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1.
Nat Prod Res ; : 1-5, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38867712

RESUMO

Two new alkenyl phenol derivatives, namely pestalol F (1) and pestalol G (2), along with two known compounds, pestalachloride A (3) and pestalotiopsin J (4), were isolated from the culture of the fungus Pestalotiopsis clavata JSQ 12. The structures of these compounds were primarily elucidated by MS, NMR and specific rotation data analysises. These secondary metabolites of Pestalotiopsis clavata were reported for the first time. Compound 2 displayed interesting cytotoxic activity against MCF-7 cell line with the IC50 value of 29.16 µM, whereas compound 3 exhibited moderate activity towards A549 cell line with the IC50 value of 35.71 µM. The positive control 5-FU showed cytotoxic effects on MCF-7 and A549 cell lines with the respective IC50 values of 26.70 and 26.07 µM. Compounds 1 and 2 displayed mild antibacterial activities against Staphylococcus aureus with MIC values of 128 and 64 µg/mL (MIC of positive control, penicillin, was 0.016 µg/mL), respectively.

2.
Int J Biol Macromol ; 273(Pt 2): 133135, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38876231

RESUMO

Largemouth bass (Micropterus salmoides) has emerged as a significant economic fish species, with a rise in Aeromonas veronii infections in farming. However, research on adjuvants for vaccines against A. veronii in largemouth bass remains scarce. In present study, recombinant largemouth bass IL-1ß (LbIL-1ß) was expressed to explore its adjuvant effect on the A. veronii inactivated vaccine. Following vaccination with recombinant LbIL-1ß (rLbIL-1ß) and the inactivated A. veronii, higher serum SOD levels and lysozyme activities were observed in largemouth bass from inactivated A. veronii + rLbIL-1ß vaccinated group. Furthermore, it was discovered that rLbIL-1ß was able to boost the serum-specific antibody levels induced by the inactivated A. veronii. The qRT-PCR analysis revealed that rLbIL-1ß also enhanced the expression of IgM, CD4, and MHC II in largemouth bass triggered by the inactivated A. veronii. After challenged with live A. veronii, the outcomes demonstrated that the relative percentage survival (RPS) for largemouth bass resulting from the inactivated A. veronii in combination with rLbIL-1ß was 76.67 %, surpassing the RPS of 60 % in the inactivated A. veronii group. Collectively, these findings indicate that rLbIL-1ß enhances the protective effect of the A. veronii inactivated vaccine on largemouth bass, showcasing potential as an adjuvant for further development.

3.
Adv Biol (Weinh) ; : e2400084, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38880850

RESUMO

Site-directed mutagenesis for creating point mutations, sometimes, gives rise to plasmids carrying variable number tandem repeats (VNTRs) locally, which are arbitrarily regarded as polymerase chain reaction (PCR) related artifacts. Here, the alternative end-joining mechanism is reported rather than PCR artifacts accounts largely for that VNTRs formation and expansion. During generating a point mutation on GPLD1 gene, an unexpected formation of VNTRs employing the 31 bp mutagenesis primers is observed as the repeat unit in the pcDNA3.1-GPLD1 plasmid. The 31 bp VNTRs are formed in 24.75% of the resulting clones with copy number varied from 2 to 13. All repeat units are aligned with the same orientation as GPLD1 gene. 43.54% of the repeat junctions harbor nucleotide mutations while the rest don't. Their demonstrated short primers spanning the 3' part of the mutagenesis primers are essential for initial creation of the 2-copy tandem repeats (TRs) in circular plasmids. The dimerization of mutagenesis primers by the alternative end-joining in a correct orientation is required for further expansion of the 2-copy TRs. Lastly, a half-double priming strategy is established, verified the findings and offered a simple method for VNTRs creation on coding genes in circular plasmids without junction mutations.

