Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 385
Filtrar
1.
Scand J Immunol ; : e13047, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33914954

RESUMO

Perforin, a pore-forming glycoprotein, has been demonstrated to play key roles in clearing virus-infected cells and tumor cells due to its ability of forming "pores" on the cell membranes. Additionally, perforin is also found to be associated with human diseases such as tumors, virus infections, immune rejection and some autoimmune diseases. Until now, plenty of perforin genes have been identified in vertebrates, especially the mammals and teleost fish. Conversely, vertebrate homologue of perforin gene was not identified in the invertebrates. Although recently there have been several reviews focusing on perforin and granzymes in mammals, no one highlighted the current advances of perforin in the other vertebrates. Here, in addition to mammalian perforin, the structure, evolution, tissue distribution and function of perforin in bony fish are summarized respectively, which will allow us to gain more insights into the perforin in lower animals and the evolution of this important pore-forming protein across vertebrates.

2.
J Wound Care ; 30(Sup4): S14-S23, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33856928

RESUMO

OBJECTIVE: This study aimed to investigate how adipose tissue-derived stem cells (ASCs) from diabetic and from non-diabetic rats affect wound healing in different microenvironments. METHOD: The two types of ASC-rich cells were distinguished by characteristic surface antigen detection. The ASC-rich cells were transplanted into the wounds of diabetic and non-diabetic rats. Wound healing rates were compared and the healing process in the wound margin sections was used to determine how ASC-rich cells affect wound healing in different microenvironments. RESULTS: ASC density was decreased in diabetic rats. The generation time of ASC-rich cells from diabetic rats (d-ASC-rich cells) was longer than that of ASC-rich cells from non-diabetic rats. The number of pre-apoptotic cells in the third generation (passage 3) of d-ASC-rich cells was higher than that among the ASC-rich cells from non-diabetic rats. CD31 and CD34 expression was higher in d-ASC-rich cells than in ASC-rich cells from non-diabetic rats, whereas CD44 and CD105 expression was lower than that in ASC-rich cells from non-diabetic rats. Transplantation of ASC-rich cells from non-diabetic rats promoted wound healing in both non-diabetic and diabetic rats. In contrast, d-ASC-rich cells and enriched nuclear cells only promoted wound healing in non-diabetic rats. ASC-rich cell transplantation promoted greater tissue regeneration than d-ASC-rich cell transplantation. CONCLUSION: ASC-rich cells promoted wound healing in diabetic and non-diabetic rats. ASC density was lower in the adipose tissue of diabetic rats compared with non-diabetic rats. d-ASC-rich cells did not promote wound healing in diabetic rats, suggesting that caution is warranted regarding the clinical use of diabetic adipose stem cell transplantation for the treatment of diabetic wounds.

3.
Cell Rep ; 34(13): 108922, 2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33789111

RESUMO

Hematopoietic stem cells (HSCs) regenerate blood cells upon hematopoietic injuries. During homeostasis, HSCs are maintained in a low reactive oxygen species (ROS) state to prevent exhaustion. However, the role of nitric oxide (NO) in controlling HSC regeneration is still unclear. Here, we find increased NO during HSC regeneration with an accumulation of protein aggregation. S-nitrosoglutathione reductase (GSNOR)-deleted HSCs exhibit a reduced reconstitution capacity and loss of self-renewal after chemotherapeutic injury, which is resolved by inhibition of NO synthesis. Deletion of GSNOR enhances protein S-nitrosylation, resulting in an accumulation of protein aggregation and activation of unfolded protein response (UPR). Treatment of taurocholic acid (TCA), a chemical chaperone, rescues the regeneration defect of Gsnor-/- HSCs after 5-fluorouracil (5-FU) treatment. Deletion of C/EBP homologous protein (Chop) restores the reconstitution capacity of Gsnor-/- HSCs. These findings establish a link between S-nitrosylation and protein aggregation in HSC in the context of blood regeneration.

