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1.
Bioresour Technol ; 343: 125986, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34653628

RESUMO

The start-up, efficient, and secure operation of Anammox treating low ammonia sewage, is an important research focus. In this study, a partial nitrification-denitrification coupled with simultaneous Anammox and denitrification (PND-SAD) process was achieved in sequencing batch reactor/up-flow anaerobic sludge bed (SBR-UASB). The key measures to maintain high efficiency PND were: (i) controlling dissolved oxygen in the SBR below 0.5 mg/L, which is not only conducive to PN, but also promotes the contribution of simultaneous nitrification and denitrification to nitrogen removal; (ii) monitoring the nitrate (NO3--N) of SBR effluent and discharging sludge to wash out nitrate oxidation bacteria when the NO3--N exceeds 1.0 mg/L. The nitrite accumulation rate reached 97.6%. SBR effluent and domestic sewage entered the UASB. Although Candidatus Brocadia only accounted for 0.8%, its contribution to nitrogen removal reached 76.8%. In PND-SAD system, the aerobic HRT was only 3.8 h, nitrogen removal efficiency up to 97.3%.


Assuntos
Nitrificação , Esgotos , Amônia , Anaerobiose , Reatores Biológicos , Desnitrificação , Nitrogênio , Oxirredução , Águas Residuárias
2.
Int Ophthalmol ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34748142

RESUMO

PURPOSE: To evaluate and compare different surgical approaches for the treatment of Helveston syndrome and provide further information for preoperative planning. METHODS: From February 2008 to December 2018, data of 52 patients with Helveston syndrome were retrospectively reviewed. Different surgical approaches were selected based on the extent of A-pattern exotropia, dissociated vertical deviation (DVD), and both superior oblique muscle overaction (SOOA) with fundus photograph intorsion. Eye position, A-pattern, DVD, superior oblique muscle function, and binocular vision function were evaluated pre- and postoperatively. The average follow-up duration was 20.5 months. RESULTS: Nine cases underwent simultaneous horizontal deviation correction with bilateral superior rectus recession, 24 underwent simultaneous horizontal deviation correction with bilateral superior oblique muscle lengthening, and 19 underwent two stages of horizontal deviation correction with superior oblique muscle lengthening, and later bilateral superior rectus recession. A-pattern, DVD, SOOA, and fundus intorsion were all collapsed in all patients postoperatively. Forty-five patients had an orthophoric eye position with considerably aligned ocular movements postoperatively. The total success rate was 86.5%. Postoperatively, eight of the 10 patients with diplopia experienced a recovery of binocular single vision and three had a recovery of rudimentary stereopsis (Titmus 3000-400 s of arc). The compensatory head posture of patients improved significantly postoperatively. CONCLUSIONS: The surgical planning of Helveston syndrome should be designed based on the degree of the A-pattern, SOOA, DVD, and the intorsion in fundus photographs, and the appropriate approach should be selected to improve patient satisfaction.

3.
J BUON ; 26(5): 2019-2025, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34761612

RESUMO

PURPOSE: To evaluate the safety and efficacy of early oral feeding (≤ 3 days) and delayed oral feeding (≥ 7 days) following total laryngectomy. METHODS: Relevant literatures on early and delayed oral feeding following total laryngectomy published before January, 2019 were searched in PubMed, EMBASE, Web of Science, Cochrane Library, CNKI and Wanfang Database. Two reviewers were responsible for selecting literatures, extracting data and cross-check. The incidence of pharyngocutaneous fistula (PCF) was evaluated by calculating OR and 95%CI. Difference in length of stay (LOS) of patients undergoing early oral feeding or delayed oral feeding was compared using standardized mean difference (SMD) and 95%CI. Sensitivity analysis and publication bias examination were conducted. RESULTS: 14 eligible literatures were enrolled, including 1824 patients who underwent total laryngectomy, with 1250 cases of early oral feeding and 574 cases of delayed oral feeding. The incidence of PCF was similar in patients receiving early oral feeding or delayed oral feeding following total laryngectomy (OR=1.12, 95%CI=0.81-1.54). LOS was shorter in cases of early oral feeding than those of delayed oral feeding (SMD=-0.77, 95%CI=-1.18-0.36). Reliable conclusions were obtained without obvious publication bias. CONCLUSIONS: Early oral feeding following total laryngectomy shortens LOS relative to delayed oral feeding. No significant difference in the incidence of PCF is observed between early oral feeding and delayed oral feeding, suggesting that early oral feeding following total laryngectomy is safe and efficacious.

