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1.
Acta Pharm ; 71(2): 245-266, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33151167

RESUMO

Tryptanthrin is an indole quinazoline alkaloid from the indigo-bearing plants, such as Isatis indigotica Fort. Typically, this natural compound shows a variety of pharmacological activities such as antitumor, antibacterial, anti-inflammatory and antioxidant effects. This study was conducted to assess the antitumor activity of tryptanthrin in breast cancer models both in vitro and in vivo, and to explore the important role of the inflammatory tumor microenvironment (TME) in the antitumor effects of tryptanthrin. Human breast adenocarcinoma MCF-7 cells were used to assess the antitumor effect of tryptanthrin in vitro. MTT assay and colony formation assay were carried out to monitor the antiproliferative effect of tryptanthrin (1.56~50.0 µmol L-1) on inhibiting the proliferation and colony formation of MCF-7 cells, respectively. The migration and invasion of MCF-7 cells were evaluated by wound healing assay and Transwell chamber assay, respectively. Moreover, the 4T1 murine breast cancer model was established to examine the pharmacological activity of tryptanthrin, and three groups with different doses of tryptanthrin (25, 50 and 100 mg kg-1) were set in study. Additionally, tumor volumes and organ coefficients were measured and calculated. After two weeks of tryptanthrin treatment, samples from serum, tumor tissue and different organs from tumor-bearing mice were collected, and the enzyme-linked immunosorbent assay (ELISA) was performed to assess the regulation of inflammatory molecules in mouse serum. Additionally, pathological examinations of tumor tissues and organs from mice were evaluated through hematoxylin and eosin (H&E) staining. The expression of inflammatory proteins in tumor tissues was measured by immunohistochemistry (IHC) and Western blotting. Tryptanthrin inhibited the proliferation, migration and invasion of MCF-7 cells, up-regulated the protein level of E-cadherin, and down-regulated those of MMP-2 and Snail, as suggested by the MCF-7 cell experiment. According to the results from in vivo experiment, tryptanthrin was effective in inhibiting tumor growth, and it showed favorable safety without inducing the fluctuations of body mass and organ coefficient (p > 0.05). In addition, tryptanthrin also suppressed the expression levels of NOS1, COX-2 and NF-κB in mouse tumor tissues, and regulated those of IL-2, IL-10 and TNF-α in the serum of tumor cells-transplanted mice. Tryptanthrin exerted its anti-breast cancer activities through modulating the inflammatory TME both in vitro and in vivo.

2.
APMIS ; 2020 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-33155332

RESUMO

We aimed to use serum metabolomics to discriminate infants with severe respiratory syncytial virus (RSV) bronchiolitis who later developed subsequent recurrent wheezing from those who did not, and to investigate the relationship between serum metabolome and host immune responses with regard to the subsequent development of recurrent wheezing. Fifty-one infants who were hospitalized during an initial episode of severe RSV bronchiolitis at 6 months of age or less were included and followed for up to the age of 3 years. Of them, 24 developed subsequent recurrent wheezing and 27 did not. Untargeted serum metabolomics was performed by ultraperformance liquid chromatography coupled with high-resolution mass spectrometry (UPLC-MS/MS). Cytokines were measured by multiplex immunoassay. Difference in serum metabolomic profiles was observed between infants who developed recurrent wheezing and those who did not. L-lactic acid level was significantly higher in infants with recurrent wheezing than those without. Pyrimidine metabolism, glycerophospholipid metabolism and arginine biosynthesis were identified as the most significant changed pathways between the two groups. Moreover, L-lactic acid level was positively associated with serum CXCL8 level. This exploratory study showed that differential serum metabolic signatures during severe RSV-bronchiolitis in early infancy were associated with the development of subsequent recurrent wheezing in later childhood.

