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1.
J Hazard Mater ; 424(Pt A): 127273, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34600391

RESUMO

Although polyacrylonitrile fiber (PANF) and metal-organic frameworks (MOFs) have been extensively investigated to remove U(VI) from water, their practical applications are seriously hindered by the relatively low stability of PANF in acidic solution and great difficulty of separating MOFs nanoparticles from solution, beside that, little attention is paid to the fabrication of MOFs and PANF composite materials (MPCMs) with excellent adsorption capacity for U(VI). Herein, we report the synthesis of novel MPCMs by decorating different concentrations of UiO-66-NH2 crystals onto polyamine and amidoxime groups functionalized PANF (PA-AO-PANF) through cross-linking method for U(VI) extraction. The characterization results reveal that the combination of PA-AO-PANF and UiO-66-NH2 crystals endows MPCMs with excellent separation ability, large surface area, good stability and plentiful surface functional groups, which contributes to good selectivity and enhanced adsorption performance. Consequently, the obtained UN-PA-AO-PANF-2 shows the maximum uptake capacity of 441.8 mg/g and equilibrium uptake time of 30 min towards U(VI). Besides, the U(VI) uptake ability and structure of UN-PA-AO-PANF-2 are well preserved after ten adsorption-desorption cycles. With these outstanding properties, the adsorbent has great potential for the capture of U(VI) from aqueous solutions. Importantly, this work provides a cost-effective and efficient way to construct extremely stable MPCMs hybrid fibers.

2.
J Hazard Mater ; 424(Pt A): 127203, 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34600392

RESUMO

With the deepening of the concept of recycling economy and green chemistry, selective capture of Cu(II) from wastewater by biosorbent and reuse of the spent Cu(II)-loaded adsorbent are of great significance. Herein, we synthesized composite of rice husk (RH) with mesoporous silica MCM-41 (RH@MCM-41) modified by organosilane containing amino and schiff groups as functional monomer and cross-linking agent. The silica modified RH@MCM-41 was employed as supporter to fabricate copper ion-imprinted polymers as absorbents (named as RM-CIIPs) via surface ion imprinting technique. Adsorption isotherms, kinetics, selectivity and mechanism of RM-CIIPs to remove Cu(II) were investigated with respect to different adsorption condition. Furthermore, we explored the catalytic activity of spent Cu(II)-loaded adsorbent in Glaser coupling reaction. Batch adsorption studies revealed that RM-CIIP-3 prepared with functional monomer shows the best adsorption capacity (91.4 mg/g) for Cu(II), and adsorption equilibrium could be reached within 30 min. RM-CIIP-3 exhibited an excellent selectivity for capturing Cu(II) and reusability in six adsorption/desorption cycles. More importantly, the spent Cu(II)-loaded adsorbent could be used as bio-heterogeneous catalyst and afford the desired product (1,4-diphenylbutadiyne) in 99.1% yield. Our research indicates an eco-friendly systematic strategy to utilize the waste material as an adsorbent for removing heavy metals and catalyst for industry.

3.
J Virol ; : JVI0150021, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34613824

RESUMO

African swine fever (ASF), a devastating infectious disease in swine, severely threatens the global pig farming industry. Disease control has been hampered by the unavailability of vaccines. Here, we report that deletion of the QP509L and QP383R genes (ASFV-ΔQP509L/QP383R) from the highly virulent ASFV CN/GS/2018 strain results in complete viral attenuation in swine. Animals inoculated with ASFV-ΔQP509L/QP383R at a 104 50% hemadsorbing dose (HAD50) remained clinically normal during the 17-day observational period. All ASFV-ΔQP509L/QP383R-infected animals had low viremia titers and developed a low-level p30-specific antibody response. However, ASFV-ΔQP509L/QP383R did not induce protection against challenge with the virulent parental ASFV CN/GS/2018 isolate. RNA-sequencing analysis revealed that innate immune-related genes (Ifnb, Traf2, Cxcl10, Isg15, Rantes, and Mx1) were significantly lower in ASFV-ΔQP509L/QP383R-infected than in ASFV-infected porcine alveolar macrophages. In addition, ASFV-ΔQP509L/QP383R-infected pigs had low levels of IFN-ß based on ELISA. These data suggest that deletion of ASFV QP509L/383R reduces virulence but does not induce protection against lethal ASFV challenge. Importance African swine fever (ASF) is endemic to several parts of the word, with outbreaks of the disease devastating the swine farming industry; currently, no commercially available vaccine exists. Here, we report that deletion of the previously uncharacterized QP509L and QP383R viral genes completely attenuates virulence in the ASFV CN/GS/2018 isolate. However, ASFV-ΔQP509L/QP383R-infected animals were not protected from developing an ASF infection after challenge with the virulent parental virus. ASFV-ΔQP509L/QP383R induced lower levels of innate immune-related genes and IFN-ß than the parental virus. Our results increase our knowledge on developing an effective and live ASF attenuated vaccine.