4.
World J Clin Cases ; 9(28): 8476-8481, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34754856

RESUMO

BACKGROUND: Intrahepatic pancreatic pseudocyst (IHPP) is an extremely rare complication of acute pancreatitis, with only a few cases previously described in the literature. To the best of our knowledge, IHPP with Budd-Chiari syndrome (BCS) has not yet been described. CASE SUMMARY: A 35-year-old male presented with abdominal pain, vomiting and anorexia, followed by severe swelling of the lower body after 4 d. The morphological assessment (using computed tomography revealed the presence of a huge cyst of 18.28 cm × 10.34 cm under the liver capsule accompanied by a large amount of ascites. Percutaneous puncture allowed us to detect a high level of amylase in the collection, confirming the diagnosis of IHPP. The cyst was treated by percutaneous drainage, producing complete resolution of the cyst. CONCLUSION: IHPP can be treated with percutaneous drainage, endoscopic drainage, surgery or even conservative treatment, depending on the specific condition. We recommend percutaneous drainage as the first choice of treatment when IHPP with secondary BCS.

5.
Materials (Basel) ; 14(21)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34771757

RESUMO

Polymer-modified concrete and fiber concrete are two excellent paving materials that improve the performance of some concrete, but the performance of single application material is still limited. In this paper, polymer-modified concrete with strong deformation and fiber concrete with obvious crack resistance and reinforcement effect were compounded by using the idea of composite material design so as to obtain a high-performance pavement material. The basic mechanical properties of high-content hybrid fiber-polymer-modified concrete, such as workability, compression, flexural resistance, and environmental durability (such as sulfate resistance) were studied by using the test regulations of cement concrete in China. The main results were as follows. (1) The hybrid fiber-polymer concrete displayed reliable working performance, high stiffness, and a modulus of elasticity as high as 35.93 GPa. (2) The hybrid fiber-polymer concrete had a compressive strength of 52.82 MPa, which was 31.2% higher than that of the plain C40 concrete (40.25 MPa); the strength of bending of the hybrid concrete was 11.51 MPa, 191.4% higher than that of the plain concrete (3.95 MPa). (3) The corrosion resistance value of the hybrid fiber-polymer concrete was 81.31%, indicating its adjustability to sulfate attack environments. (4) According to cross-sectional scanning electron microscope (SEM) images, the hybrid fiber-polymer concrete was seemingly more integrated with a dense layer of cementing substance on its surface along with fewer microholes and microcracks as when compared to the ordinary concrete. The research showed that hybrid fiber-polymer concrete had superior strength and environmental erosion resistance and was a pavement material with superior mechanical properties.

6.
J Med Chem ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34807584

RESUMO

Serine/threonine-protein kinases 3 and 4 (STK3 and STK4, respectively) are key components of the Hippo signaling pathway, which regulates cell proliferation and death and provides a potential therapeutic target for acute myeloid leukemia (AML). Herein, we report the structure-based design of a series of pyrrolopyrimidine derivatives as STK3 and STK4 inhibitors. In an initial screen, the compounds exhibited low nanomolar potency against both STK3 and STK4. Crystallization of compound 6 with STK4 revealed two-point hinge binding in the ATP-binding pocket. Further characterization and analysis demonstrated that compound 20 (SBP-3264) specifically inhibited the Hippo signaling pathway in cultured mammalian cells and possessed favorable pharmacokinetic and pharmacodynamic properties in mice. We show that genetic knockdown and pharmacological inhibition of STK3 and STK4 suppress the proliferation of AML cells in vitro. Thus, SBP-3264 is a valuable chemical probe for understanding the roles of STK3 and STK4 in AML and is a promising candidate for further advancement as a potential therapy.