3.
Sci Rep ; 10(1): 19046, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-33149201

RESUMO

Due to a poor availability of reliable biomarkers, detecting gestational diabetes mellitus (GDM) in early pregnancy remains a challenge. Novel biomarkers like Circular RNAs (circRNAs) may be a promising diagnostic tool. The aim of this study was (a) to identify circRNAs deregulated in GDM and (b) evaluate the potential of circRNAs in detecting GDM. The circRNAs expression profiling in 6 paired women (with and without GDM) was measured by microarray. The levels of five most relevant circRNAs were validated in 12 paired participants by qRT-PCR. To verify the reproducibility of qRT-PCR, significantly differential expressed circRNA levels were confirmed in 18 paired participants. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value. The areas under ROC curves of hsa_circRNA_102893 were 0.806 (95% CI 0.594-0.937) and 0.741 (0.568-0.872) in training set and test set, respectively. Circulating circRNAs reflect the presence of GDM. Hsa_circRNA_102893 may be a potential novel and stable noninvasive biomarker for detecting GDM in early pregnancy.

4.
J Nanobiotechnology ; 18(1): 161, 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33160373

RESUMO

BACKGROUND: Most cancers favor glycolytic-based glucose metabolism. Hexokinase-2 (HK2), the first glycolytic rate-limiting enzyme, shows limited expression in normal adult tissues but is overexpressed in many tumor tissues, including ovarian cancer. HK2 has been shown to be correlated with the progression and chemoresistance of ovarian cancer and could be a therapeutic target. However, the systemic toxicity of HK2 inhibitors has limited their clinical use. Since follicle-stimulating hormone (FSH) receptor (FSHR) is overexpressed in ovarian cancer but not in nonovarian healthy tissues, we designed FSHR-mediated nanocarriers for HK2 shRNA delivery to increase tumor specificity and decrease toxicity. RESULTS: HK2 shRNA was encapsulated in a polyethylene glycol-polyethylenimine copolymer modified with the FSH ß 33-53 or retro-inverso FSH ß 33-53 peptide. The nanoparticle complex with FSH peptides modification effectively depleted HK2 expression and facilitated a shift towards oxidative glucose metabolism, with evidence of increased oxygen consumption rates, decreased extracellular acidification rates, and decreased extracellular lactate and glucose consumption in A2780 ovarian cancer cells and cisplatin-resistant A2780CP counterpart cells. Consequently, cell proliferation, invasion and migration were significantly inhibited, and tumor growth was suppressed even in cisplatin-resistant ovarian cancer. No obvious systemic toxicity was observed in mice. Moreover, the nanoparticle complex modified with retro-inverso FSH peptides exhibited the strongest antitumor effects and effectively improved cisplatin sensitivity by regulating cisplatin transport proteins and increasing apoptosis through the mitochondrial pathway. CONCLUSIONS: These results established HK2 as an effective therapeutic target even for cisplatin-resistant ovarian cancer and suggested a promising targeted therapeutic approach.

5.
Ann Hepatol ; : 100290, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33221398

RESUMO

Pediatric acute liver failure (PALF) due to mushroom poisoning is a rare and life-threatening disease. There is no specific treatment. Plasma exchange (PE) is often used as a bridge to the regeneration of the liver or transplantation. However, PE is limited due to an inadequate plasma supply and transfusion-related risks. The double plasma molecular adsorption system (DPMAS) can adsorb toxins, including bilirubin and inflammatory mediators. However, the DPMAS cannot improve coagulation disorders. Combining PE and the DPMAS could compensate for the shortcomings of the two techniques. A previous study showed that the combination might be more effective than using PE or the DPMAS alone in patients with mild acute-on-chronic liver failure. To the best of our knowledge, few studies combined PE and the DPMAS for the treatment of PALF due to mushroom poisoning. Here, we specifically describe our experience with PE and the DPMAS in PALF. In conclusion, our study shows that the DPMAS and PE are safe and effective in reducing the bilirubin level and improving blood coagulation in PALF due to mushroom poisoning as a bridge to transplantation or recovery.

