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1.
Aging Male ; 24(1): 72-79, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34233582

RESUMO

BACKGROUND: Inflammation is crucial in the pathogenesis of lower urinary tract symptoms (LUTS) in men. Diet modulates inflammation. Therefore, diet could be a modifiable factor in male LUTS prevention and treatment. We aimed to investigate the association between dietary inflammatory potential and male LUTS. METHODS: We used two cycles of National Health and Nutrition Examination Survey (NHANES) with self-report LUTS data. We calculated the dietary inflammatory index (DII) based on a 24 h diet recall and evaluated male LUTS. Clinical LUTS was defined as two or more coexisting symptoms. We used univariate and multivariate logistic regression models, the smooth curve fitting to analyze the relationship between clinical LUTS and the DII score. Subgroup analyses were conducted. RESULTS: We observed a positive non-linear relationship between clinical LUTS and DII. We found that when DII was higher than the inflection point 2.39, a 1-unit increase in DII was associated with 26.1% higher adjusted odds of clinical LUTS. Subgroup analyses showed that the DII score was only positively correlated with clinical LUTS risk in non-drinkers, smokers, and non-obese people (DII >2.39). CONCLUSIONS: Inflammation might be the key mechanism bridging dietary consumption to male LUTS. Excessive pro-inflammatory food intake (DII >2.39) warrants special vigilance, especially for non-drinkers, smokers, and non-obese men.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34235678

RESUMO

In order to enhance degradation of harmful organic pollutants like Rhodamine B (RhB) dye under visible-light irradiation (λ >420 nm), a silver iodide/reduced graphene oxide/bismuth molybdate (AgI/rGO/Bi2MoO6) Z-scheme heterojunction photocatalyst was synthesized by a solvothermal process combined with an in-situ precipitation technique. The AgI (15 wt.%)/rGO/Bi2MoO6 (AGBMO-15) photocatalyst with a dosage of 0.5 g/L exhibited the highest photocatalytic activity with 98.0% RhB removal under an initial concentration of 10 mg/L within 30 min. This removal rate was approximately 65.8%, 57.7%, and 72.7% higher than that for a rGO/Bi2MoO6 (GBMO) binary composite, pure AgI powder, and pristine Bi2MoO6 nanoplates, respectively. The novel photocatalyst achieved approximately three times higher photocatalytic degradation within a shorter period of visible-light irradiation than pure Bi2MoO6. Through photoluminescence analysis and trapping experiments, this outstanding performance was attributed to the efficient separation of photogenerated electron-hole pairs owing to an internal electric field at the contact interface of AgI and Bi2MoO6, which generated more superoxide radical anions (•O2-) as primary reactive species to promote RhB degradation. Meanwhile, the rGO participated in the capture of visible-light and played a role of solid electronic medium at the AgI/Bi2MoO6 interface, which realized an effective Z-scheme electron transfer path, avoided the self oxidation of photocatalyst and prolonged the carrier life. Furthermore, the AGBMO-15 photocatalyst exhibited excellent photocatalytic degradation stability, maintaining an RhB removal rate of 96.2% after four cycles of reuse. Due to its simplicity, reusability, and controllability, the proposed photocatalyst has excellent application potential for the environmental remediation of wastewater.

3.
Genome Biol ; 22(1): 208, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34256818

RESUMO

One challenge facing omics association studies is the loss of statistical power when adjusting for confounders and multiple testing. The traditional statistical procedure involves fitting a confounder-adjusted regression model for each omics feature, followed by multiple testing correction. Here we show that the traditional procedure is not optimal and present a new approach, 2dFDR, a two-dimensional false discovery rate control procedure, for powerful confounder adjustment in multiple testing. Through extensive evaluation, we demonstrate that 2dFDR is more powerful than the traditional procedure, and in the presence of strong confounding and weak signals, the power improvement could be more than 100%.

