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1.
J Ethnopharmacol ; : 116192, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36706933

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Tiepishihu Xiyangshen granules (TXG) is a traditional Chinese medicine formula composed of Panax quinquefolius L, Dendrobium officinale Kimura & Migo and Ganoderma lucidum (Curtis) P. Karst. It has long been used as a nutritional supplement and an immune enhancer in China. However, the immunomodulatory effects and the underlying mechanisms of TXG have not been clarified. AIM OF THE STUDY: This study aims to investigate the immunomodulatory effects of TXG and clarify the underlying mechanism. MATERIALS AND METHOD: TXG was administered by gavage for 18 days. From the 15th day, the immunosuppression model was induced by intraperitoneally injecting 80 mg/kg CTX for 3 days. The immune regulatory effects of TXG on immune organs were verified by calculating the organ index and observing the spleen tissue structure through HE staining. The effects of TXG on immune cells were examined by recording the PBWC, the proliferation rate of lymphocyte and the T lymphocyte phenotype. The effects of TXG on immune molecules were measured by detecting serum hemolysin and the content of cytokines. In parallel, kit was utilized to detect its antioxidant capacity. RNA seq and Western blot were used to analyze the possible immune regulation mechanism of TXG. HPLC and UPLC-Q-TOF-MS were used to identify the chemical components in TXG. RESULTS: At the level of immune organs, TXG effectively reduced the adverse reaction to the body and the substantial damage to the spleen after chemotherapy by improving the spleen damage. At the level of immune molecules, TXG upregulated the expression of cytokines and antibodies. At the level of immune cells, TXG antagonized bone marrow suppression by increasing the PBWC of immunosuppressed mice. Meanwhile, TXG upregulated the ratio of CD4+/CD8+ lymphocytes and ameliorated the proliferation of T and B lymphocytes. And the mechanism of TXG to improve immunity might be through TLR4/MAPKs and PI3K/AKT/FOXO3a signaling pathways. CONCLUSION: The results of this study confirmed that TXG has prominent immunomodulatory activities, and the immunity regulations of TXG may be achieved by regulating TLR4/MAPKs and PI3K/AKT/FOXO3a signal pathways.

2.
ISME J ; 2023 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-36707613

RESUMO

Dimethylsulfoniopropionate (DMSP) is a ubiquitous organosulfur compound in marine environments with important functions in both microorganisms and global biogeochemical carbon and sulfur cycling. The SAR11 clade and marine Roseobacter group (MRG) represent two major groups of heterotrophic bacteria in Earth's surface oceans, which can accumulate DMSP to high millimolar intracellular concentrations. However, few studies have investigated how SAR11 and MRG bacteria import DMSP. Here, through comparative genomics analyses, genetic manipulations, and biochemical analyses, we identified an ABC (ATP-binding cassette)-type DMSP-specific transporter, DmpXWV, in Ruegeria pomeroyi DSS-3, a model strain of the MRG. Mutagenesis suggested that DmpXWV is a key transporter responsible for DMSP uptake in strain DSS-3. DmpX, the substrate binding protein of DmpXWV, had high specificity and binding affinity towards DMSP. Furthermore, the DmpX DMSP-binding mechanism was elucidated from structural analysis. DmpX proteins are prevalent in the numerous cosmopolitan marine bacteria outside the SAR11 clade and the MRG, and dmpX transcription was consistently high across Earth's entire global ocean. Therefore, DmpXWV likely enables pelagic marine bacteria to efficiently import DMSP from seawater. This study offers a new understanding of DMSP transport into marine bacteria and provides novel insights into the environmental adaption of marine bacteria.