4.
Sheng Wu Gong Cheng Xue Bao ; 37(9): 3211-3220, 2021 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-34622629

RESUMO

To develop Senecavirus A (SVA) virus-like particles (VLPs), a recombinant prokaryotic expression plasmid pET28a-SVA-VP031 was constructed to co-express SVA structural proteins VP0, VP3 and VP1, according to the genomic sequence of the field isolate CH-FJ-2017 after the recombinant proteins were expressed in E .coli system, and purified by Ni+ ion chromatographic method. The SVA VLPs self-assemble with a high yield in vitro buffer. A typical VLPs with an average diameter of 25-30 nm which is similar to native virions by using TEM detection. Animals immunized by SVA VLPs shown that the VLPs induced high titers neutralizing antibodies in Guinea pigs. This study indicated that the VLPs produced with co-expressing SVA structural proteins VP0, VP3 and VP1 in prokaryotic system is a promising candidate and laid an important foundation for the development of a novel SVA VLPs vaccine.


Assuntos
Picornaviridae , Animais , Anticorpos Neutralizantes , Escherichia coli/genética , Genômica , Cobaias , Picornaviridae/genética
5.
Chemosphere ; 282: 131150, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34470175

RESUMO

Epidemiologic studies focus on combined effects of multiple metals on bone mineral density (BMD) are scarce. Therefore, this study was conducted to examine associations of multiple metals exposure with BMD. Data of adults aged ≥20 years (n = 2545) from the US National Health and Nutrition Examination Survey (NHANES, 2011-2016) were collected and analyzed. Concentrations of metals were measured in blood (cadmium [Cd], lead [Pb], mercury [Hg], and manganese [Mn]) and serum (copper [Cu], selenium [Se], and zinc [Zn]) using inductively coupled plasma mass spectrometry and inductively coupled plasma dynamic reaction cell mass spectrometry, respectively. The weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were performed to determine the joint effects of multiple metals exposure on lumbar and total BMD. The linear regression analyses showed Pb was negatively associated with BMDs. The WQS regression analyses revealed that the WQS index was inversely related to lumbar (ß = -0.022, 95% CI: -0.036, -0.008) and total BMD (ß = -0.015, 95% CI: -0.024, -0.006), and Se, Mn, and Pb were the main contributors for the combined effects. Additionally, nonlinear dose-response relationships between Pb, Mn, and Se and BMD, as well as a synergistic interaction of Pb and Mn, were found in the BKMR analyses. Our findings suggested co-exposure to Cd, Pb, Hg, Mn, Cu, Se, and Zn (above their 50th percentiles) was associated with reduced BMD, and Pb, Mn, and Se were the main contributors driving the overall effects.


Assuntos
Densidade Óssea , Metais , Teorema de Bayes , Cádmio , Inquéritos Nutricionais
6.
J Biol Chem ; 297(5): 101190, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34517008

RESUMO

African swine fever virus (ASFV) is a large DNA virus that is highly contagious and pathogenic in domestic pigs with a mortality rate up to 100%. However, how ASFV suppresses JAK-STAT1 signaling to evade the immune response remains unclear. In this study, we found that the ASFV-encoded protein MGF-505-7R inhibited proinflammatory IFN-γ-mediated JAK-STAT1 signaling. Mechanistically, MGF-505-7R was found to interact with JAK1 and JAK2 and mediate their degradation. Further study indicated that MGF-505-7R promoted degradation of JAK1 and JAK2 by upregulating the E3 ubiquitin ligase RNF125 expression and inhibiting expression of Hes5, respectively. Consistently, MGF-505-7R-deficient ASFV induced high levels of IRF1 expression and displayed compromised replication both in primary porcine alveolar macrophages and pigs compared with wild-type ASFV. Furthermore, MGF-505-7R deficiency attenuated the virulence of the ASFV and pathogenesis of ASF in pigs. These findings suggest that the JAK-STAT1 axis mediates the innate immune response to the ASFV and that MGF-505-7R plays a critical role in the virulence of the ASFV and pathogenesis of ASF by antagonizing this axis. Thus, we conclude that deletion of MGF-505-7R may serve as a strategy to develop attenuated vaccines against the ASFV.

