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1.
Biology (Basel) ; 13(6)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38927332

RESUMO

H. perforatum, as one of the Traditional Chinese Medicinal materials, possesses a variety of pharmacological activities and high medicinal value. However, in recent years, the wild resources of H. perforatum have been severely depleted due to global climate change and human activities, and artificial cultivation faces problems such as unstable yield and active ingredient content. This poses a serious obstacle to the development and utilization of its resources. Therefore, this experiment took H. perforatum as the research object and used 894 distribution records of H. perforatum and 36 climatic environmental factors, using the MaxEnt model and GIS technology to explore the main climatic factors affecting the distribution of H. perforatum. Additionally, by utilizing the principles of ecological niche theory, the potential suitable distribution regions of H. perforatum across past, present, and future timelines were predicted, which can ascertain the dynamics of its spatial distribution patterns and the trend of centroid migration. The results indicate that the main environmental factors affecting the geographical distribution of H. perforatum are solar radiation in April (Srad4), solar radiation in September (Srad9), mean temperature of driest quarter (Bio9), solar radiation in November (Srad11), annual mean temperature (Bio1), and annual precipitation (Bio12). Under future climate scenarios, there is a remarkable trend of expansion in the suitable distribution areas of H. perforatum. The centroid migration indicates a trend of migration towards the northwest direction and high-altitude areas. These results can provide a scientific basis for formulating conservation and sustainable use management strategies for H. perforatum resources.

2.
World J Clin Cases ; 12(17): 2925-2927, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38898874

RESUMO

This article presents a comprehensive case report on an uncommon instance of metastatic clear cell sarcoma (CCS) originating from the pancreas. The high mortality rate of pancreatic carcinoma underscores the importance of precise diagnosis and early detection. The authors report a novel case of CCS with pancreatic metastasis, detailing successful surgical intervention through distal pancreatectomy and splenectomy, resulting in favourable outcomes. This study highlights the standard role of surgery in treating advanced CCS and emphasizes preoperative imaging and thorough patient history assessment. This article also underscores the necessity for long-term surveillance due to the potential for recurrence or metastasis. Despite the favourable recovery postsurgery, the absence of subsequent follow-up evaluation prompts consideration of the need for extended monitoring. This article raises questions about the nature of the pancreatic lesion and suggests the possibility of a primary lesion. Further evidence is crucial to establish the correlation between the features related to the development of the patient's primary and metastatic tumours. In conclusion, this study offers valuable insights into metastatic CCS of the pancreas, highlighting the importance of regular postoperative follow-up for improved outcomes through early detection and intervention.

3.
Nanoscale ; 16(24): 11651-11662, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38847557

RESUMO

A certain type of photoresist used for deep-UV lithography (DUVL) can also be used for other types of photolithography. Thus, to meet the requirements of two or more lithography technologies simultaneously, it is necessary to design a variety of corresponding functional groups in the molecules of materials and obtain the required properties. Herein, we designed four matrix resins based on acrylate for DUVL, employing alkyl sulfide, adamantane, methyladamantane, and hydroxyl as dangling groups and a microcrosslinking network by adding a small amount of crosslinker. These polymers were used in the thermal nanoimprint lithography (NIL) process, and distinct patterns with a resolution of 100 nm were observed. The acrylate copolymers designed for DUVL in this work can be used as thermal NIL resists and to obtain good patterns. It was found that ethylene dimethacrylate (EDMA) and adamantane endowed the matrix resins with good thermal stability and that PMMHM demonstrated the best patterning performance among the four resins. These polymers can be applied in the manufacturing of high-density integrated circuits, nano-transistors, optoelectronic devices and other components in the future.

