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1.
ACS Omega ; 9(22): 23266-23282, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38854573

RESUMO

The sandstones interbedded with shales in the lacustrine black shale have great potential to become important targets for oil and gas exploration, but there has been a lack of systematic research regarding their types and genesis. This study focused on the investigation of the Triassic Chang 73 member deep lacustrine sandstone. Eleven lithofacies are identified and classified into three different types of deposits: ash fall and intra- and extra-basinal turbidite deposits. Vitric tuff, pumice-bearing shale, and ash are the main ash fall lithofacies. The presence of reverse grading and a significant concentration of plant fragments/micas suggest extra-basinal turbidite deposits. However, the collapse of deltaic intrabasinal sediments has been well sorted and does not contain plant debris and low-density materials. These three different types of sediments combined with a humid climate are the main causes for the deposition of a large number of sandstone layers in the deep lacustrine environment. Furthermore, the abundant volcanic eruptions are associated with increased organic matter accumulation and promoted the bloom of algae. In addition, the generated oil in the black shales would then migrate and accumulate in the interbedded sandstones. This research provides geological evidence for the prospective prediction of lacustrine shale oil accumulations.

2.
Imeta ; 3(1): e155, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38868513

RESUMO

The rapidly evolving landscape of biomarkers for colorectal cancer (CRC) necessitates an integrative, updated repository. In response, we constructed the Colorectal Cancer Biomarker Database (CBD), which collected and displayed the curated biomedicine information for 870 CRC biomarkers in the previous study. Building on CBD, we have now developed CBD2, which includes information on 1569 newly reported biomarkers derived from different biological sources (DNA, RNA, protein, and others) and clinical applications (diagnosis, treatment, and prognosis). CBD2 also incorporates information on nonbiomarkers that have been identified as unsuitable for use as biomarkers in CRC. A key new feature of CBD2 is its network analysis function, by which users can investigate the visible and topological network between biomarkers and identify their relevant pathways. CBD2 also allows users to query a series of chemicals, drug combinations, or multiple targets, to enable multidrug, multitarget, multipathway analyses, toward facilitating the design of polypharmacological treatments for CRC. CBD2 is freely available at http://www.eyeseeworld.com/cbd.

3.
J Med Food ; 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38868856

RESUMO

Osteoporotic fractures seriously affect the quality of life of the elderly. Panax notoginseng saponins (PNS) have the potential function of preventing osteoporosis. The Phosphatidylinositol 3-kinase (PI3K)/protein kinase (AKT)/mammalian target of rapamycin (mTOR) pathway is involved in the regulation of osteoporosis and has been proven to be related to VEGF secretion and angiogenesis. Therefore, this study aimed to explore the effects of PNS on ovariectomized rats with osteoporotic fracture through the PI3K/AKT/mTOR pathway and angiogenesis-related factors. Female Sprague-Dawley rats were randomly divided into normal control, fracture model, ovariectomized fracture model, low-dose PNS (100 mg/kg/d), and high-dose PNS (200 mg/kg/d). The ovariectomized rat fracture model was established. In low and high dose groups, PNS was administered intraperitoneally. The vascularization of fracture ends was detected in vitro by micro-CT on the 7th, 14th, and 21st day after modeling, and the area and number of blood vessels in the unit field of vision of the callus healing plane were seen by hematoxylin-eosin staining. The expression levels of PI3K, AKT1, mTOR, hypoxia inducible factor-1; VEGF: vascular endothelial growth factor (HIF-1), VEGF, Ang-1, VEGFR2, and angiopoietin like 2 Gene (ANGPTL2) were determined using Western blotting. In the PNS treatment group, the area of cortical bone increased, the area of callus decreased, and the number and area of blood vessels increased significantly when compared with the ovariectomized fracture model group. PNS regulates the PI3K/AKT/mTOR signaling pathway and promotes the expression of vascular-related cytokines (VEGF, Ang-1, VEGFR2, and ANGPTL2) in osteoporotic fractures. PNS may regulate the expression of vascular-related factors through the PI3K/AKT/mTOR pathway and promote the healing of osteoporotic fractures in ovariectomized rats.