7.
Hepatol Commun ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34816633

RESUMO

Proprotein convertase subtilisin/kexin type 9 (Pcsk9) binds to hepatic low-density lipoprotein receptor (LDLR) and induces its internalization and degradation. Pcsk9 inhibition increases LDLR expression by hepatocytes, which causes increased uptake of circulating LDL, thereby reducing plasma LDL-cholesterol. However, by increasing the uptake of LDL by the liver, Pcsk9 inhibition increases the exposure of the liver to cholesterol, which may result in higher risk of steatohepatitis and ever carcinogenesis. We compared Pcsk9-/- knockout (KO) mice and appropriate wild-type (WT) controls of the same strain assigned to a high-fat (15%, wt/wt) diet for 9 months supplemented with 0.25%, 0.5%, or 0.75% dietary cholesterol. Pcsk9 KO mice on a high-fat, high-cholesterol diet exhibited higher levels of hepatic free cholesterol loading and hepatic cholesterol crystallization than their WT counterparts. Pcsk9 KO mice developed crown-like structures of macrophages surrounding cholesterol crystal-containing lipid droplets and hepatocytes, exhibited higher levels of apoptosis, and developed significantly more hepatic inflammation and fibrosis consistent with fibrosing steatohepatitis, including 5-fold and 11-fold more fibrosis at 0.5% and 0.75% dietary cholesterol, respectively. When injected with diethylnitrosamine, a hepatic carcinogen, early-in-life Pcsk9 KO mice were more likely to develop liver cancer than WT mice. Conclusion: Pcsk9 KO mice on high-cholesterol diets developed increased hepatic free cholesterol and cholesterol crystals and fibrosing steatohepatitis with a higher predisposition to liver cancer compared with WT mice. Future studies should evaluate whether patients on long-term treatment with anti-PSCK9 monoclonal antibodies are at increased risk of hepatic steatosis, steatohepatitis or liver cancer, while accounting for concurrent use of statins.

8.
BMC Oral Health ; 21(1): 602, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34814908

RESUMO

PURPOSE: The aim of this study was to assess the effect of high-quality nursing based on the concept of childlike interest in children with cleft lip and palate following operation on healing time, degree of pain, psychological state, quality of life, and the occurrence of complications. METHODS: A series of 62 children with cleft lip and palate was treated in our hospital from January 2019 to March 2021. The patients were randomly divided into observation group (31 cases, given high-quality nursing based on childlike interest) and control group (31 cases, given routine nursing intervention). The healing time and hospital stay of the two groups were recorded. The degree of pain, psychological state and quality of life of the two groups before and after intervention were compared, and the occurrence of complications was closely monitored. RESULTS: Compared with the control group, the healing time and hospital stay of the study group were significantly shorter after the intervention (P < 0.05). Before the intervention, no significant difference was identified in pain score between the two groups (P < 0.05), after the intervention, however, the pain score of the study group was significantly lower compared with the control group (P < 0.05). Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) scores of the two groups were comparable before intervention (P > 0.05), while after intervention the SDS and SAS scores of the two groups were lower than those before treatment. Compared with the control group, the SDS and SAS scores of the study group were remarkably lower (P < 0.05). Before the intervention, the quality of life scores of the two groups were comparable (P > 0.05), while after the intervention, the scores of quality of life in the two groups were associated with lower outcomes. Compared with the control group, the scores of quality of life in the study group were significant lower (P < 0.05). After the intervention, there were evident fewer incidence of complications in the study group compared to the control group (P < 0.05). CONCLUSIONS: High quality nursing based on childlike interest exerted beneficial outcomes in terms of shortening the healing time and hospital stay, reducing the degree of pain and complications, as well as improving the psychological state and quality of life of children harboring cleft lip and palate. Additionally, its high safety feature contributes to the wide application for clinical practice.

