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1.
Glob Health Med ; 3(5): 276-282, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34782869

RESUMO

With the introduction of effective directly acting antiviral agents (DAAs) therapy, control and elimination of hepatitis C virus (HCV) infection is becoming a feasible goal. In Hong Kong, HCV prevalence in general population is 0.3%-0.5% over the past decades. However, like other high-income areas/countries, high prevalence of HCV infection has been found in several population groups, such as people who inject drugs (PWID), patients undergoing dialysis, and human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/ AIDS) patients. Based on the epidemiological study using data retrieved from the Hong Kong HCV Registry from January 2005 to March 2017, the estimated territory-wide diagnosis rate and treatment rate of HCV infection were only 50.9% and 12.4%, respectively. Although these rates was comparable to many developed countries/areas, the performances remained substantially below 90% and 80%, the 2030 targets proposed by World Health Organization (WHO). In recognition of the challenges, the Hong Kong Government set up the Steering Committee on Prevention and Control of Viral Hepatitis (SCVH) which formulated the Hong Kong Viral Hepatitis Action Plan 2020-2024. The Action Plan adopts four key strategies, as described in the WHO framework for global action, namely, awareness, surveillance, prevention and treatment. With the effective implementation of the Action Plan, especially in targeted screening of high-risk populations and more generalized use of the highly efficacious DAAs for all diagnosed HCV subjects, the goals of reducing HCV transmission and HCV-related morbidity and mortality can be achieved in Hong Kong by 2030.

2.
Int J Nanomedicine ; 16: 6661-6679, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616150

RESUMO

Purpose: Iron-based nanomaterials have recently been developed as excellent and potent Fenton reagents to reactive oxygen species (ROS) during chemodynamic therapy (CDT). The performance of the materials, however, can be impaired by the intrinsic antioxidant defense mechanism in organisms, such as autophagy. Methods: The nanoscale metal-organic frameworks (nMOFs), nMIL-100 (Fe), were exploited and characterized. Also, the Fenton-like catalytic characteristics, anti-endometrial cancer (EC) effects and potential mechanisms of nMIL-100 (Fe) nanoparticles were investigated in vitro. Results: The synthesized nMIL-100 (Fe) nanocatalyst catalyzed hydroxyl radicals (·OH) production in the presence of hydrogen peroxide (H2O2) and simultaneously depleted intracellular glutathione (GSH). Combining with H2O2, nMIL-100 (Fe) nanoparticles exhibited enhanced cytotoxicity for EC cells, especially for progesterone treatment-insensitive KLE cells, probably due to relatively lower expression of the catalase gene. The accumulated ·OH initiated PTEN induced putative kinase 1 (PINK1)/E3 ubiquitin-protein ligase Parkin-mediated cytoprotective mitophagy in turn to partially rescue ·OH-induced cell apoptosis. Furthermore, both pretreatments of EC cells with siRNA-mediated Parkin knockdown and Mdivi-1 (a mitophagy inhibitor) addition were sufficient to ensure nMIL-100 (Fe) synergizing with H2O2-induced oxidative damages. Conclusion: These results suggest that the degree of mitophagy should be taken into consideration to optimize therapeutic efficiency when developing ROS based-CDT for EC cancer therapies. Therefore, a nMIL-100 (Fe)-guided, elevated ROS and overwhelmed mitophagy-mediated therapeutic strategy may have greater promise for EC therapy compared with current treatment modalities.