4.
Dis Esophagus ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38881278

RESUMO

The study aimed to describe the prevalence of lymph node metastases per lymph node station for esophageal squamous cell carcinoma (ESCC) after neoadjuvant treatment. Clinicopathological variables of ESCC patients were retrieved from the prospective database of the Surgical Esophageal Cancer Patient Registry in West China Hospital, Sichuan University. A two-field lymphadenectomy was routinely performed, and an extensive three-field lymphadenectomy was performed if cervical lymph node metastasis was suspected. According to AJCC/UICC 8, lymph node stations were investigated separately. The number of patients with metastatic lymph nodes divided by those who underwent lymph node dissection at that station was used to define the percentage of patients with lymph node metastases. Data are also separately analyzed according to the pathological response of the primary tumor, neoadjuvant treatment regimens, pretreatment tumor length, and tumor location. Between January 2019 and March 2023, 623 patients who underwent neoadjuvant therapy followed by transthoracic esophagectomy were enrolled. Lymph node metastases were found in 212 patients (34.0%) and most frequently seen in lymph nodes along the right recurrent nerve (10.1%, 58/575), paracardial station (11.4%, 67/587), and lymph nodes along the left gastric artery (10.9%, 65/597). For patients with pretreatment tumor length of >4 cm and non-pathological complete response of the primary tumor, the metastatic rate of the right lower cervical paratracheal lymph nodes is 10.9% (10/92) and 10.6% (11/104), respectively. For patients with an upper thoracic tumor, metastatic lymph nodes were most frequently seen along the right recurrent nerve (14.2%, 8/56). For patients with a middle thoracic tumor, metastatic lymph nodes were most commonly seen in the right lower cervical paratracheal lymph nodes (10.3%, 8/78), paracardial lymph nodes (10.2%, 29/285), and lymph nodes along the left gastric artery (10.4%, 30/289). For patients with a lower thoracic tumor, metastatic lymph nodes were most frequently seen in the paracardial station (14.2%, 35/247) and lymph nodes along the left gastric artery (13.1%, 33/252). The study precisely determined the distribution of lymph node metastases in ESCC after neoadjuvant treatment, which may help to optimize the extent of lymphadenectomy in the surgical management of ESCC patients after neoadjuvant therapy.

5.
Front Neurosci ; 18: 1416522, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872941

RESUMO

Background: Long term hypertension seriously promotes target organ damage in the brain and heart, and has increasingly become serious public health problem worldwide. The anti-hypertensive effects of capsaicin has been reported, however, the role and mechanism of capsaicin within the brain on salt-induced hypertension have yet to be elucidated. This study aimed to verify the hypothesis that capsaicin attenuates salt-induced hypertension via the AMPK/Akt/Nrf2 pathway in hypothalamic paraventricular nucleus (PVN). Methods: Dahl salt-sensitive (Dahl S) rats were used as animal model for the present study. Rats were randomly divided into four groups based on their dietary regimen (0.3% normal salt diet and 8% high salt diet) and treatment methods (infusion of vehicle or capsaicin in the PVN). Capsaicin was chronically administered in the PVN throughout the animal experiment phase of the study that lasted 6 weeks. Results: Our results demonstrated that PVN pretreatment with capsaicin can slow down raise of the blood pressure elevation and heart rate (HR) of Dahl S hypertensive rats given high salt diet. Interestingly, the cardiac hypertrophy was significantly improved. Furthermore, PVN pretreatment with capsaicin induced decrease in the expression of mRNA expression of NADPH oxidase-2 (NOX2), inducible nitric oxide synthase (iNOS), NOX4, p-IKKß and proinflammatory cytokines and increase in number of positive cell level for Nrf2 and HO-1 in the PVN of Dahl S hypertensive rats. Additionally, the protein expressions of phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase-B (p-AKT) were decreased, phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) were increased after the PVN pretreatment with capsaicin. Conclusion: Capsaicin pretreatment attenuates salt-sensitive hypertension by alleviating AMPK/Akt/iNOS pathway in the PVN.

