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2.
Nanoscale ; 13(33): 14245-14253, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34477707

RESUMO

The design of multifunctional nanoplatforms is of great importance for improving hypoxia-induced therapeutic outcomes, especially for overcoming radiotherapy (RT) tolerance. Here, two-dimensional intermetallic PtBi/Pt nanoplates (PtBi NPs) were designed as a therapeutic platform to in situ generate oxygen, and thereby overcome tumor hypoxia for boosting photothermal/radiotherapy (PTT/RT). With high X-ray attenuation coefficient, PtBi NPs exhibited outstanding radiotherapy sensitization characteristics. Moreover, the high photothermal effect of PtBi NPs could promote the catalytic activity of PtBi NPs to achieve a synergistic PTT/RT effect. PEGylated PtBi NPs (PtBi-PEG) exhibited excellent biocompatibility, prolonged blood circulation time and enhanced tumor accumulation. Finally, PtBi-PEG showed excellent trimodal contrast enhancement for infrared (IR) imaging, photoacoustic (PA) imaging and X-ray imaging, facilitating imaging-guided cancer therapy. Thus, our work highlights PtBi-PEG as a novel multifunctional theranostic nanoplatform with great potential for future multimodal imaging-guided synergistic cancer therapy.


Assuntos
Neoplasias , Técnicas Fotoacústicas , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fototerapia , Nanomedicina Teranóstica , Hipóxia Tumoral
3.
Gastroenterology ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536451

RESUMO

BACKGROUND & AIMS: G protein-coupled receptor (GPR) 120 has been implicated in regulating metabolic syndromes with anti-inflammatory function. However, the role of GPR120 in intestinal inflammation is unknown. Here, we investigated whether and how GPR120 regulates CD4+T cell function to inhibit colitis development. METHODS: Dextran sodium sulfate (DSS)-induced colitis model, Citrobacter rodentium infection model, and CD4+T cell adoptive transfer model were utilized to analyze the role of GPR120 in regulating colitis development. The effect of GPR120 on CD4+T cell functions was analyzed by RNA sequencing, flow cytometry, and Seahorse metabolic assays. Mice were administered GPR120 agonist for investigating the potential of GPR120 agonist in preventing and treating colitis. RESULTS: Deficiency of GPR120 in CD4+T cells resulted in more severe colitis in mice upon DSS insult and enteric infection. Transfer of GPR120-deficient CD4+CD45RbhiT cells induced more severe colitis in Rag-/- mice with lower intestinal IL-10+CD4+T cells. Treatment with GPR120 agonist, CpdA, promoted CD4+T cell production of IL-10 by upregulating Blimp1 and enhancing glycolysis, which was regulated by mTOR. GPR120 agonist-treated wild-type but not IL-10-deficient and Blimp1-deficient Th1 cells induced less severe colitis. Furthermore, oral administration of GPR120 agonist protected mice from intestinal inflammation in both prevention and treatment schemes. Gpr120 expression was positively correlated with Il10 expression in the human colonic mucosa, including patients with inflammatory bowel diseases (IBD). CONCLUSIONS: Our findings demonstrate the role of GPR120 in regulating intestinal CD4+T cell production of IL-10 to inhibit colitis development, which identifies GPR120 as a potential therapeutic target for treating IBD.

4.
Gen Thorac Cardiovasc Surg ; 69(11): 1515-1518, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34515949

RESUMO

Uni-portal video-assisted thoracoscopic approach is currently a popular surgical technique in general thoracic surgery. After operation, a chest tube is usually placed through the incision to drain the effusion and gas from the thoracic cavity. In the conventional method, the retaining stitches should be taken out ten days after removing chest drain. To get better would-healing and avoid unsightly scar, we explored a method of anchoring chest drain and two-layer suture for Uni-portal incision without removing stitches post operation.