4.
PhytoKeys ; 242: 1-8, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38764934

RESUMO

In this study, we describe and illustrate a new species, Primulaweiliei L.S.Yang, Z.K.Wu & G.W.Hu, from the Shennongjia Forestry District, Hubei Province in Central China. It is morphologically assigned to Primulasect.Aleuritia based on its dwarf and hairless habit, long petiole, fruits longer than calyx and covered by farina on the scape. This new species is similar to P.gemmifera and P.munroisubsp.yargongensis in the same section, but it can be distinguished by its smaller calyxes, homostylous flowers, corolla tube throat without annular appendage and only 1-2 flowers in each inflorescence. Based on the assessment conducted according to the IUCN Red List criteria, we propose that P.weiliei be classified as a Critically Endangered (CR) species.

5.
Curr Gene Ther ; 24(4): 307-320, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38783530

RESUMO

BACKGROUND: Astrocyte elevated gene-1 (AEG-1) is overexpressed in various malignancies. Exostosin-1 (EXT-1), a tumor suppressor, is an intermediate for malignant tumors. Understanding the mechanism behind the interaction between AEG-1 and EXT-1 may provide insights into colon cancer metastasis. METHODS: AOM/DSS was used to induce tumor in BALB/c mice. Using an in vivo-jetPEI transfection reagent, transient transfection of AEG-1 and EXT-1 siRNAs were achieved. Histological scoring, immunohistochemical staining, and gene expression studies were performed from excised tissues. Data from the Cancer Genomic Atlas and GEO databases were obtained to identify the expression status of AEG-1 and itsassociation with the survival. RESULTS: In BALB/c mice, the AOM+DSS treated mice developed necrotic, inflammatory and dysplastic changes in the colon with definite clinical symptoms such as loss of goblet cells, colon shortening, and collagen deposition. Administration of AEG-1 siRNA resulted in a substantial decrease in the disease activity index. Mice treated with EXT-1 siRNA showed diffusely reduced goblet cells. In vivo investigations revealed that PTCH-1 activity was influenced by upstream gene AEG-1, which in turn may affect EXT-1 activity. Data from The Cancer Genomic Atlas and GEO databases confirmed the upregulation of AEG-1 and downregulation of EXT-1 in cancer patients. CONCLUSIONS: This study revealed that AEG-1 silencing might alter EXT-1 expression indirectly through PTCH-1, influencing cell-ECM interactions, and decreasing dysplastic changes, proliferation and invasion.


Assuntos
Neoplasias do Colo , Proteínas de Membrana , Camundongos Endogâmicos BALB C , RNA Interferente Pequeno , Proteínas de Ligação a RNA , Animais , Humanos , Camundongos , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Proteínas de Membrana/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Masculino
6.
Nature ; 629(8014): 1091-1099, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38750363

RESUMO

The baobab trees (genus Adansonia) have attracted tremendous attention because of their striking shape and distinctive relationships with fauna1. These spectacular trees have also influenced human culture, inspiring innumerable arts, folklore and traditions. Here we sequenced genomes of all eight extant baobab species and argue that Madagascar should be considered the centre of origin for the extant lineages, a key issue in their evolutionary history2,3. Integrated genomic and ecological analyses revealed the reticulate evolution of baobabs, which eventually led to the species diversity seen today. Past population dynamics of Malagasy baobabs may have been influenced by both interspecific competition and the geological history of the island, especially changes in local sea levels. We propose that further attention should be paid to the conservation status of Malagasy baobabs, especially of Adansonia suarezensis and Adansonia grandidieri, and that intensive monitoring of populations of Adansonia za is required, given its propensity for negatively impacting the critically endangered Adansonia perrieri.


