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1.
J Immunol ; 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36427008

RESUMO

Abnormally high follicle-stimulating hormone (FSH) has been reported to associate with cardiovascular diseases in prostate cancer patients with specific androgen deprivation therapy and in menopausal women. All of the cardiovascular diseases were involved in atherosclerosis. However, the pathogenic mechanism of FSH-associated atherosclerosis remains uncertain. Apolipoprotein E-deficient mice were chosen to develop atherosclerosis, of which the plaques were analyzed with administration of short- and long-term FSH imitating androgen deprivation therapy-induced and menopausal FSH elevation. The study showed that short- and long-term exposure of FSH significantly accelerated atherosclerosis progression in apolipoprotein E-deficient mice, manifested as strikingly increased plaques in the aorta and its roots, increased macrophage content, reduced fibrin, and an enlarged necrotic core, suggesting a decrease in plaque stability. Furthermore, expression profiles from the Gene Expression Omnibus GSE21545 dataset revealed that macrophage inflammation was tightly associated with FSH-induced atherosclerotic progression. The human monocyte cell line THP-1 was induced by PMA and worked as a macrophage model to detect inflammatory factors and cellular functions. FSH remarkably promoted the expression of IL-1ß in macrophages and strikingly increased the chemotactic migratory capacity of macrophages toward MCP-1, but the promigratory capacity of FSH was attenuated in foam cells. Overall, we revealed that FSH significantly promoted the inflammatory response and migration of macrophages, thereby provoking atherosclerosis development.

2.
Front Immunol ; 13: 1022720, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389726

RESUMO

Numerous studies have demonstrated the important roles of epigenetic modifications in tumorigenesis, progression and prognosis. However, in hepatocellular carcinoma, the potential link between N7-methylguanosine (m7G) modification and molecular heterogeneity and tumor microenvironment (TME) remains unclear. Method: We performed a comprehensive evaluation of m7G modification patterns in 816 hepatocellular carcinoma samples based on 24 m7G regulatory factors, identified different m7G modification patterns, and made a systematic correlation of these modification patterns with the infiltration characteristics of immunocytes. Then, we built and validated a scoring tool called m7G score. Results: In this study, we revealed the presence of three distinct m7G modification patterns in liver cancer, with remarkable differences in the immunocyte infiltration characteristics of these three subtypes. The m7G scoring system of this study could assess m7G modification patterns in individual hepatocellular carcinoma patients, could predict TME infiltration characteristics, genetic variants and patient prognosis. We also found that the m7G scoring system may be useful in guiding patients' clinical use of medications. Conclusions: This study revealed that m7G methylation modifications exerted a significant role in formation of TME in hepatocellular carcinoma. Assessing the m7G modification patterns of single patients would help enhance our perception of TME infiltration characteristics and give significant insights into immunotherapy efficacy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Metilação , Epigênese Genética , Processamento de Proteína Pós-Traducional , Microambiente Tumoral
3.
J Neurosci ; 42(41): 7833-7847, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36414013

RESUMO

Autism is characterized by two key diagnostic criteria including social deficits and repetitive behaviors. Although recent studies implicated ventral striatum in social deficits and dorsal striatum in repetitive behaviors, here we revealed coexisting and opposite morphologic and functional alterations in the dorsostriatal direct and indirect pathways, and such alterations in these two pathways were found to be responsible, respectively, for the two abovementioned different autism-like behaviors exhibited by male mice prenatally exposed to valproate. The alteration in direct pathway was characterized by a potentiated state of basal activity, with impairment in transient responsiveness of D1-MSNs during social exploration. Concurrent alteration in indirect pathway was a depressed state of basal activity, with enhancement in transient responsiveness of D2-MSNs during repetitive behaviors. A causal relationship linking such differential alterations in these two pathways to the coexistence of these two autism-like behaviors was demonstrated by the cell type-specific correction of abnormal basal activity in the D1-MSNs and D2-MSNs of valproate-exposed mice. The findings support those differential alterations in two striatal pathways mediate the two coexisting autism-like behavioral abnormalities, respectively. This result will help in developing therapeutic options targeting these circuit alterations.SIGNIFICANCE STATEMENT Autism is characterized by two key diagnostic criteria including social deficits and repetitive behaviors. Although a number of recent studies have implicated ventral striatum in social deficits and dorsal striatum in repetitive behaviors, but social behaviors need to be processed by a series of actions, and repetitive behaviors, especially the high-order repetitive behaviors such as restrictive interests, have its scope to cognitive and emotional domains. The current study, for the first time, revealed that prenatal valproate exposure induced coexisting and differential alterations in the dorsomedial striatal direct and indirect pathways, and that these alterations mediate the two coexisting autism-like behavioral abnormalities, respectively. This result will help in developing therapeutic options targeting these circuit alterations to address the behavioral abnormalities.


