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1.
World J Gastroenterol ; 29(1): 144-156, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36683714

RESUMO

Minimal hepatic encephalopathy (MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety; however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.


Assuntos
Microbioma Gastrointestinal , Encefalopatia Hepática , Probióticos , Animais , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/terapia , Disbiose/complicações , Cirrose Hepática/complicações , Probióticos/uso terapêutico , Encéfalo
2.
Steroids ; 192: 109182, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36642107

RESUMO

Four new steroids, namely sinulasterols D-G (1-4), along with seven known related ones 5-11, were isolated from the Xisha soft coral Sinularia depressa. The structures of the new compounds were elucidated by a combination of extensive spectroscopic analyses, chemical conversion method, and comparison of the NMR data with those of known analogues. In in vitro bioassays, compounds 1-3 showed significant antibacterial activities against gram-positive bacteria Enterococcus faecium with minimum inhibitory concentration (MIC) values of 62.5, 125, and 125 µM, respectively, comparable with that of vancomycin (MIC: >44.2 µM).

3.
Chemistry ; 2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36617497

RESUMO

Investigation of the South China Sea nudibranch Hexabranchus sanguineus from Sanya Bay afforded, in addition to three known compounds, nine new diterpenoids of the 5,19-cycloclerodane- (sanyanolides A-D), clerodane- (sanyanolide E) and subersin- (sanyanolides F-I) type. Remarkably, six diterpenoids aforementioned from H. sanguineus were also isolated from the sponge Chelonaplysilla sp. from the same water region, suggesting a trophic relationship between H. sanguineus and Chelonaplysilla sp. The structure and absolute configuration of new compounds were established by a combination of spectroscopic data, X-ray diffraction analysis and/or time-dependent density functional theory/electronic circular dichroism calculations. A plausible biogenetic relationship between these diterpenoids, along with the chemo-ecological implications of their co-occurrence in the two organisms investigated, was proposed and discussed. In in vitro bioassays, echinoclerodane A exhibited a potent inhibitory effect (IC50 = 2.81 µM) on LPS-induced inflammatory response in RAW 264.7 macrophage cells. In addition, echinoclerodane A and oculatolide showed considerable antibacterial activities with MIC values ranging from 1.0 to 8.0 µg/mL.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36622199

RESUMO

OBJECTIVE: Spastic paraplegia type 2 (SPG2) is an X-linked recessive (XLR) form of hereditary spastic paraplegia (HSP) caused by mutations in proteolipid protein 1 (PLP1) gene. We described the clinical and genetic features of three unrelated families with PLP1 mutations and reviewed PLP1-related cases worldwide to summarize the genotype-phenotype correlations. METHODS: The three probands were 23, 26, and 27 years old, respectively, with progressively aggravated walking difficulty as well as lower limb spasticity. Detailed physical examination showed elevated muscle tone, hyperreflexia, and Babinski signs in lower limbs. Brain MRI examinations were investigated for all cases. PLP1 mutations were identified by whole exome sequencing, followed by Sanger sequencing, family co-segregation, and phenotypic reevaluation. RESULTS: A total of eight patients with SPG2 were identified in these three families. The probands additionally had cognitive impairment, urinary or fecal incontinence, ataxia, and white matter lesions (WML) in periventricular regions, with or without kinetic tremor. Three hemizygous mutations in PLP1 were identified, including c.453+159G>A, c.834A>T (p.*278C), and c.434G>A (p.W145*), of which c.834A>T was first associated with HSP. INTERPRETATION: We identified three families with complicated SPG2 due to three PLP1 mutations. Our study supports the clinically inter-and intra-family heterogeneity of SPG2. The periventricular region WML and cognitive impairment are the most common characteristics. The kinetic tremor in upper limbs was observed in 2/3 families, suggesting the spectrum of PLP1-related disorders is still expanding.