Assuntos
Neoplasias do Endométrio , Mitofagia , Neoplasias do Endométrio/tratamento farmacológico , Feminino , Humanos , Peróxido de Hidrogênio , Mitocôndrias , Proteínas Quinases , Espécies Reativas de Oxigênio , Ubiquitina-Proteína Ligases
3.
J Mater Sci Mater Med ; 32(11): 133, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34689241

RESUMO

OBJECTIVE: In our previous study, tantalum nanoparticle (Ta-NPs) was demonstrated to promote osteoblast proliferation via autophagy induction, but the specific mechanism remains unclear. In the present study, we will explore the potential mechanism. METHODS: Ta-NPs was characterized by transmission electron microscopy, scanning electron microscopy, dynamic light scattering, and BET specific surface area test. MC3T3-E1 were treated with 0 or 20 µg/mL Ta-NPs with or without pretreatment with 10 µM LY294002, Triciribine, Rapamycin (PI3K/Akt/mTOR pathway inhibitors) for 1 h respectively. Western blotting was used to detect the expressions of pathway proteins and LC3B. CCK-8 assay was used to assess cell viability. Flow cytometry was used to detect apoptosis and cell cycle. RESULTS: After pretreatment with LY294002, Triciribine and Rapamycin, the p-Akt/Akt ratio of pathway protein in Triciribine and Rapamycin groups decreased (P < 0.05), while the autophagy protein LC3-II/LC3-I in the Rapamycin group was upregulated obviously (P < 0.001). In all pretreated groups, apoptosis was increased (LY294002 group was the most obvious), G1 phase cell cycle was arrested (Triciribine and Rapamycin groups were more obvious), and MC3T3-E1 cells were proliferated much more (P < 0.01, P < 0.001, P < 0.05). CONCLUSION: Pretreatment with Triciribine or Rapamycin has a greater effect on pathway protein Akt, cell cycle arrest, autophagy protein, and cell proliferation but with inconsistent magnitude, which may be inferred that the Akt/mTOR pathway, as well as its feedback loop, were more likely involved in these processes.

4.
Int J Cancer ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34469590

RESUMO

Continuous cell lines are practical models that are widely used in the study of disease mechanisms and particularly cancers. However, the issue of cell line cross-contamination has existed since the 1960s, despite repeated advocation for cell line authentication by many experts. Furthermore, cell line abuse has been underestimated and underreported. The China Center for Type Culture Collection (CCTCC) received 1373 cell samples for authentication from 2010 to 2019, and has found that the quality of cell lines has improved during this time, offering a positive outlook for the future.

5.
Mol Genet Metab ; 134(1-2): 156-163, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34556413

RESUMO

Acyl CoA Dehydrogenase 9 (ACAD9) is a member of the family of flavoenzymes that catalyze the dehydrogenation of acyl-CoAs to 2,3 enoyl-CoAs in mitochondrial fatty acid oxidation (FAO). Inborn errors of metabolism of all family members, including ACAD9, have been described in humans, and represent significant causes of morbidity and mortality particularly in children. ACAD9 deficiency leads to a combined defect in fatty acid oxidation and oxidative phosphorylation (OXPHOS) due to a dual role in the pathways. In addition to its function in mitochondrial FAO, ACAD9 has a second function as one of 14 factors responsible for assembly of complex I of the electron transport chain (ETC). Considerable controversy remains over the relative role of these two functions in normal physiology and the disparate clinical findings described in patients with ACAD9 deficiency. To better understand the normal function of ACAD9 and the pathophysiology of its deficiency, several knock out mouse models were developed. Homozygous total body knock out appeared to be lethal as no ACAD9 animals were obtained. Cre-lox technology was then used to generate tissue-specific deletion of the gene. Cardiac-specific ACAD9 deficient animals had severe neonatal cardiomyopathy and died by 17 days of age. They had severe mitochondrial dysfunction in vitro. Muscle-specific mutants were viable but exhibited muscle weakness. Additional studies of heart muscle from the cardiac specific deficient animals were used to examine the evolutionarily conserved signaling Intermediate in toll pathway (ECSIT) protein, a known binding partner of ACAD9 in the electron chain complex I assembly pathway. As expected, ECSIT levels were significantly reduced in the absence of ACAD9 protein, consistent with the demonstrated impairment of the complex I assembly. The various ACAD9 deficient animals should serve as useful models for development of novel therapeutics for this disorder.

