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1.
Ecotoxicol Environ Saf ; 282: 116699, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38981389

RESUMO

Amidst the global antimicrobial resistance (AMR) crisis, antibiotic resistance has permeated even the most remote environments. To understand the dissemination and evolution of AMR in minimally impacted ecosystems, the resistome and mobilome of wetlands across the Qinghai-Tibetan Plateau and its marginal regions were scrutinized using metagenomic sequencing techniques. The composition of wetland microbiomes exhibits significant variability, with dominant phyla including Proteobacteria, Actinobacteria, Bacteroidetes, and Verrucomicrobia. Notably, a substantial abundance of Antibiotic Resistance Genes (ARGs) and Mobile Genetic Elements (MGEs) was detected, encompassing 17 ARG types, 132 ARG subtypes, and 5 types of MGEs (Insertion Sequences, Insertions Sequences, Genomic Islands, Transposons, and Integrative Conjugative Elements). No significant variance was observed in the prevalence of resistome and mobilome across different wetland types (i.e., the Yellow River, other rivers, lakes, and marshes) (R=-0.5882, P=0.607). The co-occurrence of 74 ARG subtypes and 22 MGEs was identified, underscoring the pivotal role of MGEs in shaping ARG pools within the Qinghai-Tibetan Plateau wetlands. Metagenomic binning and analysis of assembled genomes (MAGs) revealed that 93 out of 206 MAGs harbored ARGs (45.15 %). Predominantly, Burkholderiales, Pseudomonadales, and Enterobacterales were identified as the primary hosts of these ARGs, many of which represent novel species. Notably, a substantial proportion of ARG-carrying MAGs also contained MGEs, reaffirming the significance of MGEs in AMR dissemination. Furthermore, utilizing the arg_ranker framework for risk assessment unveiled severe contamination of high-risk ARGs across most plateau wetlands. Moreover, some prevalent human pathogens were identified as potential hosts for these high-risk ARGs, posing substantial transmission risks. This study aims to investigate the prevalence of resistome and mobilome in wetlands, along with evaluating the risk posed by high-risk ARGs. Such insights are crucial for informing environmental protection strategies and facilitating the management of water resources on the Qinghai-Tibetan Plateau.


Assuntos
Áreas Alagadas , Medição de Risco , Tibet , Resistência Microbiana a Medicamentos/genética , Microbiota/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , China , Bactérias/genética , Bactérias/efeitos dos fármacos , Bactérias/classificação , Metagenômica , Antibacterianos/farmacologia , Monitoramento Ambiental , Sequências Repetitivas Dispersas
2.
Biochem Biophys Res Commun ; 510(1): 156-162, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30678810

RESUMO

Locally applied radiation to the tumor is reported to stimulate systemic immune response. During radiotherapy to the abdominal cancer, spleen often receives certain dose, though as an important immune organ, little is known about the impact of splenic irradiation (SI) on systemic immune and local tumor control. Through a mice model, we found that the combination of SI with tumor irradiation (TI) helped in local control. The analysis of the tumor infiltrating leucocytes demonstrated that SI plus TI brought more T cell aggregation in the tumor microenvironment (TME), which helped in tumor control. Increased T cell infiltration may be partly due to higher expression of T cell chemokine in the TME and more expression of CXCR3 on the T cells in the spleen after SI. SI produced more IL-1ß in the spleen, IL-1ß stimulated the expression of CXCR3 on the T cells, and enhanced their migration ability. Taken together, radiation to the spleen combined with TI helped in local control through promoting T cell infiltration, and may be a considerable means to enhance the immunomodulatory of radiotherapy.


