Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 467
Filtrar
1.
Neural Regen Res ; 17(2): 344-353, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34269209

RESUMO

Growing evidence suggests that there are similar pathological mechanisms and closely related pathogenic risk factors for inflammatory bowel disease (IBD) and Parkinson's disease (PD). However, the epidemiological features of these two diseases are different. This review systematically evaluated the relationship between inflammatory bowel diseases and Parkinson's disease risk. We searched PubMed, Embase, and Cochrane databases to retrieve observational studies of IBD and PD published from inception to October 2019. Nine observational studies, involving 12,177,520 patients, were included in the final analysis. None of the studies had Newcastle-Ottawa Scale scores that suggested a high risk of bias. After adjusting for confounders and excluding heterogeneous studies, the overall risk of PD was significantly higher in IBD patients than in the general population (adjusted risk ratio [RR] = 1.24, 95% confidence interval [CI]: 1.15-1.34, P < 0.001). A meta-analysis of the temporal relationship revealed that the incidence of IBD was significantly increased before (adjusted hazard ratio [HR] = 1.26, 95% CI: 1.18-1.35, P < 0.001) and after (adjusted RR = 1.40, 95% CI: 1.20-1.80, P < 0.001) PD diagnosis. After excluding a heterogeneous study, the pooled risk of PD development in patients with ulcerative colitis (adjusted HR = 1.25, 95% CI: 1.13-1.38, P < 0.001) or Crohn's disease (adjusted HR = 1.33, 95% CI: 1.21-1.45, P < 0.01) was significantly increased. Subgroup analysis revealed no significant differences in risk between men (adjusted HR = 1.23, 95% CI: 1.10-1.39) and women (adjusted HR = 1.26, 95% CI: 1.10-1.43); however, older (> 65 years old) IBD patients (adjusted HR = 1.32, 95% CI: 1.17-1.48) may have a higher risk than younger (≤ 65 years old) patients (adjusted HR = 1.24, 95% CI: 1.08-1.42). Patients with IBD who were not treated with anti-tumor necrosis factor-α or azathioprine had significantly higher PD risk (adjusted HR = 1.6, 95% CI: 1.2-2.2). Thus, our meta-analysis indicates a certain correlation between IBD and PD, and suggests that IBD may moderately increase PD risk regardless of sex, especially in patients over 65 years of age. Moreover, early anti-inflammatory therapies for IBD might reduce the risk of developing PD. Our findings suggest an urgent need for an individualized screening strategy for patients with IBD. However, most studies included in this paper were observational, and more randomized controlled trials are needed to confirm the precise association between IBD and PD.

2.
Chemosphere ; : 133086, 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34848225

RESUMO

In this study, a novel eco-friendly porous double-network keratin/polyacrylic acid (keratin-PAA) hydrogel was prepared using the one-pot method to improve the adsorption performance of the hydrogel toward Pb(II). The obtained porous keratin-PAA hydrogel was then characterized using nitrogen adsorption-desorption isotherms, thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). The interaction mechanism of Pb(II) and the keratin-PAA hydrogel was further investigated using X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). The results showed that keratin-PAA hydrogel was successfully synthesized, with a specific surface area of 49.35 m2/g and a uniform pore distribution of 6.20 nm. The synthesized keratin-PAA hydrogel only took 6 min to adsorb nearly 70% of Pb(II) from the solution because of the interconnected porous network. The keratin-PAA hydrogel also showed a maximal adsorption amount of 234.6 mg/g, and satisfactory selectivity toward Pb(II). The adsorption kinetics of the keratin-PAA hydrogel binding to Pb(II) could be better described by the pseudo-second-order model, whereas the adsorption isotherms could be fitted using the Langmuir equation; this suggested that chemisorption was the main rate-limiting step. The XPS and FT-IR analysis results indicated that the sulfur-, nitrogen- and oxygen-containing groups in the keratin-PAA hydrogel were the main binding sites for Pb(II). In real aqueous samples, the keratin-PAA hydrogel could remove 93-104% of Pb(II). It is clear that the keratin-PAA hydrogel is an outstanding adsorbent material for the removal of Pb(II) from aqueous samples.