4.
Nat Commun ; 15(1): 3780, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710714

RESUMO

Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are administered via suprachoroidal injection at a higher dose. However, high doses of rAAVs tend to increase additional safety risks. Here, we present a novel AAV capsid (AAVv128), which exhibits significantly enhanced transduction efficiency for photoreceptors and retinal pigment epithelial (RPE) cells, along with a broader distribution across the layers of retinal tissues in different animal models (mice, rabbits, and NHPs) following intraocular injection. Notably, the suprachoroidal delivery of AAVv128-anti-VEGF vector completely suppresses the Grade IV lesions in a laser-induced choroidal neovascularization (CNV) NHP model for neovascular age-related macular degeneration (nAMD). Furthermore, cryo-EM analysis at 2.1 Å resolution reveals that the critical residues of AAVv128 exhibit a more robust advantage in AAV binding, the nuclear uptake and endosome escaping. Collectively, our findings highlight the potential of AAVv128 as a next generation ocular gene therapy vector, particularly using the suprachoroidal delivery route.


Assuntos
Neovascularização de Coroide , Dependovirus , Terapia Genética , Vetores Genéticos , Epitélio Pigmentado da Retina , Animais , Dependovirus/genética , Vetores Genéticos/genética , Vetores Genéticos/administração & dosagem , Terapia Genética/métodos , Camundongos , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/virologia , Neovascularização de Coroide/terapia , Neovascularização de Coroide/genética , Coelhos , Humanos , Técnicas de Transferência de Genes , Degeneração Macular/terapia , Degeneração Macular/genética , Degeneração Macular/patologia , Modelos Animais de Doenças , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Transdução Genética , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Camundongos Endogâmicos C57BL , Retina/metabolismo , Retina/virologia , Masculino , Células HEK293
5.
Front Microbiol ; 15: 1337078, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38559349

RESUMO

Slow transit constipation (STC) is a common and debilitating condition characterized by delayed colonic transit and difficulty in fecal expulsion, significantly impacting patients' physical and mental wellbeing as well as their overall quality of life. This study investigates the therapeutic potential of Liqi Tongbian Decoction (LTD) in the treatment of STC, especially in cases involving the context of Qi stagnation, through a multifaceted approach involving the modulation of intestinal flora and short-chain fatty acids (SCFAs). We employed a rat model of STC with Qi Stagnation Pattern, established using the "loperamide + tail-clamping provocation method," to explore the effects of LTD on fecal characteristics, intestinal motility, and colonic pathology. Importantly, LTD exhibited the ability to increase the richness, diversity, and homogeneity of intestinal flora while also modulating the composition of microorganisms. It significantly increased the production of SCFAs, especially butyric acid. Moreover, LTD exerted a substantial influence on the synthesis of serotonin (5-HT) by modulating the expression of tryptophan hydroxylase (TPH) and interacting with the 5-HT4 receptor (5-HT4R), resulting in enhanced colonic motility. Correlation analyses revealed a positive correlation between certain bacterial genera, such as Lachnospiraceae_NK4A136 spp. and Clostridiales spp. and the concentrations of butyric acid and 5-HT. These results suggest a mechanistic link between microbiome composition, SCFAs production, and 5-HT synthesis. These findings highlight the potential of LTD to alleviate STC by facilitating a beneficial interplay among intestinal flora, SCFAs production, and 5-HT-mediated colonic motility, providing novel insights into the management of STC with Qi Stagnation Pattern.