Assuntos
Neoplasias/radioterapia , Baço/efeitos da radiação , Animais , Movimento Celular/imunologia , Quimiocinas/metabolismo , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Linfócitos do Interstício Tumoral/citologia , Linfócitos do Interstício Tumoral/fisiologia , Camundongos , Neoplasias/prevenção & controle , Receptores CXCR3/metabolismo , Linfócitos T/citologia , Linfócitos T/imunologia , Resultado do Tratamento , Microambiente Tumoral/imunologia
3.
Molecules ; 24(2)2019 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-30642064

RESUMO

To improve the quality and safety of brown fermented milk (BFM), the formation and alterations of potentially harmful Maillard reaction products (MRPs), including 3-deoxyglucosone (3-DG), methylglyoxal (MGO), 5-(hydroxymethyl)-2-furfural (HMF), acrylamide and flavour components were investigated during the browning, fermentation and commercial storage. MRPs were shown to be produced mainly during the browning stage. The levels of different substances varied during the fermentation and commercial storage stage. The proportion and type of carboxylic acids in the flavour components significantly increased during the fermentation stage. Browning index of milk during the browning stage was shown to be positively associated with the 3-DG (Pearson's r = 0.9632), MGO (Pearson's r = 0.9915), HMF (Pearson's r = 0.9772), and acrylamide (Pearson's r = 0.7910) levels and the total percentage of the flavour components from four different categories (Pearson's r = 0.7407). Changes in physicochemical properties of BFM during production not only contribute to predict the formation of potentially unhealthy MRPs, but also Lactobacillus species used for the fermentation should be carefully selected to improve the quality of this product.


Assuntos
Produtos Fermentados do Leite/análise , Armazenamento de Alimentos , Reação de Maillard , Leite/química , Animais , Fermentação , Aromatizantes/química
4.
Mol Cell Biochem ; 443(1-2): 37-45, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29052798

RESUMO

Bone marrow mesenchymal stem cells (BMSCs)-based therapy has emerged as a desirable modality for the treatment of tissue injury with promising therapeutic effects; however, low survival rate of transplanted cells due to harsh microenvironment with hypoxia and oxidative stress results in hampered therapeutic benefits of this therapy. Curcumin, a natural bioactive product, is a dietary component which has gained increasing attention owing to its beneficial health properties. Here, we reported the protective effects of curcumin pretreatment on BMSCs injury induced by hydrogen peroxide (H2O2), which was used as ROS source of oxidative stress in vitro. We found that curcumin pretreatment remarkably inhibited H2O2-induced cell viability reduction, LDH leakage, and cell apoptosis in BMSCs. Moreover, curcumin pretreatment prevented H2O2-induced mitochondrial dysfunction via suppressing adenosine triphosphate loss, reactive oxygen species accumulation, and membrane potential decline. In addition, curcumin pretreatment markedly reduced the phosphorylation levels of Akt and Erk1/2. Taken together, our investigations demonstrated that curcumin pretreatment conferred BMSCs the ability to survive from H2O2-induced oxidative stress, which might attribute to its prevention of mitochondrial dysfunction and deactivation of Akt and Erk1/2 signaling pathways. Thus, this study sheds more light on the pharmacological mechanisms of curcumin, and suggests that BMSCs preconditioned with curcumin might be an effective way for cell therapy in tissue repair treatment.


Assuntos
Células da Medula Óssea/metabolismo , Curcumina/farmacologia , Peróxido de Hidrogênio/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Células da Medula Óssea/citologia , Células-Tronco Mesenquimais/citologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos
5.
Int J Cancer ; 140(11): 2545-2556, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28187526

RESUMO

The gut microbiota plays an important role in maintaining intestinal homeostasis. Dysbiosis is associated with intestinal tumorigenesis. Deoxycholic acid (DCA), a secondary bile acid increased by a western diet, correlates with intestinal carcinogenesis. However, evidence relating bile acids, intestinal microbiota and tumorigenesis are limited. In our study, we investigated the effect of DCA on induction of intestinal dysbiosis and its roles in intestinal carcinogenesis. Alteration of the composition of the intestinal microbiota was induced in DCA-treated APCmin/+ mice, which was accompanied by impaired intestinal barrier, gut low grade inflammation and tumor progression. The transfer of fecal microbiota from DCA-treated mice to another group of Apcmin/+ mice increased tumor multiplicity, induced inflammation and recruited M2 phenotype tumor-associated macrophages. Importantly, the fecal microbiota transplantation activated the tumor-associated Wnt/ß-catenin signaling pathway. Moreover, microbiota depletion by a cocktail of antibiotics was sufficient to block DCA-induced intestinal carcinogenesis, further suggesting the role of dysbiosis in tumor development. Our study demonstrated that alteration of the microbial community induced by DCA promoted intestinal carcinogenesis.