6.
Bioengineering (Basel) ; 8(7)2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34356201

RESUMO

Blood plasma is the most commonly used biofluid in disease diagnostic and biomedical analysis due to it contains various biomarkers. The majority of the blood plasma separation is still handled with centrifugation, which is off-chip and time-consuming. Therefore, in the Lab-on-a-chip (LOC) field, an effective microfluidic blood plasma separation platform attracts researchers' attention globally. Blood plasma self-separation technologies are usually divided into two categories: active self-separation and passive self-separation. Passive self-separation technologies, in contrast with active self-separation, only rely on microchannel geometry, microfluidic phenomena and hydrodynamic forces. Passive self-separation devices are driven by the capillary flow, which is generated due to the characteristics of the surface of the channel and its interaction with the fluid. Comparing to the active plasma separation techniques, passive plasma separation methods are more considered in the microfluidic platform, owing to their ease of fabrication, portable, user-friendly features. We propose an extensive review of mechanisms of passive self-separation technologies and enumerate some experimental details and devices to exploit these effects. The performances, limitations and challenges of these technologies and devices are also compared and discussed.

7.
Bioengineering (Basel) ; 8(7)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34356205

RESUMO

COVID-19, also known as SARS-CoV-2 is a novel, respiratory virus currently plaguing humanity. Genetically, at its core, it is a single-strand positive-sense RNA virus. It is a beta-type Coronavirus and is distinct in its structure and binding mechanism compared to other types of coronaviruses. Testing for the virus remains a challenge due to the small market available for at-home detection. Currently, there are three main types of tests for biomarker detection: viral, antigen and antibody. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) remains the gold standard for viral testing. However, the lack of quantitative detection and turnaround time for results are drawbacks. This manuscript focuses on recent advances in COVID-19 detection that have lower limits of detection and faster response times than RT-PCR testing. The advancements in sensing platforms have amplified the detection levels and provided real-time results for SARS-CoV-2 spike protein detection with limits as low as 1 fg/mL in the Graphene Field Effect Transistor (FET) sensor. Additionally, using multiple biomarkers, detection levels can achieve a specificity and sensitivity level comparable to that of PCR testing. Proper biomarker selection coupled with nano sensing detection platforms are key in the widespread use of Point of Care (POC) diagnosis in COVID-19 detection.

8.
Cell Death Discov ; 7(1): 195, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312379

RESUMO

p53 and NF-κBp65 are essential transcription factors (TFs) in the cellular response to stress. Two signaling systems can often be entwined together and generally produce opposing biological outcomes in a cell context-dependent manner. Inhibitor of apoptosis-stimulating protein of p53 (iASPP) has the potential to inhibit both p53 and NF-κBp65, yet how such activities of iASPP are integrated with cancer remains unknown. Here, we utilized different cell models with diverse p53/NF-κBp65 activities. An iASPP(295-828) mutant, which is exclusively located in the nucleus and has been shown to be essential for its inhibitory effects on p53/NF-κBp65, was used to investigate the functional interaction between iASPP and the two TFs. The results showed that iASPP inhibits apoptosis under conditions when p53 is activated, while it can also elicit a proapoptotic effect when NF-κBp65 alone is activated. Furthermore, we demonstrated that iASPP inhibited the transcriptional activity of p53/NF-κBp65, but with a preference toward p53, thereby producing an antiapoptotic outcome when both TFs were simultaneously activated. This may be due to stronger binding between p53 and iASPP than NF-κBp65 and iASPP. Overall, these findings provide important insights into how the activities of p53 and NF-κBp65 are modulated by iASPP. Despite being a well-known oncogene, iASPP may have a proapoptotic role, which will guide the development of iASPP-targeted therapies to reach optimal outcomes in the future.