6.
World J Gastrointest Oncol ; 16(3): 819-832, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38577440

RESUMO

BACKGROUND: The study on predicting the differentiation grade of colorectal cancer (CRC) based on magnetic resonance imaging (MRI) has not been reported yet. Developing a non-invasive model to predict the differentiation grade of CRC is of great value. AIM: To develop and validate machine learning-based models for predicting the differentiation grade of CRC based on T2-weighted images (T2WI). METHODS: We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July 2023. Patients were randomly assigned to a training cohort (n = 220) or a validation cohort (n = 95) at a 7:3 ratio. Lesions were delineated layer by layer on high-resolution T2WI. Least absolute shrinkage and selection operator regression was applied to screen for radiomic features. Radiomics and clinical models were constructed using the multilayer perceptron (MLP) algorithm. These radiomic features and clinically relevant variables (selected based on a significance level of P < 0.05 in the training set) were used to construct radiomics-clinical models. The performance of the three models (clinical, radiomic, and radiomic-clinical model) were evaluated using the area under the curve (AUC), calibration curve and decision curve analysis (DCA). RESULTS: After feature selection, eight radiomic features were retained from the initial 1781 features to construct the radiomic model. Eight different classifiers, including logistic regression, support vector machine, k-nearest neighbours, random forest, extreme trees, extreme gradient boosting, light gradient boosting machine, and MLP, were used to construct the model, with MLP demonstrating the best diagnostic performance. The AUC of the radiomic-clinical model was 0.862 (95%CI: 0.796-0.927) in the training cohort and 0.761 (95%CI: 0.635-0.887) in the validation cohort. The AUC for the radiomic model was 0.796 (95%CI: 0.723-0.869) in the training cohort and 0.735 (95%CI: 0.604-0.866) in the validation cohort. The clinical model achieved an AUC of 0.751 (95%CI: 0.661-0.842) in the training cohort and 0.676 (95%CI: 0.525-0.827) in the validation cohort. All three models demonstrated good accuracy. In the training cohort, the AUC of the radiomic-clinical model was significantly greater than that of the clinical model (P = 0.005) and the radiomic model (P = 0.016). DCA confirmed the clinical practicality of incorporating radiomic features into the diagnostic process. CONCLUSION: In this study, we successfully developed and validated a T2WI-based machine learning model as an auxiliary tool for the preoperative differentiation between well/moderately and poorly differentiated CRC. This novel approach may assist clinicians in personalizing treatment strategies for patients and improving treatment efficacy.

7.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(2): 207-212, 2024 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-38436321

RESUMO

Childhood trauma refers to trauma experiences encountered during childhood and adolescence. Maternal childhood trauma experiences have a lasting impact on the next generation, affecting their physical and mental well-being. The mechanisms involved include the hypothalamic-pituitary-adrenal axis, inflammatory factors, brain structure and function, gene interactions, and parenting styles. This paper systematically reviews the mechanisms of the impact of maternal childhood trauma on intergenerational transmission, providing insights for the prevention of intergenerational transmission of childhood trauma.


Assuntos
Experiências Adversas da Infância , Adolescente , Humanos , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Encéfalo , Poder Familiar
8.
Cell Commun Signal ; 22(1): 178, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38475787