3.
Abdom Radiol (NY) ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34825269

RESUMO

PURPOSE: Studies have found that both FibroScan (FS) and Gd-EOB-DTPA-enhanced T1 mapping magnetic resonance imaging (Gd-MRI) could assess liver fibrosis (LF) with high effectiveness. The aim of this study is to compare their accuracy in the quantitative evaluation of LF in patients with chronic hepatitis B (CHB), and to explore the diagnostic accuracy of their combination. METHODS: 160 patients with CHB were included in this study. FS and Gd-MRI were performed within 3 months before the pathological LF staging, which was classified according to the Scheuer-Ludwig scale. The liver stiffness measurement (LSM) was obtained by FS. T1 mapping images of the liver before and 20 min after enhancement were obtained by Look-Locker Gd-MRI. RESULTS: There were 45, 35, 31 and 49 patients with stage S1, S2, S3 and S4 LF, respectively. LSM increased and the reduction rate of T1 relaxation time of 20 min (rrT120min%) decreased with the severity of LF. The area under curve (AUC) of LSM, rrT120min% and LSM + rrT120min% for the diagnosis of ≥ S2 LF were 0.892, 0.811 and 0.900, respectively. The AUC for ≥ S3 LF was 0.883, 0.838 and 0.899, respectively. The AUC for S4 LF was 0.882, 0.894 and 0.928, respectively. CONCLUSION: The diagnostic accuracy of FS is better than that of Gd-MRI in the evaluation of ≥ S2 stage LF. The combination of these two methods significantly improved the diagnostic efficiency in the evaluation of S4 stage LF.

4.
Biomed J ; 44(5): 627-635, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34740571

RESUMO

BACKGROUND: Transcrestal sinus floor elevation is a reliable procedure when additional bone height is needed for maxillary implant placement. However, the grafted bone undergoes remodeling and the dimensional stability of grafted bone height may be affected by several clinical factors, including graft material, sinus anatomy and the morphology of grafted space. METHODS: This retrospective study examined patients who had undergone transcrestal sinus floor elevation with synthetic biphasic calcium phosphate and single implant placement. The reduction of sinus graft height (GHR) after 6-8 months healing period was measured with cone-beam computed tomography (CBCT) images. Correlating factors, including vertical amount of implant protrusion (IP), sinus width, and the morphology of grafted space were analyzed by Spearman's correlation test. RESULTS: A total of 25 implant sites were analyzed. The mean GHR was 0.57 ± 0.49 mm, which was positively correlated with IP, vertical elevation height (VEH), and the ratio of vertical to horizontal elevation of the grafted space. However, GHR was not correlated with sinus width and mesial-distal or buccal-palatal width of the grafted space. CONCLUSIONS: Synthetic biphasic calcium phosphate used in transcrestal sinus floor elevation underwent shrinkages and graft remodeling. Grafted height reduction was associated with IP, VEH, and the ratio of vertical to horizontal elevation of the grafted space.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34686911

RESUMO

Citronellyl acetate as an important flavor, can be effectively synthesized by lipase catalysis in nonaqueous system. But lipases usually behave low catalytic activity due to aggregation and denaturation of them in organic phase. To enhance the nonaqueous catalysis, based on the mechanism of lipases activated at water/oil (organic phase) interface, the inexpensive race straw was processed into powder and filaments on which Pseudomonas fluorescens lipase was immobilized by physical adsorption, used for synthesis of citronellyl acetate via transesterification of citronellol and vinyl acetate. Results showed that the desired loading was 10 mg lipase immobilized on 30 mg rice straw filaments or 25 mg rice straw powder. When the two immobilized lipases were employed in the reaction system consisted of 1-mL citronellol and 2-mL vinyl acetate at 37 â„ƒ and 160 rpm, the conversions all reached 99.8% after 12 h. Under the reaction condition, the conversion catalyzed by 10 mg native lipase was 85.1%. Undergoing six times of 8-h reuses in the organic system, the filament and power immobilized lipases had weak activity attenuation rates 0.36 and 0.32% h-1, lower than 1.52% h-1 of native lipase. Even at the room temperature and the static state without shaking and stirring, the rice straw filaments immobilized lipase could brought conversion 62.9% after 10 h but the native lipase only gave 37.0%. Obviously, the rice straw, especially its filaments, is an inexpensive and available natural material to prepare immobilized lipase with desired catalysis in organic phase, meant significant potential in flavor industry.