5.
Proc Natl Acad Sci U S A ; 120(2): e2206146120, 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36608291

RESUMO

The human ether-a-go-go-related gene (hERG) K+ channel conducts a rapidly activating delayed rectifier K+ current (IKr), which is essential for normal electrical activity of the heart. Precise regulation of hERG channel biogenesis is critical for serving its physiological functions, and deviations from the regulation result in human diseases. However, the mechanism underlying the precise regulation of hERG channel biogenesis remains elusive. Here, by using forward genetic screen, we found that PATR-1, the Caenorhabditis elegans homolog of the yeast DNA topoisomerase 2-associated protein PAT1, is a critical regulator for the biogenesis of UNC-103, the ERG K+ channel in C. elegans. A loss-of-function mutation in patr-1 down-regulates the expression level of UNC-103 proteins and suppresses the phenotypic defects resulted from a gain-of-function mutation in the unc-103 gene. Furthermore, downregulation of PATL1 and PATL2, the human homologs of PAT1, decreases protein levels and the current density of native hERG channels in SH-SY5Y cells and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Knockdown of PATL1 and PATL2 elongates the duration of action potentials in hiPSC-CMs, suggesting that PATL1 and PATL2 affect the function of hERG channels and hence electrophysiological characteristics in the human heart. Further studies found that PATL1 and PATL2 interact with TFIIE, a general transcription factor required for forming the RNA polymerase II preinitiation complex, and dual-luciferase reporter assays indicated that PATL1 and PATL2 facilitate the transcription of hERG mRNAs. Together, our study discovers that evolutionarily conserved DNA topoisomerase 2-associated proteins regulate the biogenesis of hERG channels via a transcriptional mechanism.


Assuntos
Canais de Potássio Éter-A-Go-Go , Neuroblastoma , Animais , Humanos , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , DNA Topoisomerases Tipo II/genética , DNA Topoisomerases Tipo II/metabolismo , Canal de Potássio ERG1/genética , Canal de Potássio ERG1/metabolismo , Canais de Potássio Éter-A-Go-Go/genética , Canais de Potássio Éter-A-Go-Go/metabolismo , Miócitos Cardíacos/metabolismo , Neuroblastoma/metabolismo , Proteínas de Ligação a DNA/metabolismo
6.
Anal Chem ; 95(4): 2570-2578, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36653941

RESUMO

Pathogenic bacteria are pathogens widely spread that are capable of causing mild to life-threatening diseases in human beings or other organisms. Rationally organizing the simple helical motif of double-stranded DNA (dsDNA) tiles into designed ensemble structures with architecturally defined collective properties could lead to promising biosensing applications for pathogen detection. In this work, we facilely engineered multivalent hairpin aptamer probe-tethered DNA monolayers (MHAP-DNA monolayers) and applied them to build a fluorescence polarization-responsive circular isothermal strand displacement amplification (FP-CSDA) for Salmonella assay. In this system, the MHAP-DNA monolayers were constructed based on a dsDNA tile-directed self-assembly. A FAM-labeled reporting probe (RPFAM) with an inherent low FP signal serves as the signaling unit. The presence of target Salmonella leads to the trapping of F RPFAM into the super DNA monolayers via a target-triggered CSDA to peel off the tethered hairpin-structured aptamer probes (HAPs) responsible for the binding of RPFAM. As a result, the FP signal of the FAM fluorophore can be remarkably amplified due to the recycling of target Salmonella and the capacity of structural DNA materials to strongly restrict the free rotation of the FAM fluorophore but without a fluorescence quenching effect. Experimental results demonstrate that the FP assay is able to detect Salmonella with a low limit of detection (LOD) of 7.2 × 100 CFU/mL and high specificity. As a proof-of-concept study, we envision our study using DNA nanoarchitecture as the foundation to modulate CSDA-based FP assays, promising to open up a new avenue for disease diagnosis, food safety detection, and biochemical studies.