9.
Lancet Infect Dis ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34324836

RESUMO

BACKGROUND: SARS-CoV-2 has caused millions of deaths, and, since Aug 11, 2020, 20 intramuscular COVID-19 vaccines have been approved for use. We aimed to evaluate the safety and immunogenicity of an aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in adults without COVID-19 from China. METHOD: This was a randomised, single-centre, open-label, phase 1 trial done in Zhongnan Hospital (Wuhan, China), to evaluate the safety and immunogenicity of the Ad5-nCoV vaccine by aerosol inhalation in adults (≥18 years) seronegative for SARS-CoV-2. Breastfeeding or pregnant women and people with major chronic illnesses or history of allergies were excluded. Participants were enrolled and randomly assigned (1:1:1:1:1) into five groups to be vaccinated via intramuscular injection, aerosol inhalation, or both. Randomisation was stratified by sex and age (18-55 years or ≥56 years) using computer-generated randomisation sequences (block sizes of five). Only laboratory staff were masked to group assignment. The participants in the two aerosol groups received an initial high dose (2 × 1010 viral particles; HDmu group) or low dose (1 × 1010 viral particles; LDmu group) of Ad5-nCoV vaccine on day 0, followed by a booster on day 28. The mixed vaccination group received an initial intramuscular (5 × 1010 viral particles) vaccine on day 0, followed by an aerosolised booster (2 × 1010 viral particles) vaccine on day 28 (MIX group). The intramuscular groups received one dose (5 × 1010 viral particles; 1Dim group) or two doses (10 × 1010 viral particles; 2Dim group) of Ad5-nCoV on day 0. The primary safety outcome was adverse events 7 days after each vaccination, and the primary immunogenicity outcome was anti-SARS-CoV-2 spike receptor IgG antibody and SARS-CoV-2 neutralising antibody geometric mean titres at day 28 after last vaccination. This trial is registered with ClinicalTrials.gov, number NCT04552366. FINDINGS: Between Sept 28, 2020, and Sept 30, 2020, 230 individuals were screened for inclusion, of whom 130 (56%) participants were enrolled into the trial and randomly assigned into one of the five groups (26 participants per group). Within 7 days after vaccination, adverse events occurred in 18 (69%) in the HDmu group, 19 (73%) in the LDmu group, 19 (73%) in the MIX group, 19 (73%) in the 1Dim group, and 15 (58%) in the 2Dim group. The most common adverse events reported 7 days after the first or booster vaccine were fever (62 [48%] of 130 participants), fatigue (40 [31%] participants), and headache (46 [35%] participants). More adverse events were reported in participants who received intramuscular vaccination, including participants in the MIX group (49 [63%] of 78 participants), than those who received aerosol vaccine (13 [25%] of 52 participants) after the first vaccine vaccination. No serious adverse events were noted within 56 days after the first vaccine. At days 28 after last vaccination, geometric mean titres of SARS-CoV-2 neutralising antibody was 107 (95% CI 47-245) in the HDmu group, 105 (47-232) in the LDmu group, 396 (207-758) in the MIX group, 95 (61-147) in the 1Dim group, and 180 (113-288) in the 2Dim group. The geometric mean concentrations of receptor binding domain-binding IgG was 261 EU/mL (95% CI 121-563) in the HDmu group, 289 EU/mL (138-606) in the LDmu group, 2013 EU/mL (1180-3435) in the MIX group, 915 EU/mL (588-1423) in the 1Dim group, and 1190 EU/mL (776-1824) in the 2Dim group. INTERPRETATION: Aerosolised Ad5-nCoV is well tolerated, and two doses of aerosolised Ad5-nCoV elicited neutralising antibody responses, similar to one dose of intramuscular injection. An aerosolised booster vaccination at 28 days after first intramuscular injection induced strong IgG and neutralising antibody responses. The efficacy and cost-effectiveness of aerosol vaccination should be evaluated in future studies. FUNDING: National Key Research and Development Programme of China and National Science and Technology Major Project. TRANSLATION: For the Chinese translation of the Summary see Supplementary Material.