6.
Theor Appl Genet ; 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34689213

RESUMO

KEY MESSAGE: qGSN5, a novel quantitative trait locus coordinating grain size and grain number in rice, was fine-mapped to an 85.60-kb region. GS3 may be a suppressor of qGSN5. Grain size and grain number are two factors that directly determine rice grain yield; however, the underlying genetic mechanisms are complicated and remain largely unclear. In this study, a chromosome segment substitution line (CSSL), CSSL28, which showed increased grain size and decreased grain number per panicle, was identified in a set of CSSLs derived from a cross between 93-11 (recipient) and Nipponbare (donor). Four substitution segments were identified in CSSL28, and the substitution segment located on chromosome 5 was responsible for the phenotypes of CSSL28. Thus, we defined this quantitative trait locus (QTL) as grain size and grain number 5 (qGSN5). Cytological and quantitative PCR analysis showed that qGSN5 regulates the development of the spikelet hull by affecting cell proliferation. Genetic analysis showed that qGSN5 is a semi-dominant locus regulating grain size and grain number. Through map-based cloning and overlapping substitution segment analysis, qGSN5 was finally delimited to an 85.60-kb region. Based on sequence and quantitative PCR analysis, Os05g47510, which encodes a P-type pentatricopeptide repeat protein, is the most likely candidate gene for qGSN5. Pyramiding analysis showed that the effect of qGSN5 was significantly lower in the presence of a functional GS3 gene, indicating that GS3 may be a suppressor of qGSN5. In addition, we found that qGSN5 could improve the grain shape of hybrid rice. Together, our results lay the foundation for cloning a novel QTL coordinating grain size and grain number in rice and provide a good genetic material for long-grain hybrid rice breeding.

7.
Front Oncol ; 11: 683502, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34692475

RESUMO

Introduction: Anlotinib (AL3818) is a novel multi-target tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptor (VEGFR) and suppressing tumor growth. Modulation of tumor suppressive immune microenvironment via the inhibition of vascular endothelial growth factor may augment the activity of immune checkpoint inhibitors. Here we described the results of safety, and clinical efficacy of anlotinib combined with immunotherapy in patients with advanced solid tumors, the serum cytokine levels, and peripheral blood T lymphocyte populations were detected simultaneously. Methods: Twenty six cases with advanced late-stage cancers including lung, gallbladder, endometrial, gastric, pancreatic, penile cancers and melanoma were treated since January 2019. Patients received a combination of anlotinib (12mg) once daily on day 1 to day 14 (21 days as a course) plus anti-PD-1 antibodies every 3 weeks until progression or intolerable toxicity. Imaging was performed every 6 weeks for the first year of therapy. Blood samples were collected from patients prospectively. Serum interleukin (IL)-2, IL-4, IL-6, IL-10, Tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and circulating immune cell subsets were measured at baseline and after two cycles of treatment via flow cytometry. Results: There were ten tumor types enrolled with lung, gallbladder, cholangiocarcinoma and soft tissue sarcoma being the most common. Most patients had received front line treatments for metastatic disease (80.8%). The objective response rate (ORR) was 23.1%, including one complete response (CR) (3.8%) and five partial responses (PR) (19.2%) and a disease control rate (DCR=CR+PR+SD) of 80.8% (21 of 26). The median PFS was 8.37 months (95% CI: 6.5-10.0 months). Three patients (11.5%) had grade 3 treatment-related adverse events. There were no grade 4 or 5 treatment-related adverse events. Grades 3 toxicities included hand-foot syndrome (n=2) and hypertension (n=1). Higher serum IL-2, IL-4, IL-10, TNF-α, IFN-γ levels and lower ratios of CD4/CD8 T cells were found in the responders compared with non-responders. Conclusions: The preliminary data showed that the combination of anlotinib and anti-PD-1 antibodies demonstrated promising durable antitumor efficacy with acceptable toxicity in patients with various advance tumors, and promoted favorable changes in serum IL-2, IL-4, IL-10, TNF-α, IFN-γ levels and circulating immune cell subsets in clinical responders. It is worth to further validate the efficacy in a randomized prospective trial.