6.
Front Plant Sci ; 15: 1385164, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895612

RESUMO

Biotic stresses caused by bacterial and fungal pathogens damage crops; identifying treatments that enhance disease resistance provides important information for understanding plant defenses and sustainable agriculture. Salt stress affects crop yields worldwide; however, studies have focused on the toxic sodium ion, leaving the effects of the chloride ion unclear. In this study, we found that irrigation with a combination of chloride salts (MgCl2, CaCl2, and KCl) suppressed the cell death phenotype of the ceramide kinase mutant acd5. Chloride salt pre-irrigation also significantly limited the cell death caused by Pseudomonas syringae pv maculicola infection and inhibited the multiplication of this bacterial pathogen in a mechanism partially dependent on the salicylic acid pathway. Moreover, chloride salt pre-irrigation improved plant defenses against the fungal pathogen challenge, confining the lesion area caused by Botrytis cinerea infection. Furthermore, the growth of herbivorous larvae of Spodoptera exigua was retarded by feeding on chloride salt irrigated plants. Thus, our data suggest that treatment with Cl- increases broad spectrum resistance to biotic challenges.

7.
Cell Death Dis ; 15(6): 432, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898019

RESUMO

Platinum-based chemotherapy is the standard postoperative adjuvant treatment for ovarian cancer (OC). Despite the initial response to chemotherapy, 85% of advanced OC patients will have recurrent disease. Relapsed disease and platinum resistance are the major causes of death in OC patients. In this study, we compared the global regulation of alternative polyadenylation (APA) in platinum-resistant and platinum-sensitive tissues of OC patients by analyzing a set of single-cell RNA sequencing (scRNA-seq) data from public databases and found that platinum-resistant patients exhibited global 3' untranslated region (UTR) shortening due to the different usage of polyadenylation sites (PASs). The APA regulator CSTF3 was the most significantly upregulated gene in epithelial cells of platinum-resistant OC. CSTF3 knockdown increased the sensitivity of OC cells to platinum. The lncRNA NEAT1 has two isoforms, short (NEAT1_1) and long (NEAT1_2) transcript, because of the APA processing in 3'UTR. We found that CSTF3 knockdown reduced the usage of NEAT1 proximal PAS to lengthen the transcript and facilitate the expression of NEAT1_2. Downregulation of the expression of NEAT1 (NEAT1_1/_2), but not only NEAT1_2, also increased the sensitivity of OC cells to platinum. Overexpressed NEAT1_1 reversed the platinum resistance of OC cells after knocking down CSTF3 expression. Furthermore, downregulated expression of CSTF3 and NEAT1_1, rather than NEAT1_2, was positively correlated with inactivation of the PI3K/AKT/mTOR pathway in OC cells. Together, our findings revealed a novel mechanism of APA regulation in platinum-resistant OC. CSTF3 directly bound downstream of the NEAT1 proximal PAS to generate the short isoform NEAT1_1 and was conducive to platinum resistance, which provides a potential biomarker and therapeutic strategy for platinum-resistant OC patients.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias Ovarianas , Poliadenilação , RNA Longo não Codificante , Humanos , Feminino , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Linhagem Celular Tumoral , Fator de Especificidade de Clivagem e Poliadenilação/metabolismo , Fator de Especificidade de Clivagem e Poliadenilação/genética , Regulação Neoplásica da Expressão Gênica , Animais , Platina/farmacologia , Platina/uso terapêutico , Camundongos Nus , Transdução de Sinais , Camundongos
8.
Cell Signal ; 120: 111243, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38830562

RESUMO

Studies have shown that the abnormal expression of circular RNA (circRNA) is inextricably linked to hepatocellular carcinoma (HCC). Recently, hsa_circ_0000518 (circ_0000518) was discovered in many cancer progressions. However, its function in HCC is still unclear. Through GEO database analysis combined with gene expression detection of HCC related clinical samples and cell lines, we identified that circ_0000518 was abnormally overexpressed in HCC. Cell and animal model experiments jointly indicated that circ_0000518 can stimulate HCC cell proliferation, migration, invasion and suppress apoptosis. Furthermore, we also found that knocking down the circ_0000518 could inhibit the Warburg effect in HCC cells. Mechanistically, circ_0000518 was found to be primarily localized in the cytoplasm, and sponge hsa-miR-326 (miR-326) promoted integrin alpha 5 (ITGA5) expression. In addition, circ_0000518 could enhance the stability of HuR-mediated ITGA5 mRNA, thereby activating the Warburg effect. In conclusion, this study elucidated that circ_0000518 was a cancer-promoting circRNA, which could enhance ITGA5 expression through competing endogenous RNAs (ceRNA) and RNA Binding Protein (RBP) mechanisms, thus facilitating the development of HCC. It provides a meaningful diagnostic and therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular , Proliferação de Células , Neoplasias Hepáticas , MicroRNAs , RNA Circular , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , MicroRNAs/metabolismo , MicroRNAs/genética , Animais , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Efeito Warburg em Oncologia , Integrina alfa5/metabolismo , Integrina alfa5/genética , Movimento Celular , Camundongos Nus , Camundongos , Apoptose , Progressão da Doença , Camundongos Endogâmicos BALB C , Masculino , Integrinas
9.
Aging (Albany NY) ; 16(11): 9584-9598, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38836754