Assuntos
Ácidos e Sais Biliares/efeitos adversos , Carcinogênese/induzido quimicamente , Disbiose/induzido quimicamente , Intestinos/patologia , Animais , Carcinogênese/patologia , Ácido Desoxicólico/efeitos adversos , Disbiose/microbiologia , Disbiose/patologia , Fezes/microbiologia , Inflamação/microbiologia , Inflamação/patologia , Intestinos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Microbiota/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , beta Catenina/metabolismo
6.
Appl Microbiol Biotechnol ; 101(19): 7281-7292, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28831532

RESUMO

As traditional edible fungi, Monascus spp. have been widely used as folk medicine, food colorants, and fermentation starters in East Asian countries for more than a thousand years. However, the presence of citrinin, which has nephrotoxic, hepatotoxic, and carcinogenic activities, raises suspicions about the safety of Monascus products. Citrinin biosynthesis in Monascus is known to occur via a polyketide pathway and a citrinin biosynthesis gene cluster, which include the characterized polyketide synthetase pksCT. A gene, orf6, encodes a protein that shows significant similarity to glyoxalase and is located between ctnE and orf1. This study analyzed orf6 function, and successfully obtained an orf6 disruption strain (Δorf6). Citrinin production was significantly greater (3.6-fold) in the Δorf6 strain than in the wild-type Monascus purpureus YY-1, and RT-PCR analysis further revealed increased expression of numerous genes of the citrinin biosynthesis gene cluster in Δorf6. Therefore, orf6 proved to be a major inhibitor, directly involved in citrinin biosynthesis. Moreover, pigment production in Δorf6 was reduced by approximately 30%, while the transcription levels of many genes involved in Monascus pigments (MPs) biosynthesis had increased. This dichotomy indicated that MPs and citrinin yields may be improved simultaneously; however, a portion of the pigments was consumed to protect the cells from oxidative damage in the Δorf6 strain. An Δorf6 revertant restored the citrinin and pigment yields to normal levels. This study makes a contribution to explore the citrinin biosynthesis pathway and provides some theoretical guidance to improving the safety of Monascus-related products.


Assuntos
Citrinina/biossíntese , Enzimas/metabolismo , Proteínas Fúngicas/metabolismo , Monascus/enzimologia , Clonagem Molecular , Meios de Cultura/química , Enzimas/genética , Proteínas Fúngicas/genética , Regulação Fúngica da Expressão Gênica , Monascus/genética , Família Multigênica , Metabolismo Secundário
7.
Immunology ; 148(3): 253-65, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26878424

RESUMO

Sertoli cells (SCs) possess inherent immunosuppressive properties and are major contributors to the immunoprivileged status of mammalian testis. SCs have been reported to inhibit the activation of B cells, T cells and natural killer cells but not dendritic cells (DCs). Herein, we present evidence that co-culture with SCs results in a persistent state of DC immaturity characterized by down-regulation of the surface molecules I-A/E, CD80, CD83, CD86, CCR7 and CD11c, as well as reduced production of pro-inflammatory cytokines. SC-conditioned DCs (SC-DCs) displayed low immunogenicity and enhanced immunoregulatory functions, including the inhibition of T-cell proliferation and the promotion of Foxp3(+) regulatory T-cell development. Mechanistically, the activation of p38, extracellular signal-regulated kinase 1/2, and signal transducer and activator of transcription 3 was suppressed in SC-DCs. More importantly, we demonstrate that galectin-1 secreted by SCs plays a pivotal role in the differentiation of functionally tolerogenic SC-DCs. These findings further support the role of SCs in maintaining the immunoprivileged environment of the testis and provide a novel approach to derive tolerogenic DCs, which may lead to alternative therapeutic strategies for the treatment of immunopathogenic diseases.