4.
Nat Commun ; 12(1): 4063, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210975

RESUMO

Identification of novel functional domains and characterization of detailed regulatory mechanisms in cancer-driving genes is critical for advanced cancer therapy. To date, CRISPR gene editing has primarily been applied to defining the role of individual genes. Recently, high-density mutagenesis via CRISPR tiling of gene-coding exons has been demonstrated to identify functional regions in genes. Furthermore, breakthroughs in combining CRISPR library screens with single-cell droplet RNA sequencing (sc-RNAseq) platforms have revealed the capacity to monitor gene expression changes upon genetic perturbations at single-cell resolution. Here, we present "sc-Tiling," which integrates a CRISPR gene-tiling screen with single-cell transcriptomic and protein structural analyses. Distinct from other reported single-cell CRISPR screens focused on observing gene function and gene-to-gene/enhancer-to-gene regulation, sc-Tiling enables the capacity to identify regulatory mechanisms within a gene-coding region that dictate gene activity and therapeutic response.

5.
Chemosphere ; 285: 131456, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34256203

RESUMO

Nowadays, the emergence of pesticides and its application in agriculture greatly improved the crop quality and food production. However, the resulted ecological problem caused by the widespread pesticide residues attracted more and more attention since the pesticides were harmful to most living organisms. Regulatory agencies such as Environmental Protection Agency (EPA) and European Chemicals Agency (ECHA) stipulated that a comprehensive pesticides risk assessment was essential and also underscored the application of computation method in evaluating pesticides. The present study aimed to use the Quantitative Structure-Activity Relationship (QSAR) method to establish models for quantitatively and qualitatively predicting the toxicity of pesticide against Skeletonema costatum. The regression model was developed using the Genetic Algorithm plus Multiple Linear Regression method and the classification model was established based on the Random Forest algorithm, respectively. Various internal and external validation metrics suggested that the obtained regression model was of good fitness (R2=0.722), robustness (QLOO2=0.653) and external predictive ability (QFn2:0.719-0.776, CCC = 0.878). The classification could correctly predict 79.4% of pesticides in the training set and 69.7% in the validation set. The relatively high sensitivity value of the classification model indicated its good performance in identifying high-toxic pesticides. It could be concluded from the selected modelling descriptors that molecular weight and polarizability impacted the toxicity the most. The atom-type E-state descriptors generally contributed negatively to the pesticide toxicity which verified the negative influence of molecular hydrophilicity. Moreover, the lipophilic, carbon-type, charge related descriptors demonstrated the important influence of lipophilicity and polarity on pesticide toxicity. The models presented in this work could be used to pre-evaluate the toxicity of pesticides within the applicability domain, thus focusing resources on the high-toxic pesticides and assessing the environmental risk of pesticides quickly and economically.

6.
J Cell Mol Med ; 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34288397

RESUMO

N6-Methyladenosine (m6A) is the most prevalent internal modification in messenger RNAs (mRNAs) of eukaryotes and plays a vital role in post-transcriptional regulation. Recent studies demonstrated that m6A is essential for the normal function of the central nervous system (CNS), and the deregulation of m6A leads to a series of CNS diseases. However, the functional consequences of m6A deficiency within the dopaminergic neurons of adult brain are elusive. To evaluate the necessity of m6A in dopaminergic neuron functions, we conditionally deleted Mettl14, one of the most important part of m6A methyltransferase complexes, in the substantia nigra (SN) region enriched with dopaminergic neurons. By using rotarod test, pole test, open-field test and elevated plus maze, we found that the deletion of Mettl14 in the SN region induces impaired motor function and locomotor activity. Further molecular analysis revealed that Mettl14 deletion significantly reduced the total level of m6A in the mRNA isolated from SN region. Tyrosine hydroxylase (TH), an essential enzyme for dopamine synthesis, was also down-regulated upon Mettl14 deletion, while the activation of microglia and astrocyte was enhanced. Moreover, the expression of three essential transcription factors in the regulation of TH including Nurr1, Pitx3 and En1, with abundant m6A-binding sites on their RNA 3'-untranslated regions (UTR), was significantly decreased upon Mettl14 deletion in SN. Our finding first confirmed the significance of m6A in maintaining normal dopaminergic function in the SN of adult mouse.