10.
Ultrasound Med Biol ; 47(9): 2622-2635, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34147312

RESUMO

This study aimed to establish the feasibility of ultrasound-guided high-intensity focused ultrasound (USgHIFU) for devascularization of uterine fibroids. Ultrasound color Doppler flow imaging (CDFI) and B-mode imaging were used to target fibroid vascularity. The vessels were covered and ablated by high-intensity focused ultrasound spots. In this study, 42 fibroids with a volume of 66.98 ± 4.00 cm3 were treated. No blood flow was detected by post-treatment CDFI in 40 fibroids. The 6-mo non-perfusion volume rate was 75.23% ± 34.77% (n = 40). The mean shrinkage in fibroid volume was 38.20% and 43.89%, respectively, at 1 and 6 mo after treatment (p < 0.001). The uterine fibroid symptom and quality of life scores were reduced by 9.43% at 1 mo and 26.66% at 6-mo after treatment (p < 0.001). No serious adverse event was observed. This study demonstrates the feasibility of USgHIFU-induced fibroid devascularization, and more studies are required for the evaluation of safety and efficacy.

12.
J Pain Res ; 14: 1699-1706, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34140806

RESUMO

Purpose: In patients requiring percutaneous kyphoplasty (PKP) for painful cervical spine metastases (PCSMs), the surgical approach is of utmost importance. Anterolateral and transoral routes are generally used at present, whereas PKP as well as percutaneous pediculoplasty (PPP) via posterolateral transpedicular approach (PTPA) has yet to be pursued in the treatment of PCSMs. The study was designed to evaluate safety and efficacy of PKP procedures combined with PPP via PTPA as treatment of PCSMs. Patients and Methods: The patients with PCSMs were enrolled and housed in a database. The pain intensity of enrolled patients was gauged by Visual Analog Scale (VAS), ranging from 0 (none) to 10 (extreme). After preprocedural imaging assessment, combined PKP/PPP via PTPA was performed under the guidance of CT and fluoroscopic monitoring. Postprocedural VAS scores, complications, cement dosage, and hospitalization were recorded in the database for analysis. All cases were followed up for 6 months. Results: Adult enrollees (7 women, 4 men) with PCSMs successfully underwent PKP/PPP via PTPA between February 2019 and January 2020, injected with 3.7±0.7 mL (range, 2.5-4.8 mL) of cement on average. Other than a single instance of asymptomatic cement leakage into paravertebral soft tissues, no complications ensued. Significant analgesic effects observed 24 hours after procedures were sustained for up to 6 months in follow-up surveys. Postprocedural hospitalizations were as brief as 2.2±0.8 days. Conclusion: Combined PKP/PPP via PTPA is safe and effective as treatment of PCSMs, enabling quick pain relief and patient recovery.

13.
Nat Commun ; 12(1): 3759, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34145298

RESUMO

Pol µ is capable of performing gap-filling repair synthesis in the nonhomologous end joining (NHEJ) pathway. Together with DNA ligase, misincorporation of dGTP opposite the templating T by Pol µ results in a promutagenic T:G mispair, leading to genomic instability. Here, crystal structures and kinetics of Pol µ substituting dGTP for dATP on gapped DNA substrates containing templating T were determined and compared. Pol µ is highly mutagenic on a 2-nt gapped DNA substrate, with T:dGTP base pairing at the 3' end of the gap. Two residues (Lys438 and Gln441) interact with T:dGTP and fine tune the active site microenvironments. The in-crystal misincorporation reaction of Pol µ revealed an unexpected second dGTP in the active site, suggesting its potential mutagenic role among human X family polymerases in NHEJ.