Assuntos
Transtorno Autístico , Estriado Ventral , Camundongos , Animais , Masculino , Transtorno Autístico/metabolismo , Ácido Valproico , Comportamento Social , Estriado Ventral/metabolismo
4.
Cancer Manag Res ; 14: 3175-3179, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36411743

RESUMO

Background: Lorlatinib has been suggested as the therapeutic option for patients with ROS1-rearranged non-small-cell lung cancer (NSCLC) after ROS1 tyrosine kinase inhibitor (TKI) failure. However, the mechanism mediating lorlatinib resistance has not been well elucidated in ROS1-rearranged NSCLC. Post- lorlatinib therapeutic options remain scarce. Case Presentation: Herein, we describe a 31-year-old female patient with stage IVB ROS1-rearranged NSCLC. She received 2nd line treatment with crizotinib after chemotherapy failure and achieved a partial response lasting for 15 months. An NF1 p.G127Ter mutation emerged as a potential crizotinib resistance mechanism. She subsequently received lorlatinib treatment and achieved a progression-free survival (PFS) of seven months. Based on the emergence of a resistant BRAF V600E, the patient was switched to a combinatorial targeted therapy with lorlatinib, dabrafenib, and trametinib and attained stable disease. She continued the treatment with a time-to-treatment failure of 5.5 months. The acquisition of NRAS p.Q61R and NTRK amplification may confer resistance to the combinatorial targeted therapy. Conclusion: To the best of our knowledge, we reported the first case demonstrating that BRAF p.V600E can mediate the lorlatinib resistance in ROS1-rearranged NSCLC and the combinational targeted therapy of ROS1 TKI with dabrafenib and trametinib may serve as an efficient therapeutic option for subsequent treatment.

5.
Breed Sci ; 72(3): 213-221, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36408326

RESUMO

Psathyrostachys huashanica is a relative of wheat (Triticum aestivum L.) with many disease resistance genes that can be used to improve wheat disease resistance. In order to enrich the germplasm resources available in wheat genetics and breeding, we assessed Fusarium head blight (FHB) resistance in 45 interspecific derivatives between wheat and Psathyrostachys huashanica during two years from 2017-2018. Two interspecific derivatives comprising, H-34-8-2-6-1 and H-24-3-1-5-19-1 were identified as FHB resistant lines. These two lines were examined based on their morphology and cytogenetics, as well as by genomic in situ hybridization (GISH), fluorescence in situ hybridization (FISH), molecular markers, and 660K genotyping array to determine their genetic construction. The results confirmed H-34-8-2-6-1 as a wheat-P. huashanica 1Ns long arm ditelosomic addition line and H-24-3-1-5-19-1 as a wheat-P. huashanica 2Ns substitution line. Assessments of the agronomic traits showed that H-34-8-2-6 had significantly higher kernel number per spike and self-fertility rate than parent 7182. In addition, compared with 7182, H-24-3-1-5-19-1 had a much lower plant height while the other agronomic traits were relatively similar. The two new lines are valuable germplasm materials for breeding FHB resistance in wheat.