7.
Cell Death Differ ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262144

RESUMO

Colorectal cancer (CRC) is the third most diagnosed cancer and the second leading cause of cancer-related deaths. However, there are few effective therapeutic targets for CRC patients. Here, we found that CDK15 was highly expressed in human CRC and negatively correlated with patient prognosis and overall survival in tissue microarray. Knockdown of CDK15 suppressed cell proliferation and anchorage-independent growth of CRC cells and inhibited tumor growth in cell line-derived xenograft (CDX) model. Importantly, knockout of CDK15 in mice retarded AOM/DSS-induced tumorigenesis and CDK15 silencing by lentivirus significantly suppressed tumor progression in patient-derived xenograft (PDX) model. Mechanistically, CDK15 could bind PAK4 and phosphorylate PAK4 at S291 site. Phosphorylation of PAK4 at the S291 residue promoted cell proliferation and anchorage-independent growth through ß-catenin/c-Myc, MEK/ERK signaling pathway in CRC. Moreover, inhibition of PAK4 reversed the tumorigenic function of CDK15 in CRC cells and pharmacological targeting PAK4 suppressed tumor growth in PDX models. Thus, our data reveal the pivotal role of CDK15 in CRC progression and demonstrate CDK15 promotes CRC tumorigenesis by phosphorylating PAK4. Hence, the CDK15-PAK4 axis may serve as a novel therapeutic target for CRC.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34197932

RESUMO

OBJECTIVES: China banned the use of colistin as animal growth promoter in April 2017. Herein, we report the prevalence of mcr-1 in the intestine of healthy humans and risk factors associated with mcr-1 carriage after the implementation of the ban. METHODS: We recruited 719 healthy volunteers from Shenzhen City from 1 March 2018 to 31 December 2019 to investigate the prevalence of mcr-1 in human intestine, and undertook a case-control study to ascertain the risk factors associated with the mcr-1-positive population. A further comparative study was conducted to identify differences between genetic characteristics of mcr-1-positive and mcr-1-negative Escherichia coli. RESULTS: Overall, 56 (7.8%, 95% CI 5.9%-10.0%, n = 719) individual faecal samples were positive for mcr-1, and prevalence of mcr-1 among individuals in 2019 (2.4%, 95% CI 8.7%-15.0%, 7/294) was significantly lower than that in 2018 (11.5%, 95% CI 1.0%-4.8%, 49/425) (p < 0.0001). After the colistin ban, animal-derived food (pork and chicken meat) was no longer a risk factor for mcr-1 carriage in human intestine, whereas a higher intake of fish and seafood (>75 g/day) and whole grains (>150 g/day) was associated with higher and lower risk of mcr-1 carriage, respectively (OR 2.175, 95% CI 1.047-4.517; OR 0.045, 95% CI 0.004-0.567). Compared with mcr-1-negative E. coli, the mcr-1-positive E. coli had different patterns of resistance genes and genetic heterogeneity. CONCLUSIONS: Our study implicates aquatic food as beeing associated with mcr-1 carriage in the healthy population, even after the ban on colistin. Dietary modification (e.g. whole grains) may help to combat mcr-1-positive bacterial colonization of the gut.