Assuntos
Células Dendríticas/imunologia , Galectina 1/metabolismo , Tolerância Imunológica , Células de Sertoli/imunologia , Linfócitos T Reguladores/imunologia , Animais , Diferenciação Celular , Células Cultivadas , Citocinas/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Galectina 1/imunologia , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
8.
Cell Tissue Res ; 364(2): 357-67, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26662284

RESUMO

Autologous adipose-derived stem cells (ADSCs) can protect fat grafts in cell-assisted lipotransfer (CAL). However, diabetes alters the intrinsic properties of ADSCs and impairs their function so that they lack these protective effects. We investigate whether allogeneic ADSCs from healthy donors could protect fat grafts in immunocompetent diabetic rats. Syngeniec adipose tissues and ADSCs were derived from diabetic Lewis (LEW) rats, whereas allogeneic ADSCs were from healthy brown-Norway rats. A grafted mixture containing 0.7 ml granule fat and 0.3 ml 6 × 10(6) allogeneic/syngeneic ADSCs was injected subcutaneously on the skulls of diabetic LEW rats. Fat samples were harvested to evaluate the levels of injury and vascularization as shown by perilipin A, CD34 and VEGF at 14 days. The immune response was evaluated with a lymphocytotoxicity test and the CD4/CD8 ratio in peripheral blood at 14 days. The volume retention of fat grafts was measured at 3 months. Healthy allogeneic ADSCs increased the expression levels of perilipin A, CD34 and VEGF at 14 days. The volume retention of fat grafts was improved by allogeneic ADSCs at 3 months. ADSCs were demonstrated to have low immunogenicity by the lymphocyte proliferation test and immunophenotype including MHC and co-stimulatory markers. The lymphocytotoxicity test and CD4/CD8 ratio indicated no obvious immune response elicited by allogeneic ADSCs. Thus, healthy allogeneic ADSCs can promote the survival of fat grafts in this immunocompetent diabetic rat model, with little or no obvious immune rejection.


Assuntos
Adipócitos/transplante , Tecido Adiposo/transplante , Diabetes Mellitus Experimental/patologia , Sobrevivência de Enxerto/fisiologia , Transplante de Células-Tronco , Adipócitos/citologia , Tecido Adiposo/citologia , Animais , Relação CD4-CD8 , Proliferação de Células , Células Cultivadas , Diabetes Mellitus/patologia , Masculino , Perilipina-1/metabolismo , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos Lew , Células-Tronco/citologia , Transplante Homólogo
9.
Cell Physiol Biochem ; 37(2): 666-76, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26344923

RESUMO

BACKGROUND/AIMS: Our previous study confirmed that Loureirin B (LB) can inhibit hypertrophic scar formation. However, the mechanism of LB-mediated inhibition of scar formation is still unknown. METHODS: Immunohistochemistry was used to detect expression of Col1, FN and TGF-ß1 in skin and scar tissue. Fibroblasts were stimulated with TGF-ß1 to mimic scar formation. LB or MAPK inhibitors were used to study the pathways involved in the process. Western blotting was used to evaluate the expression of p-JNK, p-ERK, p-p38, Col1 and FN. The contractile capacity of fibroblasts was evaluated using a gel contraction assay. Tissues were cultured ex vivo with LB to further investigate the participation of ERK and JNK in the LB-mediated inhibition of scar formation. RESULTS: FN and Col1 were up regulated in hypertrophic scars. LB down regulated p-ERK and p-JNK in TGF-ß1-stimulated fibroblasts, while levels of phosphorylated p38 did not change. The down regulation of p-ERK and p-JNK was associated with a reduction of Col1 and FN. Similarly, inhibition of ERK and JNK down regulated the expression of Col1 and FN in TGF-ß1-stimulated fibroblasts. LB down regulated protein levels of p-ERK and p-JNK in cultured hypertrophic scar tissue ex vivo. CONCLUSIONS: This study suggests that LB can inhibit scar formation through the ERK/JNK pathway.