7.
FASEB J ; 37(2): e22734, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36583697

RESUMO

PTPRT (receptor-type tyrosine-protein phosphatase T), a brain-specific type 1 transmembrane protein, plays an important role in neurodevelopment and synapse formation. However, whether abnormal PTPRT signaling is associated with Alzheimer's disease (AD) remains elusive. Here, we report that Ptprt mRNA expression is found to be downregulated in the brains of both human and mouse models of AD. We further identified that the PTPRT intracellular domain (PICD), which is released by ADAM10- and γ-secretase-dependent cleavage of PTPRT, efficiently translocates to the nucleus via a conserved nuclear localization signal (NLS). We show that inhibition of nuclear translocation of PICD leads to an accumulation of phosphorylated signal transducer and activator of transcription 3 (pSTAT3), a substrate of PTPRT-eventually resulting in neuronal cell death. Consistently, RNA sequencing reveals that overexpression of PICD leads to changes in the expression of genes that are functionally associated with synapse formation, cell adhesion, and protein dephosphorylation. Moreover, overexpression of PICD not only decreases the level of phospho-STAT3Y705 and amyloid ß production in the hippocampus of APP/PS1 mice but also partially improves synaptic function and behavioral deficits in this mouse model of AD. These findings suggest that a novel role of the ADAM 10- and γ-secretase-dependent cleavage of PTPRT may alleviate the AD-like neurodegenerative processes.


Assuntos
Proteína ADAM10 , Doença de Alzheimer , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores , Animais , Humanos , Camundongos , Proteína ADAM10/metabolismo , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Modelos Animais de Doenças , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Presenilina-1/genética , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo
8.
J Asian Nat Prod Res ; : 1-7, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36451544

RESUMO

Two new scalarane sesterterpenes, hyrtiosins F and G (1 and 2), along with two known related compounds, hyrtiosin D and sesterstatin 6 (3 and 4), were isolated from the Hainan marine sponge Hyrtios erecta. The structures of new compounds 1 and 2 were determined by detailed analysis of 1D and 2D NMR spectra and by comparison of the spectroscopic data with those reported in the literatures.

9.
Artigo em Inglês | MEDLINE | ID: mdl-36496508

RESUMO

Antipsychotics are thought to improve schizophrenia symptoms through the antagonism of dopamine D2 receptors, which are abundant mainly in subcortical regions. By introducing functional gradient, a novel approach to identify hierarchy alterations by capturing the similarity of whole brain fucntional connectivity (FC) profiles between two voxels, the present study aimed to characterize how the subcortical gradient is associated with treatment effects and response in first-episode schizophrenia in vivo. Two independent samples of first-episode schizophrenia (FES) patients with matched healthy controls (HC) were obtained: the discovery dataset included 71 patients (FES0W) and 64 HC at baseline, and patients were re-scanned after either 6 weeks (FES6W, N = 33) or 12 months (FES12M, N = 57) of antipsychotic treatment, of which 19 patients finished both 6-week and 12-month evaluation. The validation dataset included 22 patients and 24 HC at baseline and patients were re-scanned after 6 weeks. Gradient metrics were calculated using BrainSpace Toolbox. Voxel-based gradient values were generated and group-averaged gradient values were further extracted across all voxels (global), three systems (thalamus, limbic and striatum) and their subcortical subfields. The comparisons were conducted separately between FES0W and HC for investigating illness effects, and between FES6W/FES12M and FES0W for treatment effects. Correlational analyses were then conducted between the longitudinal gradient alterations and the improvement of clinical ratings. Before treatment, schizophrenia patients exhibited an expanded range of global gradient scores compared to HC which indicated functional segregation within subcortical systems. The increased gradient in limbic system and decreased gradient in thalamic and striatal system contributed to the baseline abnormalities and led to the disruption of the subcortical functional integration. After treatment, these disruptions were normalized and the longitudinal changes of gradient scores in limbic system were significantly associated with symptom improvement. Similar illness and treatment effects were also observed in the validation dataset. By measuring functional hierarchy of subcortical organization, our findings provide a novel imaging marker that is sensitive to treatment effects and may make a promising indicator of treatment response in schizophrenia.