Assuntos
Tubos Torácicos , Cirurgia Torácica Vídeoassistida , Humanos , Técnicas de Sutura
5.
Methods Enzymol ; 658: 83-109, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34517961

RESUMO

Unicellular parasite Trypanosoma brucei maintains an elaborate mitochondrial mRNA processing pathway including 3'-5' exonucleolytic trimming of primary precursors, 5' and 3' modifications, and, in most cases, massive U-insertion/deletion editing. Whereas the role of editing in restoring protein coding sequence is apparent, recent developments suggest that terminal modifications are equally critical for generating a stable translationally competent messenger. The enzymatic activities responsible for 5' pyrophosphate hydrolysis, 3' adenylation and uridylation, and 3'-5' decay are positively and negatively regulated by pentatricopeptide repeat-containing (PPR) proteins. These sequence-specific RNA binding factors typically contain arrays of 35-amino acid repeats each of which recognizes a single nucleotide. Here, we introduce a combinatorial CTS affinity tag, which underlies a suite of methods for PPR proteins purification, in vivo RNA binding sites mapping and sub-cellular localization studies. These approaches should be applicable to most trypanosomal RNA binding proteins.


Assuntos
Trypanosoma brucei brucei , Mitocôndrias/genética , Mitocôndrias/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Edição de RNA , RNA Mitocondrial/genética , RNA Mitocondrial/metabolismo , RNA de Protozoário/genética , RNA de Protozoário/metabolismo , Trypanosoma brucei brucei/genética , Trypanosoma brucei brucei/metabolismo
6.
Mol Nutr Food Res ; : e2100433, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34558816

RESUMO

SCOPE: Intestinal commensal microbiota interactions play critical roles in the inflammatory bowel disease (IBD) development. Candida albicans (CA) can aggravate intestinal inflammation; however, whether Faecalibacterium prausnitzii (FP) can antagonize CA is unknown. METHODS AND RESULTS: CA are co-cultured with bacteria (FP and Escherichia coli (EC)), bacterial supernatant, and bacterial medium, respectively. Then, the CA hyphae-specific genes' expression and CA cells' morphology are investigated. The Nod-like receptor pyrin-containing protein 6 (NLRP6) inflammasome, inflammatory cytokines, and antimicrobial peptides (AMPs) production are evaluated in intestinal epithelial cells pre-treated with bacteria, bacterial med, and bacterial supernatant and exposed without or with CA. Both bacteria significantly prohibit CA numbers, while only FP and FP supernatant prohibit the transformation and virulence factors (extracellular phospholipase, secreted aspartyl proteinase, and hemolysin) secretion of CA in a co-culture system compared with media controls. Further, FP and FP supernatant promote the production of the NLRP6 inflammasome, interleukin (IL)-1ß, IL-18, and antibacterial peptides (ß-defensin (BD)-2 and BD-3) and inhibit in vitro and in vivo CA growth and pathogenicity, and alleviate DSS-colitis in mice, while EC do not show the similar effect. CONCLUSION: FP improve intestinal inflammation by inhibiting CA reproduction, colonization, and pathogenicity and inducing AMP secretion in the gut. This study uncovers new relationships between intestinal microbes and fungi in IBD patients.

7.
Nat Commun ; 12(1): 4852, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381028

RESUMO

Oncogenic activation of KRAS and its surrogates is essential for tumour cell proliferation and survival, as well as for the development of protumourigenic microenvironments. Here, we show that the deubiquitinase USP12 is commonly downregulated in the KrasG12D-driven mouse lung tumour and human non-small cell lung cancer owing to the activation of AKT-mTOR signalling. Downregulation of USP12 promotes lung tumour growth and fosters an immunosuppressive microenvironment with increased macrophage recruitment, hypervascularization, and reduced T cell activation. Mechanistically, USP12 downregulation creates a tumour-promoting secretome resulting from insufficient PPM1B deubiquitination that causes NF-κB hyperactivation in tumour cells. Furthermore, USP12 inhibition desensitizes mouse lung tumour cells to anti-PD-1 immunotherapy. Thus, our findings propose a critical component downstream of the oncogenic signalling pathways in the modulation of tumour-immune cell interactions and tumour response to immune checkpoint blockade therapy.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Microambiente Tumoral/imunologia , Ubiquitina Tiolesterase/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiocinas/metabolismo , Regulação para Baixo , Humanos , Tolerância Imunológica , Imunoterapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Proteína Fosfatase 2C/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Ubiquitina Tiolesterase/antagonistas & inibidores
8.
Oncogene ; 40(36): 5482-5494, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34294846