Assuntos
Adansonia , Filogenia , Adansonia/classificação , Adansonia/genética , Biodiversidade , Conservação dos Recursos Naturais , Ecologia , Espécies em Perigo de Extinção , Evolução Molecular , Genoma de Planta/genética , Madagáscar , Dinâmica Populacional , Elevação do Nível do Mar
7.
Rev Sci Instrum ; 95(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38564327

RESUMO

The assessment of the concentration and distribution of l6N, derived from 16O in the cooling water exposed to neutron irradiation, is essential for ensuring radiation safety during nuclear reactor operation. The imaging method allows for the visualization of the intensity distribution of these l6N by capturing gamma-rays emitted during their decay process. However, the existing gamma camera is exclusively compatible with gamma-rays below 2 MeV. In this paper, a novel gamma camera featuring a thick double-conical penumbra aperture, a pixelated Lu1.8Y0.2SiO5:Ce scintillator array, and a position-sensitive photomultiplier tube is proposed to address this limitation. This innovative design offers a large field of view (FOV) and is suitable for high energy extended gamma source imaging. The optimization of key parameters of the camera was conducted, and a FOV of 60° and an angular resolution of up to 4.57° were achieved. Imaging simulations, including a simplified model of the primary loop of the pressurized-water reactor by GEANT4 code and image reconstruction using the expectation maximum algorithm, demonstrated that the proposed gamma camera could obtain a satisfactory spatial resolution for diagnosing the distribution of 16N in the primary loop of a nuclear reactor.

8.
Small ; : e2310340, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38456789

RESUMO

Chondrosarcoma(CS), a prevalent primary malignant bone tumor, frequently exhibits chemotherapy resistance attributed to upregulated anti-apoptosis pathways such as the Bcl-2 family. In this manuscript, a new strategy is presented to augment chemosensitivity and mitigate systemic toxicity by harnessing a nano-enabled drug delivery hydrogel platform. The platform utilizes "PLGA-PEG-PLGA", an amphiphilic triblock copolymer combining hydrophilic polyethylene glycol (PEG) and hydrophobic polylactide glycolide (PLGA) blocks, renowned for its properties conducive to crafting a biodegradable, temperature-sensitive hydrogel. This platform is tailored to encapsulate a ratiometrically designed dual-loaded liposomes containing a first-line chemo option for CS, Doxorubicin (Dox), plus a calculated amount of small molecule inhibitor for anti-apoptotic Bcl-2 pathway, ABT-737. In vitro and in vivo evaluations demonstrate successful Bcl-2 suppression, resulting in the restoration of Dox sensitivity, evident through impeded tumor growth and amplified necrosis rates at the tumor site. This delivery system showcases remarkable thermal responsiveness, injectability, and biodegradability, all finely aligned with the clinical demands of CS treatment. Collectively, this study introduces a transformative avenue for tackling drug resistance in CS chemotherapy, offering significant clinical potential.

9.
Cancer Res ; 84(11): 1872-1888, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38471084

RESUMO

Dysregulation of cholesterol homeostasis is implicated in the development and progression of hepatocellular carcinoma (HCC) that is characterized by intrahepatic and early extrahepatic metastases. A better understanding of the underlying mechanisms regulating cholesterol metabolism in HCC could help identify strategies to circumvent the aggressive phenotype. Here, we found that high expression of intracellular SPARC (secreted protein acidic and rich in cysteine) was significantly associated with elevated cholesterol levels and an enhanced invasive phenotype in HCC. SPARC potentiated cholesterol accumulation in HCC cells during tumor progression by stabilizing the ApoE protein. Mechanistically, SPARC competitively bound to ApoE, impairing its interaction with the E3 ligase tripartite motif containing 21 (TRIM21) and preventing its ubiquitylation and subsequent degradation. ApoE accumulation led to cholesterol enrichment in HCC cells, stimulating PI3K-AKT signaling and inducing epithelial-mesenchymal transition (EMT). Importantly, sorafenib-resistant HCC cells were characterized by increased expression of intracellular SPARC, elevated cholesterol levels, and enhanced invasive capacity. Inhibiting SPARC expression or reducing cholesterol levels enhanced the sensitivity of HCC cells to sorafenib treatment. Together, these findings unveil interplay between SPARC and cholesterol homeostasis. Targeting SPARC-triggered cholesterol-dependent oncogenic signaling is a potential therapeutic strategy for advanced HCC. SIGNIFICANCE: Intracellular SPARC boosts cholesterol availability to fuel invasion and drug resistance in hepatocellular carcinoma, providing a rational approach to improve the treatment of advanced liver cancer.