10.
J Phys Chem Lett ; 13(51): 12082-12089, 2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36546645

RESUMO

How to resolve contradictions between the nanoscale size and high saturation magnetization (Ms) remains one of the scientific challenges in nanoscale magnetism as the theoretical optimal Ms of nanocrystals is compromised by the surface spin disorder. Here, we proposed a novel nanotechnology solution, heterointerface constructions of exchange-coupling core-shell nanocrystals, to rearrange the surface spin for the enhancement of Ms of nanomagnetic materials. As a demonstration of this principle, single-interface coupling FePt@Fe3-δO4 core/shell nanocrystals and multi-interface coupling FePt@Fe3-δO4@MFe2O4 (M = Mn or Co) core/shell/shell nanocrystals were synthesized. The simulated and experimental results demonstrated that constructing coupling heterointerfaces orientates the overall magnetic moment, ultimately enhancing the Ms of nanomagnetic materials. Moreover, this work first demonstrated that the origin of coupling heterointerfaces arose from mismatched lattices rather than chemical composition mismatch at the core-shell interfaces, thus providing both a solution to unite different mechanisms and an explanation to explain the exchange coupling at heterointerfaces.

11.
J Formos Med Assoc ; 2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36517352

RESUMO

BACKGROUD/PURPOSE: Venous thromboembolism, including deep vein thrombosis (DVT) and pulmonary embolism (PE), is an important complication in patients who underwent open hepatic surgery as well as other major upper abdominal surgery. This study aims to investigate the occurrence of postoperative DVT without pharmacological thromboprophylaxis in such cohorts in Taiwan. METHODS: This is a prospective, cross-sectional cohort study conducted from March 2010 to December 2011. Patients who underwent major upper abdominal surgery, including open hepatectomy, were enrolled. Color duplex compression ultrasonography (CUS) was used to detect DVT. Symptomatic PE was excluded if there were no suggestive respiratory symptoms or sudden death. Relevant clinicopathological and surgical information of each patient was collected and analyzed. RESULTS: 195 patients (118 male and 77 female) were enrolled, with a median age of 63.6 years. The majority (169/195, 88.7%) were treated for active malignancy. Totally 147 patients received open hepatectomy. Only one asymptomatic and distal postoperative DVT event was identified by CUS, which occurred on a 73-year-old female patient who received a left lateral segmental hepatectomy for removing the advanced hepatocellular carcinoma (pathologic stage, T3aN0M0). No cases of symptomatic PE or sudden death were observed. No correlation between DVT and precipitating factor was demonstrated in our cohort. CONCLUSIONS: Without pharmacological thromboprophylaxis, a low rate of postoperative DVT among patients undergoing open hepatectomy (0.7%, 1/147) or major upper abdominal surgery (0.5%, 1/195) in Taiwan was reported. A distinctively regional role of pharmacological thromboprophylaxis for hepatic surgery was also suggested by our data.

12.
Front Immunol ; 13: 1012981, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36524116

RESUMO

Resistance to tyrosine kinase inhibitor (TKI) is a tough problem in the treatment of chronic myeloid leukemia in blastic phase (CML-BP), which was often associated with acquired mutations in the kinase domain and not eliminating the leukemic stem cells. The efficacy of TKI or combination with chemotherapy in CML-BP remains unsatisfactory. Chimeric antigen receptor T (CAR-T) cell immunotherapy may overcome TKI and chemotherapy resistance. However, lack of ideal targetable antigens is a major obstacle for treating patients with myeloid malignancies. CD38 is known to be expressed on most (acute myeloid leukemia) AML cells, and its lack of expression on hematopoietic stem cells renders it as a potential therapeutic target for myeloid CML-BP. We develop a CD38-directed CAR-T cell therapy for AML, and two patients with myeloid CML-BP were enrolled (NCT04351022). Two patients, harboring E255K and T315I mutation in the ABL kinase domain, respectively, were resistant to multiple TKIs (imatinib, dasatinib, nilotinib, and ponatinib) and intensive chemotherapy. The blasts in the bone marrow of two patients exhibited high expression of CD38. After tumor reduction chemotherapy and lymphodepletion chemotherapy, 1 × 107 CAR-T-38 cells per kilogram of body weight were administered. They achieved minimal residual disease-negative and BCR::ABL1-negative complete remission and experienced grade II cytokine release syndrome manifesting as fever. Our data highlighted that CAR-T-38 cell therapy may overcome TKI and chemotherapy resistance in patients with myeloid CML-BP.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Imunoterapia , Terapia Baseada em Transplante de Células e Tecidos
13.
Am J Cancer Res ; 12(11): 4930-4953, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36504899