RESUMO

K-RAS mutation and molecular alterations of its surrogates function essentially in lung tumorigenesis and malignant progression. However, it remains elusive how tumor-promoting and deleterious events downstream of K-RAS signaling are coordinated in lung tumorigenesis. Here, we show that USP16, a deubiquitinase involved in various biological processes, functions as a promoter for the development of K-RAS-driven lung tumor. Usp16 deletion significantly attenuates K-rasG12D-mutation-induced lung tumorigenesis in mice. USP16 upregulation upon RAS activation averts reactive oxygen species (ROS)-induced p38 activation that would otherwise detrimentally influence the survival and proliferation of tumor cells. In addition, USP16 interacts with and deubiquitinates JAK1, and thereby promoting lung tumor growth by augmenting JAK1 signaling. Therefore, our results reveal that USP16 functions critically in the K-RAS-driven lung tumorigenesis through modulating the strength of p38 and JAK1 signaling.

9.
Chem Commun (Camb) ; 57(54): 6632-6635, 2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34124740

RESUMO

A novel oxyallyl cation promoted semipinacol rearrangement of indole-type allylic alcohols was disclosed for the stereodivergent synthesis of spiro-indolines. A variety of spiro-indolines were obtained with moderate to good yields. Three contiguous stereocenters, two of which are vicinal quaternary centers, were effectively formed with good diastereoselectivity. It is worth noting that two diastereoisomers of rearranged products can be readily achieved by easily regulating the reaction conditions. This method may provide an applicable approach for the synthesis of natural indole alkaloids.

10.
Cardiovasc Intervent Radiol ; 44(8): 1204-1213, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33825064

RESUMO

PURPOSE: To evaluate the feasibility, safety, and diagnostic performance of sequential core-needle biopsy (CNB) technique following coaxial low-power microwave thermal coagulation (MTC) for ground-glass opacity (GGO) nodules. MATERIALS AND METHODS: From December 2017 to July 2019, a total of 32 GGOs (with diameter of 12 ± 4 mm) in 31 patients received two times of CNBs, both prior to and immediately after MTC at a power of 20 watts. The frequency and type of complications associated with CNBs were examined. The pathologic diagnosis and genetic analysis were performed for specimens obtained from the two types of biopsy. RESULTS: The technical success rates of pre- and post-MTC CNBs were 94% and 100%, respectively. The complication rate was significantly lower with post-MTC CNB as compared to pre-MTC CNB (42% versus 97%, p < 0.001). Larger amount of specimens could be obtained by post-MTC CNB. The pathological diagnosis rate of post-MTC CNB was significantly higher than that of pre-MTC CNB (100% versus 75%, p = 0.008), whereas the success rates of genetic analysis were comparable between the two groups (100% versus 84%, p = 0.063). Regular ablation could be further performed after post-MTC CNB to achieve local tumor control. CONCLUSION: Sequential biopsy following coaxial low-power MTC can reduce the risk of complications and provide high-quality specimens for pulmonary GGOs. Combining this technique with standard ablation allows for simultaneous diagnosis and treatment within a single procedure.