6.
Medicine (Baltimore) ; 101(45): e31361, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36397388

RESUMO

RATIONALE: Paxlovid has shown the potential decreasing the hospitalization rate of mild or moderate coronavirus disease 2019 (COVID-19) and death in few of clinical trials, and is expected to the most promising medicine targeting Severe Acute Respiratory Syndrome Coronavirus 2 (SRAS-COV-2). However, there are no enough evidences to show it effectiveness for all patients with SARS-COV-2, especially among elderly patients and newest Omicron variant. PATIENT CONCERNS AND DIAGNOSIS: A 79 year's old female patient was admitted to hospital because of the moderate COVID-19 caused by the Omicron variant BA2.0. He presented the initial syndromes including Xerostomia, cough and fever. Chest computed tomography (CT) scanning at admission showed the exudation lesions on lung. The laboratory examination revealed that there are increased C-reactive protein (CRP), Ferritin and erythrocytesedimentationrate (ESR) and decreased white blood cells. INTERVENTIONS: The oral Paxlovid (Nirmatrelvir/Ritonavir) was administrated on second day after admission. OUTCOMES: The syndromes of Xerostomia, cough and fever was improved on third day after use of Paxlovid. The levels of CRP, ESR and counts of white blood cells returned the normal after three days of admission. The chest CT scanned on the third and sixth day after Paxlovid used showed the absorption of lesions. The examination of SARS-COVS viral nucleic acid turned negative at fifth day of admission. LESSONS: As a result, we would consider that Paxlovid is a suitable oral drug for elderly patients with SARS-COV2 even Omicron variant, it's benefit to improve patient's symptom and signs and can prevents COVID-19 with the high-risk factors from severe disease, although it didn't shorten the time for viral nucleic acid to turn negative.


Assuntos
COVID-19 , Xerostomia , Masculino , Humanos , Feminino , Idoso , SARS-CoV-2 , Tosse/etiologia , RNA Viral , Febre/etiologia
7.
J Immunol ; 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36368721

RESUMO

Abnormally high follicle-stimulating hormone (FSH) has been reported to associate with cardiovascular diseases in prostate cancer patients with specific androgen deprivation therapy and in menopausal women. All of the cardiovascular diseases were involved in atherosclerosis. However, the pathogenic mechanism of FSH-associated atherosclerosis remains uncertain. Apolipoprotein E-deficient mice were chosen to develop atherosclerosis, of which the plaques were analyzed with administration of short- and long-term FSH imitating androgen deprivation therapy-induced and menopausal FSH elevation. The study showed that short- and long-term exposure of FSH significantly accelerated atherosclerosis progression in apolipoprotein E-deficient mice, manifested as strikingly increased plaques in the aorta and its roots, increased macrophage content, reduced fibrin, and an enlarged necrotic core, suggesting a decrease in plaque stability. Furthermore, expression profiles from the Gene Expression Omnibus GSE21545 dataset revealed that macrophage inflammation was tightly associated with FSH-induced atherosclerotic progression. The human monocyte cell line THP-1 was induced by PMA and worked as a macrophage model to detect inflammatory factors and cellular functions. FSH remarkably promoted the expression of IL-1ß in macrophages and strikingly increased the chemotactic migratory capacity of macrophages toward MCP-1, but the promigratory capacity of FSH was attenuated in foam cells. Overall, we revealed that FSH significantly promoted the inflammatory response and migration of macrophages, thereby provoking atherosclerosis development.

8.
Materials (Basel) ; 15(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36363277

RESUMO

A gradient structure (GS) design is a prominent strategy for strength-ductility balance in metallic materials, including Cu alloys. However, producing a thick GS surface layer without surface damage is still a challenging task limited by the available processing technology. In this work, a gradient structure (GS) surface layer with a thickness at the millimeter scale is produced in the Cu-38 wt.% Zn alloy using ultrasonic severe surface rolling technology at room temperature. The GS surface layer is as thick as 1.1 mm and involves the gradient distribution of grain size and dislocation density. The grain size is refined to 153.5 nm in the topmost surface layer and gradually increases with increasing depth. Tensile tests indicate that the single-sided USSR processed alloy exhibits balanced strength (467.5 MPa in yield strength) and ductility (10.7% in uniform elongation). Tailoring the volume fraction of the GS surface layer can tune the combination of strength and ductility in a certain range. The high strength of GS surface layer mainly stems from the high density of grain boundaries, dislocations and dislocation structures, deformation twins, and GS-induced synergistic strengthening effect. Our study elucidates the effect of the thick GS surface layer on strength and ductility, and provides a novel pathway for optimizing the strength-ductility combination of Cu alloys.