8.
Antibiotics (Basel) ; 10(10)2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34680814

RESUMO

This work aimed to characterize a 29-kb blaKPC-2-carrying plasmid, pR31-KPC, from a multidrug resistant strain of Pseudomonas aeruginosa isolated from the sputum of an elderly patient with multiple chronic conditions in China. The backbone of pR31-KPC is closely related to four other blaKPC-2-carrying plasmids, YLH6_p3, p1011-KPC2, p14057A, and pP23-KPC, none of which have been assigned to any of the known incompatibility groups. Two accessory modules, the IS26-blaKPC-2-IS26 unit and IS26-ΔTn6376-IS26 region, separated by a 5.9-kb backbone region, were identified in pR31-KPC, which was also shown to carry the unique resistance marker blaKPC-2. A comparative study of the above five plasmids showed that p1011-KPC2 may be the most complete plasmid of this group to be reported, while pR31-KPC is the smallest plasmid having lost most of its conjugative region. Regions between the iterons and orf207 in the backbone may be hot spots for the acquisition of exogenous resistance entities. The accessory regions of these plasmids have all undergone several biological events when compared with Tn6296. The further transfer of blaKPC-2 in these plasmids may be initiated by either the Tn3 family or IS26-associated transposition or homologous recombination. The data presented here will contribute to a deeper understanding of blaKPC-2 carrying plasmids in Pseudomonas.

9.
Pak J Pharm Sci ; 34(3): 1003-1010, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34602425

RESUMO

Rhizoma Musa (the Rhizome of Musa basjoo Sied.et Zucc.) is used as a traditional medical herb of Miao nationality in Guizhou province, in China. It has the efficacy of clearing heat and detoxifying, quenching thirst, diuresis, etc. Modern pharmacological studies have shown that it has hypoglycemic, inhibition of α-glucosidase, and anti-inflammatory activity. However, when the rhizomes of Musa basjoo are dug up, the rhizomes are unable regenerate, and the pseudostem and leaf are discarded, which not only pollutes the environment, but also causes a huge waste of herb resources. In this study, a UPLC-ELSD fingerprint analysis with chemometric method was applied for the evaluation of chemical similarity among rhizome, pseudostem and leaf of Musa Basjoo. The results indicated that the combined method could efficiently analyze and compare the chemical similarity among rhizome, pseudostem, and leaf of Musa Basjoo. The proposed method provides the foundation for the resource substitution of the rhizome, pseudostem, and leaf of Musa Basjoo.

10.
Front Public Health ; 9: 575315, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595146

RESUMO

Objective: The aim of this study is to analyze the latent class of basic reproduction number (R 0) trends of the 2019 novel coronavirus disease (COVID-19) in the major endemic areas of China. Methods: The provinces that reported more than 500 cases of COVID-19 till February 18, 2020 were selected as the major endemic areas. The Verhulst model was used to fit the growth rate of cumulative confirmed cases. The R 0 of COVID-19 was calculated using the parameters of severe acute respiratory syndrome (SARS) and COVID-19. The latent class of R 0 was analyzed using the latent profile analysis (LPA) model. Results: The median R 0 calculated from the SARS and COVID-19 parameters were 1.84-3.18 and 1.74-2.91, respectively. The R 0 calculated from the SARS parameters was greater than that calculated from the COVID-19 parameters (Z = -4.782 to -4.623, p < 0.01). Both R 0 can be divided into three latent classes. The initial value of R 0 in class 1 (Shandong Province, Sichuan Province, and Chongqing Municipality) was relatively low and decreased slowly. The initial value of R 0 in class 2 (Anhui Province, Hunan Province, Jiangxi Province, Henan Province, Zhejiang Province, Guangdong Province, and Jiangsu Province) was relatively high and decreased rapidly. Moreover, the initial R 0 value of class 3 (Hubei Province) was in the range between that of classes 1 and 2, but the higher R 0 level lasted longer and decreased slowly. Conclusion: The results indicated that the overall R 0 trend is decreased with the strengthening of comprehensive prevention and control measures of China for COVID-19, however, there are regional differences.