Assuntos
Pareamento Incorreto de Bases/genética , Dano ao DNA/genética , Reparo do DNA por Junção de Extremidades/genética , DNA Polimerase Dirigida por DNA/metabolismo , Instabilidade Genômica/genética , Pareamento de Bases/genética , DNA/química , DNA Ligases/metabolismo , DNA Polimerase Dirigida por DNA/genética , Guanosina Trifosfato/química , Humanos
14.
J Int Med Res ; 49(5): 3000605211015018, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34038214

RESUMO

OBJECTIVE: To summarize the clinical features of secondary hyperparathyroidism (SHPT) in patients with chronic renal failure and to explore the predictive factors of postoperative hypocalcemia after total parathyroidectomy in these patients. METHODS: The clinical data of 87 patients admitted to Guangdong Electric Power Hospital from May 2013 to February 2020 were reviewed. All patients underwent total parathyroid resection and sternocleidomastoid microtransplantation. Age, sex, and the serum calcium, phosphorus, alkaline phosphatase (ALP), and intact parathyroid hormone (iPTH) concentrations were analyzed as predictive factors of postoperative hypocalcemia. RESULTS: Bone pain was the most common clinical manifestation in this study population, and all 87 patients experienced relief from their clinical symptoms after the surgical procedure. Age and the preoperative serum calcium, ALP, and iPTH concentrations were determined to be early predictive factors of postoperative hypocalcemia. CONCLUSIONS: Age and the preoperative calcium, ALP, and iPTH concentrations are independent risk factors for postoperative hypocalcemia in patients with SHPT and renal disease who undergo total parathyroidectomy with sternocleidomastoid microtransplantation. These factors can help identify high-risk patients who can be managed by a multidisciplinary team to improve graft survival and quality of life.


Assuntos
Hiperparatireoidismo Secundário , Hipocalcemia , Cálcio , Humanos , Hiperparatireoidismo Secundário/etiologia , Hiperparatireoidismo Secundário/cirurgia , Hipocalcemia/diagnóstico , Hipocalcemia/etiologia , Hormônio Paratireóideo , Paratireoidectomia , Qualidade de Vida , Estudos Retrospectivos
16.
Front Oncol ; 11: 665832, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33937078

RESUMO

Medroxyprogesterone acetate (MPA) is the main conservative treatment for endometrial cancer (EC) patients desirable to preserve fertility and those who cannot suffer from surgery. Considering the high incidence of progestin resistance and recurrence of MPA treatment, we reproposed antipsychotics chlorpromazine (CPZ) as a new strategy for both progestin-sensitive and -resistant endometrial cancer. Cytobiology experiments indicated that CPZ could significantly suppress proliferation, migration/invasion and induce apoptosis in Ishikawa (ISK) and KLE EC cell lines. And xenograft mouse models were constructed to validate the antitumor effect and toxicity of CPZ in-vivo. CPZ inhibited the growth at a low dose of 3mg/kg and the mice exhibited no signs of toxicity. Next, concomitant treatment and sequential treatment with CPZ and MPA were proceeded to analysis the synergistic effect in EC cells. Concomitant treatment only performed a limited synergistic effect on apoptosis in ISK and KLE cells. Nevertheless, sequential treatment showed favorable synergistic effects in progestin-resistant KLE cells. Finally, a stable MPA-resistant cell line shRNA was established to explore the mechanism of CPZ reversing progestin resistance. Immunoblot data showed that CPZ inhibited the activation of PI3K/AKT signal in ISK and KLE cells and upregulated PRB expression in progestin-resistant cells, by which CPZ overcame progestin resistance to MPA. Thus, CPZ might act as a candidate drug for conservative treatment and sequential treatment with CPZ and MPA could be a suitable therapeutic option for progestin resistant patients.