3.
Ann Med ; 55(1): 305-310, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36594484

RESUMO

BACKGROUND: Pouchitis is the most common complication following restorative proctocolectomy and ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). Fecal calprotectin (FC) is a noninvasive indicator of the intestinal inflammatory status. This study was conducted to evaluate the clinical value of the FC concentration for the diagnosis and risk assessment of pouchitis. PATIENTS AND METHODS: This retrospective study involved patients who underwent IPAA for UC at Tianjin Medical University General Hospital from January 2015 to January 2019. The patients were categorized into pouchitis and non-pouchitis groups based on their Pouchitis Disease Activity Index (PDAI) score. Laboratory indicators, including the FC concentration, were collected from both groups. RESULTS: Sixty-six patients with UC after IPAA were included in the study and divided into the non-pouchitis group (n = 40) and pouchitis group (n = 26). The correlation coefficient between the FC concentration and the PDAI score was 0.651 (p < 0.001). Receiver operating characteristic analysis showed that the FC cut-off value for predicting pouchitis was 579.60 µg/g (area under the curve, 0.938). The patients were then divided into three subgroups according to their PDAI score (0-2, 3-6, and ≥7), and significant differences in the FC concentration were found among the three subgroups. The best FC cut-off value for predicting a high risk of pouchitis (PDAI score of 3-6) was 143.25 µg/g (area under the curve, 0.876). CONCLUSIONS: FC is a useful biomarker in patients with pouchitis. Patients are advised to regularly undergo FC measurement to monitor for pouchitis. An FC concentration in the range of 143.25-579.60 µg/g is predictive of a high risk for pouchitis, and further examination and preventive treatment are necessary in such patients.KEY MESSAGESFecal calprotectin can be used to quantify pouch inflammation.Fecal calprotectin can be used to predict a high risk of pouchitis.


Assuntos
Colite Ulcerativa , Pouchite , Proctocolectomia Restauradora , Humanos , Proctocolectomia Restauradora/efeitos adversos , Colite Ulcerativa/cirurgia , Estudos Retrospectivos , Complexo Antígeno L1 Leucocitário/análise , Pouchite/diagnóstico , Pouchite/etiologia , Pouchite/cirurgia , Medição de Risco , Anastomose Cirúrgica/efeitos adversos
4.
Skin Res Technol ; 29(1): e13255, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36704886

RESUMO

OBJECTIVE: To study the expression of interleukin-1ß (IL-1ß), interleukin-4 (IL-4), interferon-γ (IFN-γ) and tumour necrosis factor α (TNF-α) in different tissue in a dinitrochlorobenzene (DNCB)-induced ear swelling test in mice and further evaluate the correlation between the cytokine expression in different tissues and the degree of ear swelling. METHODS: The mice were sensitised with a 0.50% DNCB solution on their back for 3 days. After 7 days, the thickness of their ears was measured and grouped. Different concentrations of the DNCB solution were challenged in the left ear of each group of mice, and the right ear was used as the control. The thickness of both ears was measured every 24 h, and the mice were sacrificed 72 h after the challenge. The expressions of IL-1ß, IL-4, IFN-γ and TNF-α in the mouse serum, lymph node and ear tissue were quantified by enzyme-linked immunosorbent assay, respectively. RESULTS: There was a linear positive correlation between the swelling index of the mouse lateral ear and the challenge concentration of DNCB (r = 0.96, p < 0.01). The high expression of IL-1ß and IL-4 in the lateral ear tissue of the mice was positively correlated with the ear swelling index 48 h after the challenge. The correlation coefficient was 0.78 (p < 0.01). Furthermore, IFN-γ and TNF-α had no significant correlation with the ear swelling index 48 h after the challenge. CONCLUSION: There is a correlation between the degree of ear swelling in mice and the concentration of DNCB and the expression of IL-1ß and IL-4 in the lateral ear tissue. There is a sub-clinical skin sensitivity state in contact allergy.

5.
ACS Appl Mater Interfaces ; 15(3): 4208-4215, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36625524

RESUMO

Metal-organic frameworks (MOFs) have been proven promising in addressing many critical issues related to gas separation and purification. However, it remains a great challenge to optimize the pore environment of MOFs for purification of specific gas mixtures. Herein, we report the rational construction of three isostructural microporous MOFs with the 4,4',4"-tricarboxyltriphenylamine (H3TCA) ligand, unusual hexaprismane Ni6O6 cluster, and functionalized pyrazine pillars [PYZ-x, x = -H (DZU-10), -NH2 (DZU-11), and -OH (DZU-12)], where the building blocks of Ni6O6 clusters and huddled pyrazine pillars are reported in porous MOFs for the first time. These building blocks have enabled the resulting materials to exhibit good chemical stability and variable pore chemistry, which thus contribute to distinct performances toward C2H2/CO2 separation. Both single-component isotherms and dynamic column breakthrough experiments demonstrate that DZU-11 with the PYZ-NH2 pillar outperforms its hydrogen and hydroxy analogues. Density functional theory calculations reveal that the higher C2H2 affinity of DZU-11 over CO2 is attributed to multiple electrostatic interactions between C2H2 and the framework, including strong C≡C···H-N (2.80 Å) interactions. This work highlights the potential of pore environment optimization to construct smart MOF adsorbents for some challenging gas separations.