7.
Mol Cell Proteomics ; 20: 100147, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34530158

RESUMO

Seneca Valley virus (SVV) or commonly known as senecavirus A, is one of the picornavirus that is associated with vesicular disease and neonatal mortality in swine herds. Our previous study found that SVV replicates extremely faster in porcine Instituto Biologico-Rim Suino-2 (IBRS-2) cells than that in porcine kidney-15 (PK-15) cells. However, the underlying mechanism remains unknown. In this study, we comprehensively compared the expression features between IBRS-2 cells and PK-15 cells in response to SVV infection by an unbiased high-throughput quantitative proteomic analysis. We found that the innate immune response-related pathways were efficiently activated in PK-15 cells but not in IBRS-2 cells during SVV infection. A large amount of interferon (IFN)-stimulated genes were induced in PK-15 cells. In contrast, no IFN-stimulated genes were induced in IBRS-2 cells. Besides, we determined similar results in the two cell lines infected by another porcine picornavirus foot-and-mouth disease virus. Further study demonstrated that the Janus kinase signal transducer and activator of transcription signaling pathway was functioning properly in both IBRS-2 and PK-15 cells. A systematic screening study revealed that the aberrant signal transduction from TANK-binding kinase 1 to IFN regulatory factor 3 in the retinoic acid-inducible gene I-like receptor signaling pathway in IBRS-2 cells was the fundamental cause of the different innate immune response manifestation and different viral replication rate in the two cell lines. Together, our findings determined the different features of IBRS-2 and PK-15 cell lines, which will help for clarification of the pathogenesis of SVV. Besides, identification of the underlying mechanisms will provide new targets and an insight for decreasing the viral clearance rate and probably improve the oncolytic effect by SVV in cancer cells.

8.
Int J Med Sci ; 18(15): 3373-3379, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522163

RESUMO

Background: Mucopolysaccharidoses (MPSs) are lysosomal storage disorders wherein glycosaminoglycans accumulate because the enzymes that degrade them are insufficient. The earliest symptoms, which are the main reasons for seeking consultation, are otorhinolaryngological and commonly occur in MPS I, II, IV, and VI. This retrospective study aimed to determine the occurrence of otorhinolaryngological manifestations in MPS patients in Taiwan and to analyze the prognosis of surgical intervention, including its effect on symptoms. Methods: We reviewed 42 patients (30 males and 12 females), with a median age of 20.5 years, who had MPS (16.7% type I, 35.7% type II, 19.0% type IIIB, 21.4% type IVA, and 7.2% type VI). The following otorhinolaryngological manifestations were collected: annual number of upper respiratory tract infections (URTIs) and otitis media with effusion (OME) episodes, adenoid size, tonsillar size, and apnea-hypopnea index (AHI). Results: Among 42 patients, we found recurrent otitis media in 42.9% of the patients, hearing loss in 83.3% (mixed: 52.4%, conductive: 21.4%, and sensorineural: 9.5%), frequent URTIs in 47.6%, and obstructive sleep apnea syndrome in 35.7%. Moreover, 76% of the patients underwent ear, nose, and throat (ENT) surgery, including adenoidectomy, tonsillectomy, tympanostomy with ventilation tube insertion, tracheotomy, and supraglottoplasty. Conclusions: MPS patients had a high incidence of ENT problems. ENT surgery reduced the severity of hearing loss, degree of symptoms related to upper airway obstruction, and severity of respiratory tract and otological infections of patients with MPS.