RESUMO

Cancer is one of the main causes of death in humans worldwide, the development of more effective anticancer drugs that can inhibit the malignant progression of cancer cells is of great significance. Aiphanol is a natural product identified from the seeds of Arecaceae and the rhizome of Smilax glabra Roxb. Our preliminary studies revealed that it had potential antiangiogenic and antilymphangiogenic activity by directly targeting VEGFR2/3 and COX2 in endothelial cells. However, the influence of aiphanol on cancer cells per se remains largely undefined. In this study, the effects and related mechanisms of aiphanol on cancer growth and metastasis were evaluated in vitro and in vivo. Acute toxicity assay and pharmacokinetic analysis were utilized to investigate the safety profile and metabolism characteristics of aiphanol. We revealed that aiphanol inhibited the proliferation of various types of cancer cells and the growth of xenograft tumors in mice and zebrafish models. The possible mechanism was associated with the inactivation of multiple kinases, including FAK, AKT and ERK, and the upregulation of BAX and cleaved caspase-3 to promote cancer cell apoptosis. Aiphanol significantly inhibited cancer cell migration and invasion, which was related to the inhibition of epithelial-mesenchymal transition (EMT) and F-actin aggregation. Aiphanol effectively attenuated the metastasis of several types of cancer cells in vivo. In addition, aiphanol exerted no significant toxicity and had fast metabolism. Collectively, we demonstrated the anticancer effects of aiphanol and suggested that aiphanol has potential as a safe and effective therapeutic agent to treat cancer.

15.
Front Cell Dev Biol ; 10: 1007924, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36531961

RESUMO

Serum- and glucocorticoid-induced kinase 3 (SGK3), which is ubiquitously expressed in mammals, is regulated by estrogens and androgens. SGK3 is activated by insulin and growth factors through signaling pathways involving phosphatidylinositol-3-kinase (PI3K), 3-phosphoinositide-dependent kinase-1 (PDK-1), and mammalian target of rapamycin complex 2 (mTORC2). Activated SGK3 can activate ion channels (TRPV5/6, SOC, Kv1.3, Kv1.5, Kv7.1, BKCa, Kir2.1, Kir2.2, ENaC, Nav1.5, ClC-2, and ClC Ka), carriers and receptors (Npt2a, Npt2b, NHE3, GluR1, GluR6, SN1, EAAT1, EAAT2, EAAT4, EAAT5, SGLT1, SLC1A5, SLC6A19, SLC6A8, and NaDC1), and Na+/K+-ATPase, promoting the transportation of calcium, phosphorus, sodium, glucose, and neutral amino acids in the kidney and intestine, the absorption of potassium and neutral amino acids in the renal tubules, the transportation of glutamate and glutamine in the nervous system, and the transportation of creatine. SGK3-sensitive transporters contribute to a variety of physiological and pathophysiological processes, such as maintaining calcium and phosphorus homeostasis, hydro-salinity balance and acid-base balance, cell proliferation, muscle action potential, cardiac and neural electrophysiological disturbances, bone density, intestinal nutrition absorption, immune function, and multiple substance metabolism. These processes are related to kidney stones, hypophosphorous rickets, multiple syndromes, arrhythmia, hypertension, heart failure, epilepsy, Alzheimer's disease, amyotrophic lateral sclerosis, glaucoma, ataxia idiopathic deafness, and other diseases.

16.
Int J Biol Macromol ; 229: 724-731, 2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36572080

RESUMO

SCA36 is a neurodegenerative disease mainly caused by the abnormal expansion of the GGGCCT repeat sequence in intron 1 of NOP56. The RNA sequences of this gene are expected to form large amounts of G-quadruplexes in the cytoplasm, which may be a potential intervention and detection target for SCA36. Here, we have developed a small-molecular compound named TCB-1, which shows good selectivity to the G-quadruplex structure, and its fluorescence can be enhanced by hundreds of folds. Interestingly, TCB-1 can avoid lysosome capture, evenly disperse in the cytoplasm, and selectively light up the cytoplasmic RNA G-quadruplexes. This property allows TCB-1 to sensitively detect the increased formation of cytoplasmic RNA G-quadruplexes in SCA36 model cells. This work not only provides new ideas for the design of small-molecule compounds targeting RNA G-quadruplexes in living cells, but also intuitively demonstrates the increased formation of RNA G-quadruplexes caused by NOP56 gene mutation, providing a possible tool for the detection of SCA36.