6.
Anal Chem ; 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36622664

RESUMO

Adenosine triphosphate (ATP), as an indispensable biomolecule, is the main energy source of cells and is used as a marker for diseases such as cancer and fatty liver. It is of great significance to design a near-infrared fluorescent nanoprobe with excellent performance and apply it to various disease models. Here, a near-infrared fluorescent nanoprobe (ZIF-90@SiR) based on a zeolitic imidazole framework is proposed. The fluorescent nanoprobes are synthesized by encapsulating the dye (SiR) into the framework of ZIF-90. Upon the addition of ATP, the structure of the ZIF-90@SiR nanoprobe is disrupted and SiR is released to generate near-infrared fluorescence at 670 nm. In the process of ATP detection, ZIF-90@SiR shows high sensitivity and good selectivity. Moreover, the ZIF-90@SiR nanoprobe has good biocompatibility due to its low toxicity to cells. It is used for fluorescence imaging of ATP in living cells and thus distinguishing normal cells and cancer cells, as well as distinguishing fatty liver cells. Due to excellent near-infrared fluorescence properties, the ZIF-90@SiR nanoprobe can not only distinguish normal mice and tumor mice but also differentiate normal mice and fatty liver mice for the first time.

7.
Sci Rep ; 13(1): 16, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36604433

RESUMO

Sauropterygia is the largest, most successful group of Mesozoic marine diapsids, spanning from the late Early Triassic to the Late Cretaceous. Plesiomorphic for sauropterygians, pachypleurosauroids are important for our understanding on the early evolution of this group. Here, we present a new pachypleurosaurid, Luopingosaurus imparilis gen. et sp. nov., based on an exceptionally preserved skeleton from the early Middle Triassic Luoping Lagerstätte in Yunnan, China. The discovery documents the first long-snouted pachypleurosaurid with an unexpected hyperphalangy in the manus, providing new insights into the morphological diversification, ecological adaption and biogeographic evolution of this clade. The discovery further indicates that there is a morphological divergence between short-snouted (brevirostrine) keichousaurids and relatively long-snouted (longirostrine) pachypleurosaurids, which was probably driven by ecological specializations related to feeding and foraging. Additionally, an evolutionary trend towards the reduction of the ratio of the hyoid length to mandibular length (HM ratio) is recognized in pachypleurosauroids. This reduction of HM ratio, associated with the increase of the snout length, might implicate a gradual recession of suction feeding in pachypleurosauroid evolution. Phylogenetic studies incorporating Luopingosaurus recover European pachypleurosaurids as successive sister groups to Chinese derived pachypleurosaurids, supporting a western Tethyan origin for this family.


Assuntos
Evolução Biológica , Fósseis , Animais , Filogenia , China , Répteis/anatomia & histologia
8.
Artigo em Inglês | MEDLINE | ID: mdl-36613134

RESUMO

This study aimed to examine the associations between parental mindfulness and preschool child behavior problems and to investigate the mediating role of marital satisfaction and coparenting in the relationship between mindfulness and preschool child behavior problems. This was a cross-sectional study in which general sociodemographic data were obtained from 3448 parents of children in grades junior to senior of kindergarten who were assessed using instruments such as the Mindful Attention Awareness Scale (MAAS), the Strengths and Difficulties Questionnaire (SDQ), the ENRICH Marital Satisfaction Scale (TEMSS), and the Parents' Perceptions of the Coparenting Relationship Questionnaire (PPCR). (1) Mindfulness, preschool child behavior problems, marital satisfaction, and coparenting were significantly correlated with each other, where mindfulness was positively correlated with marital satisfaction and coparenting and significantly negatively correlated with preschool child behavior problems. (2) Mindfulness negatively predicted preschool children's problem behaviors. (3) Marital satisfaction independently mediated the relationship between mindfulness and preschool child behavior problems. (4) Coparenting also independently mediated the relationship between mindfulness and preschool child behavior problems. (5) Marital satisfaction and coparenting play a chain-mediating role between mindfulness and preschool children's problem behaviors. Mindfulness predicted preschool child behavior problems, with marital satisfaction and coparenting as mediators.