Assuntos
Cicatriz Hipertrófica/tratamento farmacológico , Cicatriz Hipertrófica/metabolismo , Fibronectinas/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Resinas Vegetais/farmacologia , Adolescente , Adulto , Células Cultivadas , Colágeno Tipo I/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Técnicas de Cultura de Tecidos , Fator de Crescimento Transformador beta1/metabolismo , Adulto Jovem , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
10.
J Immunol ; 191(1): 500-8, 2013 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-23733881

RESUMO

Critical roles of IL-27 in autoimmune diseases and infections have been reported; however, the contribution of endogenous IL-27 to tumor progression remains elusive. In this study, by using IL-27p28 conditional knockout mice, we demonstrate that IL-27 is critical in protective immune response against methyl-cholanthrene-induced fibrosarcoma and transplanted B16 melanoma, and dendritic cells (DCs) are the primary source. DC-derived IL-27 is required for shaping tumor microenvironment by inducing CXCL-10 expression in myeloid-derived suppressor cells and regulating IL-12 production from DCs, which lead to the recruitment and activation of NK and NKT cells resulting in immunological control of tumors. Indeed, reconstitution of IL-27 or CXCL-10 in tumor site significantly inhibits tumor growth and restores the number and activation of NK and NKT cells. In summary, our study identifies a previous unknown critical role of DC-derived IL-27 in NK and NKT cell-dependent antitumor immunity through shaping tumor microenvironment, and sheds light on developing novel therapeutic approaches based on IL-27.


Assuntos
Células Dendríticas/imunologia , Interleucinas/fisiologia , Células Matadoras Naturais/imunologia , Ativação Linfocitária/imunologia , Melanoma Experimental/imunologia , Melanoma Experimental/prevenção & controle , Células T Matadoras Naturais/imunologia , Animais , Diferenciação Celular/imunologia , Linhagem Celular Tumoral , Células Dendríticas/metabolismo , Tolerância Imunológica , Células Matadoras Naturais/metabolismo , Melanoma Experimental/patologia , Camundongos , Camundongos Knockout , Células T Matadoras Naturais/metabolismo
11.
Mediators Inflamm ; 2015: 720457, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26576075

RESUMO

The NLRP3 inflammasome is necessary for initiating acute sterile inflammation. However, its role in the pathogenesis of burn-induced acute lung injury (ALI) is unknown. This study aimed to determine the role of the NLRP3 inflammasome and the signaling pathways involved in burn-induced ALI. We observed that the rat lungs exhibited enhanced inflammasome activity after burn, as evidenced by increased levels of NLRP3 expression and Caspase-1 activity and augmented inflammatory cytokines. Inhibition of NLRP3 inflammasome by BAY11-7082 attenuated burn-induced ALI, as demonstrated by the concomitant remission of histopathologic changes and the reduction of myeloperoxidase (MPO) activity, inflammatory cytokines in rat lung tissue, and protein concentrations in the bronchoalveolar lavage fluid (BALF). In the in vitro experiments, we used AMs (alveolar macrophages) challenged with burn serum to mimic the postburn microenvironment and noted that the serum significantly upregulated NLRP3 inflammasome signaling and reactive oxygen species (ROS) production. The use of ROS scavenger N-acetylcysteine (NAC) partially reversed NLRP3 inflammasome activity in cells exposed to burn serum. These results indicate that the NLRP3 inflammasome plays an essential role in burn-induced ALI and that burn-induced NLRP3 inflammasome activity is a partly ROS-dependent process. Targeting this axis may represent a promising therapeutic strategy for the treatment of burn-induced ALI.


Assuntos
Lesão Pulmonar Aguda/etiologia , Queimaduras/complicações , Proteínas de Transporte/fisiologia , Inflamassomos/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Lesão Pulmonar Aguda/prevenção & controle , Animais , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/genética , Caspase 1/genética , Caspase 1/fisiologia , Células Cultivadas , Interleucina-18/análise , Interleucina-18/fisiologia , Interleucina-1beta/análise , Interleucina-1beta/fisiologia , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR , Nitrilas/farmacologia , Ratos , Ratos Sprague-Dawley , Sulfonas/farmacologia
12.
Talanta ; 270: 125553, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38128283