RESUMO

BACKGROUND: Carthamus tinctorius L., a traditional herbal medicine used for atherosclerosis (AS), lacks a clear understanding of its therapeutic mechanisms. This study aimed to investigate the therapeutic effects and mechanisms of Carthamus tinctorius L.-derived nanovesicles (CDNVs) in AS treatment. METHODS: CDNVs were isolated and characterized using improved isolation methods. Transmission electron microscopy, nanoparticle tracking analysis, and protein analysis confirmed their morphology, size, and protein composition. Small RNA sequencing was performed to identify the miRNA profile of CDNVs, and bioinformatics analysis was used to determine their potential biological roles. In vivo biodistribution and toxicity studies were conducted in mice to assess the stability and safety of orally administered CDNVs. The anti-atherosclerotic effects of CDNVs were evaluated in ApoE-/- mice through plaque burden analysis. The protective effects of CDNVs on ox-LDL-treated endothelial cells were assessed through proliferation, apoptosis, reactive oxygen species activation, and monocyte adhesion assays. miRNA and mRNA sequencing of CDNV-treated endothelial cells were performed to explore their regulatory effects and potential target genes. RESULTS: CDNVs were successfully isolated and purified from Carthamus tinctorius L. tissue lysates. They exhibited a saucer-shaped or cup-shaped morphology, with an average particle size of 142.6 ± 0.7 nm, and expressed EV markers CD63 and TSG101. CDNVs contained proteins, small RNAs, and metabolites, including the therapeutic compound HSYA. Small RNA sequencing identified 95 miRNAs, with 10 common miRNAs accounting for 72.63% of the total miRNAs. These miRNAs targeted genes involved in cell adhesion, apoptosis, and cell proliferation, suggesting their relevance in cardiovascular disease. Orally administered CDNVs were stable in the gastrointestinal tract, absorbed into the bloodstream, and accumulated in the liver, lungs, heart, and aorta. They significantly reduced the burden of atherosclerotic plaques in ApoE-/- mice and exhibited superior effects compared to HSYA. In vitro studies demonstrated that CDNVs were taken up by HUVECs, promoted proliferation, attenuated ox-LDL-induced apoptosis and ROS activation, and reduced monocyte adhesion. CDNV treatment resulted in significant changes in miRNA and mRNA expression profiles of HUVECs, with enrichment in inflammation-related genes. CXCL12 was identified as a potential direct target of miR166a-3p. CONCLUSION: CDNVs isolated from Carthamus tinctorius L. tissue lysates represent a promising oral therapeutic option for cardiovascular diseases. The delivery of miRNAs by CDNVs regulates inflammation-related genes, including CXCL12, in HUVECs, suggesting their potential role in modulating endothelial inflammation. These findings provide valuable insights into the therapeutic potential of CDNVs and their miRNAs in cardiovascular disease.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Carthamus tinctorius , MicroRNAs , Camundongos , Animais , Células Endoteliais/metabolismo , Carthamus tinctorius/genética , Carthamus tinctorius/metabolismo , Doenças Cardiovasculares/metabolismo , Distribuição Tecidual , Camundongos Knockout para ApoE , MicroRNAs/genética , Aterosclerose/metabolismo , Inflamação/metabolismo , Apoptose , RNA Mensageiro/metabolismo , Apolipoproteínas E/metabolismo
9.
J Am Heart Assoc ; 13(4): e030054, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38348774

RESUMO

BACKGROUND: This study investigated whether gCTRP9 (globular C1q/tumor necrosis factor-related protein-9) could restore high-glucose (HG)-suppressed endothelial progenitor cell (EPC) functions by activating the endothelial nitric oxide synthase (eNOS). METHODS AND RESULTS: EPCs were treated with HG (25 mmol/L) and gCTRP9. Migration, adhesion, and tube formation assays were performed. Adiponectin receptor 1, adiponectin receptor 2, and N-cadherin expression and AMP-activated protein kinase, protein kinase B, and eNOS phosphorylation were measured by Western blotting. eNOS activity was determined using nitrite production measurement. In vivo reendothelialization and EPC homing assays were performed using Evans blue and immunofluorescence in mice. Treatment with gCTRP9 at physiological levels enhanced migration, adhesion, and tube formation of EPCs. gCTRP9 upregulated the phosphorylation of AMP-activated protein kinase, protein kinase B, and eNOS and increased nitrite production in a concentration-dependent manner. Exposure of EPCs to HG-attenuated EPC functions induced cellular senescence and decreased eNOS activity and nitric oxide synthesis; the effects of HG were reversed by gCTRP9. Protein kinase B knockdown inhibited eNOS phosphorylation but did not affect gCTRP9-induced AMP-activated protein kinase phosphorylation. HG impaired N-cadherin expression, but treatment with gCTRP9 restored N-cadherin expression after HG stimulation. gCTRP9 restored HG-impaired EPC functions through both adiponectin receptor 1 and N-cadherin-mediated AMP-activated protein kinase /protein kinase B/eNOS signaling. Nude mice that received EPCs treated with gCTRP9 under HG medium showed a significant enhancement of the reendothelialization capacity compared with those with EPCs incubated under HG conditions. CONCLUSIONS: CTRP9 promotes EPC migration, adhesion, and tube formation and restores these functions under HG conditions through eNOS-mediated signaling mechanisms. Therefore, CTRP9 modulation could eventually be used for vascular healing after injury.