9.
Acta Haematol ; : 1-9, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284381

RESUMO

INTRODUCTION: Autoimmune hemolytic anemia is a potentially lethal disease characterized by autoimmune hemolysis. Although human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been reported as a promising therapy, there is limited evidence regarding warm autoimmune hemolytic anemia (wAIHA) patients. This study aimed to investigate the potential therapeutic effects of hUC-MSCs via immune regulation in wAIHA patients. METHODS: Peripheral blood mononuclear cells (PBMCs) from 10 wAIHA patients and 8 healthy controls were isolated from peripheral blood and cultured for 3 days with or without the presence of hUC-MSCs; PBMCs were co-cultured with hUC-MSCs using Transwell assays. The supernatant cytokine levels were measured after culture through AimPlex Multiple Immunoassays for Flow, including IL-2, IL-4, IL-10, IFN-γ, TNF-α, and IL-17A. The percentages of regulatory T cells, regulatory B cells, and Th1/Th2 in PBMCs were also assessed before and after culturing. RESULTS: In the wAIHA group, hUC-MSCs could upregulate the Treg and Breg proportions after culturing for 3 days, and the Treg and Breg percentages increased after co-culturing with hUC-MSCs in the wAIHA group compared with PBMC cultured alone for 3 days (8.29 ± 8.59 vs. 6.82 ± 1.32, 3.82 ± 1.87 vs. 1.75 ± 1.20, respectively). Compared with the PBMC wAIHA group, the levels of TNF-α (2.13 ± 2.07 vs. 16.20 ± 21.13 pg/mL, p = 0.019) and IL-10 (10.51 ± 18.42 vs. 37.78 ± 44.20 pg/mL, p = 0.012) were significantly elevated in the PBMC + hUC-MSCs wAIHA group. CONCLUSION: The hUC-MSCs contributed to the increasing proportion of regulatory cell populations in PBMCs of wAIHA patients, thereby potentially regulating autoimmune response; thus, hUC-MSCs may be a promising approach for wAIHA treatment.

10.
Opt Lett ; 46(13): 3304-3307, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34197442

RESUMO

Depletion beams with long pulse durations (∼600ps) have recently been applied in stimulated emission depletion (STED) microscopy to reduce photobleaching and phototoxicity. Therefore, improving the resolution of pulse STED at lower depletion power for the super-resolution imaging of live biological specimens has attracted increasing interest. Herein, we present a simple method termed ratiometric photon reassignment based on the fluorescence lifetime, in which highly spatially resolved long-lifetime fluorophore components in the center are extracted, and short-lifetime fluorophore components in the periphery are discarded to improve resolution without increasing the depletion power. The experimental results demonstrate improved resolution and signal-to-noise ratio compared with traditional time-gated STED. Our proposed method requires lower budget and data processing because, in contrast to the separation of photons by lifetime tuning), lifetime measurements are not required.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34212323

RESUMO

Tetracyclines are frequently detected in water bodies due to their widespread use in aquaculture and animal husbandry. A hydroponic experiment was conducted to explore the phytotoxic effects of Vallisneria natans (Lour.) Hare exposed to various concentrations of chlortetracycline (CTC) and oxytetracycline (OTC) (0, 0.1, 1, 10, 30, 50, and 100 mg/L) for 7 days (7 D) and 14 days (14 D), respectively. The results showed that similar to OTC treatment for 7 D, the relative growth rates (RGR) and catalase (CAT) activity of V. natans, after 7 D of CTC exposure, decreased significantly at 10 mg/L and 30 mg/L, respectively. The content of soluble protein notably decreased when CTC ≥ 10 mg/L and OTC ≥ 30 mg/L. The hydrogen peroxide (H2O2) content was significantly stimulated when OTC ≥ 10 mg/L, while it hardly changed when exposed to CTC. After 14 D, the malondialdehyde (MDA) and H2O2 contents of V. natans were significantly higher than those of the control group under a high concentration of OTC (≥ 30 mg/L), but they did not change significantly under a high concentration of CTC. The activity of polyphenol oxidase (PPO), under CTC treatment after 14 D, showed first a significant increase then decreases; the maximum value (125% of the control) was noticed at 10 mg/L CTC, while it remained unchanged when exposed to OTC. The soluble protein content significantly decreased at 10 mg/L CTC and 0.1 mg/L OTC, respectively. The RGR, CAT, and peroxidase (POD) activities, similar to OTC treatment after 14 D, decreased evidently when CTC was 10 mg/L, 30 mg/L, and 0.1 mg/L, respectively. CTC and OTC harm the chlorophyll content of V. natans after 14 D, and the reductions of chlorophyll a and carotenoid were more pronounced than chlorophyll b. The results suggest that CTC and OTC both have a negative effect on the growth of V. natans, and OTC can cause oxidative damage in V. natans but CTC harms the metabolism process without inducing oxidative damage. Overall, the toxicity of OTC to V. natans is stronger than that of CTC.