Assuntos
Atenção Plena , Comportamento Problema , Humanos , Pré-Escolar , Criança , Estudos Transversais , Poder Familiar , Atenção , Comportamento Infantil
9.
Anal Chim Acta ; 1242: 340813, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36657896

RESUMO

Viscosity is an important component of cell microenvironment, and abnormal mitochondrial viscosity is associated with many diseases such as tumor and fatty liver. Herein, a near-infrared fluorescence probe (QX-V) based on quinoline-xanthene dye for detecting viscosity is constructed. In high viscosity medium, the free rotation of single bond is inhibited and the fluorescence is released. The probe shows high sensitivity together with good selectivity. Notably, QX-V has a long excitation wavelength (710 nm) and emission wavelength (786 nm). At the same time, the probe is a positively charged molecule that can target mitochondria. QX-V can not only distinguish cancer cells from normal cells, but also make a distinction between normal cells and fatty hepatocytes. In addition, QX-V is used to image viscosity abnormality in tumor-bearing mice. The probe also has a good ability to image viscosity abnormality caused by liver injury in fatty-liver mice.


Assuntos
Fígado Gorduroso , Neoplasias , Humanos , Camundongos , Animais , Corantes Fluorescentes/química , Viscosidade , Imagem Óptica/métodos , Mitocôndrias/química , Células HeLa , Fígado Gorduroso/patologia , Neoplasias/diagnóstico por imagem , Neoplasias/patologia
10.
Neuropsychobiology ; : 1-9, 2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36623478

RESUMO

INTRODUCTION: Observational studies highlight associations of common diseases with individual schizophrenia symptoms. However, it is unclear whether these diseases are associated with individual treatment-resistant schizophrenia (TRS). We aimed to explore the genetic associations between common immune diseases, metabolic diseases, psychiatric disorders, gut microbiota and TRS. METHODS: Genome-wide association study (GWAS) summary data of European participants (n = ∼456,327) included TRS, 11 psychiatric disorders, 23 immune and metabolic diseases, body mass index, height, and 211 gut microbiota. In this genetic correlation and two-sample Mendelian randomization (MR) study, linkage disequilibrium score (LDSC) regression was applied to infer genetic correlation estimates. Two-sample MR tested potential causal associations of genetic variants associated with common immune diseases, metabolic diseases, psychiatric disorders, and gut microbiota with TRS. RESULTS: LDSC revealed candidate associations between attention deficit/hyperactivity disorder (ADHD), schizophrenia, intestinal infectious diseases, obesity and TRS (genetic correlation range, 0.230-0.702; p < 0.05). Two-sample MR analyses suggested that ADHD was positively associated with TRS (estimate [SE] = 0.204 [0.073], p = 0.005), a finding that remained stable across statistical models. Besides, schizophrenia and genus Barnesiella levels were causally associated with TRS but not consistent across MR approaches. CONCLUSION: This study reports genetic correlations between ADHD, schizophrenia, intestinal infectious diseases, obesity and TRS. The study also found that genus Barnesiella was associated with TRS. These findings may have clinical implications, highlighting the possible strategy for TRS prevention.

11.
Anal Chem ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36633481

RESUMO

Owing to the excellent structural rigidity and programmable reaction sites, DNA nanostructures are more and more widely used, but they are limited by high cost, strict sequence requirements, and time-consuming preparation. Herein, a general signal amplifier based on a micelle-supported entropy-driven circuit (MEDC) was designed and prepared for sensitive quantification of biomarkers. By modifying a hydrophobic cholesterol molecule onto a hydrophilic DNA strand, the amphiphilic DNA strand was first prepared and then self-assembled into DNA micelles (DMs) driven by hydrophobic effects. The as-developed DM showed unique advantages of sequence-independence, easy preparation, and low cost. Subsequently, amplifier units DMF and DMTD were successfully fabricated by connecting fuel strands and three-strand duplexes (TDs) to DMs, respectively. Finally, the MEDC was triggered by microRNA-155 (miR-155), which herein acted as a model analyte, resulting in dynamic self-assembly of poly-DNA micelles (PDMs) and causing the recovery of cyanine 3 (Cy3) fluorescence as the DMTD dissociated. Benefiting from the "diffusion effect", the MEDC herein had a nearly 2.9-fold increase in sensitivity and a nearly 97-fold reduction in detection limit compared to conventional EDC. This amplifier exhibited excellent sensitivity of microRNAs, such as miR-155 detection in a dynamic range from 0.05 to 4 nM with a detection limit of 3.1 pM, and demonstrated outstanding selectivity with the distinguishing ability of a single-base mismatched sequence of microRNAs. Overall, the proposed strategy demonstrated that this sequence-independent DNA nanostructure improved the performance of traditional DNA probes and provided a versatile method for the development of DNA nanotechnology in biosensing.