17.
J Adv Res ; 29: 191-205, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33842016

RESUMO

Introduction: Environmental stress is both a major force of natural selection and a prime factor affecting crop qualities and yields. The impact of the GRAS [gibberellic acid-insensitive (GAI), repressor of GA1-3 mutant (RGA), and scarecrow (SCR)] family on plant development and the potential to resist environmental stress needs much emphasis. Objectives: This study aims to investigate the evolution, expansion, and adaptive mechanisms of GRASs of important representative plants during polyploidization. Methods: We explored the evolutionary characteristics of GRASs in 15 representative plant species by systematic biological analysis of the genome, transcriptome, metabolite, protein complex map and phenotype. Results: The GRAS family was systematically identified from 15 representative plant species of scientific and agricultural importance. The detection of gene duplication types of GRASs in all species showed that the widespread expansion of GRASs in these species was mainly contributed by polyploidization events. Evolutionary analysis reveals that most species experience independent genome-wide duplication (WGD) events and that interspecies GRAS functions may be broadly conserved. Polyploidy-related Chenopodium quinoa GRASs (CqGRASs) and Arabidopsis thaliana GRASs (AtGRASs) formed robust networks with flavonoid pathways by crosstalk with auxin and photosynthetic pathways. Furthermore, Arabidopsis thaliana population transcriptomes and the 1000 Plants (OneKP) project confirmed that GRASs are components of flavonoid biosynthesis, which enables plants to adapt to the environment by promoting flavonoid accumulation. More importantly, the GRASs of important species that may potentially improve important agronomic traits were mapped through TAIR and RARGE-II publicly available phenotypic data. Determining protein interactions and target genes contributes to determining GRAS functions. Conclusion: The results of this study suggest that polyploidy-related GRASs in multiple species may be a target for improving plant growth, development, and environmental adaptation.


Assuntos
Giberelinas/metabolismo , Reguladores de Crescimento de Plantas/genética , Proteínas de Plantas/genética , Fatores de Transcrição/genética , Adaptação Biológica , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Chenopodium quinoa/genética , Chenopodium quinoa/crescimento & desenvolvimento , Meio Ambiente , Evolução Molecular , Flavonoides/metabolismo , Duplicação Gênica , Regulação da Expressão Gênica de Plantas , Ácidos Indolacéticos/metabolismo , Fotossíntese/genética , Desenvolvimento Vegetal/genética , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/metabolismo , Poliploidia , Seleção Genética/genética , Fatores de Transcrição/metabolismo , Transcriptoma
18.
Turk J Gastroenterol ; 32(1): 1-10, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33893761

RESUMO

Endoscopic retrograde cholangiopancreatography (ERCP) is technically demanding and carries significant risks. It is performed by gastrointestinal and surgical endoscopists. There is no consensus on the minimum number of ERCPs required during training. This study was conducted to analyze the minimum number of clinical ERCPs that a trainee needs to perform to achieve competency. PubMed, Ovid-Embase, and the Cochrane library were searched systematically for prospective and retrospective studies reporting on trainees' ERCP performance. Mete-analysis was conducted to analyze the success rate of cannulation, other basic techniques, and adverse event rate, using the random-effect model with Review Manager 5.3. Thirteen studies met the inclusion criteria, with 149 trainees performing a total of 18 794 ERCP procedures. The pooled cannulation success rate was 85.7% (95% CI: 78.1%-91.0%) at completion of training. The cannulation success rate was 76.5% (95% CI: 69.2%-82.5%) when the trainees had completed 180 ERCPs, which increased to 81.8% (95% CI: 69.8%-90.6%) after 200 ERCP procedures. Adverse events and post-ERCP pancreatitis rates were 4.7% (95% CI: 2.9%-9.1%) and 2.0% (0.9%-3.9%), respectively. Achieving a cannulation success rate of >90% was considered a quality indicator for ERCP training by most societal guidelines. However, our retrospective analysis indicated that trainees only attained a pooled cannulation success rate of only 81.8% after 200 procedures. Therefore, the minimum number of ERCPs required to achieve competency during training may need to be redefined to meet the basic requirement.