Assuntos
Eletrocoagulação/métodos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Nódulos Pulmonares Múltiplos/patologia , Nódulos Pulmonares Múltiplos/cirurgia , Mutação/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia com Agulha de Grande Calibre/métodos , Estudos de Viabilidade , Humanos , Biópsia Guiada por Imagem/métodos , Pulmão/patologia , Pulmão/cirurgia , Neoplasias Pulmonares/genética , Masculino , Micro-Ondas , Pessoa de Meia-Idade , Nódulos Pulmonares Múltiplos/genética , Estudos Prospectivos , Radiografia Intervencionista , Estudos Retrospectivos
11.
Zhongguo Fei Ai Za Zhi ; 24(5): 305-322, 2021 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-33896152

RESUMO

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
.

12.
Cancer Res ; 81(11): 3105-3120, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33853831

RESUMO

Hedgehog signaling is aberrantly activated in hematologic malignancies and solid tumors, and targeting it is a promising therapeutic strategy against these cancers. Resistance to clinically available hedgehog-targeted Smoothened inhibitor (SMOi) drugs has become a critical issue in hedgehog-driven cancer treatment. Our previous studies identified inhibition of BET and CDK7 as two epigenetic/transcriptional-targeted therapeutic strategies for overcoming SMOi resistance, providing a promising direction for anti-hedgehog drug development. To uncover additional strategies for inhibiting aberrant hedgehog activity, here we performed CRISPR-Cas9 screening with an single-guide RNA library targeting epigenetic and transcriptional modulators in hedgehog-driven medulloblastoma cells, combined with tumor dataset analyses. Structure specific recognition protein 1 (SSRP1), a subunit of facilitates chromatin transcription (FACT) complex, was identified as a hedgehog-induced essential oncogene and therapeutic target in hedgehog-driven cancer. The FACT inhibitor CBL0137, which has entered clinical trials for cancer, effectively suppressed in vitro and in vivo growth of multiple SMOi-responsive and SMOi-resistant hedgehog-driven cancer models. Mechanistically, CBL0137 exerted anti-hedgehog activity by targeting transcription of GLI1 and GLI2, which are core transcription factors of the hedgehog pathway. SSRP1 bound the promoter regions of GLI1 and GLI2, while CBL0137 treatment substantially disrupted these interactions. Moreover, CBL0137 synergized with BET or CDK7 inhibitors to antagonize aberrant hedgehog pathway and growth of hedgehog-driven cancer models. Taken together, these results identify FACT inhibition as a promising epigenetic/transcriptional-targeted therapeutic strategy for treating hedgehog-driven cancers and overcoming SMOi resistance. SIGNIFICANCE: This study identifies FACT inhibition as an anti-hedgehog therapeutic strategy for overcoming resistance to Smoothened inhibitors and provides preclinical support for initiating clinical trials of FACT-targeted drug CBL0137 against hedgehog-driven cancers.

13.
Materials (Basel) ; 14(7)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808454

RESUMO

Photosensitive resins used in three-dimensional (3D) printing are characterized by high forming precision and fast processing speed; however, they often possess poor mechanical properties and heat resistance. In this study, we report a photocurable bismaleimide ink with excellent comprehensive performance for stereolithography (SLA) 3D printing. First, the main chain of bismaleimide with an amino group (BDM) was synthesized, and then, the glycidyl methacrylate was grafted to the amino group to obtain the bismaleimide oligomer with an unsaturated double bond. The oligomers were combined with reaction diluents and photo-initiators to form photocurable inks that can be used for SLA 3D printing. The viscosity and curing behavior of the inks were studied, and the mechanical properties and heat resistance were tested. The tensile strength of 3D-printed samples based on BDM inks could reach 72.6 MPa (166% of that of commercial inks), glass transition temperature could reach 155 °C (205% of that of commercial inks), and energy storage modulus was 3625 MPa at 35 °C (327% of that of commercial inks). The maximum values of T-5%, T-50%, and Tmax of the 3D samples printed by BDM inks reached 351.5, 449.6, and 451.9 °C, respectively. These photocured BDM inks can be used to produce complex structural components and models with excellent mechanical and thermal properties, such as car parts, building models, and pipes.

