptome analysis of BA treatment 'Akibae' pear fruit was performed in this study. Transcriptome results revealed a total of 3146 up-regulated and 1145 down-regulated differentially expressed genes (DEGs) between control and treated fruits of 'Akibae' pear. BA significantly induced the expression of sorbitol metabolism and sucrose metabolism genes. In addition, BA also increased the expression of starch degradation, fatty acid synthesis, IAA (indole-3-acetic acid) degradation, and GA (gibberellin acid) synthesis genes and inhibited the expression of ethylene synthesis genes. CONCLUSIONS: These findings suggested that BA probably alleviates 'Akibae' watercore occurrence and improves fruit quality by regulating the decrease in sorbitol and sucrose, the increase in fatty acids and the balance of plant hormones. Our results provide further information for understanding the molecular mechanism of the effect of BA on pear fruit.


Assuntos
Pyrus , Pyrus/genética , Pyrus/metabolismo , Frutas/genética , Frutas/metabolismo , Transcriptoma/genética , Boro/farmacologia , Boro/metabolismo , Regulação da Expressão Gênica de Plantas , Perfilação da Expressão Gênica , Sacarose/farmacologia , Sacarose/metabolismo , Sorbitol
18.
Anal Chim Acta ; 1232: 340457, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36257741

RESUMO

Different chemical forms of sex hormones including free/conjugated metabolites as well as their protein/DNA adducts in human serum are a panel of important indicators of health conditions. It is, however, hard to quantify all species simultaneously due to the lack of general extraction, derivatization, and de-conjugation methods. Here we developed a label-free and de-conjugation-free workflow to quantify 11 free/conjugated estrogen metabolites including depurinating DNA and protein adduct forms of 4-hydroxyestradiol (4OHE2) in human serum. Acetonitrile acts as an excellent solvent to purify adducted and non-adducted human serum albumin (HSA) by precipitation as well as to extract free/conjugated metabolites and depurinating DNA adducts from the supernatant by salting-out effect. The adduction level of 4OHE2 on HSA was determined by proteomics; free/conjugated metabolites were quantified by a newly developed microflow liquid chromatography (microflow LC)-nanoelectrospray ionization (nanoESI)-multiple reaction monitoring (MRM) method with high reproducibility (7-22% RSD, n > 3) and sub-picogram levels (0.6-20 pg/mL) of quantification limits (S/N = 8) by using non-pulled capillary as nano-ESI emitter. This workflow was demonstrated to reveal endogenous adduction level of 4OHE2 on HSA as well as circulation levels of free/conjugated metabolites in clinical samples. 4OHE2 in human serum were solely detected as protein-bound form, indicating the merit of such integrated platform covering unstable or active metabolites. Compared to traditional methods using labeling or de-conjugation reaction, this workflow is much simplier, more sensitive, and more specific. Moreover, it can be widely applied in omics to concurrently access various bio-transformed known and un-known markers or drugs.


Assuntos
Adutos de DNA , Estrogênios Conjugados (USP) , Humanos , Fluxo de Trabalho , Reprodutibilidade dos Testes , Estrogênios , DNA/química , Albumina Sérica Humana , Acetonitrilas , Solventes
19.
Surg Endosc ; 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36261643

RESUMO

BACKGROUND: Patients with pancreatic cancer-caused biliary obstruction (PC-BO) have poor prognosis, but we lack of tools to predict survival for clinical decision-making. This study aims to establish a model for survival prediction among patients with PC-BO. METHODS: A total of 172 patients with PC-BO treated with percutaneous biliary drainage were randomly divided into a training group (n = 120) and a validation group (n = 52). The independent risk factors for overall survival were selected to develop a Cox model. The predictive performance of M stage, hepatic metastases, cancer antigen 199, and the Cox model was determined. Naples prognostic score (NPS), the prognostic nutritional index (PNI), and the controlling nutritional status (CONUT) for 1-month mortality risk were compared with the Cox model. RESULTS: The Cox model was developed based on total cholesterol, direct bilirubin, hepatic metastases, cancer antigen 199, stenosis type, and preprocedural infection (all P < 0.05), which named "COMBO-PaS." The COMBO-PaS model had the highest area under the curves (AUC) (0.801-0.933) comparing with other predictors (0.506-0.740) for 1-, 3-, and 6-month survival prediction. For 1-month mortality risk prediction, the COMBO-PaS model had the highest AUC of 0.829 comparing with NPS, PNI, and CONUT. CONCLUSION: The COMBO-PaS model was useful for survival prediction among patients with PC-BO.

20.
Front Endocrinol (Lausanne) ; 13: 995028, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36246918

RESUMO

Backgrounds: Ectopic fat deposition is closely related to chronic kidney disease (CKD). Currently, there are few population studies that have been conducted to determine the relationship between renal parenchyma fat deposition and the risk of CKD among patients with type 2 diabetes mellitus (T2DM). Therefore, we employed magnetic resonance imaging (MRI) to detect renal parenchyma fat content in individuals with T2DM, expressed as renal fat fraction (FF), to explore whether renal FF is an important risk factor for CKD in patients with T2DM. Methods: In this cross-sectional study, 189 subjects with T2DM were enrolled. CKD was defined as the estimated glomerular filtration rate (eGFR)<60 mL/min/1.73m2. Measurement of the renal FF was performed on a 3.0-T MRI (MAGNETOM Skyra, Siemens, Erlangen, Germany). Binary logistic regression was used to determine the association between tertiles of renal FF and risk of CKD. Receiver-operator characteristic (ROC) curves were constructed to evaluate the sensitivity and specificity of renal FF in detecting CKD in T2DM patients. Results: The patients were divided into three groups according to tertiles of the renal FF level (2.498 - 7.434). As renal FF increases, patients tend to be older, and more abdominally obese, with a decreased eGFR (p<0.05). After adjustment for potential confounders, patients in the highest tertile of renal FF had a significantly increased risk of CKD than those in the lowest tertile (odds ratio (OR) = 3.98, 95% confidence interval (CI) = 1.12 - 14.09, p = 0.032), and the area under the ROC curve for this model was 0.836 (0.765-0.907). Conclusions: The renal FF is significantly independently associated with CKD in patients with T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Estudos Transversais , Diabetes Mellitus Tipo 2/patologia , Taxa de Filtração Glomerular , Humanos , Rim/diagnóstico por imagem , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/diagnóstico
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