9.
Hum Exp Toxicol ; : 9603271211059503, 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34779285

RESUMO

Silicosis is a lung fibrotic disease caused by chronic silica exposure. Aberrations in long non-coding RNA (lncRNA) expression are associated with fibrotic diseases, but the role of lncRNAs in silicosis pathogenesis remains unclear. Here, we investigated the expression of lncRNAs during silicosis and the role of MRAK050699 in epithelial-mesenchymal transition (EMT). Differentially expressed lncRNAs in the lung tissues of normal and silicosis rats were compared, and their biological effects were determined using the Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. There were 1077 differentially expressed lncRNAs (378 upregulated and 699 downregulated). MRAK052509, MRAK139674, AY539881, MRAK050699, XR_6113, and BC167061 were selected to verify expression in silicosis rats using quantitative reverse transcription polymerase chain reaction. MRAK050699 was knocked down in rat alveolar type II epithelial cells, and the molecular mechanism of transforming growth factor-ß (TGF-ß)-induced EMT in these cells was studied. All selected lncRNAs were upregulated in the silicosis rats, consistent with the sequencing results. MRAK050699 knockdown inhibited EMT of RLE-6TN cells by regulating the TGF-ß/Smad3 signaling pathway. Thus, the differential expression of lncRNAs is related to silicosis development, and MRAK050699 plays an important role in EMT, suggesting a potential therapeutic target for silicosis.

10.
Knee ; 33: 243-251, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34739955

RESUMO

BACKGROUND: An attribute that may influence knee replacement survivorship is tibial polyethylene (PE) insert thickness. Previous studies have suggested thin polyethylene made from ultra-high molecular weight polyethylene (UHMWPE) leads to higher rates of revision surgery. This study aimed to determine if modern polyethylene thickness is associated with altered survivorship of primary total knee arthroplasty (TKA) procedures. METHODS: A retrospective analysis of data from Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) was done on well performing total knee arthroplasty prostheses used in Australia from 1999-2018. Six of the best performing minimally stabilized prostheses were examined and categorized into three PE thickness subgroups: A (≤10 mm), B (11-14 mm) and C (≥15 mm). There were 185,539 TKA procedures, of which 64.3% (n = 119,382) were ≤ 10 mm, 33.5% (n = 62,173) 11-14 mm, and 2.2% (n = 3984) ≥ 15 mm. Differences in revision rates were analysed for all causes, including loosening, wear, and instability. RESULTS: At 14 years, respective cumulative point revision (CPR) was A: 4.8, B: 4.2 and C: 6.0. The thickest polyethylene group (≥15 mm) had a higher rate of revision for any reason compared to both 11-14 mm and ≤ 10 mm groups. When non-XLPE was analysed the ≤ 10 mm group had higher rates of revision compared to the 11-14 mm group, but this difference was not seen with XLPE. CONCLUSION: Higher rates of revision were seen overall in the thicker PE group (≥15 mm). This group also had higher rates of revision for loosening, instability, and infection. The use of a thicker insert may be a sign of surgical complexity, but is associated with increased revision.