Assuntos
Apolipoproteínas E , Carcinoma Hepatocelular , Colesterol , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas , Invasividade Neoplásica , Osteonectina , Sorafenibe , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Osteonectina/metabolismo , Osteonectina/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Humanos , Sorafenibe/farmacologia , Colesterol/metabolismo , Animais , Camundongos , Apolipoproteínas E/metabolismo , Apolipoproteínas E/genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos Nus , Masculino , Ensaios Antitumorais Modelo de Xenoenxerto , Antineoplásicos/farmacologia , Transdução de Sinais/efeitos dos fármacos
10.
Elife ; 122024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372724

RESUMO

Epigenetic regulators present novel opportunities for both ischemic stroke research and therapeutic interventions. While previous work has implicated that they may provide neuroprotection by potentially influencing coordinated sets of genes and pathways, most of them remain largely uncharacterized in ischemic conditions. In this study, we used the oxygen-glucose deprivation (OGD) model in the immortalized mouse hippocampal neuronal cell line HT-22 and carried out an RNAi screen on epigenetic regulators. PRMT5 was identified as a novel negative regulator of neuronal cell survival after OGD, which presented a phenotype of translocation from the cytosol to the nucleus upon oxygen and energy depletion both in vitro and in vivo. PRMT5 bound to the chromatin and a large number of promoter regions to repress downstream gene expression. Silencing Prmt5 significantly dampened the OGD-induced changes for a large-scale of genes, and gene ontology analysis showed that PRMT5-target genes were highly enriched for Hedgehog signaling. Encouraged by the above observation, mice were treated with middle cerebral artery occlusion with the PRMT5 inhibitor EPZ015666 and found that PRMT5 inhibition sustains protection against neuronal death in vivo. Together, these findings revealed a novel epigenetic mechanism of PRMT5 in cerebral ischemia and uncovered a potential target for neuroprotection.


Assuntos
Isquemia Encefálica , Proteínas Hedgehog , Proteína-Arginina N-Metiltransferases , Animais , Camundongos , Isquemia Encefálica/genética , Glucose , Neuroproteção/genética , Oxigênio , Fenótipo , Proteína-Arginina N-Metiltransferases/genética
11.
J Ethnobiol Ethnomed ; 20(1): 28, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38419092

RESUMO

BACKGROUND: Medicinal plants have been used for centuries and are still relied upon by over 80% of the Ethiopian population. The people of Gamo, southern Ethiopia, have a rich cultural and traditional lifestyle with a long history of using plant resources for various uses including traditional herbal medicine. However, their traditional knowledge of traditional medicinal plants in Boreda Abaya District has not been explored Ethnobotanically yet, despite preserving diverse indigenous traditional medicinal plants. Hence, the study aimed to document and analyze traditional medicinal plants and associated traditional knowledge and practices used by local people. MATERIALS AND METHODS: Quantitative ethnobotanical data were collected via semi-structured interviews, face-to-face conversations, group discussions, and guided field trips between September 2022 and February 2023. In total, 92 informants participated, of which 25 were key informants. Quantitative data indices (informant consensus factor-ICF-and use report-Ur) were computed by MS Excel spreadsheet software. Scientific names of medicinal plants were checked via World Flora Online. RESULTS: In the present study, we recorded 188 traditional medicinal plant species belonging to 163 genera and 73 plant families. Lamiaceae (16 species), Asteraceae (16 species), Fabaceae (11 species), and Euphorbiaceae (8 species) contributed highest number of species and were found to be predominant family in the area. Leaves and seeds were most frequently used plant parts, and pounding (46%) was the main method to prepare remedies. The sudden sickness disease category scored the highest consensus (ICF: 0.35), followed by blood and circulatory-related disease categories (ICF: 0.33). The highest number of plant taxa (61 species) used to treat dermal disease has a 71-use report score, while fewer plant taxa (21 species) were utilized to treat genitourinary system-related disease category, having 25 use reports. Ocimum lamiifolium (Ur:56) and Moringa stenopetala (Ur:51) are widely used species and received highest use report value. CONCLUSION: Gamo people possess extensive traditional knowledge of ethnomedicine. The region's vegetation hosts diverse medicinal species, but deforestation, agriculture, and droughts threaten them. Local conservation practices require scientific support, prioritizing species having higher use reports (Ur), and in-depth investigations of promising species for drug development are essential.