12.
Cancer Res ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215622

RESUMO

The somatic landscape of the cancer genome results from different mutational processes represented by distinct "mutational signatures". Although several mutagenic mechanisms are known to cause specific mutational signatures in cell lines, the variation of somatic mutational activities in patients, which is mostly attributed to somatic selection, is still poorly explained. Here we introduce a quantitative trait, mutational propensity (MP), and describe an integrated method to infer genetic determinants of variations in the mutational processes in 3,566 cancers with specific underlying mechanisms. As a result, we report 2,314 candidate determinants with both significant germline and somatic effects on somatic selection of mutational processes, of which 485 act via cancer gene expression and 1,427 act through the tumor immune microenvironment. These data demonstrate that the genetic determinants of MPs provide complementary information to known cancer driver genes, clonal evolution, and clinical biomarkers.

13.
MAbs ; 13(1): 1930636, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34097570

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hACE2) via its spike 1 protein during infection. After the virus sequence was published, we identified two potent antibodies against the SARS-CoV-2 receptor binding domain (RBD) from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a Phase 1 clinical trial (ChiCTR2100042150), showed broad-spectrum in vitro blocking activity against hACE2 binding to the RBD of multiple SARS-CoV-2 variants, including B.1.351 that was reportedly much more resistant to neutralization by convalescent plasma, vaccine sera and some clinical-stage neutralizing antibodies. Furthermore, JMB2002 has demonstrated complete prophylactic and potent therapeutic efficacy in a rhesus macaque disease model. Prophylactic and therapeutic countermeasure intervention of SARS-CoV-2 using JMB2002 would likely slow down the transmission of currently emerged SARS-CoV-2 variants and result in more efficient control of the COVID-19 pandemic.


Assuntos
Enzima de Conversão de Angiotensina 2/antagonistas & inibidores , Anticorpos Neutralizantes/farmacologia , Antivirais/farmacologia , COVID-19/tratamento farmacológico , COVID-19/prevenção & controle , SARS-CoV-2/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/imunologia , Animais , Especificidade de Anticorpos , Sítios de Ligação de Anticorpos , Células CHO , COVID-19/imunologia , COVID-19/metabolismo , COVID-19/virologia , Chlorocebus aethiops , Cricetulus , Modelos Animais de Doenças , Epitopos , Macaca mulatta , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Células Vero
14.
Nat Commun ; 12(1): 3708, 2021 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-34140506

RESUMO

3D genome alternations can dysregulate gene expression by rewiring enhancer-promoter interactions and lead to diseases. We report integrated analyses of 3D genome alterations and differential gene expressions in 18 newly diagnosed T-lineage acute lymphoblastic leukemia (T-ALL) patients and 4 healthy controls. 3D genome organizations at the levels of compartment, topologically associated domains and loop could hierarchically classify different subtypes of T-ALL according to T cell differentiation trajectory, similar to gene expressions-based classification. Thirty-four previously unrecognized translocations and 44 translocation-mediated neo-loops are mapped by Hi-C analysis. We find that neo-loops formed in the non-coding region of the genome could potentially regulate ectopic expressions of TLX3, TAL2 and HOXA transcription factors via enhancer hijacking. Importantly, both translocation-mediated neo-loops and NUP98-related fusions are associated with HOXA13 ectopic expressions. Patients with HOXA11-A13 expressions, but not other genes in the HOXA cluster, have immature immunophenotype and poor outcomes. Here, we highlight the potentially important roles of 3D genome alterations in the etiology and prognosis of T-ALL.


Assuntos
Cromossomos/metabolismo , Proteínas de Homeodomínio/genética , Leucemia-Linfoma de Células T do Adulto/genética , Conformação Molecular , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Linfócitos T/metabolismo , Translocação Genética , Acetilação , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem Celular Tumoral , Linhagem da Célula , Criança , Sequenciamento de Cromatina por Imunoprecipitação , Cromossomos/genética , Progressão da Doença , Elementos Facilitadores Genéticos , Perfilação da Expressão Gênica , Regulação Leucêmica da Expressão Gênica/genética , Regulação Leucêmica da Expressão Gênica/imunologia , Ontologia Genética , Hematopoese/genética , Histonas/metabolismo , Proteínas de Homeodomínio/metabolismo , Humanos , Imunofenotipagem , Leucemia-Linfoma de Células T do Adulto/metabolismo , Leucemia-Linfoma de Células T do Adulto/mortalidade , Leucemia-Linfoma de Células T do Adulto/patologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Prognóstico , Linfócitos T/patologia , Adulto Jovem
15.
JAMA Dermatol ; 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34160552
16.
Front Public Health ; 9: 689870, 2021.
Artigo em Inglês | MEDLINE | ID: covidwho-1282426