14.
FASEB J ; 35(4): e21554, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33742715

RESUMO

Lactate, one of the most common primary metabolites of bacteria and human cells, has been shown to play essential roles in the regulation of inflammatory diseases, including inflammatory bowel diseases. However, whether and how host-derived lactate affects intestinal epithelial homeostasis is still not completely understood. Here, we investigated how L-lactate, mainly produced by host cells, regulates intestinal epithelial cell (IEC) migration to promote intestinal wound healing. Using video microscopy and tracking individual cells, we found that L-lactate enhanced IEC migration in direction persistence and speed. Mechanistically, L-lactate promoted IEC mitochondrial ATP production. The mitochondrial ATP synthase inhibitor, oligomycin, significantly decreased IEC persistence and speed, which inhibited cell migration induced by L-lactate. Furthermore, administering mice with L-lactate suppressed colitis induced by dextran sulfate sodium. In conclusion, our study demonstrates that host-derived L-lactate promotes IEC mitochondrial ATP production to drive cell migration, promoting intestinal wound healing to alleviate intestinal inflammation.


Assuntos
Movimento Celular/efeitos dos fármacos , Colite/tratamento farmacológico , Células Epiteliais/metabolismo , Lactatos/farmacologia , Animais , Colite/induzido quimicamente , Homeostase/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Lactatos/metabolismo , Camundongos Endogâmicos C57BL
15.
J Urban Health ; 98(3): 328-343, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33665783

RESUMO

The incidence of lung cancer is affected by air pollution, especially in high-density urban areas with heavy road traffic and dense urban form. Several studies have examined the direct relationship between lung cancer incidence and road traffic as well as urban form. However, the results are still inconsistent for high-density urban areas. This study focused on urban form and road traffic, aiming at revealing their relationship with lung cancer incidence in high-density urban areas at the neighborhood level. For this, an ecological study was conducted in downtown Shanghai to identify important indicators and explore quantitative associations. Negative binomial regression was fitted with lung cancer incidence as the dependent variable. The independent variables included indicators for road traffic and urban form, greenness, demographic, and socio-economic factors. The results showed that building coverage, averaged block perimeter area ratio, density of metro station without the glass barrier system, and the percentage of low-quality residential land were positively correlated with lung cancer incidence in the neighborhood, while population density was negatively correlated with lung cancer incidence. This study found a strong self-selection effect of socio-economic factors in the relationship between lung cancer incidence and greenness. These results may be useful for conducting health impact assessments and developing spatial planning interventions for respiratory health in high-density urban areas.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Neoplasias Pulmonares , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , China/epidemiologia , Humanos , Incidência , Neoplasias Pulmonares/epidemiologia
16.
Pest Manag Sci ; 77(7): 3341-3348, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33773020

RESUMO

Semiochemical use is a promising way to reduce damage from pests by improving natural control in agro-ecosystems. The aphid alarm pheromone (E)-ß-farnesene (EßF) and herbivore-induced methyl salicylate (MeSA) are two volatile cues to induce changes in aphid behavior with functional significance. Because of limitations related to the volatility and oxidization of EßF and MeSA under natural conditions, slow-release and antioxidant techniques should be developed and optimized before application. Here, a slow-release alginate bead of EßF mixed with MeSA was first designed and manufactured. We hypothesized that a mixture of these two semiochemicals could be effective in controlling Sitobion miscanthi in wheat crops. Both MeSA and EßF in alginate beads were released stably and continuously for at least 15 days in the laboratory, whereas EßF in paraffin oil and pure MeSA were released for only 2 and 7 days, respectively. In 2018 field experiments, EßF and MeSA alone or in association significantly decreased the abundance of alate and apterous aphids. An increased abundance of mummified aphids enhanced by higher parasitism rates was observed when using EßF and MeSA in association, with a significant reduction of apterous abundance, more so than EßF or MeSA alone. In 2019, plots treated with a mixture of EßF and MeSA showed significantly decreased abundance of alate and apterous aphids with higher parasitism rates compared with the control. The new slow-release alginate bead containing a mixture of EßF with MeSA could be the most efficient formulation to control S. miscanthi population by attracting parasitoids in the wheat agro-ecosystem. © 2021 Society of Chemical Industry. © 2021 Society of Chemical Industry.