4.
Life Sci ; 274: 119346, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33713667

RESUMO

AIMS: Fibroblast growth factor 21 (FGF21) has been identified as the master hormonal regulator of energy balance, its elevation is observed in a series of metabolic and cardiovascular diseases. Studies have implicated the role of FGF21 signaling in the pathogenesis of abdominal aortic aneurysm (AAA). We will investigate the association of FGF21 and AAA development. MATERIALS AND METHODS: In this study, we assayed plasma levels of FGF21 in 82 patients with AAA and 44 control subjects, then analyzed their relationship with clinical, biochemical and histological phenotypes. The expression of ß-klotho, an essential co-receptor of FGF21, was assessed with IHC staining and RT-qPCR. Machine learning models incorporate a combination of FGF21 and clinical data were utilized in the prediction of AAA occurrence. KEY FINDINGS: FGF21 was statistically higher in patients with AAA (781 pg/ml [533, 1213]) than in control subjects (567 pg/ml [324, 939]). After adjustment for age and BMI, we found a positive association of FGF21 levels with AAA diameters, hypertension rate and hsCRP, and a negative correlation between FGF21 levels and HDL-c. Furthermore, the protein levels of ß-klotho in abdominal aorta of AAA were found significantly lower than in control group indicating the presence of FGF21 resistance. Combining FGF21 levels with four clinical characteristics significantly improved the stratification of AAA and control groups with an AUC of 0.778. SIGNIFICANCE: Combining detection of plasma FGF21 and clinical characteristics may be reliable for identifying the presence of AAA. The role of FGF21 as a therapeutic target of AAA warrants further investigation.


Assuntos
Aneurisma da Aorta Abdominal/diagnóstico , Biomarcadores/sangue , Fatores de Crescimento de Fibroblastos/sangue , Proteínas de Membrana/metabolismo , Idoso , Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/patologia , Estudos de Casos e Controles , Feminino , Fatores de Crescimento de Fibroblastos/genética , Humanos , Masculino , Proteínas de Membrana/genética , Prognóstico
5.
Int Wound J ; 2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33754459

RESUMO

The objectives of this study were to investigate the status and influence factors of caregiver's quality of life (QOL) on caring for patients with chronic wound during COVID-19 epidemic. A prospective cross-sectional study of 83 informal caregivers was included. The characteristics of informal caregivers as well as their QOL assessment by the Family Dermatology Life Quality Index (FDLQI) were measured, respectively. Single-factor analysis and multiple regression analysis were carried out to explore the independent influence factors of QOL of caregiver on caring for patient with chronic wound. 62.65% of the caregivers were female with a mean age of (54.24 ± 12.6) years, and 34.9% of the caregivers were parents. The mean FDLQI score was 13.01 ± 7.53 at a high level. The following variables influenced the FDLQI scores of caregivers: self-care ability of patients, patient's satisfaction of home-based wound care, and home-based wound care need of caregivers. The model was able to explain 29.9% of variance in QOL of caregiver (F = 6.561, P = .000, R2 = 0.299, adjusted R2 = 0.253). In conclusion, the impact of chronic wound disease on the QOL of caregivers is heavy during COVID-19 epidemic. Wound professionals are suggested to pay attention to wound care need at home and QOL of caregiver on caring for patients with chronic wound during COVID-19 epidemic and develop tailored wound health education and support programme in order to improve the QOL of caregivers.

6.
Front Immunol ; 12: 631044, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613576

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic has been raging around the world since January 2020. Pregnancy places the women in a unique immune scenario which may allow severe COVID-19 disease. In this regard, the potential unknown effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on mothers and fetuses have attracted considerable attention. There is no clear consistent evidence of the changes in the immune status of pregnant women after recovery from COVID-19. In this study, we use multiparameter flow cytometry and Luminex assay to determine the immune cell subsets and cytokines, respectively, in the peripheral blood and umbilical cord blood from pregnant women recovering from COVID-19 about 3 months (n=5). Our results showed decreased percentages of Tc2, Tfh17, memory B cells, virus-specific NK cells, and increased percentages of naive B cells in the peripheral blood. Serum levels of IL-1ra and MCP-1 showed a decreased tendency in late recovery stage (LRS) patients. Meanwhile, there was no significant difference in immune cell subsets in the umbilical cord blood. The placentas from LRS patients showed increased CD68+ macrophages infiltration and mild hypoxic features. The inflammatory damage of the placenta may be related to the antiviral response. Since the receptors, ACE2 and TMPRSS2, utilized by SARS-CoV-2 are not co-expressed in the placenta, so it is extremely rare for SARS-CoV-2 to cause infection through this route and the impact on the fetus is negligible.