17.
Molecules ; 27(24)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36557804

RESUMO

Natural medicine has been widely used for clinical treatment and health care in many countries and regions. Additionally, extracting active ingredients from traditional Chinese medicine and other natural plants, defining their chemical structure and pharmacological effects, and screening potential druggable candidates are also uprising directions in new drug research and development. Physiologically based pharmacokinetic (PBPK) modeling is a mathematical modeling technique that simulates the absorption, distribution, metabolism, and elimination of drugs in various tissues and organs in vivo based on physiological and anatomical characteristics and physicochemical properties. PBPK modeling in drug research and development has gradually been recognized by regulatory authorities in recent years, including the U.S. Food and Drug Administration. This review summarizes the general situation and shortcomings of the current research on the pharmacokinetics of natural medicine and introduces the concept and the advantages of the PBPK model in the study of pharmacokinetics of natural medicine. Finally, the pharmacokinetic studies of natural medicine using the PBPK models are summed up, followed by discussions on the applications of PBPK modeling to the enzyme-mediated pharmacokinetic changes, special populations, new drug research and development, and new indication adding for natural medicine. This paper aims to provide a novel strategy for the preclinical research and clinical use of natural medicine.


Assuntos
Medicina , Preparações Farmacêuticas/química , Modelos Biológicos , Farmacocinética
18.
Foods ; 11(24)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36553711

RESUMO

In the present study, we investigated the in vitro digestion and fermentation characteristics of three peach gum polysaccharides (PGPs) of different molecular weights; i.e., AEPG2 (1.64 × 107 g/mol), DPG2 (5.21 × 105 g/mol), and LP100R (8.50 × 104 g/mol). We observed that PGPs were indigestible during the oral, gastrointestinal, and intestinal stages. However, they were utilized by the gut microbiota with utilization rates in the order of DPG2 > AEPG2 > LP100R. Furthermore, arabinose in PGPs was preferentially utilized by the gut microbiota followed by galactose and xylose. Fermentation of peach gum polysaccharides could significantly increase the production of short-chain fatty acids (SCFAs), especially n-butyric acid. In addition, PGPs with different molecular weights values were predominantly fermented by different bacterial species. AEPG2 and DPG2 were fermented by the Bacteroidetes bacteria Bacteroides, while the dominant n-butyrate-producing bacteria was Faecalibacterium. While the LP100R was fermented by Bacteroides, Parabacteroides, Phascolarctobacterium, Dialister, Lachnospiraceae, and Blautia, the dominant n-butyrate-producing bacteria was Megamonas. These results indicated that PGPs are potential prebiotics for the food industry.

19.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 38(4): 289-294, 2022 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-36414548