9.
Infect Drug Resist ; 15: 6613-6623, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386421

RESUMO

Background: Severe complications may cause a fatal or disabling outcome in patients with Rickettsia japonica infection but are poorly understood. Methods: We identified 11 patients with only Rickettsia japonica infection with metagenomics next generation sequencing (mNGS) during April to November 2021 at Yichang Central People's Hospital, China. Clinical data were obtained through review of medical records. Results: Most patients realized that they had symptoms about one or two days after being bitten. Fever (91%), pulmonary effusion (91%), rash or erythema (100%), abnormal urine (100%), neutropenia (100%), lymphopenia (100%), and thrombocytopenia (100%) were the most common clinical signs. Six severely ill patients were admitted to the intensive care unit and five had mild symptoms. Systemic manifestations such as vomiting (83%), neurological manifestations (100%), and disseminated intravascular coagulation (100%) were more frequently observed in the severe cases, 33.3% of whom developed purpura fulminans requiring amputation or skin graft, and 16.6% died two days after admission. Some patients experienced sequelae. Conclusion: Our study found that patients with critical Rickettsia japonica infection complicating disseminated intravascular coagulation had high risk of poor outcome.

10.
Sci Total Environ ; : 160433, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36435253

RESUMO

Phosphorus is an essential element for food production, but the distribution of its global reserve is highly uneven. With the increasing demand for products from all sectors of the phosphorus supply chain, the international phosphorus material trade is becoming increasingly intensive. However, the evolution of the global phosphorus trade network and potential supply risks caused by the trade structure and trade stability are rarely evaluated. By employing the complex network theory, a phosphorus material trade network and a quantitative evaluation index of the trade risk using the external supply risks are proposed to evaluate the supply risk in different countries from 2000 to 2020. According to the network analysis of global phosphorus trades for phosphate rock, phosphorus fertilizer and phosphoric acid, the number of trading countries and trading links has generally increased during the last twenty years. However, the trade structure was found to be significantly altered due to the stresses on the phosphorus reserve scarcity and trade restrictions from countries such as the United States and China. Correspondingly, Morocco has become the largest phosphorus-exporting country since 2016, while India was the world's largest phosphorus-importing country between 2008 and 2015. The topological network characteristics indicate that the phosphorus trade is well connected and more stable over time, but high supply risks were also identified, especially in developing countries in Africa within their phosphate rock and phosphorus fertilizer trade, which might threaten their food security. The obtained findings would be helpful for phosphorus trading countries to manage their trade risks in a timely manner.

11.
Brain Res ; 1798: 148158, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36368459

RESUMO

Chronic cerebral hypoperfusion (CCH) is a major risk factor for cognitive decline and degenerative processes. Shunaoxin dropping pill (SNX) has been clinically used to treat cerebrovascular diseases. However, the effect and mechanism of SNX in treating CCH-induced cognitive impairment remain unclear. In this study, CCH was induced in rats using permanent bilateral common carotid artery ligation (2-VO). CCH rats were characterized by impaired spatial learning and memory ability, as well as increased oxidative stress and inflammation in the hippocampus. Additionally, CCH rats had reduced richness and biodiversity of fecal microbiota, which showed a strong correlation with altered serum metabolites. SNX significantly improved the cognitive impairment and restored the dysbiosis of fecal microbiota and serum metabolites in CCH rats. Notably, SNX did not prevent cognitive impairment in antibiotics-treated CCH rats. Our findings suggest that the microbiota-gut-brain axis is a promising therapeutic target for the treatment of CCH-induced cognitive impairment.

12.
Artigo em Inglês | MEDLINE | ID: mdl-36435444

RESUMO

PURPOSES: Large-scale jaw reconstruction can hardly achieve satisfactory results only by relying on doctors' experience. In this study, we assessed a new approach using a machine learning algorithm based on jaw feature points to assist complex jaw reconstruction in patients with maxillary and mandibular defects. METHODS: One hundred and two computed tomography (CT) data on the jaw were collected and 16 skeletal marker points on the jaw were selected. The machine learning algorithm learned the positional relationship between points and built a model, which was used to predict the coordinate position of an unknown point. Then the model was used for a surgical plan in clinical cases. RESULTS: The linear regression model based on machine learning can control the error within 3 mm. In linear models, Lasso has a slight advantage over the others. We used Lasso to predict the missing points for two patients with maxillary and mandibular defect, respectively. The operation was carried out as planned, and the defects were successfully repaired. CONCLUSIONS: The restoration of jaw feature points based on a machine learning algorithm is expected to solve large-scale jaw defects without contralateral reference.