Assuntos
Linfócitos B/imunologia , Sangue Fetal/imunologia , Centro Germinativo/imunologia , Placenta/imunologia , Células Th17/imunologia , /metabolismo , Autoantígenos/metabolismo , Feminino , Citometria de Fluxo , Humanos , Memória Imunológica , Imunofenotipagem , Células Matadoras Naturais , Gravidez , Receptores de Interleucina-1/metabolismo , Serina Endopeptidases/metabolismo
7.
Chemistry ; 2021 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-33554407

RESUMO

Efficient separation of photogenerated electron-hole pairs is a crucial factor for high-performance photocatalysts. Effective electron-hole separation and migration could be achieved by heterojunctions with suitable band structures. Herein, a porous SrTiO3 /SrSO4 heterojunction is prepared by a sol-gel method at room temperature followed by an annealing process. XRD characterization suggests high crystallinity of the heterostructure. A well-defined interface between the two phases is confirmed by high-resolution (HR)TEM. The photocatalytic H2 evolution productivity of the SrTiO3 /SrSO4 heterojunction with Pt as co-catalyst reaches 396.82 µmol g-1 h-1 , which is 16 times higher than that of SrTiO3 /Pt. The boosted photocatalytic activity of SrTiO3 /SrSO4 /Pt can be ascribed to the presence of SrSO4 , which promotes the transfer and migration of photogenerated carriers by forming the heterojunction and porous structure, which provides a large amount of active sites. This novel porous heterostructure brings new ideas for the development of high-efficiency photocatalysts for H2 release.

8.
J Psychiatr Res ; 136: 358-365, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33636692

RESUMO

MicroRNA (miR)-181b-5p is considered to be involved in the pathogenesis of schizophrenia, and one of its regulatory target genes BCL-2 (B-cell lymphoma 2) is suggested to associate with cognition of schizophrenia. Cognitive deficit is a core trait of schizophrenia. However, it remains unclear whether miR-181b-5p affects cognition and its possible pathway in schizophrenia. We hypothesized that miR-181b-5p affects cognition by targeting BCL-2 mRNA and downregulating BCL-2 protein expression in schizophrenia patients. In this study, first-episode patients with schizophrenia (FEPS, n = 123) and age- and gender-matched healthy controls (HCs, n = 50) were enrolled in Chinese populations. Expression levels of miR-181b-5p and BCL-2 mRNA in peripheral whole blood were measured with quantitative real-time PCR (Q-PCR) and BCL-2 protein in plasma were measured with Enzyme Linked Immunosorbent Assay (ELISA). Psychopathology was assessed with the Positive and Negative Syndrome Scale (PANSS), cognitive function was evaluated using the MATRICS Consensus Cognitive Battery (MCCB). Peripheral blood miR-181b-5p expression level was significantly upregulated (p = 0.001) whereas BCL-2 mRNA and BCL-2 protein levels were significantly downregulated (p = 0.002, p = 0.023 respectively) in the FEPS compared with those in the HCs. The miR-181b-5p level was negatively (p = 0.005), whereas the BCL-2 mRNA level was positively (p < 0.001), correlated with working memory in FEPS. Mediating effect analysis showed that the effect of miR-181b-5p on working memory in the FEPS was exerted via targeting BCL-2 mRNA. MiR-181b-5p in combination with BCL-2 mRNA might be suggested as potential biomarker for schizophrenia in our discovery sample. In conclusion, overexpressed miR-181b-5p may affect cognitive function in patients with schizophrenia.