Assuntos
Afídeos , Animais , Ecossistema , Feromônios/farmacologia , Salicilatos , Sesquiterpenos , Triticum
17.
Nanotechnology ; 32(22): 225101, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33690190

RESUMO

The development of safe and efficient nanocomposites remains a huge challenge in targeted therapy of glioma. Nanostructured lipid carriers (NLCs), which facilitate specific site drug delivery, have been widely used in glioma treatment. Herein, we aimed to investigate the underlying mechanisms and therapeutic impact of paclitaxel (PTX) and doxorubicin (DOX) loaded NLC (PTX-DOX-NLC) on glioma stem cells (GSCs). To this end, we used a melt-emulsification technique to generate PTX loaded NLC (PTX-NLC), DOX loaded NLC (DOX-NLC), and NLC loaded with both drugs (PTX-DOX-NLC). We firstly confirmed the stability of PTX-DOX-NLC and their ability to gradually release PTX and DOX. Next, we evaluated the effects of PTX-DOX-NLC on apoptosis and proliferation of GSCs by flow cytometry and CellTiter-Glo assay. Besides, the expression of relevant mRNA and proteins was determined by RT-qPCR and Western blot analysis, respectively. Mechanism of action of PTX-DOX-NLC was determined though bioinformatic analysis based on RNA-seq data performed in GSCs derived from different NLC-treated groups. In addition, a mouse xenograft model of glioma was established to evaluate the anti-tumor effects of PTX-DOX-NLC in vivo. Results indicated thar PTX-DOX-NLC showed greater inhibitory effects on proliferation and promotive effects on apoptosis of GSCs compared with PTX-NLC, DOX-NLC, free PTX, and free DOX treatment. Mechanistic investigations evidenced that PTX-DOX-NLC inhibited tumor progression by suppressing the PI3K/AKT/mTOR signaling in vitro and in vivo. Taken together, PTX-DOX-NLC played an inhibitory role in GSC growth, highlighting a potential therapeutic option against glioma.

18.
J Dairy Sci ; 104(1): 381-390, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33272580

RESUMO

This study was conducted to examine the effect of active dry yeast (ADY) supplementation on lactation performance, ruminal fermentation patterns, and CH4 emissions and to determine an optimal ADY dose. Sixty Holstein dairy cows in early lactation (52 ± 1.2 DIM) were used in a randomized complete design. Cows were blocked by parity (2.1 ± 0.2), milk production (35 ± 4.6 kg/d), and body weight (642 ± 53 kg) and assigned to 1 of 4 treatments. Cows were fed ADY at doses of 0, 10, 20, or 30 g/d per head for 91 d, with 84 d for adaptation and 7 d for sampling. Although dry matter intake was not affected by ADY supplementation, the yield of actual milk, 4% fat-corrected milk, milk fat yield, and feed efficiency increased quadratically with increasing ADY supplementation. Yields of milk protein and lactose increased linearly with increasing ADY doses, whereas milk urea nitrogen concentration and somatic cell count decreased quadratically. Ruminal pH and ammonia concentration were not affected by ADY supplementation, whereas ruminal concentration of total volatile fatty acid increased quadratically. Digestibility of dry matter, organic matter, neutral detergent fiber, acid detergent fiber, nonfiber carbohydrate, and crude protein increased quadratically with increasing ADY supplementation. Supplementation of ADY did not affect blood concentration of total protein, triglyceride, aspartate aminotransferase, and alanine aminotransferase, whereas blood urea nitrogen, cholesterol, and nonesterified fatty acid concentrations decreased quadratically with increasing ADY supplementation. Methane production was not affected by ADY supplementation when expressed as grams per day or per kilogram of actual milk yield, dry matter intake, digested organic matter, and digested nonfiber carbohydrate, whereas a trend of linear and quadratic decrease of CH4 production was observed when expressed as grams per kilogram of fat-corrected milk and digested neutral detergent fiber. In conclusion, feeding ADY to early-lactating cows improved lactation performance by increasing nutrient digestibility. The optimal ADY dose should be 20 g/d per head.