RESUMO

Objective: To investigate the protective effects and potential mechanisms of estrogen modified human bone marrow mesenchymal stem cells (hBMSC) on high glucose (HG)-induced injury of vascular endothelial cells. Methods: hBMSCs were cultured under 30 mmol/l glucose to establish a high glucose model (HG), and then were divided into four groups as following: HG group (HG control, without any treatment), HG+E2 group (cells were treated with 20 µmol/L estrogen), HG+E2+ Triciribine group (cells were pretreated with 5 µmol/L protein kinase B (PKB/Akt) inhibitor for 45 min, and then modified by 20 µmol/L estrogen), and NG group (cells were cultured under normal conditions). After 12 h treatment, the cell viability of hBMSC was detected by CCK8 assay, and the contents of NO, VEGF and IL8 in the supernatant of cultured medium in each group were detected by nitrate reductase and ELISA assay (n=6). After 48 h, the expression levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS (p-eNOS) were detected by Western blot (n=3). In addition, the cell supernatant of each group was further extracted as conditioned medium to culture HUVECs, and the cells were subsequently divided into HG-CM group (HUVECs were treated with HG group's conditioned medium), HG+E2-CM group (HUVECs were treated with HG+E2 group's conditioned medium), HG+E2+Triciribine-CM group (HUVECs were treated with HG+E2+ Triciribine group's conditioned medium) and HG-H group (HUVEC were cultured under HG condition, which were treated with final concentration 30 mmol/l glucose). The cell viability of HUVECs in each group was detected by CCK8 assay after 12 h cultured (n=6). After 24 h treatment, the apoptosis rate of HUVECs in each group was detected by flow cytometry (n=3). Furthermore, the migration rate of HUVECs in each group was observed by wound healing assay after 48 h cultured (n=3). Results: Compared with NG group, the cell viability and eNOS protein phosphorylation level of hBMSC in HG group and the contents of NO, VEGF and IL-8 in the supernatant of cultured medium were decreased (P<0.05). Compared with HG group, the cell viability and eNOS protein phosphorylation level in HG+E2 group and the contents of NO, VEGF and IL-8 in cultured medium supernatant were increased significantly (P<0.05), whereas pre-treatment of hBMSC cells with a Akt inhibitor Triciribine, the above indexes showed reverse changes (P<0.05). Furthermore, compared with HG-CM group, the cell viability and migration ability (P<0.05) of HUVECs in HG+E2-CM group were increased significantly (P<0.05), and the proportion of apoptosis was decreased (P<0.05). While compared with HG+E2-CM group, the cell viability and migration ability of HUVECs in HG+E2+Triciribine-CM group were decreased (P<0.05), and the proportion of apoptosis was increased (P<0.05). Conclusion: Estrogen may promote the secretion of NO, VEGF and IL-8 by activating the Akt/eNOS signaling pathway of hBMSC cells, increase the cell viability and migration ability of HUVECs and inhibit the occurrence of apoptosis, play a protective role against the injury of HUVECs induced by HG condition.


Assuntos
Células-Tronco Mesenquimais , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Células Endoteliais da Veia Umbilical Humana , Fator A de Crescimento do Endotélio Vascular/metabolismo , Meios de Cultivo Condicionados/metabolismo , Meios de Cultivo Condicionados/farmacologia , Interleucina-8/metabolismo , Glucose/metabolismo , Estrogênios/farmacologia , Estrogênios/metabolismo
20.
Schizophr Bull ; 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36402458

RESUMO

BACKGROUND AND HYPOTHESIS: Disrupted control of brain state transitions may contribute to the diverse dysfunctions of cognition, emotion, and behavior that are fundamental to schizophrenia. Control theory provides the rationale for evaluating brain state transitions from a controllability perspective, which may help reveal the brain mechanism for clinical features such as cognitive control deficits associated with schizophrenia. We hypothesized that brain controllability would be altered in patients with schizophrenia, and that controllability of brain networks would be related to clinical symptomatology. STUDY DESIGN: Controllability measurements of functional brain networks, including average controllability and modal controllability, were calculated and compared between 125 first-episode never-treated patients with schizophrenia and 133 healthy controls (HCs). Associations between controllability metrics and clinical symptoms were evaluated using sparse canonical correlation analysis. STUDY RESULTS: Compared to HCs, patients showed significantly increased average controllability (PFDR = .023) and decreased modal controllability (PFDR = .023) in dorsal anterior cingulate cortex (dACC). General psychopathology symptoms and positive symptoms were positively correlated with average controllability in regions of default mode network and negatively associated with average controllability in regions of sensorimotor, dorsal attention, and frontoparietal networks. CONCLUSIONS: Our findings suggest that altered controllability of functional activity in dACC may play a critical role in the pathophysiology of schizophrenia, consistent with the importance of this region in cognitive and brain state control operations. The demonstration of associations of functional controllability with psychosis symptoms suggests that the identified alterations in average controllability of brain function may contribute to the severity of acute psychotic illness in schizophrenia.

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