9.
Inflammation ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33598777

RESUMO

Programmed necrosis factor 1 (PD-1) is significantly overexpressed in lymphocytes, neutrophils, and macrophages and has been studied in depth in tumors. As a member of the negative costimulatory family of immune regulatory molecules, expression of PD-1 and its primary regulatory pathway are related to immune cells. Recently, PD-1 was demonstrated to be clinically important in inflammatory diseases, such as multiple sclerosis, glomerulonephritis, and inflammatory bowel disease. PD-1, a negative regulator molecule, was recently found to protect tissues from the inflammatory response and inflammatory cell infiltration. Conversely, PD-1 deficiency may contribute to the occurrence of a diverse array of inflammatory diseases. However, whether PD-1 regulates the pathogenesis of acute pancreatitis (AP) is unclear. AP is a noninfectious inflammatory disease with primary pathological manifestations that include edema, inflammatory cell infiltration, and acinar cell necrosis. Among these features, costimulatory molecules including PD-1/PDL1 play a critical role in the regulation of immune response and immune activation. Here, we first found that PD-1 is notably upregulated in neutrophils and macrophages in peripheral blood and pancreatic injury tissue in AP mice. PD-1 gene deficiency exacerbated pancreatic injury in an experimental mouse model of AP. We observed more severe pancreatic injury in PD-1-deficient mice than in control mice, including increased pancreatic edema, inflammatory cells, infiltration, and acinar cell necrosis. We also found that PD-1-deficient mice exhibited higher levels of serum enzymology and inflammatory factors in AP. Furthermore, PD-1/PDL1 neutralizing antibodies significantly aggravated pancreatic and lung injury and increased serum inflammatory cytokine levels. These findings were consistent with those in PD-1-deficient mice. In summary, PD-1 may protect against AP in mice and act as a potential target for the prevention of AP in the future.

10.
IEEE Trans Cybern ; PP2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33606649

RESUMO

Hyperspectral images (HSIs) are inevitably contaminated by the mixed noise (such as Gaussian noise, impulse noise, deadlines, and stripes), which could influence the subsequent processing accuracy. Generally, HSI restoration can be transformed into the low-rank matrix recovery (LRMR). In the LRMR, the nuclear norm is widely used to substitute the matrix rank, but its effectiveness is still worth improving. Besides, the l0-norm cannot capture the sparse noise's structured sparsity property. To handle these issues, the adaptive rank and structured sparsity corrections (ARSSC) are presented for HSI restoration. The ARSSC introduces two convex regularizers, that is: 1) the rank correction (RC) and 2) the structured sparsity correction (SSC), to, respectively, approximate the matrix rank and the l2,0-norm. The RC and the SSC can adaptively offset the penalization of large entries from the nuclear norm and the l2,1-norm, respectively, where the larger the entry, the greater its offset. Therefore, the proposed ARSSC achieves a tighter approximation of the noise-free HSI low-rank structure and promotes the structured sparsity of sparse noise. An efficient alternative direction method of multipliers (ADMM) algorithm is applied to solve the resulting convex optimization problem. The superiority of the ARSSC in terms of the mixed noise removal and spatial-spectral structure information preserving, is demonstrated by several experimental results both on simulated and real datasets, compared with other state-of-the-art HSI restoration approaches.

11.
J Phys Chem Lett ; : 844-849, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33427476

RESUMO

Carbon disulfide (CS2) is a typical triatomic molecule. Its photodissociation process has generally been assumed to proceed to CS and S primary products via single bond fission. However, recent theoretical calculations suggested that an exit channel to produce C + S2 should also be energetically accessible. Here, we report the direct experimental evidence for the C + S2 channel in CS2 photodissociation by using the velocity map ion imaging technique with two-photon UV and one-photon vacuum UV (VUV) excitations. The detection of the C (3P) products illustrates that the ground state and the electronically excited states of S2 coproducts are formed within highly excited vibrational states. The very weak anisotropic distributions indicate relatively slow dissociation processes. The possible dissociation mechanism involves molecular isomerization of CS2 to linear-CSS from the excited 1B2 (21Σ+) state via vibronic coupling with the 1Π state followed by an avoided crossing with the ground state surface. Our results imply that the S2 molecules observed in comets might be primarily formed in CS2 photodissociation.