RESUMO

Salmonella spp., as one of the foodborne pathogens, is a severe threat to global public health. Rapid screening of salmonella spp. in contaminated food with low infective doses is the key to preventing food poisoning. In this study, a fast visualization method for detecting Salmonella typhimurium (S. typhimurium) was developed based on photonic PCR and AuNPs lateral-flow immunochromatography strip (LFIS). In addition, quantitative detection of target bacteria could be achieved by utilizing the photothermal effect of AuNPs, and the sensitivity could be improved by amplifying the photothermal signal. On the optimized conditions, the developed photonic PCR-LFIS assay was highly sensitive, with a detection limit as low as 19 cfu mL-1 of bacteria in pure culture after laser irradiation, and highly specific, exhibiting no cross-reaction with Salmonella enteritidis, Listeria monocytogenes, Escherichia coli, and Staphylococcus aureus. Notably, S. typhimurium could be detected in pork, egg white, and milk without pre-treatment, with the recovery rates of the three samples between 81 % and 109 %. In conclusion, the photonic PCR-LFIS assay realizes sensitive, simple, and rapid detection of S. typhimurium.


Assuntos
Nanopartículas Metálicas , Salmonella typhimurium , Salmonella typhimurium/genética , Ouro , Sensibilidade e Especificidade , Microbiologia de Alimentos , Cromatografia de Afinidade , Reação em Cadeia da Polimerase
13.
Anal Methods ; 16(13): 1887-1893, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38482559

RESUMO

Microplastics can enter the human body through the food chain and can cause cardiovascular or cerebrovascular diseases; thus, it is essential to detect microplastics sensitively and accurately. Traditional methods have some drawbacks, such as a low sensitivity and complicated experimental procedures, so it is difficult to detect microplastics less than 1 µm. While surface enhanced Raman scattering technology can compensate for these shortcomings, there are fewer reports on the quantitative detection of microplastics using SERS technology. In this study, SERS and an internal standard method were utilized to detect microplastics qualitatively and quantitatively. The electric field enhancement effect of common gold, silver, and copper substrates were simulated by the finite element method, and the influence rule of structural parameters on the enhancement factor was obtained to optimize structural parameters. Subsequently, a gold nanopyramid array substrate was prepared using the colloidal sphere template method. Finally, the prepared substrate was applied to detect polystyrene microplastics with a diameter of 500 nm, and the detection of limit is 1.8 × 10-4 mg mL-1 in the quantitative range of 2-2 × 10-4 mg mL-1, and the correlation coefficient of the linear regression equation is 0.9918. The experimental results showed that this proposal has a lower detection limit and a wider quantitative range and expands ideas for the qualitative and quantitative detection of microplastics in seawater.

14.
World J Emerg Med ; 15(1): 10-15, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38188550

RESUMO

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) can temporarily control traumatic bleeding. However, its prolonged use potentially leads to ischemia-reperfusion injury (IRI). Partial REBOA (pREBOA) can alleviate ischemic burden; however, its security and effectiveness prior to operative hemorrhage control remains unknown. Hence, we aimed to estimate the efficacy of pREBOA in a swine model of liver injury using an experimental sliding-chamber ballistic gun. METHODS: Twenty Landrace pigs were randomized into control (no aortic occlusion) (n=5), intervention with complete REBOA (cREBOA) (n=5), continuous pREBOA (C-pREBOA) (n=5), and sequential pREBOA (S-pREBOA) (n=5) groups. In the cREBOA and C-pREBOA groups, the balloon was inflated for 60 min. The hemodynamic and laboratory values were compared at various observation time points. Tissue samples immediately after animal euthanasia from the myocardium, liver, kidneys, and duodenum were collected for histological assessment using hematoxylin and eosin staining. RESULTS: Compared with the control group, the survival rate of the REBOA groups was prominently improved (all P<0.05). The total volume of blood loss was markedly lower in the cREBOA group (493.14±127.31 mL) compared with other groups (P<0.01). The pH was significantly lower at 180 min in the cREBOA and S-pREBOA groups (P<0.05). At 120 min, the S-pREBOA group showed higher alanine aminotransferase (P<0.05) but lower blood urea nitrogen compared with the cREBOA group (P<0.05). CONCLUSION: In this trauma model with liver injury, a 60-minute pREBOA resulted in improved survival rate and was effective in maintaining reliable aortic pressure, despite persistent hemorrhage. Extended tolerance time for aortic occlusion in Zone I for non-compressible torso hemorrhage was feasible with both continuous partial and sequential partial measures, and the significant improvement in the severity of acidosis and distal organ injury was observed in the sequential pREBOA.