RESUMO

BACKGROUND: Prostate cancer is one of the most common types of cancer in the US, and it has a high mortality rate. Diabetes mellitus is also a dangerous health condition. While some studies have examined the relationship between diabetes mellitus and the risk of prostate cancer, there is still some debate on the matter. This study aims to carefully assess the relationship between prostate cancer and diabetes from both real-world and genetic-level data. METHODS: This meta-analysis was conducted following the PRISMA 2020 reporting guidelines. The study searched three databases including Medline, Embase and Cochrane. The studies about the incidence risk of prostate cancer with diabetes mellitus were included and used to evaluate the association. The odds ratio (OR), risk ratio (RR) and 95% confidence intervals (95% CI) were estimated using Random Effects models and Fixed Effects models. Mendelian randomization study using genetic variants was also conducted. RESULTS: A total of 72 articles were included in this study. The results showed that risk of prostate cancer decreased in diabetes patients. And the influence was different in different regions. This study also estimated the impact of body mass index (BMI) in the diabetes populations and found that the risk decreased in higher BMI populations. The MR analysis found that diabetes mellitus exposure reduced the risk of prostate cancer in the European population and Asia populations. Conclusions The diabetes mellitus has a protective effect on prostate cancer. And the influence of obesity in diabetes mellitus plays an important role in this effect.


Assuntos
Diabetes Mellitus , Análise da Randomização Mendeliana , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/epidemiologia , Diabetes Mellitus/genética , Diabetes Mellitus/epidemiologia , Índice de Massa Corporal , Fatores de Risco
10.
Adv Healthc Mater ; : e2401198, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38899383

RESUMO

Reactive oxygen species (ROS) scavenging of nanozymes toward acute kidney injury (AKI) is a current promising strategy, however, the glomerular filtration barrier (GFB) limits their application for treating kidney related diseases. Here, a neutrophil-mediated delivery system able to hijack neutrophil to transport nanozyme-loaded cRGD-liposomes to inflamed kidney for AKI treatment by cRGD targeting integrin αvß1 is reported. The neutrophil-mediated nanozyme delivery system was demonstrated great antioxidant and anti-apoptosis ability in HK-2 and NRK-52E cell lines. Moreover, in ischemia-reperfusion (I/R) induced AKI mice, a single dose of LM@cRGD-LPs 12 h post-ischemia significantly reduced renal function indicators, alleviated renal pathological changes and inhibited apoptosis of renal tubular cells and the expression of renal tubular injured marker, thus remarkably reducing the damage of AKI. Mechanistically, the treatment of LM@cRGD-LPs markedly inhibited the process of Nrf2 to the nucleus and reduced the expression of the downstream HO-1, achieved a 99.51% increase in renal tissue Nrf2 levels and an 86.31% decrease in HO-1 levels after LM@cRGD-LPs treatment. In short, the strategy of neutrophil-mediated nanozyme delivery system hold great promise as a potential therapy for AKI or other inflammatory diseases. This article is protected by copyright. All rights reserved.