6.
Immunotherapy ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33225803

RESUMO

Despite the success of antiretroviral therapy in suppressing HIV to an undetectable level in the blood and improving patients' quality of life, HIV persists in antiretroviral therapy-treated patients and threatens their lives. Anti-HIV chimeric antigen receptor (CAR) T cells could offer a cure by recognizing and killing virus-producing cells in an Env-specific manner. In this review, the authors summarize several important aspects of the development of anti-HIV CAR T cells, with a special focus on the evolution of CAR design for enhanced potency and targeting specificity, and also outline the challenges that still need to be addressed to take anti-HIV CAR T cells from a hopeful approach to a real HIV cure.

7.
J Infect Dis ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33197260

RESUMO

BACKGROUND: The immune protective mechanisms during SARS-CoV-2 infection remain to be deciphered for the development of an effective intervention approach. METHODS: We examined early responses of IL-37, a powerful anti-inflammatory cytokine, in 254 SARS-CoV-2-infected patients prior to any clinical intervention and determined its correlation with clinical prognosis. RESULTS: Our results demonstrated that SARS-CoV-2 infection causes elevation of plasma IL-37. Higher early IL-37 responses correlated with earlier viral RNA negative conversion, chest CT image improvement and cough relief, consequently resulted in earlier hospital discharge. Further assays showed that higher IL-37 was associated with lower IL-6 and IL-8 and higher IFN-α and facilitated biochemical homeostasis. Low IL-37 responses predicted severe clinical prognosis in combination with IL-8 and CRP. In addition, we observed that IL-37 administration was able to attenuate lung inflammation and alleviate respiratory tissue damage in human angiotensin-converting enzyme 2 (hACE2)-transgenic mice infected with SARS-CoV-2. CONCLUSIONS: Overall, we found that IL-37 plays a protective role by antagonizing inflammatory responses while retaining type I IFN, thereby maintaining the functionalities of vital organs. IL-37, IL-8 and CRP might be formulated as a precise prediction model for screening severe clinical cases and have good value in clinical practice.

8.
BMC Ophthalmol ; 20(1): 446, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33187499

RESUMO

BACKGROUND: To report a case of malignant acanthosis nigricans with two unusual aspects, including the patient's young age and the development of filiform papillomas on the eyelid margins. CASE PRESENTATION: A 30-year-old woman presented with dry eye symptoms. Examination revealed filiform papillomas on the eyelid margins, gums, lips, hands, and axillae and excessive pigmentation localized to the neck, axillae, and groin. Biopsies of stomach, pancreatic, and thyroid lesions revealed gastric adenocarcinoma, pancreatic adenocarcinoma, and thyroid cancer, respectively. Systemic investigations showed gastric adenocarcinoma with metastatic spread. The patient was ultimately diagnosed with malignant acanthosis nigricans and died 4 months later. CONCLUSIONS: Acanthosis nigricans on the eyelid margins with a velvety overgrowth is highly suggestive of an internal malignancy, and full systemic investigations are warranted in these cases. In this patient, early signs were ignored, leading to the loss of a timely diagnosis and treatment.

9.
Glob Chang Biol ; 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33237629

RESUMO

Berenguer et al. (2020) (hereafter B2020) raised issues on the spatio-temporal details of our analysis of Amazon fires (Xu, Jia, Zhang, Riley, & Xue, 2020). We respond to their points below, most of which either misrepresent our analysis or are tangential to our paper. Further, B2020 ignored our major conclusion regarding the vulnerability of Amazon forests in the context of the large-scale coupled system.

10.
Nano Lett ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33164515

RESUMO

Here we reported a hierarchical self-assembly approach toward well-defined superlattices in supramolecular liquid crystals by fullerene-based sphere-cone block molecules. The fullerenes crystallize to form monolayer nanosheets intercalated by the attached soft hydrocarbon cones. The frustration caused by cross-sectional area mismatch between the spheres and the somewhat oversize cones leads to a unique lamellar superlattice whereby each stack of six pairs of alternating sphere-cone sublayers is followed by a cone double layer. While such areal mismatch problems in soft matter are usually solved by interface curvature, the lamellar superlattice solution is best suited to systems with rigid layers. Meanwhile, formation of the superlattice significantly improves the material's transient electron conductivity, with the maximum value being among the highest for π-conjugated organic materials. The design principle of solving steric frustration by forming a superlattice opens a new avenue toward self-assembled optoelectronic materials.