Assuntos
Adiponectina , Células Progenitoras Endoteliais , Glicoproteínas , Proteínas Proto-Oncogênicas c-akt , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Progenitoras Endoteliais/metabolismo , Complemento C1q/metabolismo , Complemento C1q/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Citocinas/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Camundongos Nus , Receptores de Adiponectina/metabolismo , Nitritos , Movimento Celular , Glucose/farmacologia , Glucose/metabolismo , Caderinas/metabolismo , Fatores de Necrose Tumoral/metabolismo , Fatores de Necrose Tumoral/farmacologia , Óxido Nítrico/metabolismo , Células Cultivadas
10.
Zookeys ; 1189: 33-54, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38314114

RESUMO

The Torrent frogs of the genus Amolops are widely distributed in Nepal and northern India eastwards to southern China and southwards to Malaysia. The genus currently contains 84 species. Previous studies indicated underestimated species diversity in the genus. In the context, a new species occurring from the mountains in the northwestern Guizhou Province, China is found and described based on morphological comparisons and molecular phylogenetic analyses, Amolopsdafangensissp. nov. Phylogenetic analyses based on DNA sequences of the mitochondrial 16S rRNA and COI genes supported the new species as an independent lineage. The uncorrected genetic distances between the 16S rRNA and COI genes in the new species and its closest congener were 0.7% and 2.6%, respectively, which are higher than or at the same level as those among many pairs of congeners. Morphologically, the new species can be distinguished from its congeners by a combination of the following characters: body size moderate (SVL 43.2-46.8 mm in males); head length larger than head width slightly; tympanum distinct, oval; vocal sacs absent; vomerine teeth present; dorsolateral folds weak formed by series of glands; nuptial pads present on the base of finger I; heels overlapping when thighs are positioned at right angles to the body; tibiotarsal articulation reaching the level far beyond the tip of the snout when leg stretched forward.

11.
J Autism Dev Disord ; 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-38060105

RESUMO

BACKGROUND: Autism spectrum disorder (ASD) is a multifactorial, pervasive, neurodevelopmental disorder, of which intestinal symptoms collectively represent one of the most common comorbidities. METHODS: In this study, 1,222 children with ASD and 1,206 typically developing (TD) children aged 2-7 years were enrolled from 13 cities in China. Physical measurement and basic information questionnaires were conducted in ASD and TD children. The Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Autism Behavior Checklist (ABC) were used to evaluate the clinical symptoms of children with ASD. The six-item Gastrointestinal Severity Index (6-GSI) was used to evaluate the prevalence of intestinal symptoms in two groups. RESULTS: The detection rates of constipation, stool odor, and total intestinal symptoms in ASD children were significantly higher than those in TD children (40.098% vs. 25.622%, 17.021% vs. 9.287%, and 53.601% vs. 41.294%, respectively). Autistic children presenting with intestinal comorbidity had significantly higher scores on the ABC, SRS, CARS, and multiple subscales than autistic children without intestinal symptoms, suggesting that intestinal comorbidity may exacerbates the core symptoms of ASD children. CONCLUSION: Intestinal dysfunction was significantly more common in autistic than in TD children. This dysfunction may aggravate the core symptoms of children with ASD.

12.
Acta Ophthalmol ; 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38009430

RESUMO

PURPOSE: To evaluate the safety and efficacy of intravitreal injections of 0.5 mg conbercept in patients with choroidal neovascularization secondary to pathological myopia (pmCNV). METHODS: The 177 pmCNV patients were randomly assigned in a 3:1 ratio to receive conbercept or sham injection, respectively. The conbercept group receive conbercept intravitreal injections administered on a pro re nata (PRN) basis after 3 monthly loading doses. The sham group received three consecutive monthly sham injections and then one conbercept injection followed by PRN conbercept intravitreal injections. RESULTS: At month 3, the mean BCVA for the two groups were improved by 12.0 letters (conbercept group, from 54.05 letters to 66.05 letters) and 0.6 letters (sham group, from 49.77 letters to 50.33 letters), respectively (p < 0.001). The mean central retinal thickness (CRT) at month 3 in the two groups decreased 62.0 µm (conbercept group, from 348.90 µm to 286.18 µm) and 4.4 µm (sham group, from 347.86 µm to 343.47 µm) (p < 0.001). At month 9, the mean BCVA improved by 13.3 letters in the conbercept group and 11.3 letters in the sham group. The mean CRT decreased 73.6 µm in the conbercept group and 55.9 µm in the sham group (p < 0.001). The most common ocular adverse events were associated with intravitreal injections, such as conjunctival haemorrhage and increased intraocular pressure. CONCLUSION: Intravitreal injections of 0.5 mg conbercept provided improvement in visual and anatomical outcomes in pmCNV patients with low rates of ocular and nonocular safety events.