11.
Biotechnol J ; 19(6): e2400202, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38896411

RESUMO

Daptomycin, a lipopeptide comprising an N-decanoyl fatty acyl chain and a peptide core, is used clinically as an antimicrobial agent. The start condensation domain (dptC1) is an enzyme that catalyzes the lipoinitiation step of the daptomycin synthesis. In this study, we integrated enzymology, protein engineering, and computer simulation to study the substrate selectivity of the start condensation domain (dptC1) and to screen mutants with improved activity for decanoyl loading. Through molecular docking and computer simulation, the fatty acyl substrate channel and the protein-protein interaction interface of dptC1 are analyzed. Key residues at the protein-protein interface between dptC1 and the acyl carrier were mutated, and a single-point mutant showed more than three-folds improved catalytic efficiency of the target n-decanoyl substrate in comparing with the wild type. Moreover, molecular dynamics simulations suggested that mutants with increased catalytic activity may correlated with a more "open" and contracted substrate binding channel. Our work provides a new perspective for the elucidation of lipopeptide natural products biosynthesis, and also provides new resources to enrich its diversity and optimize the production of important components.


Assuntos
Daptomicina , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Engenharia de Proteínas , Daptomicina/biossíntese , Daptomicina/química , Engenharia de Proteínas/métodos , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Especificidade por Substrato , Antibacterianos/biossíntese , Antibacterianos/química , Antibacterianos/metabolismo , Domínios Proteicos
12.
J Clin Gastroenterol ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38896424

RESUMO

OBJECTIVE: The diagnosis of RGERD in patients typically involves 24-hour esophageal pH monitoring, but due to its invasiveness and low patient compliance, new screening methods are needed. In this study, a lactulose breath test (LBT) was conducted to detect the growth of small intestine bacteria (SIBO) and explore the potential relationship between LBT and RGERD to identify a new treatment method for RGERD. METHODS: A total of 178 patients with gastroesophageal reflux were enrolled from June 2020 to December 2022 in the Gastroenterology Department, Building 3, the First Affiliated Hospital of Kunming Medical University; these patients included 96 patients with nonrefractory GERD (NRGERD) and 82 patients with RGERD. The Gerd Q score, reflux symptom index (RSI) score, gastroscopy results, clinical symptoms, and other related indicators were collected. Statistical methods were used to analyze the gathered data. RESULTS: The incidence of acid reflux and heartburn in patients with RGERD was significantly greater than that in patients with NRGERD (67.10% vs. 42.70%, P<0.01 and 65.00% vs. 34.40%, P<0.01). The CH4 values of patients with RGERD were significantly greater than those of patients with NRGERD at each time point, and there was a correlation between the CH4 values at 60 min and RGERD (P<0.05). For patients with RGERD, the incidence of abdominal pain, acid regurgitation, and heartburn was greater in the CH4-positive group than in the CH4-negative group (61.90% vs. 57.50%, 69.05% vs. 65.00%, 69.05% vs. 57.50%, P>0.05). The incidence of nausea was also greater in the CH4-positive group than in the CH4-negative group (61.90% vs. 35.00%, P<0.05). CONCLUSION: Increased CH4 levels are correlated with RGERD. In addition, patients with RGERD may develop SIBO after long-term use of PPIs, and interventions involving SIBO could provide new ideas for the treatment of RGERD.

13.
Sci Rep ; 14(1): 13430, 2024 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862696

RESUMO

Previous studies have shown that scutellarin inhibits the excessive activation of microglia, reduces neuronal apoptosis, and exerts neuroprotective effects. However, whether scutellarin regulates activated microglia-mediated neuronal apoptosis and its mechanisms remains unclear. This study aimed to investigate whether scutellarin can attenuate PC12 cell apoptosis induced by activated microglia via the JAK2/STAT3 signalling pathway. Microglia were cultured in oxygen-glucose deprivation (OGD) medium, which acted as a conditioning medium (CM) to activate PC12 cells, to investigate the expression of apoptosis and JAK2/STAT3 signalling-related proteins. We observed that PC12 cells apoptosis in CM was significantly increased, the expression and fluorescence intensity of the pro-apoptotic protein Bax and apoptosis-related protein cleaved caspase-3 were increased, and expression of the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) was decreased. Phosphorylation levels and fluorescence intensity of the JAK2/STAT3 signalling pathway-related proteins JAK2 and STAT3 decreased. After treatment with scutellarin, PC12 cells apoptosis as well as cleaved caspase-3 and Bax protein expression and fluorescence intensity decreased. The expression and fluorescence intensity of Bcl-2, phosphorylated JAK2, and STAT3 increased. AG490, a specific inhibitor of the JAK2/STAT3 signalling pathway, was used. Our findings suggest that AG490 attenuates the effects of scutellarin. Our study revealed that scutellarin inhibited OGD-activated microglia-mediated PC12 cells apoptosis which was regulated via the JAK2/STAT3 signalling pathway.