Assuntos
COVID-19 , SARS-CoV-2 , Número Básico de Reprodução , China/epidemiologia , Humanos , Incidência
11.
J Clin Oncol ; : JCO2100608, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34648352

RESUMO

PURPOSE: In a previous phase II trial, hepatic arterial infusion chemotherapy (HAIC) with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) yielded higher treatment responses than transarterial chemoembolization (TACE) in large unresectable hepatocellular carcinoma. We aimed to compare the overall survival of patients treated with FOLFOX-HAIC versus TACE as first-line treatment in this population. METHODS: In this randomized, multicenter, open-label trial, adults with unresectable hepatocellular carcinoma (largest diameter ≥ 7 cm) without macrovascular invasion or extrahepatic spread were randomly assigned 1:1 to FOLFOX-HAIC (oxaliplatin 130 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2,400 mg/m2 for 24 hours, once every 3 weeks) or TACE (epirubicin 50 mg, lobaplatin 50 mg, and lipiodol and polyvinyl alcohol particles). The primary end point was overall survival by intention-to-treat analysis. Safety was assessed in patients who received ≥ 1 cycle of study treatment. RESULTS: Between October 1, 2016, and November 23, 2018, 315 patients were randomly assigned to FOLFOX-HAIC (n = 159) or TACE (n = 156). The median overall survival in the FOLFOX-HAIC group was 23.1 months (95% CI, 18.5 to 27.7) versus 16.1 months (95% CI, 14.3 to 17.9) in the TACE group (hazard ratio, 0.58; 95% CI, 0.45 to 0.75; P < .001). The FOLFOX-HAIC group showed a higher response rate than the TACE group (73 [46%] v 28 [18%]; P < .001) and a longer median progression-free survival (9.6 [95% CI, 7.4 to 11.9] v 5.4 months [95% CI, 3.8 to 7.0], P < .001). The incidence of serious adverse events was higher in the TACE group than in the FOLFOX-HAIC group (30% v 19%, P = .03). Two deaths in the FOLFOX-HAIC group and two in the TACE group were deemed to be treatment-related. CONCLUSION: FOLFOX-HAIC significantly improved overall survival over TACE in patients with unresectable large hepatocellular carcinoma.

12.
FASEB J ; 35(11): e21947, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34637552

RESUMO

Vascular remodeling is a prominent trait during the development of hypertension, attributable to the phenotypic transition of vascular smooth muscle cells (VSMCs). Increasing studies demonstrate that microRNA plays an important role in this process. Here, we surprisingly found that smooth muscle cell-specific miR-214 knockout (miR-214 cKO) significantly alleviates angiotensin II (Ang II)-induced hypertension, which has the same effect as that of miR-214 global knockout mice in response to Ang II stimulation. Under the treatment of Ang II, miR-214 cKO mice exhibit substantially reduced systolic blood pressure. The vascular medial thickness and area in miR-214 cKO blood vessels were obviously reduced, the expression of collagen I and proinflammatory factors were also inhibited. VSMC-specific deletion of miR-214 blunts the response of blood vessels to the stimulation of endothelium-dependent and -independent vasorelaxation and phenylephrine and 5-HT induced vasocontraction. In vitro, Ang II-induced VSMC proliferation, migration, contraction, hypertrophy, and stiffness were all repressed with miR-214 KO in VSMC. To further explore the mechanism of miR-214 in the regulation of the VSMC function, it is very interesting to find that the TGF-ß signaling pathway is mostly enriched in miR-214 KO VSMC. Smad7, the potent negative regulator of the TGF-ß/Smad pathway, is identified to be the target of miR-214 in VSMC. By which, miR-214 KO sharply enhances Smad7 levels and decreases the phosphorylation of Smad3, and accordingly alleviates the downstream gene expression. Further, Ang II-induced hypertension and vascular dysfunction were reversed by antagomir-214. These results indicate that miR-214 in VSMC established a crosstalk between Ang II-induced AT1R signaling and TGF-ß induced TßRI /Smad signaling, by which it exerts a pivotal role in vascular remodeling and hypertension and imply that miR-214 has the potential as a therapeutic target for the treatment of hypertension.