13.
Chin J Nat Med ; 20(11): 863-872, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36427920

RESUMO

Peptide dual agonists toward both glucagon-like peptide 1 receptor (GLP-1R) and glucagon receptor (GCGR) are emerging as novel therapeutics for the treatment of type 2 diabetes mellitus (T2DM) patients with obesity. Our previous work identified a Xenopus GLP-1-based dual GLP-1R/GCGR agonist termed xGLP/GCG-13, which showed decent hypoglycemic and body weight lowering activity. However, the clinical utility of xGLP/GCG-13 is limited due to its short in vivo half-life. Inspired by the fact that O-GlcNAcylation of intracellular proteins leads to increased stability of secreted proteins, we rationally designed a panel of O-GlcNAcylated xGLP/GCG-13 analogs as potential long-acting GLP-1R/ GCGR dual agonists. One of the synthesized glycopeptides 1f was found to be equipotent to xGLP/GCG-13 in cell-based receptor activation assays. As expected, O-GlcNAcylation effectively improved the stability of xGLP/GCG-13 in vivo. Importantly, chronic administration of 1f potently induced body weight loss and hypoglycemic effects, improved glucose tolerance, and normalized lipid metabolism and adiposity in both db/db and diet induced obesity (DIO) mice models. These results supported the hypothesis that glycosylation is a useful strategy for improving the in vivo stability of GLP-1-based peptides and promoted the development of dual GLP-1R/GCGR agonists as antidiabetic/antiobesity drugs.


Assuntos
Diabetes Mellitus Tipo 2 , Peptídeo 1 Semelhante ao Glucagon , Camundongos , Animais , Peptídeo 1 Semelhante ao Glucagon/agonistas , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Receptores de Glucagon/agonistas , Receptores de Glucagon/uso terapêutico , Xenopus laevis/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glicopeptídeos/uso terapêutico , Obesidade/tratamento farmacológico , Hipoglicemiantes/farmacologia , Peptídeos/farmacologia
14.
FEBS J ; 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36380688

RESUMO

High-mobility group box 1 (HMGB1) is critical for inflammatory homeostasis and successful pregnancy, and there is a strong association between elevated levels of HMGB1, polycystic ovary syndrome (PCOS), chronic inflammation, and pregnancy loss. However, the mechanisms responsible for PCOS-driven regulation of uterine HMGB1 and its candidate receptors (toll-like receptor (TLR) 2 and 4) and inflammatory responses during pregnancy remain unclear. In this study, we found a gestational stage-dependent decrease in uterine HMGB1 and TLR4 protein abundance in rats during normal pregnancy. We demonstrated that increased expression of HMGB1, TLR2, and TLR4 proteins was associated with activation of inflammation-related signaling pathways in the gravid uterus exposed to 5α-dihydrotestosterone and insulin, mimicking the clinical features (hyperandrogenism and insulin resistance) of PCOS, and this elevation was completely inhibited by treatment with the androgen receptor (AR) antagonist flutamide. Interestingly, acute exposure to lipopolysaccharide suppressed HMGB1, TLR4, and inflammation-related protein abundance but did not affect androgen levels or AR expression in the gravid uterus with viable fetuses. Furthermore, immunohistochemical analysis revealed that, in addition to being localized predominately in the nuclear compartment, HMGB1 immunoreactivity was also detected in the cytoplasm in the PCOS-like rat uterus, PCOS endometrium, and pregnant rat uterus with hemorrhagic and resorbed fetuses, possibly via activation of nuclear factor κB signaling. These results suggest that both AR-dependent and AR-independent mechanisms contribute to the modulation of HMGB1/TLR2/TLR4-mediated uterine inflammation. We propose that elevation of HMGB1 and its receptors and disruption of the pro-/anti-inflammatory balance in the gravid uterus may participate in the pathophysiology of PCOS-associated pregnancy loss.

15.
Nanomaterials (Basel) ; 12(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36364666

RESUMO

Hafnium oxide (HfO2) thin film has remarkable physical and chemical properties, which makes it useful for a variety of applications. In this work, HfO2 films were prepared on silicon through plasma enhanced atomic layer deposition (PEALD) at various substrate temperatures. The growth per cycle, structural, morphology and crystalline properties of HfO2 films were measured by spectroscopic ellipsometer, grazing-incidence X-ray diffraction (GIXRD), X-ray reflectivity (XRR), field-emission scanning electron microscopy, atomic force microscopy and x-ray photoelectron spectroscopy. The substrate temperature dependent electrical properties of PEALD-HfO2 films were obtained by capacitance-voltage and current-voltage measurements. GIXRD patterns and XRR investigations show that increasing the substrate temperature improved the crystallinity and density of HfO2 films. The crystallinity of HfO2 films has a major effect on electrical properties of the films. HfO2 thin film deposited at 300 °C possesses the highest dielectric constant and breakdown electric field.