Assuntos
Apigenina , Apoptose , Glucuronatos , Janus Quinase 2 , Microglia , Fator de Transcrição STAT3 , Transdução de Sinais , Animais , Apigenina/farmacologia , Fator de Transcrição STAT3/metabolismo , Janus Quinase 2/metabolismo , Glucuronatos/farmacologia , Células PC12 , Apoptose/efeitos dos fármacos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ratos , Camundongos , Caspase 3/metabolismo , Glucose/metabolismo , Fármacos Neuroprotetores/farmacologia , Fosforilação/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo , Tirfostinas/farmacologia
14.
BMC Psychiatry ; 24(1): 434, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38862969

RESUMO

BACKGROUND: Cognitive impairment is a recognized fundamental deficit in individuals diagnosed with schizophrenia (SZ), bipolar II disorder (BD II), and major depressive disorder (MDD), among other psychiatric disorders. However, limited research has compared cognitive function among first-episode drug-naïve individuals with SZ, BD II, or MDD. METHODS: This study aimed to address this gap by assessing the cognitive performance of 235 participants (40 healthy controls, 58 SZ patients, 72 BD II patients, and 65 MDD patients) using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) before and after 12 weeks of treatment in SZ, BD II, and MDD patients. To clarify, the healthy controls only underwent RBANS testing at baseline, whereas the patient groups were assessed before and after treatment. The severity of symptoms in SZ patients was measured using the Positive and Negative Syndrome Scale (PANSS), and depression in BD II and MDD patients was assessed using the Hamilton Depression Scale-24 items (HAMD-24 items). RESULTS: Two hundred participants completed the 12-week treatment period, with 35 participants dropping out due to various reasons. This group included 49 SZ patients, 58 BD II patients, and 53 MDD patients. Among SZ patients, significant improvements in immediate and delayed memory were observed after 12 weeks of treatment compared to their initial scores. Similarly, BD II patients showed significant improvement in immediate and delayed memory following treatment. However, there were no significant differences in RBANS scores for MDD patients after 12 weeks of treatment. CONCLUSIONS: In conclusion, the findings of this study suggest that individuals with BD II and SZ may share similar deficits in cognitive domains. It is important to note that standardized clinical treatment may have varying degrees of effectiveness in improving cognitive function in patients with BD II and SZ, which could potentially alleviate cognitive dysfunction.


Assuntos
Transtorno Bipolar , Transtorno Depressivo Maior , Esquizofrenia , Humanos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/psicologia , Masculino , Feminino , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/psicologia , Adulto , Esquizofrenia/tratamento farmacológico , Esquizofrenia/fisiopatologia , Esquizofrenia/complicações , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Adulto Jovem , Testes Neuropsicológicos , Antipsicóticos/uso terapêutico , Escalas de Graduação Psiquiátrica , Pessoa de Meia-Idade
15.
ACS Synth Biol ; 13(6): 1647-1662, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38860708

RESUMO

Monoterpenoids are an important subclass of terpenoids that play important roles in the energy, cosmetics, pharmaceuticals, and fragrances fields. With the development of biotechnology, microbial synthesis of monoterpenoids has received great attention. Yeasts such Saccharomyces cerevisiae and Yarrowia lipolytica are emerging as potential hosts for monoterpenoids production because of unique advantages including rapid growth cycles, mature gene editing tools, and clear genetic background. Recently, advancements in metabolic engineering and fermentation engineering have significantly enhanced the accumulation of monoterpenoids in cell factories. First, this review introduces the biosynthetic pathway of monoterpenoids and comprehensively summarizes the latest production strategies, which encompass enhancing precursor flux, modulating the expression of rate-limited enzymes, suppressing competitive pathway flux, mitigating cytotoxicity, optimizing substrate utilization, and refining the fermentation process. Subsequently, this review introduces four representative monoterpenoids. Finally, we outline the future prospects for efficient construction cell factories tailored for the production of monoterpenoids and other terpenoids.