RESUMO

China is an emerging country, and government intervention is always considered as an important part of the solutions when people facing challenges in China. Under the impact of the coronavirus disease 2019 (COVID-19) epidemic and the global economic downturn, the Chinese government quickly brought the epidemic under control and restored the positive economic growth through strong intervention. Based on the panel data of provincial level in China and the government intervention as the threshold variable, this paper empirically analyzed the non-linear effect of business cycle on population health by using the panel threshold regression model. The empirical results show that the impact of the business cycle on population health is significantly negative, and government intervention has a single threshold effect on the relationship between business cycle and population health. When the government intervention is below the threshold value, the business cycle has a significant negative effect on the improvement of the population health level; when the level of government intervention exceeds the threshold value, the relationship between business cycle and population health becomes significantly positive. To some extent, the conclusions of this paper can guide the formulation and revision of government health policy and help to adjust the direction and intensity of government intervention. The Chinese government and other governments of emerging countries should do more to harness the power of state intervention in their response to the business cycle.


Assuntos
COVID-19 , Saúde da População , China/epidemiologia , Governo , Humanos , SARS-CoV-2
17.
MAbs ; 13(1): 1930636, 2021.
Artigo em Inglês | MEDLINE | ID: covidwho-1258715

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease-2019 (COVID-19), interacts with the host cell receptor angiotensin-converting enzyme 2 (hACE2) via its spike 1 protein during infection. After the virus sequence was published, we identified two potent antibodies against the SARS-CoV-2 receptor binding domain (RBD) from antibody libraries using a phage-to-yeast (PtY) display platform in only 10 days. Our lead antibody JMB2002, now in a Phase 1 clinical trial (ChiCTR2100042150), showed broad-spectrum in vitro blocking activity against hACE2 binding to the RBD of multiple SARS-CoV-2 variants, including B.1.351 that was reportedly much more resistant to neutralization by convalescent plasma, vaccine sera and some clinical-stage neutralizing antibodies. Furthermore, JMB2002 has demonstrated complete prophylactic and potent therapeutic efficacy in a rhesus macaque disease model. Prophylactic and therapeutic countermeasure intervention of SARS-CoV-2 using JMB2002 would likely slow down the transmission of currently emerged SARS-CoV-2 variants and result in more efficient control of the COVID-19 pandemic.


Assuntos
Enzima de Conversão de Angiotensina 2/antagonistas & inibidores , Anticorpos Neutralizantes/farmacologia , Antivirais/farmacologia , COVID-19/tratamento farmacológico , COVID-19/prevenção & controle , SARS-CoV-2/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/imunologia , Animais , Especificidade de Anticorpos , Sítios de Ligação de Anticorpos , Células CHO , COVID-19/imunologia , COVID-19/metabolismo , COVID-19/virologia , Chlorocebus aethiops , Cricetulus , Modelos Animais de Doenças , Epitopos , Macaca mulatta , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade , Células Vero
18.
J Proteomics ; 245: 104292, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34089897