9.
Neoplasma ; 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34427100

RESUMO

The cystine/glutamate antiporter xCT (SLC7A11) is frequently upregulated in many cancers, including glioblastoma (GBM). SLC7A11-mediated cystine taken up is reduced to cysteine, a precursor amino acid for glutathione synthesis and antioxidant cellular defense. However, little is known about the biological functions of SLC7A11 and its effect on therapeutic response in GBM. Here, we report that the expression of SLC7A11 is higher in GBM compared with normal brain tissue, but is negatively associated with tumor grades and positively impacts survival in the bioinformatic analysis of TCGA and CGGA database. Additionally, a negative association between SLC7A11 and mismatch repair (MMR) gene expression was identified by Pearson correlation analysis. In the GBM cells with glucose-limited culture conditions, overexpression of SLC7A11 significantly decreased MMR gene expression, including MLH1, MSH6, and EXO1. SLC7A11-overexpressed GBM cells demonstrated elevated double-strand break (DSB) levels and increased sensitivity to radiation treatment. Taken together, our work indicates that SLC7A11 might be a potential biomarker for predicting a better response to radiotherapy in GBM.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34376132

RESUMO

BACKGROUND: Low-molecular citrus pectin (LCP) is a pectin polysaccharide with low molecular weight, low degree of crux, and no branching. It is obtained by degrading natural citrus pectin (CP) through physical, chemical and enzymatic methods. LCP has received considerable attention in recent years due to its potential applications in the medical and biological fields. METHODS: In our previous study, LCP was prepared from CP by using recombinant Bacillus subtilis pectate lyase B. Monosaccharide comparative analysis revealed that the galacturonic acid content of LCP was higher than that of CP. The cell viability effect of LCP was elucidated by using HepG2 cells and the Cell Counting Kit-8 (CCK-8) assay. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, Annexin V-FITC/PI staining, and flow cytometer propidium iodide staining were performed to detect the effects of LCP on apoptosis and cell cycle arrest in HepG2 cells. Mitochondrial membrane potential (MMP) was observed through 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine assay. RESULTS & DISCUSSION: The Mw of the prepared LCP was 7.6 kDa, which was significantly lower than that of CP (140 kDa). Cell viability decreased with the increase in the concentration of LCP. The half-inhibitory concentration of 1.46 ± 0.02 mg/mL was determined. Treatment with 1.6 mg/mL LCP induced the apoptosis of HepG2 cells with the inhibition rate of 83.10% ± 4.72%, and the cell cycle was arrested in the S phase. Furthermore, the MMP of HepG2 cells decreased with the increase in LCP concentration. CONCLUSION: The enzymatically prepared LCP could inhibit the proliferation of HepG2 cells. This study provided a partial experimental basis and reference for LCP to become a potential functional food for anti-liver cancer.

11.
J Ethnopharmacol ; 280: 114485, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34348195

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Taodan granules (TDG) have been observed to decrease interleukins, or psoriasis area and severity index (PASI) score for psoriasis vulgaris, without significant adverse events. However, the regulatory network remains elucidated. AIM OF THE STUDY: The objective is to identify critical genes and kernel pathways of TDG treated psoriasis. MATERIALS AND METHODS: Firstly, construct a network of components-targets of TDG using network pharmacology. Secondly, the ClusterONE algorithm was used to build a modular network and identify critical genes and corresponding pathways. Thirdly, the critical genes and kernel pathways were verified in imiquimod (IMQ) induced psoriasis-like mice model. RESULTS: The results validated that TDG downregulated the mRNA expression of MMP2 (degree = 5, P < 0.05), IL6 (degree = 9, P < 0.05), TNF (degree = 14, P < 0.05), CCL2 (degree = 8, P < 0.05), CXCL2 (degree = 8, P < 0.05), IL1B (degree = 9, P < 0.05), and JUN (degree = 9, P < 0.05), while upregulated IL10 (degree = 8) expression. Besides, TDG were observed to regulate IL17 signaling pathway and TNF signaling pathway (size = 18), via the skin tissue homogenate of psoriasis-like mice. CONCLUSION: In summary, this study identified the potential targets and pathways, providing additional evidence for the clinical application of TDG treated psoriasis.

12.
J Formos Med Assoc ; 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34420841

RESUMO

The present study included the first case of mucopolysaccharidosis (MPS) type VII in Taiwan. During pregnancy, the patient was diagnosed with hydrops fetalis and had ascites aspiration 4 times. In the following years, she presented gradually with chronic lung disease, developmental delay, short stature, dysmorphic features of coarse face, macroglossia and pigeon chest with scoliosis. Upon referral at age 4 years, she had corneal clouding, mild limitation of range of motion (ROM) and hepatosplenomegaly. X-ray showed paddle ribs and dysplastic vertebral bodies. MPS was suspected and urine glycosaminoglycans (GAGs) elevated were noted. The leukocyte enzymatic analyses for MPS I, MPS II, MPS IIIB, MPS IVA, and MPS VI were all normal. Afterward, the molecular analysis showed two heterozygous genetic variants of c.104C > A and c.1454C > T in trans in the GUSB gene (NM_000181.4) which were the causes for MPS VII. Then, we checked the leukocyte ß-glucuronidase activity for MPS VII and showed extremely low, therefore confirmed the diagnosis. Clinicians should increase the awareness on the early signs of MPS to have a prompt diagnosis and offer the correct treatment like enzyme replacement therapy (ERT) as early as possible.