12.
Int J Mol Sci ; 24(2)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36675232

RESUMO

Despite recent advances in oncology, cancer has remained an enormous global health burden, accounting for about 10 million deaths in 2020. A third of the cancer cases in developing counties are caused by microbial infections such as human papillomavirus (HPV), Epstein-Barr Virus (EBV), and hepatitis B and C viruses. EBV, a member of the human gamma herpesvirus family, is a double-stranded DNA virus and the primary cause of infectious mononucleosis. Most EBV infections cause no long-term complications. However, it was reported that EBV infection is responsible for around 200,000 malignancies worldwide every year. Currently, there are no vaccines or antiviral drugs for the prophylaxis or treatment of EBV infection. Recently, the gut microbiota has been investigated for its pivotal roles in pathogen protection and regulating metabolic, endocrine, and immune functions. Several studies have investigated the efficacy of antiviral agents, gut microbial metabolites, and natural products against EBV infection. In this review, we aim to summarise and analyse the reported molecular mechanistic and clinical studies on the activities of gut microbial metabolites and natural medicines against carcinogenic viruses, with a particular emphasis on EBV. Gut microbial metabolites such as short-chain fatty acids were reported to activate the EBV lytic cycle, while bacteriocins, produced by Enterococcus durans strains, have shown antiviral properties. Furthermore, several natural products and dietary bioactive compounds, such as curcumin, epigallocatechin gallate, resveratrol, moronic acid, and andrographolide, have shown antiviral activity against EBV. In this review, we proposed several exciting future directions for research on carcinogenic viruses.


Assuntos
Infecções por Vírus Epstein-Barr , Microbioma Gastrointestinal , Neoplasias , Humanos , Herpesvirus Humano 4/fisiologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Carcinógenos/metabolismo , Neoplasias/tratamento farmacológico , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/metabolismo , Carcinogênese
13.
J Orthop Surg Res ; 18(1): 5, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36593454

RESUMO

BACKGROUND: A minimally invasive technique with various screw configurations without open surgery is currently used for the fixation of transverse patellar fractures. Percutaneous crossing screw configuration has been reported to have a good bone union rate in patellar fractures. However, the difference in mechanical stability of the fractured patella between different screw-included angles has not been fully investigated. Hence, this study aims to compare the mechanical stability of parallel and crossing screw fixations with different screw-included angles for the fixation of transverse patellar fractures during level walking. METHODS: A finite element knee model containing a patella with a transverse fracture is created. Two headless compression screws with different angles (0°, 30°, 60°, and 90°) are used to fix the fracture. The loading conditions of the knee joint during level walking are used to compare the stability of the fractured patella with different fixation screw configurations. RESULTS: The results indicate that the maximum fracture gap opening distance increased with an increase in the included angle. Two parallel screws yield the smallest gap distance among all screw configurations. The maximum gap opening distances at the anterior leading edge of the fractured patella with two parallel screws and two screws having an included angle of 90° are 0.73 mm and 1.31 mm, respectively, at 15% walking cycle. CONCLUSIONS: Based on these results, the superior performance of two parallel screws over crossing screw fixations in the fixation of transverse patellar fractures is established. Furthermore, the smaller the angle between the crossing screws, the better is the stability of the fractured patella.


Assuntos
Fraturas Ósseas , Traumatismos do Joelho , Humanos , Fixação Interna de Fraturas/métodos , Análise de Elementos Finitos , Parafusos Ósseos , Fraturas Ósseas/cirurgia , Patela/cirurgia , Fenômenos Biomecânicos
14.
Signal Transduct Target Ther ; 8(1): 5, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36596762

RESUMO

Chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA) have great potentials in autoimmune diseases and could be novel therapeutics for relapsed/refractory neuromyelitis optica spectrum disorder (NMOSD). To evaluate the safety and efficacy of the CT103A, a self-developed BCMA-targeting CAR construct against BCMA, in patients with AQP4-IgG seropositive NMOSD, an ongoing, investigator-initiated, open-label, single-arm, phase 1 clinical trial is conducted at our center. In total, 12 patients were administered with a CAR-BCMA infusion. Ten of the 12 patients dosed were women (83.3%), with a median age of 49.5 years (range, 30-67). were The most common events of grade 3 or higher were hematologic toxic effects. Seven patients (58%) developed infections, but no grade 4 infections occurred. Cytokine release syndrome was reported in all patients with only events of grade 1 or 2 observed. During the follow-up of a median 5.5 months, 11 patients had no relapse; all patients generally reported improvement in disabilities and quality-of-life outcomes; 11 patients' AQP-4 antibodies in serum showed a downward trend by the cutoff date. CAR T-cell expansion was associated with responses, and persisted more than 6 months post-infusion in 17% of the patients. In summary, CAR T-cell therapy shows a manageable safety profile and therapeutic potentials for patients with relapsed/refractory AQP4-IgG seropositive NMOSD. Another expansion phase is currently underway to determine the safety and efficacy of CAR T-BCMA infusion in patients with other neuro-inflammatory diseases.