Assuntos
Angiotensina II/farmacologia , Técnicas de Inativação de Genes/métodos , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Transdução de Sinais/genética , Proteína Smad7/metabolismo , Regulação para Cima/genética , Animais , Pressão Sanguínea/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Células Cultivadas , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , MicroRNAs/genética , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Remodelação Vascular/genética
13.
J Immunother Cancer ; 9(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34615704

RESUMO

BACKGROUND: Hypoxia is a striking feature of most solid tumors and could be used to discriminate tumors from normoxic tissues. Therefore, the design of hypoxia-conditioned Chimeric Antigen Receptor (CAR) T cells is a promising strategy to reduce on-target off-tumor toxicity in adoptive cell therapy. However, existing hypoxia-conditioned CAR-T designs have been only partially successful in enhancing safety profile but accompanied with reduced cytotoxic efficacy. Our goal is to further improve safety profile with retained excellent antitumor efficacy. METHODS: In this study, we designed and constructed a hypoxia-inducible transcription amplification system (HiTA-system) to control the expression of CAR in T (HiTA-CAR-T) cells. CAR expression was determined by Flow cytometry, and the activation and cytotoxicity of HiTA-CAR-T cells in vitro were evaluated in response to antigenic stimulations under hypoxic or normoxic conditions. The safety of HiTA-CAR-T cells was profiled in a mouse model for its on-target toxicity to normal liver and other tissues, and antitumor efficacy in vivo was monitored in murine xenograft models. RESULTS: Our results showed that HiTA-CAR-T cells are highly restricted to hypoxia for their CAR expression, activation and cytotoxicity to tumor cells in vitro. In a mouse model in vivo, HiTA-CAR-T cells targeting Her2 antigen showed undetectable CAR expression in all different normoxic tissues including human Her2-expresing liver, accordingly, no liver and systemic toxicity were observed; In contrast, regular CAR-T cells targeting Her2 displayed significant toxicity on human Her2-expression liver. Importantly, HiTA-CAR-T cells were able to achieve significant tumor suppression in murine xenograft models. CONCLUSION: Our HiTA system showed a remarkable improvement in hypoxia-restricted transgene expression in comparison with currently available systems. HiTA-CAR-T cells presented significant antitumor activities in absence of any significant liver or systemic toxicity in vivo. This approach could be also applied to design CAR-T cell targeting other tumor antigens.

14.
Bioengineered ; 12(1): 8233-8246, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34592890

RESUMO

The gut microbiota system plays a vital role in liver diseases. This study aimed to address the diversity of gut microbiota and its correlations with clinical parameters in healthy individuals, chronic liver disease (CLD), and hepatocellular carcinoma (HCC) patients. Fecal specimens of nine healthy individuals, 11 CLD, and 21 HCC were collected. The diversity of gut microbiota was examined by PCR and Illumina MiSeq sequencing and analyzed using 16S rRNA gene sequencing database. The correlations between gut microbiota and the clinical parameters of participants were also addressed. Compared to healthy individuals, Firmicutes at a phylum level decreased in CLD and HCC patients and Proteobacteria increased (p < 0.05). The composition of Blautia on a genus level in CLD and HCC patients significantly decreased compared to healthy controls (p < 0.05). Firmicutes composition was negatively associated with age and number of males (p < 0.05) and was positively associated with monocytes, high-density lipoprotein cholesterol (HDL-C), and estimated glomerular filtration rate (eGFR) levels (p < 0.05). At a genus level, Blautia composition was negatively associated with cirrhosis, age, and number of males (p < 0.01), while it was positively associated with red blood cells (RBCs), triglycerides, HDL-C, and lymphocyte levels (p < 0.05). Conclusively, there was a significant compositional difference in gut microbiota in CLD and HCC patients compared with healthy subjects. Firmicutes and Blautia in gut microbiota system lessened in CLD and HCC patients. Clinical biochemical parameters have an impact on the diversity of gut microbiota in liver diseases.