11.
Transl Oncol ; 14(1): 100935, 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33190042

RESUMO

BACKGROUND: In vitro patient tumor models such as patient-derived organoids (PDO) and conditionally reprogrammed (CR) cell culture are important for translational research and pre-clinical drug testing. In this study we present a personalized drug sensitivity test for late stage, potentially operable colorectal cancer (CRC) using patient-derived primary tumor cells isolated with i-CR technology, an optimized CR method. We explored the clinical feasibility of using i-CR platform to guide CRC chemotherapy, and established the correlation between in vitro drug sensitivity and patient clinical response. METHODS: Primary CRC tumor cells were isolated and cultured with the i-CR technology. NGS was performed and the WES and CNV results of i-CR cells were compared with that of the original patient tumor samples. In vitro drug screenings were done with guideline chemotherapy drugs for CRC. In vivo drug response was examined with paired PDX mouse models. A double-blind co-clinical cohort study was carried out and the clinical outcomes of the enrolled patients were compared with the i-CR results. RESULTS: i-CR platform could be used to rapidly propagate primary colorectal tumor cells that represent individual patient tumors effectively by keeping the clonal heterogeneity and the genetic characteristics. Chemotherapy drug screenings with i-CR cells were comparable with that of PDX models. More importantly, i-CR results showed high accordance with the clinical outcomes of the enrolled CRC patients. CONCLUSION: i-CR platform was capable to test and optimize therapeutic regimens pre-clinically, study cancer cell biology, and model tumor re-emergence to identify new targeted therapeutics from an effective personalized medicine standpoint.

12.
Signal Transduct Target Ther ; 5(1): 215, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33093457

RESUMO

Immunotherapy has limited efficacy against locally advanced pancreatic cancer (LAPC) due to the presence of an immunosuppressive microenvironment (ISM). Irreversible electroporation (IRE) can not only induce immunogenic cell death, but also alleviate immunosuppression. This study aimed to investigate the antitumor efficacy of IRE plus allogeneic γδ T cells in LAPC patients. A total of 62 patients who met the eligibility criteria were enrolled in this trial, then randomized into two groups (A: n = 30 and B: n = 32). All patients received IRE therapy and after receiving IRE, the group A patients received at least two cycles of γδ T-cell infusion as one course continuously. Group A patients had better survival than group B patients (median OS: 14.5 months vs. 11 months; median PFS: 11 months vs. 8.5 months). Moreover, the group A patients treated with multiple courses of γδ T-cell infusion had longer OS (17 months) than those who received a single course (13.5 months). IRE combined with allogeneic γδ T-cell infusion is a promising strategy to enhance the antitumor efficacy in LAPC patients, yielding extended survival benefits.ClinicalTrials.gov ID: NCT03180437.

13.
Front Immunol ; 11: 2188, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072082

RESUMO

The understanding of protective immunity during HIV infection remains elusive. Here we showed that CD160 defines a polyfunctional and proliferative CD8+ T cell subset with a protective role during chronic HIV-1 infection. CD160+ CD8+ T cells derived from HIV+ patients correlated with slow progressions both in a cross-sectional study and in a 60-month longitudinal cohort, displaying enhanced cytotoxicity and proliferative capacity in response to HIV Gag stimulation; triggering CD160 promoted their functionalities through MEK-ERK and PI3K-AKT pathways. These observations were corroborated by studying chronic lymphocytic choriomeningitis virus (LCMV) infection in mice. The genetic ablation of CD160 severely impaired LCMV-specific CD8+ T cell functionalities and thereby resulted in loss of virus control. Interestingly, transcriptional profiling showed multiple costimulatory and survival pathways likely to be involved in CD160+ T cell development. Our data demonstrated that CD160 acts as a costimulatory molecule positively regulating CD8+ T cells during chronic viral infections, thus representing a potential target for immune intervention.