15.
Phytochemistry ; 222: 114069, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38548035

RESUMO

Seventeen piperidine alkaloids, including 15 previously undescribed 2-substituted-6-(9-phenylnonyl)-piperidine-3,4-diol alkaloids and a previously undescribed 2-substituted-6-(9-phenylnonyl)-piperidine-3-ol alkaloid, were isolated from the leaves of Alocasia macrorrhiza (L.) Schott. Their planar structures and configurations were elucidated based on HR-ESI-MS, 1D and 2D NMR, Snatzke's method, modified Mosher method, single-crystal X-ray crystallography, as well as quantum chemical calculation. It was found that ΔδH5b-H5a can be used to elucidate the relative configuration of 2,3,4,6-tetrasubstituted piperidine, by analyzing the NMR data of 2-substituted-6-(9-phenylnonyl)-piperidine-3,4-diol. Antiproliferative activity was evaluated for all of the alkaloids, and compounds 6-8 showed considerable inhibitory activity against K562 cell line, with the IC50 values of 17.24 ± 1.62, 19.31 ± 0.9 and 18.77 ± 1.09µM, respectively. Furthermore, compounds 6 and 7 exerted an antiproliferative effect by inducing apoptosis.


Assuntos
Alcaloides , Alocasia , Antineoplásicos Fitogênicos , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Piperidinas , Folhas de Planta , Folhas de Planta/química , Alcaloides/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Humanos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Piperidinas/farmacologia , Piperidinas/química , Piperidinas/isolamento & purificação , Alocasia/química , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Células K562 , Cristalografia por Raios X
16.
IEEE Open J Eng Med Biol ; 5: 485-493, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050974

RESUMO

Goal: Vascular surgical procedures are challenging and require proficient suturing skills. To develop these skills, medical training simulators with objective feedback for formative assessment are gaining popularity. As hardware advancements offer more complex, unique sensors, determining effective task performance measures becomes imperative for efficient suturing training. Methods: 97 subjects of varying clinical expertise completed four trials on a suturing skills measurement and feedback platform (SutureCoach). Instrument handling metrics were calculated from electromagnetic motion trackers affixed to the needle driver. Results: The results of the study showed that all metrics significantly differentiated between novices (no medical experience) from both experts (attending surgeons/fellows) and intermediates (residents). Rotational motion metrics were more consistent in differentiating experts and intermediates over traditionally used tooltip motion metrics. Conclusions: Our work emphasizes the importance of tool motion metrics for open suturing skills assessment and establishes groundwork to explore rotational motion for quantifying a critical facet of surgical performance.

17.
J Agric Food Chem ; 72(1): 424-436, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38126326

RESUMO

Shell ginger (Alpinia zerumbet) is a perennial ornamental plant of ginger native to East Asia, which can be used as a flavoring agent in food or beverage, as well as a traditional Chinese medicine. In this study, a total of 37 terpenoids, including 7 new compounds, zerumin D1 to zerumin D7 (2, 3, 28-30, 36, and 37), and 5 new naturally occurring compounds, zerumin D10 to zerumin D14 (9, 12, 15, 20, and 24), were isolated and identified from the rhizomes of shell ginger. Compound 3 was an unprecedented variant labdane diterpenoid featuring a unique 6/7/6/3 tetracyclic cyclic ether system in its side chain. The anti-inflammatory activities of the isolated terpenoids were assessed in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). Compound 4 significantly inhibited the production of nitric oxide with an IC50 value of 5.4 µM. Further investigation revealed that compounds 2 and 3 may inhibit the nuclear translocation of NF-κB, thus suppressing the expression of IL-6, IL-1ß, iNOS, and COX-2 to exert the anti-inflammatory effects.