16.
Analyst ; 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36444671

RESUMO

In this study, a cathodic intra-molecular electrochemiluminescence resonance energy transfer (ECL-RET) probe was exquisitely designed via the integration of an ECL donor (Cu NCs) with an acceptor (Ru(dcbpy)32+), and further employed the 3D bipedal DNA walker amplification strategy to monitor the platelet-derived growth factor BB (PDGF-BB). Specifically, blue emission Cu NCs with low consumption, biocompatibility and numerous resources, act as well-overlapped donors and significantly improve the ECL efficiency of Ru(dcbpy)32+. More impressively, the intra-molecular ECL-RET of Cu NC-Ru endowed a better and more stable ECL signal by reducing the electron-transfer distance and decreasing the energy loss. Furthermore, 3D bipedal DNA walker amplification was employed to efficiently convert the target PDGF-BB into numerous DNA strands, achieving sensitive target amplification. By virtue of such design, the constructed aptasensor exhibited a sensitive and selective assay for PDGF-BB with a detection range from 0.01 pM to 10 nM and a detection limit of 3.3 fM. The intramolecular ECL-RET and 3D bipedal DNA walker amplification strategy designed in this study will provide valuable insight into promising ultrasensitive ECL bioanalysis.

17.
Exp Cell Res ; 422(1): 113406, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36332684

RESUMO

The reduction of insulin secretion due to pancreatic ß cell injury caused by autoimmune reaction is the pathological basis of Type 1 diabetes mellitus (T1DM). Therefore, seeking new molecular targets for alleviating pancreatic ß cell injury will provide experimental basis for the prevention and treatment of T1DM. SRY-box 9 (Sox9) is not only an important molecule regulating the development of various organs, but also its high expression can aggravate the pathological process of various diseases. In addition, Sox9+ cells are also pancreatic progenitor cells, participating in pancreatic repair reaction induced by injury. In our study, elevated blood glucose and lack of pancreatic ß cells almost returned to normal over time after streptozotocin (STZ)-induced pancreatic ß cell damage, implying that pancreatic ß cells were regenerated after STZ-induced injury. In particular, the expression of Sox9 was significantly elevated during pancreatic ß cell regeneration. On this basis, we conducted in vitro experiments to verify whether overexpression of Sox9 could inhibit the damage of pancreatic ß cells by inflammatory factors. Our results showed that overexpression of Sox9 alleviated the damage of pancreatic ß cells by inflammatory factors and improved the inhibitory effect of inflammatory factors on insulin secretion of pancreatic ß cells. Unsurprising, blood glucose levels, insulin content and pancreatic ß cell number failed to return to near-normal levels timely after pancreatic ß cells specific knockout Sox9 mice were treated with STZ, further confirming the importance of Sox9 in facilitating pancreatic ß cell repair or regeneration. Our study indicate that enhanced Sox9 activity might protect pancreatic ß cells from autoimmune induced damage and thus improve the pathological process of T1DM.

18.
RSC Adv ; 12(44): 28629-28636, 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36320548

RESUMO

Heteroatom doping has proved to be one of the most effective approaches to further improve the photocatalytic activities of semiconducting oxides originating from the modulation of their electronic structures. Herein, nitrogen-doped SnO2 nanorods were synthesized via facile solvothermal processes using polyvinylpyrrolidone (PVP) as a dispersing agent and ammonium water as the N source, respectively. Compared with pure SnO2 sample, the as-synthesized nitrogen-doped SnO2 nanorods demonstrated enhanced photocatalytic performances, evaluated by the degradation of rhodamine B (RhB), revealing the effectiveness of nitrogen doping towards photocatalysis. In particular, the optimal photocatalyst (using 0.6 g PVP and 1 mL ammonia water) could achieve up to 86.23% pollutant removal efficiency under ultraviolet (UV) light irradiation within 150 min, showing 17.78% higher efficiency than pure SnO2. Detailed structural and spectroscopic characterization reveals the origin of activity enhancement of nitrogen-doping SnO2 in contrast with pure SnO2. Specifically, the bandgap and the morphologies of nitrogen-doped SnO2 have changed with more chemisorbed sites, which is supposed to result in the enhancement of photocatalytic efficiency. Moreover, the possible formation mechanism of nitrogen-doped SnO2 nanorods was discussed, in which PVP played a crucial role as the structure orientator.