14.
Front Immunol ; 11: 571248, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33072113

RESUMO

As the entry sites of many pathogens such as human immunodeficiency virus (HIV), mucosal sites are defended by rapidly reacting resident memory T cells (TRM). TRMs represent a special subpopulation of memory T cells that persist long term in non-lymphoid sites without entering the circulation and provide the "sensing and alarming" role in the first-line defense against infection. The rectum and vagina are the two primary mucosal portals for HIV entry. However, compared to vaginal TRM, rectal TRM is poorly understood. Herein, we investigated the optimal vaccination strategy to induce rectal TRM. We identified an intranasal prime-intrarectal boost (pull) strategy that is effective in engaging rectal TRM alongside circulating memory T cells and demonstrated its protective efficacy in mice against infection of Listeria monocytogenes. On the contrary, the same vaccine delivered via either intranasal or intrarectal route failed to raise rectal TRM, setting it apart from vaginal TRM, which can be induced by both intranasal and intrarectal immunizations. Moreover, intramuscular prime was also effective in inducing rectal TRM in combination with intrarectal pull, highlighting the need of a primed systemic T cell response. A comparison of different pull modalities led to the identification that raising rectal TRM is mainly driven by local antigen presence. We further demonstrated the interval between prime and boost steps to be critical for the induction of rectal TRM, revealing circulating recently activated CD8+ T cells as the likely primary pullable precursor of rectal TRM. Altogether, our studies lay a new framework for harnessing rectal TRM in vaccine development.

15.
Medicine (Baltimore) ; 99(42): e22733, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080731

RESUMO

BACKGROUND: Oligoasthenotspermia is a condition in which the number and motility of sperm in the semen of fertile men are lower than the normal level. Oligoasthenotspermia not only causes damage to the reproductive system, but also causes infertility in severe cases. Compound Xuanju capsule is a kind of Chinese patent medicine. Traditional medicine believes that compound Xuanju capsule can nourish kidney Yang, benefit kidney essence, improve semen quality, and treat infertility caused by oligoasthenotspermia. Clinical practice shows that compound Xuanju capsule combined with western medicine has a good therapeutic effect on male oligoasthenotspermia, but there is no evidence of evidence-based medicine. The purpose of this study is to systematically evaluate the efficacy and safety of compound Xuanju capsule combined with western medicine in the treatment of male oligoasthenotspermia, and to improve the evidence-based basis for the clinical application of compound Xuanju capsule in the treatment of male oligoasthenotspermia. METHODS: A systematic search was performed by retrieving on English database (PubMed, Embase, Web of Science, and The Cochrane Library) and Chinese database (CNKI, Wanfang, Weipu (VIP), CBM). Besides, manually search for Google and Baidu academic of compound XuanJu capsule combined western medicine in the treatment of male oligoasthenotspermia in randomized controlled clinical research. The retrieval time limit was from the establishment of the database to July 2020. Two researchers independently extracted and evaluated the quality of the data in the included study. A meta-analysis was performed using RevMan5.3 software, no language restrictions. RESULTS: In this study, the efficacy and safety of compound Xuanju capsule combined with western medicine in the treatment of male oligoasthenotspermia were evaluated by the total effective rate, semen parameters and other indexes. CONCLUSIONS: This study will provide reliable evidence-based evidence for the clinical application of compound Xuanju capsule combined with western medicine in the treatment of male oligoasthenotspermia. ETHICS AND DISSEMINATION: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval was not required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.OSF Registration number: DOI 10.17605/OSF.IO/2PM8T.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Oligospermia/tratamento farmacológico , Cápsulas , Medicamentos de Ervas Chinesas/administração & dosagem , Humanos , Masculino , Análise do Sêmen
16.
BMC Geriatr ; 20(1): 414, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076841