15.
Mol Med Rep ; 24(5)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34468006

RESUMO

The aim of the present study was to investigate the effect of penehyclidine hydrochloride (PHC) pretreatment on mice with lipopolysaccharide (LPS)­induced acute lung injury (ALI) and its possible underlying mechanisms. Mice were randomly separated into six groups: i) Sham group; ii) LPS group; iii) LPS + PHC group; iv) tumor necrosis factor a­induced protein 8­like protein 2 (TIPE2) group; v) LPS + TIPE2 group; and vi) LPS + TIPE2 + PHC group. The ALI model was induced using LPS through intratracheal injection. The mice received adenovirus gene to induce the overexpression of TIPE2. After mice were sacrificed, lung injury indices were assessed, and arterial blood, bronchoalveolar lavage fluid and lung tissues were collected for subsequent assays. Expression levels of related proteins were detected by using western blotting. It was found that compared with the sham group, the mice treated with LPS showed increased lung injury and dysfunctions of gas exchange. However, these trends were significantly ameliorated in the LPS + PHC group. Evaluation of protein expression in lung tissues showed that the increased expression of nuclear NF­κB p65 and p­c­Jun N­terminal kinase (JNK) induced by LPS were suppressed in the LPS + PHC group and the expression of TIPE2 was increased. The mice that received adenovirus gene to induce TIPE2 overexpression could also showed protective effects compared with the mice in the LPS group. However, the expression of TIPE2 decreased rather than increased in LPS group. In the mice pretreated with PHC, the expression of TIPE2 increased in mice with LPS­induced ALI. To conclude, PHC pretreatment could inhibit the occurrence of inflammation and apoptosis in LPS­induced ALI. This process may be related to the activation of TIPE2 and the inhibition of NF­κB and JNK signaling pathway in the lungs of mice.

16.
Luminescence ; 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34519153

RESUMO

Due to the threat to health of heavy metal contamination, simple and rapid detection methods for heavy metals are an urgent needed in environment protection and food safety. In this work, we have developed a fluorescent aptasensor for the 'turn-off' model detection of Pb2+ . The key feature of the aptasensor is that the dye-labelled nucleic acid strand can be folded into a G-quadruplex structure in the presence of Pb2+ . This conformational change induces photoinduced electron transfer (PET) between a G-quadruplex-hemin complex and 6-carboxyrhodamine X (ROX), which results in fluorescence quenching of ROX. We systematically investigated the interaction mechanism between Pb2+ and the aptasensor and the effects of several environmental parameters were also studied. Under the optimum conditions, the proposed method exhibited a good liner relationship between the concentration of Pb2+ and fluorescence quenching efficiency in the range 25-500 nM and the limit of detection was 1.02 nM. In addition, this method also manifested good performance in spiked lettuce samples with satisfactory recoveries of 87.10-109.6%. This target-induced PET platform can be further expanded to other heavy metal analysis.

17.
Metabolites ; 11(9)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34564443

RESUMO

Mitochondria are dynamic organelles that constantly alter their shape through the recruitment of specialized proteins, like mitofusin-2 (Mfn2) and dynamin-related protein 1 (Drp1). Mfn2 induces the fusion of nearby mitochondria, while Drp1 mediates mitochondrial fission. We previously found that the genetic or pharmacological activation of mitochondrial fusion was tumor suppressive against pancreatic ductal adenocarcinoma (PDAC) in several model systems. The mechanisms of how these different inducers of mitochondrial fusion reduce pancreatic cancer growth are still unknown. Here, we characterized and compared the metabolic reprogramming of these three independent methods of inducing mitochondrial fusion in KPC cells: overexpression of Mfn2, genetic editing of Drp1, or treatment with leflunomide. We identified significantly altered metabolites via robust, orthogonal statistical analyses and found that mitochondrial fusion consistently produces alterations in the metabolism of amino acids. Our unbiased methodology revealed that metabolic perturbations were similar across all these methods of inducing mitochondrial fusion, proposing a common pathway for metabolic targeting with other drugs.