11.
Leuk Lymphoma ; : 1-11, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34643153

RESUMO

To describe patient characteristics, treatment patterns, and survival among elderly patients (≥66 years) newly diagnosed with acute myeloid leukemia (AML) meeting ≥1 ineligibility criteria for high-intensity chemotherapy (HIC; i.e. age >75 years, cardiac disease/prior anthracycline therapy, or secondary AML), we analyzed 2007-2017 100% Medicare hematologic cancer data. Patients were stratified based on whether they received HIC or low-intensity chemotherapy (LIC) or best supportive care (BSC) within 60 days after AML diagnosis. Of 4,152 patients, 43.2% received chemotherapy, 33.8% BSC, and 23.1% no therapy. Among chemotherapy-treated patients, HIC was more common than LIC (58.8 vs 41.2%), despite targeting patients meeting ≥1 ineligibility criteria for HIC. Poor overall survival was observed for patients receiving chemotherapy and BSC (median overall survival [interquartile range]: HIC, 1.9 [0.8, 6.6] months; LIC, 3.8 [1.4, 9.3] months; BSC, 1.0 [0.4, 2.5] months). Results highlight the need for additional effective and tolerable treatments for this population.

12.
J Orthop Surg Res ; 16(1): 615, 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663371

RESUMO

OBJECTIVE: We aimed to determine the association between serum receptor activator of nuclear factor-kappa B ligand (sRANKL) levels and ankylosing spondylitis (AS) in Chinese patients. METHODS: The PubMed, Cochrane Library, Embase, Chinese Biomedical Database, Web of Science, China National Knowledge Infrastructure, VIP, and Wan Fang databases were searched for studies conducted before October 1, 2020, without language restrictions. STATA version 12.0 and Revman version 5.3 were used to analyze the data. The standard mean differences (SMDs) and corresponding 95% confidence intervals (95% CIs) were calculated. RESULTS: Twelve clinical case-control studies, including 585 patients with AS and 423 healthy controls, were included. The combined SMD for sRANKL suggested that the sRANKL level was significantly higher in Chinese patients with AS than in healthy controls (SMD: 3.27, 95% CI 2.11-4.43, P < 0.00001). Serum RANKL-related factor osteoprotegerin (OPG) levels (SMD: 0.86, 95% CI 0.09-1.64, P < 0.03) were lower in the Chinese patients with AS than in healthy controls, and the RANKL/OPG ratio (SMD = 1.05, 95% CI 0.64-1.46, P < 0.00001) in Chinese patients with AS was approximately the same as that of healthy controls. Subgroup analysis indicated that patients from North and South China had higher sRANKL levels than controls; the sRANKL levels of patients from South China were higher in the subgroup with a Bath Ankylosing Spondylitis Functional Index (BASFI) of > 4 than those of patients in other subgroups. In terms of duration, patients with AS for > 8 years had higher sRANKL levels than health controls. Other subgroup analyses were conducted by region, language, source of control, age, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). In these subgroups, the sRANKL levels were significantly higher in the patients with AS than in healthy controls. The BASFI and BASDAI were sources of heterogeneity. CONCLUSIONS: The sRANKL levels are higher in Chinese patients with AS, especially among those from South China. sRANKL levels may be positively correlated with the pathogenesis of AS among Chinese patients.

13.
Front Cell Dev Biol ; 9: 673873, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692669

RESUMO

Background: Gene expression and alternative splicing (AS) can promote cancer development via complex mechanisms. We aimed to identify and verify the hub AS events and splicing factors associated with the progression of colorectal cancer (CRC). Methods: RNA-Seq data, clinical data, and AS events of 590 CRC samples were obtained from the TCGA and TCGASpliceSeq databases. Cox univariable and multivariable analyses, KEGG, and GO pathway analyses were performed to identify hub AS events and splicing factor/spliceosome genes, which were further validated in five CRCs. Results: In this study, we first compared differentially expressed genes and gene AS events between normal and tumor tissues. Differentially expressed genes were different from genes with differentially expressed AS events. Prognostic analysis and co-expression network analysis of gene expression and gene AS events were conducted to screen five hub gene AS events involved in CRC progression: EPB41L2, CELF2, TMEM130, VCL, and SORBS2. Using qRT-PCR, we also verified that the gene AS events SORBS2 were downregulated in tumor tissue, and gene AS events EPB41L2, CELF2, TMEM130, and VCL were upregulated in tumor tissue. The genes whose mRNA levels were significantly related to the five hub gene AS events were significantly enriched in the GO term of cell division and Notch signaling pathway. Further coexpression of gene AS events and alternative splicing factor genes revealed NOVA1 as a crucial factor regulating the hub gene AS event expression in CRC. Through in vitro experiments, we found that NOVA1 inhibited gene AS event SORBS2, which induced the migration of CRC cells via the Notch pathway. Conclusion: Integrated analysis of gene expression and gene AS events and further experiments revealed that NOVA1-mediated SORBS2 promoted the migration of CRC, indicating its potential as a therapeutic target.