RESUMO

BACKGROUND: Frailty is now seen as a significant factor in older people with diabetes, whose mortality and disability increased. This study aims to investigate the association between calf circumference (CC) with frailty in diabetic adults aged over 80 years. METHODS: A cross-sectional analysis was performed on the data of 426 diabetic adults aged over 80 years. On admission, demographic data and laboratory parameters were recorded. CC was measured on the lower right leg at the point of the maximal circumference. All participants accepted frailty assessments. Frailty was mainly defined using the Fried frailty phenotype criteria. RESULTS: The CC levels were significantly lower in the frail than the non-frail (26.7 ± 4.0 vs. 31.2 ± 4.0, P < 0.001). CC was negatively correlated with the Fried frailty phenotype index (P < 0.001). Logistic regression analysis of frailty revealed that age (Odds Ratio (OR), 1.368; 95% Confidential Interval (CI) 1.002-1.869; P = 0.049), CC (OR, 0.756; 95%CI 0.598-0.956; P = 0.019) were independent impact factors of frailty after adjusting all the potential confounders. Participants with low CC tertile had a significantly higher Fried frailty phenotype index than those with high CC tertiles. The best CC cut-off value for predicting frailty was 29.3 cm, its sensitivity was 75.0%, and the specificity was 78.6%, and areas under the curve (AUC) was 0.786 (P < 0.001). CONCLUSIONS: CC was strongly related to frailty in diabetic adults aged over 80 years, suggesting that CC may be helpful for monitoring physical frailty in older adults in clinical and research settings.

17.
Biochim Biophys Acta Mol Basis Dis ; : 165996, 2020 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-33127475

RESUMO

Cisplatin-induced acute kidney injury (CAKI) has been recognized as one of the most serious side effects of cisplatin. Pregnane X receptor (PXR) is a ligand-dependent nuclear receptor and serves as a master regulator of xenobiotic detoxification. Increasing evidence also suggests PXR has many other functions including the regulation of cell proliferation, inflammatory response, and glucose and lipid metabolism. In this study, we aimed to investigate the role of PXR in cisplatin-induced nephrotoxicity in mice. CAKI model was performed in wild-type or PXR knockout mice. Pregnenolone 16α­carbonitrile (PCN), a mouse PXR specific agonist, was used for PXR activation. The renal function, biochemical, histopathological and molecular alterations were examined in mouse blood, urine or renal tissues. Whole transcriptome analysis was performed by RNA sequencing. We found that PXR activation significantly attenuated CAKI as reflected by improved renal function, reduced renal tubular apoptosis, ameliorated oxidative and endoplasmic reticulum stress, and suppressed inflammatory gene expression. RNA sequencing analysis revealed that the renoprotective effect of PXR was associated with multiple crucial signaling pathways, especially the PI3K/AKT pathway. In vitro study further revealed that PXR protected against cisplatin-induced apoptosis of cultured proximal tubule cells in a PI3K-dependent manner. Our results demonstrate that PXR activation can preserve renal function in cisplatin-induced AKI and suggest a possibility of PXR as a novel protective target for cisplatin-induced nephrotoxicity.