Assuntos
Engenharia Metabólica , Monoterpenos , Saccharomyces cerevisiae , Yarrowia , Yarrowia/metabolismo , Yarrowia/genética , Engenharia Metabólica/métodos , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Monoterpenos/metabolismo , Fermentação , Vias Biossintéticas/genética , Terpenos/metabolismo , Edição de Genes/métodos
16.
J Transl Med ; 22(1): 564, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38872164

RESUMO

BACKGROUND/PURPOSE(S): The gut microbiota and its metabolites play crucial roles in pathogenesis of arthritis, highlighting gut microbiota as a promising avenue for modulating autoimmunity. However, the characterization of the gut virome in arthritis patients, including osteoarthritis (OA) and gouty arthritis (GA), requires further investigation. METHODS: We employed virus-like particle (VLP)-based metagenomic sequencing to analyze gut viral community in 20 OA patients, 26 GA patients, and 31 healthy controls, encompassing a total of 77 fecal samples. RESULTS: Our analysis generated 6819 vOTUs, with a considerable proportion of viral genomes differing from existing catalogs. The gut virome in OA and GA patients differed significantly from healthy controls, showing variations in diversity and viral family abundances. We identified 157 OA-associated and 94 GA-associated vOTUs, achieving high accuracy in patient-control discrimination with random forest models. OA-associated viruses were predicted to infect pro-inflammatory bacteria or bacteria associated with immunoglobulin A production, while GA-associated viruses were linked to Bacteroidaceae or Lachnospiraceae phages. Furthermore, several viral functional orthologs displayed significant differences in frequency between OA-enriched and GA-enriched vOTUs, suggesting potential functional roles of these viruses. Additionally, we trained classification models based on gut viral signatures to effectively discriminate OA or GA patients from healthy controls, yielding AUC values up to 0.97, indicating the clinical utility of the gut virome in diagnosing OA or GA. CONCLUSION: Our study highlights distinctive alterations in viral diversity and taxonomy within gut virome of OA and GA patients, offering insights into arthritis etiology and potential treatment and prevention strategies.


Assuntos
Artrite Gotosa , Microbioma Gastrointestinal , Osteoartrite , Viroma , Humanos , Artrite Gotosa/virologia , Artrite Gotosa/microbiologia , Masculino , Osteoartrite/virologia , Osteoartrite/microbiologia , Feminino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Idoso , Metagenômica , Fezes/virologia , Fezes/microbiologia
17.
Biotechnol Biofuels Bioprod ; 17(1): 80, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877488

RESUMO

To increase the production of biomass and astaxanthin from Haematococcus pluvialis to meet the high market demand for astaxanthin, this study recruited two typical and negligible phytohormones (namely resveratrol and catechol) for the stepwise treatments of H. pluvialis. It was found that the hybrid and sequential treatments of resveratrol (200 µmol) and catechol (100 µmol) had achieved the maximum astaxanthin content at 33.96 mg/L and 42.99 mg/L, respectively. Compared with the hybrid treatment, the physiological data of H. pluvialis using the sequential strategy revealed that the enhanced photosynthetic performance via the Calvin cycle by RuBisCO improved the biomass accumulation during the macrozooid stage; meanwhile, the excessive ROS production had occurred to enhance astaxanthin production with the help of NADPH overproduction during the hematocyst stage. Overall, this study provides improved knowledge of the impacts of phytohormones in improving biomass and astaxanthin of H. pluvialis, which shed valuable insights for advancing microalgae-based biorefinery.