19.
Artigo em Inglês | MEDLINE | ID: mdl-36317102

RESUMO

Background: The classical prescription Gualou Guizhi decoction (GL), a mixture of Radix Trichosanthis, Ramulus Cinnamomi, Radix Paeoniae Alba, Radix Glycyrrhizae, Zingiberis Rhizoma Recens, and Fructus Ziziphus Jujuba, was clinically used in the treatment of limb spasms after stroke and has achieved remarkable therapeutic effects. However, the underlying mechanism still needs to be further explored. Methods: Cerebral ischemia/reperfusion (CI/R) in Sprague-Dawley rats was induced by middle cerebral artery occlusion followed by filament removal. GL was intragastrically administered once daily for 7 or 14 consecutive days. The effect of GL on neurobehavioral impairment was evaluated. 18F-FDG micro-PET imaging was used to detect the effects of GL on glucose utilization in neural cells after CI/R. Immunohistochemical staining of glucose transporter 1 (Glut-1), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule-1 (Iba-1) was further performed to show the effects of GL on cerebral glucose transport and the activation of inflammatory-related glial cells. Markers related to the microglial subtype were also assessed to investigate the effects of GL on microglia polarization. Results: Neurological deficits induced by CI/R were significantly improved by GL administration. GL restored the glucose uptake in the ischemic hemisphere. Glut-1, the major glucose transporter in the brain, was significantly increased after GL treatment. Moreover, GL mitigated the activation of astrocytes and microglia after CI/R. Furthermore, GL significantly decreased proinflammatory M1-type microglial markers TNF-α and iNOS, while increasing anti-inflammatory M2 microglial markers CD206 and Arg-1. Conclusion: GL enhanced the uptake and utilization of glucose in neural cells after CI/R. It exerted significant anti-inflammatory effects by regulating the polarization of microglia. These results provided further evidence supporting the clinical application of GL in the treatment of cerebral ischemic stroke.

20.
Emerg Med Int ; 2022: 4774195, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36225715

RESUMO

Background: Nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis B (CHB) are both the most common underlying diseases leading to cirrhosis and hepatocellular carcinoma, and NAFLD and HBV infection are the first and second leading causes of chronic liver disease in China. However, there are still a lot of controversies about whether the combined presence of CHB and NAFLD will affect the course or outcome of liver disease together with HBV, and how the two affect each other. Objective: To investigate the effect of nonalcoholic fatty liver disease (NAFLD) on antiviral therapy in patients with chronic hepatitis B (CHB). Methods: Computer searches of databases such as PubMed, CNKI, VIP.com, and Wanfang Data Knowledge Service Platform were used. The time frame was from the creation of the database to June 2022. The search subject terms were hepatitis B, CHB, or NAFLD. The observation group consisted of patients with e antigen-positive CHB with NAFLD, and the control group consisted of patients with e-antigen + CHB. Extracts including title, name, date of publication, number of samples, antiviral drugs, and outcome indicators were used for Meta-analysis. Funnel plots were drawn to analyze literature bias. Results: Seven papers including 1348 patients with HBeAg + CHB (observation group: n = 547, control group: n = 801) were finally included. Results: Seven papers including 1348 patients with HBeAg + CHB (observation group: n = 547, control group: n = 801) were finally included. Results. Meta-analysis showed that CHB patients with NAFLD had lower efficacy than CHB patients after 48 weeks of antiviral treatment with nucleotide analogs, as measured by three outcome indicators HBV DNA conversion rate, ALT-normalization, and HBeAg conversion rate. Conclusion: NAFLD reduces the effect of antiviral therapy in CHB patients, and the clinicopathological features of patients with NAFLD combined with chronic hepatitis B are different from those of patients with chronic hepatitis B alone, so early diagnosis by liver histological examination should be actively performed and reasonable antiviral therapy should be administered.

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