18.
PLoS One ; 15(10): e0240187, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33027312

RESUMO

Lignin, a characteristic component of terrestrial plants. Rivers transport large amounts of vascular plant organic matter into the oceans where lignin can degrade over time; however, microorganisms involved in this degradation have not been identified. In this study, several bacterial strains were isolated from marine samples using the lignin-derived compound vanillic acid (4-hydroxy-3-methoxybenzoic acid) as the sole carbon and energy source. The optimum growth temperature for all isolates ranged from 30 to 35°C. All isolates grew well in a wide NaCl concentration range of 0 to over 50 g/L, with an optimum concentration of 22.8 g/L, which is the same as natural seawater. Phylogenetic analysis indicates that these strains are the members of Halomonas, Arthrobacter, Pseudoalteromonas, Marinomonas, and Thalassospira. These isolates are also able to use other lignin-derived compounds, such as 4-hydroxybenzoic acid, ferulic acid, syringic acid, and benzoic acid. Vanillic acid was detected in all culture media when isolates were grown on ferulic acid as the sole carbon source; however, no 4-hydroxy-3-methoxystyrene was detected, indicating that ferulic acid metabolism by these strains occurs via the elimination of two side chain carbons. Furthermore, the isolates exhibit 3,4-dioxygenase or 4,5-dioxygenase activity for protocatechuic acid ring-cleavage, which is consistent with the genetic sequences of related genera. This study was conducted to isolate and characterize marine bacteria of degrading lignin-derived compounds, thereby revealing the degradation of aromatic compounds in the marine environment and opening up new avenues for the development and utilization of marine biological resources.

19.
Cell Biochem Funct ; 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32876972

RESUMO

Cancer cell derived exosomes play important roles in cancer progression and modulation of the tumour microenvironment. This study aims to investigate the role of prokineticin receptor 1 (PKR1) positive exosomes on angiogenesis. In the present study, PKR1 expression in tumour samples from ovarian cancer patients were examined firstly. Then, two ovarian cancer cell lines, namely A2780 and HO-8910 cells, were used to isolate and obtain the PKR1 positive exosomes from the serum free medium. The function analysis of PKR1 positive exosomes on angiogenesis was conducted by cell proliferation and migration assay, tube formation analysis, and tumour volume assay. The results showed that PKR1 expression was down regulated in tumour samples of ovarian cancer patients compared with adjacent normal tissues. The intracellular expression of PKR1 could be detected in A2780 and HO-8910 cells. And, the isolated exosomes from the serum free medium were confirmed by transmission electron microscopic and NTA analysis, as well as the co-presence of PKR1 with exosome marker CD63. The function analysis of PKR1 positive exosomes on angiogenesis demonstrated the uptake of PKR1 positive exosomes by human umbilical vein endothelial cells through immunofluorescence staining. The angiogenesis assays in vitro indicated that PKR1 positive exosomes promoted migration and tube formation of HUVECs but not proliferation. The endogenous PKR1 was also verified to help to enhance migration and promote tube formation of vascular endothelial cells, which might involved in the phosphorylation of STAT3. Additionally, The tumour volume from exosomes treated A2780 tumour-bearing mice was significantly increased compared with the control group, accompanied with the induced PKR1 expression and phosphorylation of STAT3 level. SIGNIFICANCE OF THE STUDY: This study proved the important role of PKR1 positive exosomes released from ovarian cancer cells on promoting angiogenesis. The data indicated that PKR1 derived from ovarian cancer cells could act as an important tumour associated antigen and biomolecular factor for cellular communication in tumour microenvironment.

20.
Sci Adv ; 6(37)2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32917715

RESUMO

Hepatic steatosis is a widespread metabolic disease characterized by excessive accumulation of triglyceride (TG) in liver. So far, effective approved drugs for hepatic steatosis are still in development, and removing the unnecessary TG from the hepatocytes is an enormous challenge. Here, we explore a promising anti-hepatic steatosis strategy by boosting hepatocellular TG transport using ß-alanine-modified gadofullerene (GF-Ala) nanoparticles. We confirm that GF-Ala could reverse hepatic steatosis in oleic acid-induced hepatocytes, fructose-induced mice, and obesity-associated transgenic ob/ob mice. Observably, GF-Ala improves hepatomegaly and hepatic lipid accumulation, reduces lipid peroxidation, and repairs abnormal mitochondria. Of note, we demonstrate that GF-Ala markedly inhibits the posttranslational degradation of apolipoprotein B100 (ApoB100) and boosts hepatocellular TG transport based on their superior antioxidant property. Together, we conclude that GF-Ala could potently ameliorate hepatic TG transport and maintain hepatic metabolic homeostasis without apparent toxicity, being beneficial for treatments of hepatic steatosis and other fatty liver diseases.

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