18.
DNA Cell Biol ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829105

RESUMO

This study aimed to determine the function of angiopoietin-related protein 4 (ANGPTL4) and bone morphogenetic protein 7 (BMP7) on hepatocellular carcinoma (HCC). Overexpressing plasmids were cotransfected into HepG2 cells to determine the interaction between ANGPTL4 and BMP7. The effect of ANGPTL4 on the stability of BMP7 is examined by detecting the expression and ubiquitination levels. In vitro and in vivo experiments of knocking down ANGPTL4 while overexpressing BMP7 were performed to investigate whether the effects of ANGPTL4 on HCC proliferation, migration, and downstream signaling pathways were dependent on BMP7. ANGPTL4 is able to interact with BMP7, and knockdown of ANGPTL4 increased BMP7 expression and ubiquitination. Overexpression of BMP7 reversed the inhibition of HCC proliferation and migration as well as the decrease in the expression levels of Smad1/5/8 and MAPK14 caused by knockdown of ANGPTL4. ANGPTL4 promotes the proliferation and migration of HCC by inhibiting the ubiquitination degradation of BMP7 and the Smad/MAPK pathway, providing a novel mechanism and a potential therapeutic target for the treatment of HCC.

19.
Nat Commun ; 15(1): 4779, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839782

RESUMO

Despite the profound implications of self-organization in animal groups for collective behaviors, understanding the fundamental principles and applying them to swarm robotics remains incomplete. Here we propose a heuristic measure of perception of motion salience (MS) to quantify relative motion changes of neighbors from first-person view. Leveraging three large bird-flocking datasets, we explore how this perception of MS relates to the structure of leader-follower (LF) relations, and further perform an individual-level correlation analysis between past perception of MS and future change rate of velocity consensus. We observe prevalence of the positive correlations in real flocks, which demonstrates that individuals will accelerate the convergence of velocity with neighbors who have higher MS. This empirical finding motivates us to introduce the concept of adaptive MS-based (AMS) interaction in swarm model. Finally, we implement AMS in a swarm of ~102 miniature robots. Swarm experiments show the significant advantage of AMS in enhancing self-organization of the swarm for smooth evacuations from confined environments.


Assuntos
Aves , Robótica , Animais , Aves/fisiologia , Percepção de Movimento/fisiologia , Comportamento Animal/fisiologia , Movimento (Física) , Voo Animal/fisiologia , Comportamento Social
20.
Infect Drug Resist ; 17: 2273-2283, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38854780

RESUMO

Background: To explore the plasmid characteristics and transfer mechanisms of an extensive drug resistant (XDR) clinical isolate, Citrobacter portucalensis L2724hy, co-producing bla SFO-1, bla NDM-1, and bla KPC-2. Methods: Species confirmation of L2724hy was achieved through 16S rRNA sequencing and Average Nucleotide Identity (ANI) analysis. Antimicrobial susceptibility testing (AST) employed the agar dilution and micro broth dilution methods. Identification of resistance genes was carried out by PCR and whole-genome sequencing (WGS). Essential resistance gene locations were verified by S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and southern hybridization experiments. Subsequent WGS data analysis delved into drug resistance genes and plasmids. Results: The confirmation of the strain L2724hy as an extensive drug-resistant Citrobacter portucalensis, resistant to almost all antibiotics tested except polymyxin B and tigecycline, was achieved through 16S rRNA sequencing, ANI analysis and AST results. WGS and subsequent analysis revealed L2724hy carrying bla SFO-1, bla NDM-1, and bla KPC-2 on plasmids of various sizes. The uncommon ESBL gene bla SFO-1 coexists with the fosA3 gene on an IncFII plasmid, featuring the genetic environment IS26-fosA3-IS26-ampR-bla SFO-1-IS26. The bla NDM-1 was found on an IncX3 plasmid, coexisting with bla SHV-12, displaying the sequence IS5-IS3000-IS3000-Tn2-bla NDM-1-ble-trpF-dsbD-cutA-gros-groL, lacking ISAa125. The bla KPC-2 is located on an unclassified plasmid, exhibiting the sequence Tn2-tnpR-ISKpn27-bla KPC-2-ISKpn6-korC. Conjugation assays confirmed the transferability of both bla NDM-1 and bla KPC-2. Conclusion: We discovered the coexistence of bla SFO-1, bla NDM-1, and bla KPC-2 in C. portucalensis for the first time, delving into plasmid characteristics and transfer mechanisms. Our finding highlights the importance of vigilant monitoring of drug-resistance genes and insertion elements in uncommon strains.

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