Assuntos
População da África Oriental , Plantas Medicinais , Humanos , Fitoterapia/métodos , Etiópia , Etnobotânica/métodos
12.
Kaohsiung J Med Sci ; 40(2): 119-130, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38305705

RESUMO

Alzheimer's disease (AD) is a progressively debilitating neurodegenerative condition primarily affecting the elderly. Emerging research suggests that microRNAs (miRNAs) play a role in the development of AD. This study investigates the impact of miR-107-5p on neurological damage, oxidative stress, and immune responses in AD. We utilized APP/PS1 mice as AD mouse models and C57BL/6 J mice as controls. AD mice received treatment with agomir miR-107-5p (to overexpress miR-107-5p) or BAY11-7082 (an NF-κB pathway inhibitor). We evaluated learning and memory abilities through the Morris water maze test. Histopathological changes, hippocampal neuron distribution, and apoptosis were assessed using hematoxylin-eosin, Nissl, and TUNEL staining. Reactive oxygen species (ROS) levels, amyloid-Aß (Aß1-40/42) contents, and inflammatory factors (TNF-α, IL-6, IL-1ß) in hippocampal tissues were measured using ROS kits and enzyme-linked immunosorbent assay (ELISA). Microglial activation in hippocampal tissues was observed under a fluorescence microscope. miR-107-5p's binding to TLR4 was predicted via the TargetScan database and confirmed through a dual-luciferase assay. miR-107-5p expression, along with TLR4, APOE, and TREM2 in hippocampal tissue homogenate, and NF-κB p65 protein expression in the nucleus and cytoplasm were assessed via RT-qPCR and Western blot. Overexpression of miR-107-5p ameliorated hippocampal neurological damage, oxidative stress, and immune responses. This was evidenced by improved enhanced learning/memory abilities, reduced Aß1-40 and Aß1-42 levels, diminished neuronal injuries, decreased ROS and TNF-α, IL-6, and IL-1ß levels, increased APOE and TREM2 levels, and suppressed microglial activation. miR-107-5p directly targeted and inhibited TLR4 expression, leading to reduced nuclear translocation of NF-κB p65 in the NF-κB pathway. Inhibition of the NF-κB pathway similarly improved neurological damage, oxidative stress, and immune response in AD mice. miR-107-5p exerts its beneficial effects by suppressing the TLR4/NF-κB pathway, ultimately ameliorating neurological damage, oxidative stress, and immune responses in AD mice.


Assuntos
Doença de Alzheimer , MicroRNAs , Animais , Humanos , Camundongos , Doença de Alzheimer/genética , Apolipoproteínas E/metabolismo , Imunidade , Interleucina-6/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/genética , MicroRNAs/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo/genética , Espécies Reativas de Oxigênio , Transdução de Sinais/genética , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
13.
Plant Divers ; 46(1): 91-100, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38343590

RESUMO

Climate change poses a serious long-term threat to biodiversity. To effectively reduce biodiversity loss, conservationists need to have a thorough understanding of the preferred habitats of species and the variables that affect their distribution. Therefore, predicting the impact of climate change on species-appropriate habitats may help mitigate the potential threats to biodiversity distribution. Xerophyta, a monocotyledonous genus of the family Velloziaceae is native to mainland Africa, Madagascar, and the Arabian Peninsula. The key drivers of Xerophyta habitat distribution and preference are unknown. Using 308 species occurrence data and eight environmental variables, the MaxEnt model was used to determine the potential distribution of six Xerophyta species in Africa under past, current and future climate change scenarios. The results showed that the models had a good predictive ability (Area Under the Curve and True Skill Statistics values for all SDMs were more than 0.902), indicating high accuracy in forecasting the potential geographic distribution of Xerophyta species. The main bioclimatic variables that impacted potential distributions of most Xerophyta species were mean temperature of the driest quarter (Bio9) and precipitation of the warmest quarter (Bio18). According to our models, tropical Africa has zones of moderate and high suitability for Xerophyta taxa, which is consistent with the majority of documented species localities. The habitat suitability of the existing range of the Xerophyta species varied based on the climate scenario, with most species experiencing a range loss greater than the range gain regardless of the climate scenario. The projected spatiotemporal patterns of Xerophyta species help guide recommendations for conservation efforts.