14.
J Phycol ; 59(5): 822-834, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37656660

RESUMO

Sargassum (Sargassaceae) is widely distributed globally and plays an important role in regulating climate change, but the landscape of genomes and transcripts is less known. High-quality nucleic acids are the basis for molecular biology experiments such as high-throughput sequencing. Although extensive studies have documented methods of RNA extraction, these methods are not very applicable to Sargassum, which contains high levels of polysaccharides and polyphenols. To find a suitable method to improve the quality of RNA extracted, we compared and modified several popular RNA extraction methods and screened one practical method with three specific Sargassum spp. The results showed that three CTAB methods (denoted as Methods 1, 2, and 3) and the RNAprep Pure Plant Kit (denoted as Method 4) could, with slight modifications, effectively isolate RNA from Sargassum species, except for Method 4 used with S. fusiforme. By performing further screening, we determined Method 4 was the best choice for S. hemiphyllum and S. henslowianum, as revealed by RNA yields, RNA Integrity Number (RIN), extraction time, and unigene mapped ratio. For S. fusiforme, Methods 1, 2, and 3 showed no obvious differences among the yields, quality, or time to perform. In addition, one other method was tested, but we found the quality of the RNA extracted by TRIzol reagent methods (denoted as Method 5) performed the worst when compared with the above four methods. Therefore, our study provides four suitable methods for RNA extraction in Sargassum and is essential for future genetic exploration of Sargassum.

15.
Microorganisms ; 11(9)2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37764072

RESUMO

N-acyl homoserine lactones (AHLs) are small, diffusible chemical signal molecules that serve as social interaction tools for bacteria, enabling them to synchronize their collective actions in a density-dependent manner through quorum sensing (QS). The QS activity from epiphytic bacteria of the red macroalgae Porphyra haitanensis, along with its involvement in biofilm formation and regulation, remains unexplored in prior scientific inquiries. Therefore, this study explores the AHL signal molecules produced by epiphytic bacteria. The bacterium isolated from the surface of P. haitanensis was identified as Pseudoalteromonas galatheae by 16s rRNA gene sequencing and screened for AHLs using two AHL reporter strains, Agrobacterium tumefaciens A136 and Chromobacterium violaceum CV026. The crystal violet assay was used for the biofilm-forming phenotype. The inferences revealed that P. galatheae produces four different types of AHL molecules, i.e., C4-HSL, C8-HSL, C18-HSL, and 3-oxo-C16-HSL, and it was observed that its biofilm formation phenotype is regulated by QS molecules. This is the first study providing insights into the QS activity, diverse AHL profile, and regulatory mechanisms that govern the biofilm formation phenotype of P. galatheae. These findings offer valuable insights for future investigations exploring the role of AHL producing epiphytes and biofilms in the life cycle of P. haitanensis.

16.
Mol Ther ; 31(11): 3308-3321, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37752703

RESUMO

The upregulation of vascular endothelial growth factor (VEGF) is strongly associated with the development of choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (nAMD). Currently, the standard treatment for nAMD involves frequent intravitreal injections of anti-VEGF agents, which inhibit the growth of new blood vessels and prevent leakage. However, this treatment regimen places a significant burden on patients, their families, and healthcare providers due to the need for repeated visits to the clinic for injections. Gene therapy, which enables the sustained expression of anti-VEGF proteins after a single injection, can dramatically reduce the treatment burden. KH631 is a recombinant adeno-associated virus 8 vector that encodes a human VEGF receptor fusion protein, and it is being developed as a long-term treatment for nAMD. In preclinical studies using non-human primates, subretinal administration of KH631 at a low dose of 3 × 108 vg/eye resulted in remarkable retention of the transgene product in the retina and prevented the formation and progression of grade IV CNV lesions. Furthermore, sustained transgene expression was observed for more than 96 weeks. These findings suggest that a single subretinal injection of KH631 has the potential to offer a one-time, low-dose treatment for nAMD patients.