Assuntos
Imunoterapia Adotiva , Neuromielite Óptica , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Masculino , Imunoterapia Adotiva/efeitos adversos , Neuromielite Óptica/terapia , Neuromielite Óptica/etiologia , Imunoglobulina G
15.
Clin Rheumatol ; 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36604358

RESUMO

OBJECTIVE: To determine diagnostic accuracy and evaluate the predictive value of autoantibody profiles in patients with systemic sclerosis (SSc). METHODS: A total of 140 patients with SSc (125 female, mean age 54.2 ± 14.2 years) were analyzed by a multiplex line immunoassay (Euroimmun) for autoantibodies against 12 SSc-related antigens. Associations between the presence of the autoantibodies and demographic clinical manifestations of patients with SSc were investigated. RESULTS: The sensitivity and specificity of this assay were as follows: 32.9% and 99.4% for anti-Scl-70, 29.3% and 88.9% for anti-CENP A, 28.6% and 87.8% for anti-CENP B, 7.1% and 97.8% for anti-RP11, 5.7% and 100% for anti-RP155, 2.9% and 99.4% for anti-NOR 90, 2.9% and 98.9% for anti-Th/To, 1.4% and 96.7% for anti-PM-Scl-100, 5.0% and 98.3% for anti-PM-Scl-75, and 2.9% and 97.2% for anti-Ku, respectively. Anti-Scl-70 was significantly associated with sine scleroderma (P = 0.003), digital ulcers (P = 0.047), and Raynaud's phenomenon as the first clinical manifestation of onset (P = 0.017). SSc-ILD was more common in patients with anti-Scl-70 (P = 0.029) and less frequent in patients with anti-CENP A (P < 0.001) and anti-CENP B (P < 0.001). There was a significant association between PAH with anti-CENP A (P = 0.008) and anti-CENP B (P = 0.025). Renal involvement was significantly related to anti-NOR90 (P = 0.026) and anti-Th/To (P = 0.026). CONCLUSIONS: This study confirmed the important role of autoantibodies in accurately diagnosing SSc. The autoimmune profile of patients with SSc was related to specific disease manifestations. Key Points • Autoantibody profiles were useful for diagnosing SSc and predicting clinical features of patients.

16.
J Food Sci ; 2023 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-36617678

RESUMO

The impact of phenolic compounds on the human body depended on the type, content, bioavailability, and antioxidant activity. After digestion, different phenolic compounds had different changes of bioavailability and antioxidant activity, which needed to be considered in the application. In this experiment, the structural stability and antioxidant activity of 27 phenolic compounds (phenolic acids, flavonols, flavonoids, and flavanones) were investigated during the in vitro simulated digestion. This experiment eliminated the influence of food matrix, provide a basis for regularity for the changes of phenolic substances in different materials. Results showed that the bioaccessibility of phenolic compounds with different structures varied, and there was a conformational relationship between the structure and stability. After oral digestion, most of the phenolic compounds underwent degradation and the cellular antioxidant activity (CAA) values decreased to a large extent (p < 0.05). After gastric digestion, the content (p > 0.05) and CAA values (p < 0.05) of most phenolic compounds increased. However, after intestinal digestion, the phenolic compounds were degraded to a greater extent, and different structures of phenolic compounds had different changes in CAA values (p < 0.05). In general, the CAA values of most phenolic compounds after in vitro digestion were lower than the initial value. The 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ehylbenzthiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) values of phenolic acids and flavonols decreased after in vitro simulated digestion (p < 0.05), while the values of DPPH, ABTS, and FRAP of most flavonoids (p < 0.05) increased. The increased oxygen radical absorption capacity (ORAC) values were found in most phenolic acids, flavonols, and flavonoids (p < 0.05), and most flavanones showed unremarkable changes in ORAC values (p > 0.05). In general, the changing trend of chemical-based antioxidant activity was consistent with the content of phenolic compounds.