19.
Mol Genet Metab ; 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33846068

RESUMO

Classical phenylketonuria (PKU, OMIM 261600) owes to hepatic deficiency of phenylalanine hydroxylase (PAH) that enzymatically converts phenylalanine (Phe) to tyrosine (Tyr). PKU neurologic phenotypes include impaired brain development, decreased myelination, early onset mental retardation, seizures, and late-onset features (neuropsychiatric, Parkinsonism). PAH deficiency leads to systemic hyperphenylalaninemia; however, the impact of Phe varies between tissues. To characterize tissue response to hyperphenylalaninemia, metabolomics was applied to tissue from therapy noncompliant classical PKU patients (blood, liver), the Pahenu2 classical PKU mouse (blood, liver, brain) and the PAH deficient pig (blood, liver, brain, cerebrospinal fluid). In blood, liver, and CSF from both patients and animal models over-represented analytes were principally Phe, Phe catabolites, and Phe-related analytes (conjugates, Phe-containing dipeptides). In addition to Phe and Phe-related analytes, the metabolomic profile of PKU brain tissue (mouse, pig) evidenced oxidative stress responses and energy dysregulation. In Pahenu2 and PKU pig brain tissues, anti-oxidative response by glutathione and homocarnosine is apparent. Oxidative stress in Pahenu2 brain was further demonstrated by increased reactive oxygen species. In Pahenu2 and PKU pig brain, an increased NADH/NAD ratio suggests a respiratory chain dysfunction. Respirometry in PKU brain mitochondria (mouse, pig) functionally confirmed reduced respiratory chain activity. Glycolysis pathway analytes are over-represented in PKU brain tissue (mouse, pig). PKU pathologies owe to liver metabolic deficiency; yet, PKU liver tissue (mouse, pig, human) shows neither energy disruption nor anti-oxidative response. Unique aspects of metabolomic homeostasis in PKU brain tissue along with increased reactive oxygen species and respiratory chain deficit provide insight to neurologic disease mechanisms. While some elements of assumed, long standing PKU neuropathology are enforced by metabolomic data (e.g. reduced tryptophan and serotonin representation), energy dysregulation and tissue oxidative stress expand mechanisms underlying neuropathology.

20.
Metabol Open ; 10: 100090, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33889834

RESUMO

Background and aim: The incidence of hepatocellular carcinoma (HCC) decreases significantly in chronic hepatitis C (CHC) patients with sustained virologic response (SVR) after pegylated-interferon plus ribavirin (PR) or direct-acting antiviral (DAAs) therapy. We follow-up a single cohort of CHC patients to identify risk factors associated with HCC development post-SVR. Method: CHC patients with SVR in Beijing/Hong Kong were followed up at 12-24 weekly intervals with surveillance for HCC by ultrasonography and alpha-fetoprotein (AFP). Multivariate Cox proportional hazards regression analysis was used to explore factors associated with HCC occurrence. Results: Between October 2015 and May 2017, SVR was observed in 519 and 817 CHC patients after DAAs and PR therapy respectively. After a median post -SVR follow-up of 48 months, HCC developed in 54 (4.4%) SVR subjects. By adjusted Cox analysis, older age (≥55 years) [HR 2.4, 95% CI (1.3-4.3)], non-alcoholic fatty liver diseases [HR 2.4, 95%CI (1.3-4.2), higher AFP level (≥20 ng/ml) [HR 3.4, 95%CI (2.0-5.8)], higher liver stiffness measurement (≥14.6 kPa) [HR 4.2, 95%CI (2.3-7.6)], diabetes mellitus [HR 4.2, 95%CI (2.4-7.4)] at pre-treatment were associated with HCC occurrence. HCC patients in the DAAs induced SVR group had a higher prevalence of NAFLD as compared with those in the PR induced SVR group, 62% (18/29) vs 28% (7/25), p = 0.026. A nomogram formulated with the above six independent variables had a Concordance-Index of 0.835 (95% CI 0.783-0.866). Conclusion: Underlying NAFLD is associated with increased incidence of HCC in chronic HCV patients post-SVR, particularly in those treated with DAA.

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