18.
Glob Health Promot ; : 17579759211033831, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34553622

RESUMO

In the fight against the COVID-19 pandemic, Taiwan, with its universal masking policy, slowed down the spread of cases and flattened its epidemic curve without enforcing lockdown or mass quarantine in 2020. This study identifies the distinguishing features of Taiwan's universal masking policy practice, such as priority, continuous improvement, multi-stakeholder partnership, transparency and accountability, and altruism and social solidarity. By confronting uncertainty through the COVID-19 crisis, this study suggests that face masking, rather than being just a physical barrier of non-pharmacological intervention, can be adopted as an interactive policy platform to empower the public for stimulating cross-sector collaboration towards social innovation and creating spillover effects, such as acts of public trust, altruism, and solidarity.

19.
Genetica ; 149(5-6): 313-325, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34480683

RESUMO

Reducing false discoveries caused by population stratification (PS) has always been a challenge in genome-wide association studies (GWAS). The current literature established several single marker approaches including genomic control (GC), EIGENSTRAT and generalized linear mixed model association test (GMMAT) and multi-marker methods such as LASSO mixed model (LASSOMM). However, the single-marker methods require prespecifying an arbitrary p value threshold in the selection process, likely resulting in suboptimal precision or recall. On the other hand, it appears that LASSOMM is extremely computationally intensive and may not suitable for large-scale GWAS. In this paper, we proposed a simple multi-marker approach (PCA-LASSO) combining principal component analysis (PCA) and least absolute shrinkage and selection operator (LASSO). We utilize PCA to correct for the confounding effects of PS and LASSO with built-in cross-validation for a data-driven selection. Compared to the current single-marker approaches, the proposed PCA-LASSO provides optimal balance between precision and recall, and consequently superior F1 scores. Similarly, compared to LASSOMM, PCA-LASSO markedly increases the precision while minimizing the loss of recall, and therefore improves the overall F1 score in presence of PS. More importantly, PCA-LASSO drastically reduces the computational time by > 1000 times when compared to LASSOMM. We applied PCA-LASSO to a real dataset of Alzheimer's disease and successfully identified SNP rs429358 (Gene APOE4) which has been widely reported to be associated with the onset and elevated risk of Alzheimer's disease. In conclusion, PCA-LASSO is a simple, fast, but accurate approach for GWAS in presence of latent PS.

20.
Front Cell Infect Microbiol ; 11: 737636, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513738

RESUMO

Objectives: This prospective study was carried out to investigate molecular characteristics and antimicrobial susceptibility patterns of Citrobacter spp. from extraintestinal infections. Methods: Forty-six clinical Citrobacter spp. isolates were isolated from hospital patients with extraintestinal infections and analyzed by multilocus sequence typing (MLST) using seven housekeeping genes. Antimicrobial susceptibility testing was performed by disk diffusion method according to the Clinical and Laboratory Standards Institute (CLSI) recommendations. Adhesion and cytotoxicity to HEp-2 cells were assessed. Results: The 46 clinical Citrobacter spp. isolates were typed into 38 sequence types (STs), 9 of which belonged to four clonal complexes (CCs). None of the isolates shared the same ST or CCs with isolates from other countries or from other parts of China. Over half of the isolates were multidrug-resistant (MDR), with 17/26 C. freundii, 5/6 C. braakii, and 3/14 C. koseri isolates being MDR. Moreover, four isolates were carbapenem resistant with resistance to imipenem or meropenem. Among eight quinolone resistant C. freundii, all had a mutation in codon 59 (Thr59Ile) in quinolone resistance determining region of the gyrA gene. Only a small proportion of the isolates were found to be highly cytotoxic and adhesive with no correlation to sample sources. Conclusions: There was a diverse range of Citrobacter isolates causing extraintestinal infections and a high prevalence of MDR.


Assuntos
Antibacterianos , Citrobacter , Antibacterianos/farmacologia , Citrobacter/genética , Farmacorresistência Bacteriana/genética , Humanos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Estudos Prospectivos , beta-Lactamases
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...