12.
Cell Rep ; 34(2): 108603, 2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33440163

RESUMO

Anterior segment dysgenesis is often associated with cornea diseases, cataracts, and glaucoma. In the anterior segment, the ciliary body (CB) containing inner and outer ciliary epithelia (ICE and OCE) secretes aqueous humor that maintains intraocular pressure (IOP). However, CB development and function remain poorly understood. Here, this study shows that NOTCH signaling in the CB maintains the vitreous, IOP, and eye structures by regulating CB morphogenesis, aqueous humor secretion, and vitreous protein expression. Notch2 and Notch3 function via RBPJ in the CB to control ICE-OCE adhesion, CB morphogenesis, aqueous humor secretion, and protein expression, thus maintaining IOP and eye structures. Mechanistically, NOTCH signaling transcriptionally controls Nectin1 expression in the OCE to promote cell adhesion for driving CB morphogenesis and to directly stabilize Cx43 for controlling aqueous humor secretion. Finally, NOTCH signaling directly controls vitreous protein secretion in the ICE. Therefore, this study provides important insight into CB functions and involvement in eye diseases.

13.
Trials ; 22(1): 67, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468222

RESUMO

BACKGROUND: Atopic dermatitis (AD) is a complex, common inflammatory skin disease. The Chinese herbal formula Huoxiang Zhengqi (HXZQ) has been a common dermatosis treatment in China for many years, but there is no high-level evidence for its effect on AD/eczema. The aim of this trial is to examine the efficacy and safety of HXZQ treating AD/eczema patients. METHODS: This is a double-blind, multi-center, randomized controlled trial comparing HXZQ to a placebo. It will consist of 4 weeks' treatment and 4 weeks of follow-up. A total of 218 participants will be randomly allocated into two groups-an HXZQ group and a placebo group, from 7 hospitals in China. Patients diagnosed with AD will be enrolled if they are in accordance with CM dampness pattern, have body surface area (BSA) of 1-10%, have investigator's global assessment (IGA) of 1-3, have age between 18 and 70 years, and provide signed informed consent. The Eczema Area and Severity Index (EASI) is the primary outcome. The secondary outcomes are the numerical itch rating scale, IGA, BSA, Skindex-29, and EQ-5D-5L score, from baseline to the end of the treatment. Analysis will be on intention-to-treat and per-protocol subject analysis principles. DISCUSSION: The goal of this trial is to evaluate the efficacy and availability of HXZQ oral liquid in treating AD/eczema in terms of symptoms and eczematous lesions. It will also address whether it has positive effect on QoL. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn/index.aspx ): Chinese herbal formula Huoxiang Zhengqi for atopic dermatitis with dampness pattern (CHARM): a double-blinded randomized controlled trial, ChiCTR1900026700 . Registered on 19 October 2019.

14.
Clin Immunol ; 224: 108663, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33401032

RESUMO

Autoimmune thyroiditis (AIT) is a common organ-specific autoimmune disease with a high incidence among women of childbearing age. Recent studies have reported that women with AIT are more susceptible to infertility, miscarriage and preterm birth. It has been investigated that abnormal changes in maternal immune system and maternal-fetal interface can dampen the immune tolerance between mother and fetus, which underlie the pathogenesis of adverse pregnancy outcomes. Hence, we summarize the immunological changes related to adverse reproductive outcomes in AIT and highlight the respective contributions of both humoral and cellular immune dysfunctions to pregnancy failures. Moreover, the direct impacts of AIT on maternal-fetal immune activation and biological influences to trophoblasts are discussed as well. All these associations require confirmation in larger studies, and the pathogenic mechanisms need to be better understood, which might provide useful information for clinical diagnosis and therapy of AIT.