Assuntos
Alpinia , Zingiber officinale , Rizoma , Terpenos/farmacologia , Anti-Inflamatórios/farmacologia , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo
18.
Oncol Rep ; 51(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38624021

RESUMO

It has been reported that PL2L60 proteins, a product of PIWIL2 gene which might be activated by an intragenic promoter, could mediate a common pathway specifically for tumorigenesis. In the present study, it was further identified by using western blot assay that the PL2L60 proteins could be degraded in cancer cells through a mechanism of selective autophagy in response to oxidative stress. The PL2L60 was downregulated in various types of cancer cells under the hypoxic condition independently of HIF­1α, resulting in apoptosis of cancer cells. Inhibition of autophagy by small interfering RNA targeting of either Beclin­1 (BECN1) or Atg5 resulted in restoration of PL2L60 expression in hypoxic cancer cell. The hypoxic degradation of PL2L60 was also blocked by the attenuation of the autophagosome membrane protein Atg8/microtubule­associated protein 1 light chain 3 (LC3) or autophagy cargo protein p62 expression. Surprisingly, Immunofluorescence analysis demonstrated that LC3 could be directly bound to PL2L60 and was required for the transport of PL2L60 from the nucleus to the cytoplasm for lysosomal flux under basal or activated autophagy in cancer cells. Moreover, flow cytometric analysis displayed that knocking down of PL2L60 mRNA but not PIWIL2 mRNA effectively inhibited cancer cell proliferation and promoted apoptosis of cancer cells. The similar results were obtained from in vivo tumorigenic experiment, in which PL2L60 downregulation in necroptosis areas was confirmed by immunohistochemistry. These results suggested that various cancer could be suppressed by promoting autophagy. The present study revealed a key role of autophagic degradation of PL2L60 in hypoxia­induced cancer cell death, which could be used as a novel therapeutic target of cancer.


Assuntos
Neoplasias , Humanos , RNA Interferente Pequeno/metabolismo , Hipóxia/metabolismo , Apoptose , Autofagia , Estresse Fisiológico , RNA Mensageiro , Proteínas Argonautas/metabolismo
19.
Sci Rep ; 13(1): 15780, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37737246

RESUMO

In this paper, an array multi-transmitter multi-mode wireless power transfer system is proposed. The system realizes the joint modulation of three transmitter coil working modes of single transmitter coil, dual transmittercoil and four transmitter coils in the wireless power transfer system through PI closed-loop control, which can realize the stable output of WPT system in three different transmitter coil work modes. It effectively compensates for the shortcomings of the single working mode of a single transmitter coil and the limited range of effective working areas, and improves the robustness of the wireless power transfer system.

20.
PeerJ ; 11: e14988, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36908810

RESUMO

Rhizosphere microorganisms play a key role in affecting plant quality and productivity through its interaction with plant root system. To figure out the bottleneck of the decline of yield and quality in the traditional Chinese medicinal herbs Glehnia littoralis they now encounter, it is important to study the dynamics of rhizosphere microbiota during the cultivation of G. littoralis. In the present study, the composition, diversity and function of rhizosphere microbes at different development stages of G. littoralis, as well as the correlation between rhizosphere microbes and environmental factors were systematically studied by high-throughput sequencing. There were significant differences between the rhizosphere microbes at early and middle-late development stages. More beneficial bacteria, such as Proteobacteria, and more symbiotic and saprophytic fungi were observed at the middle-late development stage of G. littoralis, while beneficial bacteria such as Actinobacteria and polytrophic transitional fungi were abundant at all development stages. The results of redundancy analysis show that eight environmental factors drive the changes of microflora at different development stages. pH, soil organic matter (SOM) and available phosphorus (AP) had important positive effects on the bacterial and fungal communities at the early development stage; saccharase (SC) and nitrate nitrogen (NN) showed significant positive effects on the bacterial and fungal communities at the middle and late stages; while urease (UE), available potassium (AK), and alkaline phosphatase (AKP) have different effects on bacterial and fungal communities at different development stages. Random forest analysis identified 47 bacterial markers and 22 fungal markers that could be used to distinguish G. littoralis at different development stages. Network analysis showed that the rhizosphere microbes formed a complex mutualistic symbiosis network, which is beneficial to the growth and development of G. littoralis. These results suggest that host development stage and environmental factors have profound influence on the composition, diversity, community structure and function of plant rhizosphere microorganisms. This study provides a reference for optimizing the cultivation of G. littoralis.


Assuntos
Microbiota , Plantas Medicinais , Rizosfera , Microbiologia do Solo , Bactérias , Microbiota/fisiologia
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