17.
ACS Synth Biol ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36649530

RESUMO

Yeast surface display is an appealing technique for constructing multienzyme cascades. This technique is commonly achieved using a scaffold for the ordered arrangement of various enzymes. However, this method is typically complicated because scaffold use may engender extra metabolic burden on the cell host. Here, we established a direct yeast surface codisplay strategy by employing two complementary anchor motifs, Agα1 and Pir1. These motifs allow for the codisplay of sequential uridine diphosphate-glycosyltransferase (UGT) and sucrose synthase (SUS) on the surface of Pichia pastoris (syn. Komagataella phaffii) for the glycosylation of natural products. We manipulated the displayed stoichiometry, amount, and assembly order of UGT and SUS by coupling them with anchor motifs. Furthermore, their effect on enzyme activity was thoroughly investigated. The surface-codisplayed strain UGT-Pir-SUS-Agα exhibited greater thermostability than the single-displayed strains and their free counterparts. Moreover, the strain UGT-Pir-SUS-Agα was successfully applied to glycyrrhetinic acid (GA) glycosylation to produce GA-3-O-Glc, with sucrose being the sugar donor in this process. This generated 7.5- to 20- and 5.3-fold higher GA-3-O-Glc concentration compared with the free counterparts (enzyme mass loading of 20-fold in excess) and mixed single-displayed strains of UGT-Agα and SUS-Pir, respectively. This increase was due to the improved biochemical properties and substrate channeling effect of strain UGT-Pir-SUS-Agα. This controllable direct surface codisplay strategy, based on complementary anchor motifs, is readily extendable to other enzyme cascades.

18.
Phytomedicine ; 111: 154653, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36641976

RESUMO

BACKGROUND: Xingpi Capsule (XP), a commercially available over-the-counter herbal medicine in China, plays a prominent role in treating diarrhea-predominant irritable bowel syndrome (IBS-D). Nevertheless, the potential mechanisms remain unclear. PURPOSE: This study aimed to investigate XP efficacy in IBS-D and elucidate the underlying molecular mechanisms. METHODS: A rat IBS-D model was established by senna decoction gavage combined with restraint stress and swimming exhaustion. The changes in rat body weight and stool were recorded daily. Colon pathological changes and the number of colonic goblet cells of rats were observed by hematoxylin-eosin (HE) staining and Alcian blue plus periodic acid-Schiff (AB-PAS) staining, respectively. The expression of Occludin, a tight-junction-associated protein, was examined via immunohistochemistry. Images of colonic microvilli were obtained by TEM. Western blotting (WB) was used to analyze the protein expression of the ASK1/P38 MAPK pathway. The composition of the rat intestinal microbiota was detected by 16S rRNA sequencing. Changes in colonic metabolites were evaluated by liquid chromatography-mass spectrometry (LC-MS). Changes in colon RNA expression were assessed by RNA sequencing (RNA-Seq). The nontoxic range of hypoxanthine (HPX) was screened by Cell Counting Kit-8 (CCK8), the cell model of human colonic epithelial cells (NCM460) induced by lipopolysaccharide (LPS) was established, and the effective concentration of HPX was screened by CCK8. After transfection of pcDNA3.1-MAP3K5, Hoechst 33,342 staining, flow cytometry to detect cell apoptosis, and immunofluorescence to detect the fluorescence changes of ASK1 and ZO-1. WB detection of ASK1/P38 MAPK pathway protein expression changes. RESULTS: XP increased the body weight of IBS-D patients and reduced the loose stool rate, loose stool index, and Bristo score. In addition, XP mitigated colon lesions, increased the number of goblet cells and the expression of Occludin, and prevented severe distortion and effacement of the microvillous structure. Specifically, 16S rRNA gene sequence analysis showed that XP decreased the abundance of Desulfurium and Prevotella 9 at the phylum and genus levels while increasing the abundance of Bacteroides at the genus level. RNA-Seq combined with WB validation showed that XP exerted antidiarrheal effects by inhibiting the ASK1/P38 MAPK signaling pathway. Additionally, XP also increased the relative expression level of the metabolite HPX, as revealed by untargeted metabolomics analysis. Impressively, the correlation analysis between 16S rRNA sequencing and LC-MS suggested that HPX and Prevotella 9 are negatively correlated, which indicated that XP might increase the content of HPX by reducing the abundance of Prevotella 9. Meanwhile, a negative correlation between HPX and ASK1 was indicated through RNA-Seq and LC-MS, which suggested that the inhibition of ASK1 (Map3k5) may be ascribed to the increase in HPX after XP treatment. In vitro experiments have proven that HPX can alleviate LPS-induced NCM460 damage, specifically manifested as enhancing cell viability, reducing cell apoptosis, increasing ZO-1 expression, reducing the fluorescence intensity of MAP3K5 in the model group, and inhibiting the expression of ASK1/P38 MAPK pathway proteins. The protective effect of HPX was reversed after transfection with pcDNA 3.1-MAP3K5, which fully demonstrated that the protective mechanism of HPX was achieved by inhibiting MAP3K5 and its downstream pathways. CONCLUSION: XP displayed multifaceted protection against IBS-D in rats by regulating the intestinal microbiota, increasing the relative expression level of HPX, a metabolite of the microbiota, and inhibiting the ASK1/P38 MAPK signaling pathway.