15.
Curr Biol ; 31(4): 827-839.e3, 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33357404

RESUMO

The niche controls stem cell self-renewal and progenitor differentiation for maintaining adult tissue homeostasis in various organisms. However, it remains unclear whether the niche is compartmentalized to control stem cell self-renewal and stepwise progeny differentiation. In the Drosophila ovary, inner germarial sheath (IGS) cells form a niche for controlling germline stem cell (GSC) progeny differentiation. In this study, we have identified four IGS subpopulations, which form linearly arranged niche compartments for controlling GSC maintenance and multi-step progeny differentiation. Single-cell analysis of the adult ovary has identified four IGS subpopulations (IGS1-IGS4), the identities and cellular locations of which have been further confirmed by fluorescent in situ hybridization. IGS1 and IGS2 physically interact with GSCs and mitotic cysts to control GSC maintenance and cyst formation, respectively, whereas IGS3 and IGS4 physically interact with 16-cell cysts to regulate meiosis, oocyte development, and cyst morphological change. Finally, one follicle cell progenitor population has also been transcriptionally defined for facilitating future studies on follicle stem cell regulation. Therefore, this study has structurally revealed that the niche is organized into multiple compartments for orchestrating stepwise adult stem cell development and has also provided useful resources and tools for further functional characterization of the niche in the future.

16.
J Nanobiotechnology ; 18(1): 175, 2020 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-33256741

RESUMO

BACKGROUND: Development of sensitive and specific imaging approaches for the detection of ovarian cancer holds great promise for improving the therapeutic efficacy and the lifespan of the patients. RESULTS: In this study, manganese-nitrogen doped carbon nanosheets (Mn-N-CNSs) coupled with Anti-HE4 monoclonal antibody (Mn-N-CNSs@Anti-HE4) were synthesized for the specific and targeted fluorescence/MR dual-modal imaging of ovarian carcinoma. The prepared Mn-N-CNSs revealed excellent aqueous dispersity, good colloidal stability, great optical properties and high longtudinal relaxivity rate (r1 = 10.30 mM-1 s-1). Encouraged by the tunable photoluminiscence of the nanoprobe and Anti-HE4 targeting ligand, the ovarian carcinoma cells were specifically labeled by the Mn-N-CNSs@Anti-HE4 nanoprobe with multi-color fluorescences. Benefiting from the high r1 relaxivity, the nanoprobe exhibited targeted and enhanced MR contrast effect in the ovarian carcinoma cells and tumor bearing mice model. Besides, the high biocompatibility and easy excretion from the body of the nanoprobe were further confirmed in vivo. CONCLUSION: The prepared Mn-N-CNSs@Anti-HE4 with excellent biocompatibility, high-performance and superior tumor-targeting ability provides a novel fluorescence/MR dual-modal nanoprobe for specific labeling and detection of ovarian carcinoma cells in vitro and in vivo.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33269903

RESUMO

We report the mechanism of hydrogel formation in dilute aqueous solutions (>15 mg/mL) by 2 nm metal-organic cages (MOCs). Experiments and all-atom simulations confirm that with the addition of small electrolytes, the MOCs self-assemble into 2D nanosheets via counterion-mediated attraction because of their unique molecular structure and charge distribution as well as σ-π interactions. The stiff nanosheets are difficult to bend into 3-D hollow, spherical blackberry type structures, as observed in many other macroion systems. Instead, they stay in solution and their very large excluded volumes lead to gelation at low (∼1.5 wt %) MOC concentrations, with additional help from hydrophobic and partial π-π interactions similar to the gelation of graphene oxides.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33270507