14.
J Oncol ; 2021: 4529915, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659410

RESUMO

Background: To explore the effect of paroxetine combined with probiotics in patients with type 2 diabetes mellitus with gastrointestinal dysfunction and liver cancer and its effect on nutritional status. Materials and Methods: 96 patients with type 2 diabetes mellitus combined with gastrointestinal dysfunction and liver cancer were selected as subjects from March 2018 to March 2021. They were randomly divided into control group and observation group, with 48 cases in each group. The control group was treated with probiotics, and the observation group was combined with paroxetine on the basis of the control group. After 4 weeks of treatment, the gastrointestinal mucosal function, nutritional status, Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) score, and the safety were compared between the two groups. Results: The levels of D-lactic acid, PCT, and endotoxin in the observation group were (1.75 ± 0.38), (4.39 ± 0.79), and (0.20 ± 0.06), respectively, which were significantly lower than those in the control group (2.69 ± 0.46), (7.84 ± 1.32), and (0.29 ± 0.08) (P < 0.05). Moreover, the nutritional status TP, ALB, Hb, PA, and TLC levels of the observation group were higher than those of the control group (P < 0.05). The HAMA and HAMD scores in the observation group were (5.76 ± 1.06) and (8.94 ± 1.26), respectively, which were significantly lower than those in the control group (10.69 ± 2.21) and (13.42 ± 2.34) (P < 0.05). However, there was no statistical significance in the incidence of nausea and vomiting, blurred vision, chest arthralgia, palpitation, anaesthesia, dizziness, and drowsiness between the two groups (P > 0.05). Conclusions: Paroxetine combined with probiotics could help to improve the gastrointestinal mucosal function of patients with type 2 diabetes mellitus complicated with gastrointestinal dysfunction and liver cancer, improve the nutritional status of patients, and reduce anxiety and depression, and the drug was safe and worthy of promotion and application.

15.
Build Simul ; : 1-18, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34659649

RESUMO

This study conducted the numerical models validated by wind-tunnel experiments to investigate the issues of Re-independence of indoor airflow and pollutant dispersion within an isolated building. The window Reynolds number (Re w ) was specified to characterize the indoor flow and dispersion. The indicators of RRC (ratio of relative change) or DR (K_DR) (difference ratio of dimensionless concentration) ≤ 5% were applied to quantitatively determine the critical Re w for indoor flow and turbulent diffusion. The results show that the critical Re (Re crit) value is position-dependent, and Re crit at the most unfavorable position should be suggested as the optimal value within the whole areas of interest. Thus Re H,crit = 27,000 is recommended for the outdoor flows; while Re w,crit = 15,000 is determined for the indoor flows due to the lower part below the window showing the most unfavorable. The suggested Re w,crit (=15,000) for indoor airflow and cross ventilation is independence of the window size. Moreover, taking K_DR ≤ 5% as the indicator, the suggested Re w,crit for ensuring indoor pollutant diffusion enter the Re-independence regime should also be 15,000, indicating that indoor passive diffusion is completely determined by the flow structures. The contours of dimensionless velocity (U/U 0) and concentration (K) against the increasing Re w further confirmed this critical value. This study further reveals the Re-independence issues for indoor flow and dispersion to ensure the reliability of the data obtained by reduced-scale numerical or wind-tunnel models.