19.
Biotechnol Bioeng ; 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36593696

RESUMO

As a plant-derived pentacyclic triterpenoid, ß-amyrin has been heterogeneously synthesized in Saccharomyces cerevisiae. However, ß-amyrin is intracellularly produced in a lower gram scale using recombinant S. cerevisiae, which limits the industrial applications. Although many strategies have been proven to be effective to improve the production of ß-amyrin, the intracellularly accumulation is still a challenge in reaching higher titer and simplifying the extraction process. To solve this problem, the amphiphilic ß-cyclodextrin (ß-CD) has been previously employed to aid the efflux of ß-amyrin out of the cells. Nevertheless, the supplemented ß-CD in the medium is not consistent with ß-amyrin synthesis and has the disadvantage of rather high cost. Therefore, an aided-efflux system based on in situ synthesis of ß-CD was developed in this study to enhance the biosynthesis of ß-amyrin and its efflux. The in situ synthesis of ß-CD was started from starch by the surface displayed cyclodextrin glycosyltransferase (CGTase) on yeast cells. As a result, the synthesized ß-CD could capture 16% of the intracellular ß-amyrin and improve the total production by 77%. Furthermore, more strategies including inducing system remodeling, precursor supply enhancement, two-phase fermentation and lipid synthesis regulation were employed. Finally, the production of ß-amyrin was increased to 73 mg/L in shake flask, 31 folds higher than the original strain, containing 31 mg/L of extracellular ß-amyrin. Overall, this work provides novel strategies for the aided-efflux of natural products with high hydrophobicity in engineered S. cerevisiae.

20.
BMJ ; 380: e071952, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36631148

RESUMO

OBJECTIVE: To assess the recent trends in prevalence and management of hypertension in China, nationally and by population subgroups. DESIGN: Six rounds of a national survey, China. SETTING: China Chronic Disease and Risk Factors Surveillance, 2004-18. PARTICIPANTS: 642 523 community dwelling adults aged 18-69 years (30 501 in 2004, 47 353 in 2007, 90 491 in 2010, 156 836 in 2013, 162 293 in 2015, and 155 049 in 2018). MAIN OUTCOME MEASURES: Hypertension was defined as a blood pressure of ≥140/90 mm Hg or taking antihypertensive drugs. The main outcome measures were hypertension prevalence and proportion of people with hypertension who were aware of their hypertension, who were treated for hypertension, and whose blood pressure was controlled below 140/90 mm Hg. RESULTS: The standardised prevalence of hypertension in adults aged 18-69 years in China increased from 20.8% (95% confidence interval 19.0% to 22.5%) in 2004 to 29.6% (27.8% to 31.3%) in 2010, then decreased to 24.7% (23.2% to 26.1%) in 2018. During 2010-18, the absolute annual decline in prevalence of hypertension among women was more than twice that among men (-0.83 percentage points (95% confidence interval -1.13 to -0.52) v -0.40 percentage points (-0.73 to -0.07)). Despite modest improvements in the awareness, treatment, and control of hypertension since 2004, rates remained low in 2018, at 38.3% (36.3% to 40.4%), 34.6% (32.6% to 36.7%), and 12.0% (10.6% to 13.4%). Of 274 million (95% confidence interval 238 to 311 million) adults aged 18-69 years with hypertension in 2018, control was inadequate in an estimated 240 million (215 to 264 million). Across all surveys, women with low educational attainment had higher prevalence of hypertension than those with higher education, but the finding was mixed for men. The gap in hypertension control between urban and rural areas persisted, despite larger improvements in diagnosis and control in rural than in urban areas. CONCLUSIONS: The prevalence of hypertension in China has slightly declined since 2010, but treatment and control remain low. The findings highlight the need for improving detection and treatment of hypertension through the strengthening of primary care in China, especially in rural areas.


Assuntos
Hipertensão , Adulto , Masculino , Humanos , Feminino , Prevalência , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Hipertensão/diagnóstico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , China/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Conscientização
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