Assuntos
Neovascularização de Coroide , Degeneração Macular , Animais , Humanos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Retina/metabolismo , Neovascularização de Coroide/genética , Neovascularização de Coroide/terapia , Primatas/genética , Primatas/metabolismo , Injeções Intravítreas , RNA , Degeneração Macular/patologia , Terapia Genética/métodos , Inibidores da Angiogênese/farmacologia , Proteínas Recombinantes de Fusão
17.
Front Pharmacol ; 14: 1176579, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37576825

RESUMO

Background: Qing Hua Chang Yin (QHCY) is a famous formula of traditional Chinese medicine (TCM) and has been proven to have protective effect on ulcerative colitis. However, its protective effect and potential therapeutic mechanisms in chronic colitis remain unclear. The purpose of this study is to explore the effects and underlying mechanisms of QHCY on dextran sulfate sodium (DSS)-induced chronic colitis mice model. Methods: The chronic colitis model was established by administration of 2% DSS for three consecutive cycles of 7 days with two intervals of 14 days for recovery by drinking water. The experiment lasted 49 days. The DSS + QHCY group received QHCY administration by oral gavage at doses of 1.6 g/kg/d, DSS + Mesalazine group was administrated Mesalazine by oral gavage at doses of 0.2 g/kg/d. The control and DSS group were given equal volume of distilled water. The body weight, stool consistency and blood in stool were monitored every 2 days. The disease activity index (DAI) was calculated. The colon length was measured after the mice were sacrificed. The histomorphology of colonic tissues was checked by the HE and PAS staining. Immunohistochemistry was performed to detect the expressions of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6), tight junction proteins (ZO-1, occludin) and Mucin2 (MUC2). 16S rRNA sequencing analysis was conducted to study the diversity and abundance of gut microbiota changes. Results: QHCY treatment not only significantly attenuated DSS-induced the weight loss, DAI score increase, colon shortening and histological damage in mice, but also decreased the expression of pro-inflammatory cytokines in colonic tissues and increased the expression of ZO-1, occludin, and MUC2. Furthermore, QHCY enhanced the diversity of gut microbes and regulated the structure and composition of intestinal microflora in mice with chronic colitis. Conclusion: QHCY has a therapeutic effect on a murine model of chronic colitis. It can effectively reduce the clinical and pathological manifestations of colitis and prevent alterations in the gut microbiota.

18.
Molecules ; 28(4)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36838709

RESUMO

π-Extended pyrene compounds possess remarkable luminescent and semiconducting properties and are being intensively investigated as electroluminescent materials for potential uses in organic light-emitting diodes, transistors, and solar cells. Here, the synthesis of two sets of pyrene-containing π-conjugated polyaromatic regioisomers, namely 2,3,10,11,14,15,20,21-octaalkyloxypentabenzo[a,c,m,o,rst]pentaphene (BBPn) and 2,3,6,7,13,14,17,18-octaalkyloxydibenzo[j,tuv]phenanthro [9,10-b]picene (DBPn), is reported. They were obtained using the Suzuki-Miyaura cross-coupling in tandem with Scholl oxidative cyclodehydrogenation reactions from the easily accessible precursors 1,8- and 1,6-dibromopyrene, respectively. Both sets of compounds, equipped with eight peripheral aliphatic chains, self-assemble into a single hexagonal columnar mesophase, with one short-chain BBPn homolog also exhibiting another columnar mesophase at a lower temperature, with a rectangular symmetry; BBPn isomers also possess wider mesophase ranges and higher mesophases' stability than their DBPn homologs. These polycyclic aromatic hydrocarbons all show a strong tendency of face-on orientation on the substrate and could be controlled to edge-on alignment through mechanical shearing of interest for their implementation in photoelectronic devices. In addition, both series BBPn and DBPn display green-yellow luminescence, with high fluorescence quantum yields, around 30%. In particular, BBPn exhibit a blue shift phenomenon in both absorption and emission with respect to their DBPn isomers. DFT results were in good agreement with the optical properties and with the stability ranges of the mesophases by confirming the higher divergence from the flatness of DBPn compared with BBPn. Based on these interesting properties, these isomers could be potentially applied not only in the field of fluorescent dyes but also in the field of organic photoelectric semiconductor materials as electron transport materials.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Pirenos , Transporte de Elétrons , Fluorescência , Poli A
19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(1): 148-153, 2023 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-36765492