16.
Front Cell Dev Biol ; 9: 721130, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595173

RESUMO

The zebrafish as an alternative animal model for developmental toxicity testing has been extensively investigated, but its assay protocol was not harmonized yet. This study has validated and optimized the zebrafish developmental toxicity assay previously reported by multiple inter-laboratory studies in the United States and Europe. In this study, using this classical protocol, of 31 ICH-positive compounds, 23 compounds (74.2%) were teratogenic in zebrafish, five had false-negative results, and three were neither teratogenic nor non-teratogenic according to the protocol standard; of 14 ICH-negative compounds, 12 compounds (85.7%) were non-teratogenic in zebrafish and two had false-positive results. After we added an additional TI value in the zebrafish treated with testing compounds at 2 dpf along with the original 5 dpf, proposed a new category as the uncategorized compounds for those TI values smaller than the cutoff both at 2 dpf and 5 dpf but inducing toxic phenotypes, refined the testing concentration ranges, and optimized the TI cut-off value from ≥ 10 to ≥ 3 for compounds with refined testing concentrations, this optimized zebrafish developmental assay reached 90.3% sensitivity (28/31 positive compounds were teratogenic in zebrafish) and 88.9% (40/45) overall predictability. Our results from this study strongly support the use of zebrafish as an alternative in vivo method for screening and assessing the teratogenicity of candidate drugs for regulatory acceptance.

17.
J Clin Med ; 10(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34640514

RESUMO

Proteolytic fragments of fibronectin can have catabolic effects on cartilage, menisci, and synovium. Previous studies have reported that Toll-like receptor (TLR) signaling pathways might be associated with joint inflammation and joint destruction. Platelet-rich plasma (PRP) is increasingly being used to treat a range of joint conditions; however, it has yet to be determined whether PRP influences fibronectin fragment (FN-f) procatabolic activity and TLRs. In this study, human primary culture cells were treated with 30 kDa FN-f with/without PRP co-incubation, and then analyzed using real-time PCR to determine gene expression levels in articular chondrocytes, meniscal fibrochondrocytes, and synovial fibroblasts. Protein levels were evaluated by Western immunoblotting. This study observed an increase in the protein expression of matrix metalloproteinases (MMPs), Toll-like receptor 2 (TLR2), nitric oxide synthase 2 (NOS2), prostaglandin-endoperoxide synthase (PTGS2), and cyclooxygenase 2 (COX2) in articular chondrocytes, meniscal fibrochondrocytes, and synovial fibroblasts following insult with 30 kDa FN-f. Upregulation of these genes was significantly attenuated by PRP treatment. TLR2 and matrix metalloproteinase 13 (MMP-13) were also significantly attenuated by cotreatment with 30 kDa FN-f + PRP + TLR2 inhibitor. PRP treatment was shown to attenuate the 30 kDa FN-f-induced MMP-13 expression associated with the decreased expression of TLR2 in osteoarthritic chondrocytes and synovial fibroblasts. PRP treatment was also shown to attenuate procatabolic activity associated with MMP-13 expression via the TLR2 signaling pathway.