Assuntos
Lactação/efeitos dos fármacos , Metano/biossíntese , Rúmen/metabolismo , Saccharomyces cerevisiae , Fermento Seco/farmacologia , Amônia/metabolismo , Animais , Bovinos , Dieta/veterinária , Fibras na Dieta/metabolismo , Digestão/efeitos dos fármacos , Ácidos Graxos Voláteis/metabolismo , Feminino , Fermentação , Lactose/metabolismo , Leite , Proteínas do Leite/metabolismo , Nitrogênio/metabolismo , Gravidez , Saccharomyces cerevisiae/metabolismo , Fermento Seco/administração & dosagem
19.
Cell Mol Gastroenterol Hepatol ; 11(4): 1023-1044, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33238220

RESUMO

BACKGROUND AND AIMS: Gut bacteria-derived short-chain fatty acids (SCFAs) play crucial roles in the maintenance of intestinal homeostasis. However, how SCFAs regulate epithelial turnover and tissue repair remain incompletely understood. In this study, we investigated how the SCFA propionate regulates cell migration to promote epithelial renewal and repair. METHODS: Mouse small intestinal epithelial cells (MSIE) and human Caco-2 cells were used to determine the effects of SCFAs on gene expression, proliferation, migration, and cell spreading in vitro. Video microscopy and single cell tracking were used to assess cell migration kinetically. 5-bromo-2'-deoxyuridine (BrdU) and hydroxyurea were used to assess the effects of SCFAs on migration in vivo. Lastly, an acute colitis model using dextran sulfate sodium (DSS) was used to examine the effects of SCFAs in vivo. RESULTS: Using video microscopy and single cell tracking, we found that propionate promoted intestinal epithelial cell migration by enhancing cell spreading and polarization, which led to increases in both cell speed and persistence. This novel function of propionate was dependent on inhibition of class I histone deacetylases (HDAC) and GPR43 and required signal transducer and activator of transcription 3 (STAT3). Furthermore, using 5-bromo-2'-deoxyuridine (BrdU) and hydroxyurea in vivo, we found that propionate enhanced cell migration up the crypt-villus axis under homeostatic conditions, while also protecting against ulcer formation in experimental colitis. CONCLUSION: Our results demonstrate a mechanism by which propionate stimulates cell migration in an HDAC inhibition, GPR43, and STAT3 dependent manner, and suggest that propionate plays an important role in epithelial migration independent of proliferation.

20.
Angew Chem Int Ed Engl ; 60(13): 7061-7065, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33369843

RESUMO

A challenging direct asymmetric catalytic aerobic oxidative cross-coupling of 2-naphthylamine and 2-naphthol, using a novel CuI /SPDO system, has been successfully developed for the first time. Enantioenriched 3,3'-disubstituted NOBINs were achieved and could be readily derived to divergent chiral ligands and catalysts. This reaction features high enantioselectivities (up to 96 % ee) and good yields (up to 80 %). The DFT calculations suggest that the F-H interactions between CF3 of L17 and H-1,8 of 2-naphthol, and the π-π stacking between the two coupling partners could play vital roles in the enantiocontrol of this cross-coupling reaction.

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