RESUMO

OBJECTIVE: To investigate the influece of early relapse in the era of novel drugs on the prognosis of the patients with newly diagnosed multiple myeloma(NDMM) and risk factors, and to provide the basis for the early identification of the high-risk patients and guiding the treatment. METHODS: The clinical data of the patients with NDMM admitted to our hospital from November 2011 to May 2022 were retrospectively analyzed. According to whether the progression free survival(PFS) was more than 12 months, they were divided into early relapse group(≤12 months) and late relapse group(>12 months). The high-risk factors of the patients in two groups were analyzed, including age, anemia, renal insufficiency, hypercalcemia, increasing of lactate dehydrogenase(LDH) level, Extramedullary disease (EMD), International Staging System(ISS) stage, Revised International Staging System (R-ISS) stage, cytogenetic abnormalities(CA) detected by fluorescence in situ hybridization(FISH), and treatment efficacy. The meaningful clinical indicators were screened, and multivariate analysis was used to explore the high-risk factors of early relapse. RESULTS: 170 patients with NDMM were collected, including 25 cases in early relapse group and 145 cases in late relapse group. The median OS time of the patients in early death group was 20 months, and 140 months in late relapse group by the end of follow-up, there was significant difference in OS of the patients between two groups(P<0.001). Fifteen patients(56.0%)in early relapse group obtained ≥VGPR, and 113(77.9%) patients in late relapse group, the difference was statistically significant(P=0.011). Survival outcomes remained poor among early relapse patients irrespective of depth of response to initial therapy. Multivariate analysis showed that the EMD and high-risk CA predicted early relapse. CONCLUSION: The prognosis of patients with early relapse in NDMM is poor. EMD and high-risk CA is an independent prognostic factor of early relapse.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Prognóstico , Hibridização in Situ Fluorescente , Estudos Retrospectivos , Recidiva Local de Neoplasia , Fatores de Risco
20.
World J Clin Cases ; 11(2): 255-267, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36686364

RESUMO

The cortical bone trajectory (CBT) is a novel technique in lumbar fixation and fusion. The unique caudocephalad and medial-lateral screw trajectories endow it with excellent screw purchase for vertebral fixation via a minimally invasive method. The combined use of CBT screws with transforaminal or posterior lumbar interbody fusion can treat a variety of lumbar diseases, including spondylolisthesis or stenosis, and can also be used as a remedy for revision surgery when the pedicle screw fails. CBT has obvious advantages in terms of surgical trauma, postoperative recovery, prevention and treatment of adjacent vertebral disease, and the surgical treatment of obese and osteoporosis patients. However, the concept of CBT internal fixation technology appeared relatively recently; consequently, there are few relevant clinical studies, and the long-term clinical efficacy and related complications have not been reported. Therefore, large sample and prospective studies are needed to further reveal the long-term complications and fusion rate. As a supplement to the traditional pedicle trajectory fixation technique, the CBT technique is a good choice for the treatment of lumbar diseases with accurate screw placement and strict indications and is thus deserving of clinical recommendation.

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