RESUMO

Wheat is one of the most widely grown and important food crops in the world, providing approximately 20% of the food energy and protein produced for human consumption. The progress of wheat breeding is seriously restricted by the narrow genetic basis of common wheat germplasms. Dasypyrum villosum, a wild grass species that is commonly used in wheat improvement, has many excellent traits such as disease resistance, drought resistance, cold resistance, strong tillering ability, and processing quality. In this study, we compared and analyzed the cultivated wheat variety Chinese Spring (CS) and D. villosum using comparative proteomics. A total of 883 different abundant proteins (DAPs) were identified. Some of these different abundant proteins are associated with defense and stress, such as the Gα subunit, zinc finger protein family, PR1, HSP family, LEA protein, and serpin family. And a total of 24 different abundant proteins are gluten proteins. There are also 24 different abundant proteins associated with starch and sucrose metabolism. These results will provide potential candidate genes and a foundation for further research on resistance and quality for wheat genetics and breeding. SIGNIFICANCE: Proteins are the direct functional molecules of living organisms. It is of great significance to study the function of plant related genes from the perspective of protein. In this study, proteomics methods based on iTRAQ were used to compare the proteomic differences between wheat varieties Chinese Spring (CS) and D. villosum. The results provide novel insight into improving the quality of wheat. It is helpful to search for potential candidate genes for improving wheat quality and elucidate the molecular mechanisms associated with these genes.

19.
Aging (Albany NY) ; 13(12): 15785-15800, 2021 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-34176789

RESUMO

Recent reports indicate that patients with hepatocholangiocarcinoma (CHOL) have a higher morbidity and mortality rate for coronavirus disease (COVID-19). Anti-CHOL/COVID-19 medicines are inexistent. Vitamin A (VA) refers to a potent nutrient with anti-cytotoxic and anti-inflammatory actions. Therefore, this study aimed to determine the potential functions and molecular mechanisms of VA as a potential treatment for patients with both CHOL and COVID-19 (CHOL/COVID-19). The transcriptome data of CHOL patients were obtained from the Cancer Genome Analysis database. Furthermore, the network pharmacology approach and bioinformatics analysis were used to identify and reveal the molecular functions, therapeutic biotargets, and signaling of VA against CHOL/COVID-19. First, clinical findings identified the medical characteristics of CHOL patients with COVID-19, such as susceptibility gene, prognosis, recurrence, and survival rate. Anti-viral and anti-inflammatory pathways, and immunopotentiation were found as potential targets of VA against CHOL/COVID-19. These findings illustrated that VA may contribute to the clinical management of CHOL/COVID-19 achieved by induction of cell repair, suppression of oxidative stress and inflammatory reaction, and amelioration of immunity. Nine vital therapeutic targets (BRD2, NOS2, GPT, MAPK1, CXCR3, ICAM1, CDK4, CAT, and TMPRSS13) of VA against CHOL/COVID-19 were identified. For the first time, the potential pharmacological biotargets, function, and mechanism of action of VA in CHOL/COVID-19 were elucidated.

20.
Aging (Albany NY) ; 13(12): 15785-15800, 2021 06 27.
Artigo em Inglês | MEDLINE | ID: covidwho-1285613

RESUMO

Recent reports indicate that patients with hepatocholangiocarcinoma (CHOL) have a higher morbidity and mortality rate for coronavirus disease (COVID-19). Anti-CHOL/COVID-19 medicines are inexistent. Vitamin A (VA) refers to a potent nutrient with anti-cytotoxic and anti-inflammatory actions. Therefore, this study aimed to determine the potential functions and molecular mechanisms of VA as a potential treatment for patients with both CHOL and COVID-19 (CHOL/COVID-19). The transcriptome data of CHOL patients were obtained from the Cancer Genome Analysis database. Furthermore, the network pharmacology approach and bioinformatics analysis were used to identify and reveal the molecular functions, therapeutic biotargets, and signaling of VA against CHOL/COVID-19. First, clinical findings identified the medical characteristics of CHOL patients with COVID-19, such as susceptibility gene, prognosis, recurrence, and survival rate. Anti-viral and anti-inflammatory pathways, and immunopotentiation were found as potential targets of VA against CHOL/COVID-19. These findings illustrated that VA may contribute to the clinical management of CHOL/COVID-19 achieved by induction of cell repair, suppression of oxidative stress and inflammatory reaction, and amelioration of immunity. Nine vital therapeutic targets (BRD2, NOS2, GPT, MAPK1, CXCR3, ICAM1, CDK4, CAT, and TMPRSS13) of VA against CHOL/COVID-19 were identified. For the first time, the potential pharmacological biotargets, function, and mechanism of action of VA in CHOL/COVID-19 were elucidated.

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