RESUMO

Significance: The redox balance of cells provides a stable microenvironment for biological macromolecules to perform their physiological functions. As redox imbalance is closely related to the occurrence and development of a variety of diseases, antioxidant therapies are an attractive option. However, redox-based therapeutic strategies have not yet shown satisfactory results. To find the key reason is of great significance. Recent Advances: We emphasize the precise nature of redox regulation and elucidate the importance and necessity of precision redox strategies from three aspects: differences in redox status, differences in redox function, and differences in the effects of redox therapy. We then propose the "5R" principle of precision redox in antioxidant pharmacology: "Right species, Right place, Right time, Right level, and Right target." Critical Issues: Redox status must be considered in the context of species, time, place, level, and target. The function of a biomacromolecule and its cellular signaling role are closely dependent on redox status. Accurate evaluation of redox status and specific interventions are critical for the success of redox treatments. Precision redox is the key for antioxidant pharmacology. The precise application of antioxidants as nutritional supplements is also key to the general health of the population. Future Directions: Future studies to develop more accurate methods for detecting redox status and accurately evaluating the redox state of different physiological and pathological processes are needed. Antioxidant pharmacology should consider the "5R" principle rather than continuing to apply global nonspecific antioxidant treatments.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33252417

RESUMO

Peroral endoscopic myotomy (POEM) is a rapidly evolving technique for the treatment of esophageal diverticulum. The aim of this study was to perform a systematic review and meta-analysis of the literature focusing on POEM for symptomatic esophageal diverticula, including an in-depth evaluation of its efficacy, safety, and limitations. A comprehensive literature search was completed to identify articles that examined the efficacy and safety of POEM for esophageal diverticula. Heterogeneity among studies was assessed using the I statistic. Meta-regression and sensitivity analyses were performed to explore the sources of heterogeneity and assess potentially important covariates influencing the main outcomes. Primary endpoints such as rates of success, adverse events, and recurrences were evaluated. P values of ≤0.05 were considered statistically significant. Nine studies with a total of 153 patients were enrolled. Pooled technical success, clinical success, adverse events, and recurrence rates were 99% [95% confidence interval (CI), 97-100%; I = 0%), 94% (95% CI, 89-97%; I = 24%), 2% (95% CI, 0-6%, I = 0%), and 0% (95% CI, 0-1%; I = 0%), respectively. The pooled perforation rate was 6% (95% CI, 1-11%; I = 0%). Meta-regression analysis indicated that esophageal diverticula types and motility disorders were not associated with the clinical success rate (P > 0.05). POEM is a feasible, safe, and effective treatment for symptomatic esophageal diverticula, with low adverse events and recurrence rates.

20.
Nat Microbiol ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33199863

RESUMO

Coronavirus disease 2019 (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)1-3 and individuals with COVID-19 have symptoms that can be asymptomatic, mild, moderate or severe4,5. In the early phase of infection, T- and B-cell counts are substantially decreased6,7; however, IgM8-11 and IgG12-14 are detectable within 14 d after symptom onset. In COVID-19-convalescent individuals, spike-specific neutralizing antibodies are variable3,15,16. No specific drug or vaccine is available for COVID-19 at the time of writing; however, patients benefit from treatment with serum from COVID-19-convalescent individuals17,18. Nevertheless, antibody responses and cross-reactivity with other coronaviruses in COVID-19-convalescent individuals are largely unknown. Here, we show that the majority of COVID-19-convalescent individuals maintained SARS-CoV-2 spike S1- and S2-specific antibodies with neutralizing activity against the SARS-CoV-2 pseudotyped virus, and that some of the antibodies cross-neutralized SARS-CoV, Middle East respiratory syndrome coronavirus or both pseudotyped viruses. Convalescent individuals who experienced severe COVID-19 showed higher neutralizing antibody titres, a faster increase in lymphocyte counts and a higher frequency of CXCR3+ T follicular help (TFH) cells compared with COVID-19-convalescent individuals who experienced non-severe disease. Circulating TFH cells were spike specific and functional, and the frequencies of CXCR3+ TFH cells were positively associated with neutralizing antibody titres in COVID-19-convalescent individuals. No individuals had detectable autoantibodies. These findings provide insights into neutralizing antibody responses in COVID-19-convalescent individuals and facilitate the treatment and vaccine development for SARS-CoV-2 infection.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...