13.
Ann Palliat Med ; 10(7): 8215-8231, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34263629

RESUMO

BACKGROUND: Tripterygium glycosides (TGs) has been widely used in the treatment of Sjögren's syndrome (SS). METHODS: Seven databases, PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang Medical Database, China Science and Technology Journal Database, and the Chinese Biomedicine database, were selected to collect randomized controlled trials (RCTs) related to the treatment of SS with TGs alone or in combination. The participants, intervention, comparison, outcome, and study design principle were adopted for the inclusion of related studies. The risk of bias was assessed using the Cochrane Collaboration's tool. Meta-analysis was conducted using RevMan 5.3, with risk ratios (RRs) or standard mean differences (SMDs) and 95% confidence intervals (CIs). RESULTS: Overall, 12 trials involving 668 patients were analyzed. The results of the meta-analysis showed that TGs in combination with total glucosides of paeony (TGP) had significantly lower symptom scores than TGs alone on dry eyes (SMD =-0.61, 95% CI: -1.12 to -0.10, P=0.02) or dry mouth (SMD =-1.29, 95% CI: -1.84 to -0.74, P<0.00001). The efficacy rates of TG + TGP vs. TGs (P<0.00001) and TG + HM vs. TGs (P=0.01) were significantly different. In addition, compared to hydroxychloroquine (HCQ), TGs could induce expression of C-reactive protein (P=0.007), globulin (P<0.00001), and immunoglobulin A (IgA) (P=0.006), whereas the TG + TGP group had lower levels of immunoglobulin G (IgG) (P<0.00001), immunoglobulin M (IgM) (P=0.02), and IgA (P<0.00001), as well as saliva flow rate (P<0.00001) and lacrimal gland function (P<0.00001). The adverse events between TGs and HCQ were not evident, and there was no increase in the risk of adverse reactions when combined with other drugs. DISCUSSION: TGs are potentially effective for treating SS without increasing the risk of adverse events. High-quality, multi-center, and large-scale RCTs are required.


Assuntos
Síndrome de Sjogren , Tripterygium , China , Glicosídeos/uso terapêutico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Síndrome de Sjogren/tratamento farmacológico
14.
Sci Prog ; 104(3): 368504211031711, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34260315

RESUMO

Endoscopic variceal ligation (EVL) with vasoconstrictors has been recommended for acute esophageal variceal bleeding. However, the optimal duration of vasoconstrictors after EVL is controversial. This systematic review and meta-analysis was conducted to explore the efficacy of short-course vasoconstrictors (≤3 days) versus standard combination (3-5 days). A comprehensive literature review was conducted using the PubMed, Embase, and Cochrane library databases with subsequent meta-analysis. The primary outcomes were 5-day rebleeding, mortality, and treatment failure rates. A risk ratio (RR) with 95% confidence interval is used for outcome comparison. Nine randomized studies with 838 patients were included. The initial hemostasis (96.8% vs 97.4%, p = 0.919), 5-day rebleeding (11.2% vs 8.3%, RR = 1.05, 95% CI = 0.62-1.76), mortality (0 vs 1.3%, RR = 0.48, 95% CI = 0.10-2.39), and treatment failure (7.4% vs 5.9%, RR = 1.10, 95% CI = 0.48-2.49) were similar in both groups. Subgroup analysis suggested EVL alone had no significant difference of 5-day re-bleeding (15.9% vs 7.1%, RR = 2.25, 95% CI = 0.87-5.77), mortality (0 vs 0.7%, RR = 0.71, 95% CI = 0.08-6.03), treatment failure (9.6% vs 6.7%, RR = 1.43, 95% CI = 0.54-3.75) compared to standard combination. Clinical heterogeneity was found for the rebleeding rate for the subgroup during sensitivity analysis. EVL with short-course vasoconstrictors is highly efficacious for esophageal variceal bleeding. Further studies are required to determine the genuine need of subsequent vasoconstrictor after successful EVL.