18.
J Bone Joint Surg Am ; 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34648474

RESUMO

BACKGROUND: Compared with other total hip arthroplasty (THA) approaches, the anterior approach has an increased rate of revision for femoral-sided complications, and certain stems may increase this risk. The present study aimed to assess the outcome of THA by surgical approach, according to the femoral stem utilized in the procedure. METHODS: Data from the Australian Orthopaedic Association National Joint Replacement Registry were analyzed for patients undergoing primary THA for osteoarthritis via the anterior or posterior approach with use of 1 of 5 of the most common cementless femoral stems from January 2015 to December 2019. The primary outcome measures were the cumulative percent revision (CPR) for all causes and for femoral stem loosening and fracture. The CPR was compared between THAs performed via the anterior and posterior approaches for all stems and for each individual femoral stem, as well as between individual femoral stems for each approach. RESULTS: The study included 48,716 THAs performed with use of cementless stems, of which 22,840 utilized an anterior approach and 25,876 utilized a posterior approach. There was no difference in the all-cause CPR between the anterior and the posterior approach, but the anterior approach had a higher CPR for loosening (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.48 to 2.69; p < 0.001) and fracture (HR, 1.78; 95% CI, 1.34 to 2.35; p < 0.001). There was apparent variation in the CPR across the different cementless stems when an anterior approach was utilized. The Quadra-H (Medacta) had a higher all-cause CPR when compared with the Polarstem (Smith & Nephew; HR, 1.49; 95% CI, 1.16 to 1.91; p = 0.002) and Corail (DePuy Synthes; HR, 1.31; 95% CI, 1.00 to 1.70; p = 0.0478). Variation was less apparent with the posterior approach. CONCLUSIONS: THAs performed via the anterior approach had higher rates of revision for femoral stem loosening and fracture, with greater variation in outcomes between individual stems. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

19.
Toxicol Lett ; 354: 1-13, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34718095

RESUMO

Aurantio-obtusin (AO) is a major anthraquinone (AQ) compound derived from Cassiae semen (CS). Although pharmacological studies have shown that the CS extracts can serve as effective agents in preclinical and clinical practice, AQ-induced hepatotoxicity in humans has attracted widespread attention. To explore whether AO induces hepatotoxicity and its underlying mechanisms, we exposed larval zebrafish and mice to AO. We found that AO delayed yolk sac absorption, and increased liver area and inflammation in the larval zebrafish. This inflammation was manifested as an increase in liver neutrophils and the up-regulated mRNA expression of interleukin-6 (Il-6) and tumor necrosis factor-α (Tnf-α) in the larval zebrafish. Furthermore, a pharmacokinetics study showed that AO was quickly absorbed into the blood and rapidly metabolized in the mice. Of note, AO induced hepatotoxicity in a gender-dependent manner, characterized by liver dysfunction, increased hepatocyte necrosis with inflammatory infiltration, and up-regulated mRNAs of Il-6, Tnf-α and monocyte chemotactic protein 1(Mcp1) in the female mice after 28-day oral administration. It also highlighted that AO triggered NOD-like receptor protein (NLRP) signaling in the female mice, as evidenced by the increased NLRP3, Caspase-1, pro-IL-1ß, IL-1ß and IL-18. Finally, we found that AO led to a significant increase in potassium calcium-activated channel, subfamily N, member 4 (KCNN4) and reactive oxygen species (ROS) levels, along with decreased nuclear factor kappa B p65 (NF-κB p65), in the female mouse livers. In conclusion, AO induced hepatotoxicity by activating NLRP3 inflammasome signaling, at least in part, through increased KCNN4 and ROS production, and NF-κB inhibition.

20.
J Cell Biol ; 220(12)2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34596663

RESUMO

Neurons use multiple modes of endocytosis, including clathrin-mediated endocytosis (CME) and activity-dependent bulk endocytosis (ADBE), during mild and intense neuronal activity, respectively, to maintain stable neurotransmission. While molecular players modulating CME are well characterized, factors regulating ADBE and mechanisms coordinating CME and ADBE activations remain poorly understood. Here we report that Minibrain/DYRK1A (Mnb), a kinase mutated in autism and up-regulated in Down's syndrome, plays a novel role in suppressing ADBE. We demonstrate that Mnb, together with calcineurin, delicately coordinates CME and ADBE by controlling the phosphoinositol phosphatase activity of synaptojanin (Synj) during varying synaptic demands. Functional domain analyses reveal that Synj's 5'-phosphoinositol phosphatase activity suppresses ADBE, while SAC1 activity is required for efficient ADBE. Consequently, Parkinson's disease mutation in Synj's SAC1 domain impairs ADBE. These data identify Mnb and Synj as novel regulators of ADBE and further indicate that CME and ADBE are differentially governed by Synj's dual phosphatase domains.

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