15.
J Invest Dermatol ; 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34293353

RESUMO

Persistent chronic inflammation and delayed epithelialization lead to stalled healing in diabetic ulcers (DUs). PD-L1 shows anti-inflammatory and proliferative activities in healing defects, whereas its function in DU pathogenesis remains unknown. Lower levels of PD-L1 were found in DU tissues, and exogenous PD-L1 has therapeutic effects in the healing process by accelerating re-epithelialization and attenuating prolonged inflammation, which contributed to the delayed wound closure. We detected the downstream effectors of PD-L1 using transcriptional profiles and screened the interacting proteins using immunoprecipitation in combination with mass spectrometry and coimmunoprecipitation assays. The biological functions of eIF3I‒PD-L1‒IRS4 axis were tested both in vivo and in vitro. Finally, we validated the expression levels of eIF3I, PD-L1, and IRS4 in DU tissues from human clinical samples by immunohistochemistry staining. Mechanistically, PD-L1 binds to eIF3I and promotes cutaneous diabetic wound healing by downregulating IRS4. These findings identify that the eIF3I‒PD-L1‒IRS4 axis contributes to wound healing defects, which can serve as a potential therapeutic target in DUs.

16.
Front Immunol ; 12: 670398, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34177909

RESUMO

Background: Anti-interleukin (IL)-23 agents are widely used for autoimmune disease treatment; however, the safety and risks of specific symptoms have not been systematically assessed. Objectives: The aim of this study was to summarize the characteristics and mechanisms of occurrence of five immunological and non-immunological adverse events caused by different anti-IL-23 agents. Methods: The Cochrane Library, EMBASE, PubMed, and Web of Science databases were searched for eligible randomized clinical trials published from inception through May 1, 2020. Randomized clinical trials that reported at least one type of adverse event after treatment were included, regardless of sex, age, ethnicity, and diagnosis. Two investigators independently screened and extracted the characteristics of the studies, participants, drugs, and adverse event types. The Cochrane Handbook was used to assess the methodological quality of the included randomized clinical trials. Heterogeneity was assessed using the I2 statistic. Meta-regression was applied to determine the sources of heterogeneity, and subgroup analysis was used to identify the factors contributing to adverse events. Results: Forty-eight studies were included in the meta-analysis, comprising 25,624 patients treated with anti-IL-23 agents. Serious immunological or non-immunological adverse events were rare. Anti-IL-12/23-p40 agents appeared to cause adverse events more easily than anti-IL-23-p19 agents. The incidence of cancer did not appear to be related to anti-IL-23 agent treatment, and long-term medication could lead to mental diseases. The prevention of complications should be carefully monitored when administered for over approximately 40 weeks to avoid further adverse reactions, and the incidence of infection was the highest among general immunological adverse events. Conclusions: The application of anti-IL-23 agents induced a series of immunological and non-immunological adverse events, but these agents tend to be well-tolerated with good safety profiles.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Interleucina-23/antagonistas & inibidores , Humanos
17.
Mol Genet Genomics ; 296(5): 1027-1040, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34137900

RESUMO

Psoriasis is a chronic inflammatory skin disease characterized by excessive proliferation of keratinocytes (KCs). Onset of psoriasis is related to genetic, immune and environmental factors. The environment can interact with the genome through epigenetic modifications, including DNA methylation, and this modification is involved in the pathogenesis of psoriasis. In addition to a skin disease, psoriasis is also considered a systemic disease. We reviewed the current literature of psoriatic DNA methylation for studies from several aspects on the DNA methylation distribution patterns in different tissues/cells, single-nucleotide polymorphisms, and candidate disease genes and identified target genes regulated by DNA methylation that have been directly/indirectly validated. This review contributes to a comprehensive understanding of the important a role that DNA methylation plays in psoriasis from a holistic perspective and will promote the implementation of DNA methylation in diagnostic and therapeutic strategies for psoriatic patients.


Assuntos
Metilação de DNA , Epigênese Genética , Polimorfismo de Nucleotídeo Único , Psoríase/genética , Linfócitos T CD4-Positivos/fisiologia , Estudo de Associação Genômica Ampla , Humanos , Leucócitos Mononucleares/fisiologia , Psoríase/patologia
18.
Food Chem ; 363: 130322, 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34147900

RESUMO

Zijuan tea is a representative anthocyanin-rich tea cultivar in China. In this study, Zijuan tea was used to produce a novel kombucha beverage (ZTK). The physicochemical, sensory properties, and antioxidant activity of ZTK were compared with that of black tea kombucha (BTK) and green tea kombucha (GTK). Results indicated that after fermentation, the color of ZTK changed from yellowish-brown to salmon-pink, because its anthocyanins (4.5 mg/L) appeared red in acidic conditions. Meanwhile no significant changes of color were observed in BTK and GTK. The dynamic changes of pH, biomass, and concentrations of sugars, amino acids, and main organic acids were similar in three kombucha beverages, except catechins showing different trends. Moreover, ZTK showed the highest overall acceptability score, antioxidant activity, and concentration of volatiles among the three kombucha beverages. Therefore, Zijuan tea is suitable for the preparation of kombucha beverage with attractive color and health benefits.


Assuntos
Antioxidantes , Camellia sinensis , Antocianinas , Antioxidantes/análise , Fermentação , Chá
19.
Neuropharmacology ; 191: 108584, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-33933475

RESUMO

Sevoflurane exposure in neonates induces long-term impairment of learning and memory; however, its effect on cognition in the later developmental period and the underlying mechanisms remain unclear. In the present study, we showed that multiple sevoflurane exposures impaired fear memory at long retention delays in neonatal (postnatal day 7) and preadolescent mice (postnatal day 22), but not in mice at older ages. After the fear memory test, expression of phosphorylated extracellular signaling-regulated kinase (p-ERK) and c-fos were elevated in the bed nucleus of the stria terminalis (BNST) and central amygdala, but not in the hippocampus or prefrontal cortex. The upregulation of p-ERK was restricted to populations of γ-aminobutyric acid (GABAergic) neurons and was inhibited by multiple sevoflurane exposures. Intra-BNST injection of ERK inhibitor also impaired fear memory at long retention delays. In contrast, intra-BNST injection of ERK agonist attenuated impaired fear memory caused by repeated sevoflurane exposures. Injection of sevoflurane in the BNST but not the caudate putamen impaired the fear memory at long retention delays in preadolescent mice. Finally, chemogenetic activation of BNST GABAergic neurons by designer receptors exclusively activated by designer drug (DREADD) reversed the impaired fear memory at long retention delays by multiple sevoflurane exposures. These findings suggest that multiple sevoflurane exposures impaired fear memory at long retention delays in preadolescent mice by suppressing the ERK signaling in GABAergic neurons in the BNST.

20.
J Cell Mol Med ; 25(11): 5202-5219, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33942991

RESUMO

Pulmonary arterial hypertension (PAH) featured a debilitating progressive disorder. Here, we intend to determine diagnosis-valuable biomarkers for PAH and decode the fundamental mechanisms of the biological function of these markers. Two mRNA microarray profiles (GSE70456 and GSE117261) and two microRNA microarray profiles (GSE55427 and GSE67597) were mined from the Gene Expression Omnibus platform. Then, we identified the differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs), respectively. Besides, we investigated online miRNA prediction tools to screen the target gene of DEMs. In this study, 185 DEGs and three common DEMs were screened as well as 1266 target genes of the three DEMs were identified. Next, 16 overlapping dysregulated genes from 185 DEGs and 1266 target gene were obtained. Meanwhile, we constructed the miRNA gene regulatory network and determined miRNA-508-3p-NR4A3 pair for deeper exploring. Experiment methods verified the functional expression of miR-508-3p in PAH and its signalling cascade. We observed that ectopic miR-508-3p expression promotes proliferation and migration of pulmonary artery smooth muscle cell (PASMC). Bioinformatic, dual-luciferase assay showed NR4A3 represents directly targeted gene of miR-508-3p. Mechanistically, we demonstrated that down-regulation of miR-508-3p advances PASMC proliferation and migration via inducing NR4A3 to activate MAPK/ERK kinase signalling pathway. Altogether, our research provides a promising diagnosis of predictor and therapeutic avenues for patients in PAH.


Assuntos
Biomarcadores/metabolismo , Biologia Computacional/métodos , Proteínas de Ligação a DNA/metabolismo , Regulação da Expressão Gênica , MicroRNAs/genética , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Hipertensão Arterial Pulmonar/patologia , Animais , Proteínas de Ligação a DNA/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Masculino , Quinases de Proteína Quinase Ativadas por Mitógeno/genética , Proteínas do Tecido Nervoso/genética , Hipertensão Arterial Pulmonar/genética , Hipertensão Arterial Pulmonar/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
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