14.
Cell Rep ; 43(2): 113688, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38245869

RESUMO

Macrophages are phenotypically and functionally diverse in the tumor microenvironment (TME). However, how to remodel macrophages with a protumor phenotype and how to manipulate them for therapeutic purposes remain to be explored. Here, we show that in the TME, RARγ is downregulated in macrophages, and its expression correlates with poor prognosis in patients with colorectal cancer (CRC). In macrophages, RARγ interacts with tumor necrosis factor receptor-associated factor 6 (TRAF6), which prevents TRAF6 oligomerization and autoubiquitination, leading to inhibition of nuclear factor κB signaling. However, tumor-derived lactate fuels H3K18 lactylation to prohibit RARγ gene transcription in macrophages, consequently enhancing interleukin-6 (IL-6) levels in the TME and endowing macrophages with tumor-promoting functions via activation of signal transducer and activator of transcription 3 (STAT3) signaling in CRC cells. We identified that nordihydroguaiaretic acid (NDGA) exerts effective antitumor action by directly binding to RARγ to inhibit TRAF6-IL-6-STAT3 signaling. This study unravels lactate-driven macrophage function remodeling by inhibition of RARγ expression and highlights NDGA as a candidate compound for treating CRC.


Assuntos
Neoplasias Colorretais , Interleucina-6 , Humanos , Carcinogênese/metabolismo , Transformação Celular Neoplásica/metabolismo , Neoplasias Colorretais/patologia , Histonas/metabolismo , Interleucina-6/metabolismo , Lactatos/metabolismo , Macrófagos/metabolismo , Fator de Transcrição STAT3/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , Microambiente Tumoral
15.
Eur J Oncol Nurs ; 68: 102499, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38199087

RESUMO

PURPOSE: Whether brain connectomics can predict 1-year decreased Quality of Life (QoL) in patients with breast cancer are unclear. A longitudinal study was utilized to explore their prediction abilities with a multi-center sample. METHODS: 232 breast cancer patients were consecutively enrolled and 214 completed the 1-year QoL assessment (92.2%). Resting state functional magnetic resonance imaging was collected before the treatment and a multivoxel pattern analysis (MVPA) was performed to differentiate whole-brain resting-state connectivity patterns. Net Reclassification Improvement (NRI) as well as Integrated Discrimination Improvement (IDI) were calculated to estimate the incremental value of brain connectomics over conventional risk factors. RESULTS: Paracingulate Gyrus, Superior Frontal Gyrus and Frontal Pole were three significant brain areas. Brain connectomics yielded 7.8-17.2% of AUC improvement in predicting 1-year decreased QoL. The NRI and IDI ranged from 20.27 to 54.05%, 13.21-33.34% respectively. CONCLUSION: Brain connectomics contribute to a more accurate prediction of 1-year decreased QoL in breast cancer. Significant brain areas in the prefrontal lobe could be used as potential intervention targets (i.e., Cognitive Behavioral Group Therapy) to improve long-term QoL outcomes in breast cancer.


Assuntos
Neoplasias da Mama , Conectoma , Humanos , Feminino , Qualidade de Vida , Estudos Longitudinais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapia , Imageamento por Ressonância Magnética/métodos
16.
Int Immunopharmacol ; 126: 111273, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38041957

RESUMO

Since the approval of the first chimeric antigen receptor (CAR)-T product in 2017, the number of new CAR-T clinical trials worldwide exceeds 100 per year. 1649 clinical studies have been conducted to explore possible future clinical applications of targets or target pairs through different biotechnologies. In this study, we aim to take a data-driven analytical approach to explore potential dual-target pairs based on clinical trial information. We screened 1283 non-withdrawal interventional CAR-T clinical trials spanning 96 different targets and 74 target pairs from clinicaltrials.gov. Through the Circos plot and temporal network plots, the information between targets and indications was visualized. Based on the assumption that two targets of a target pair must target the same indication, five new target pairs were inferred, including CD19/CD7, CD19/CD5, CD19/CD37, and CD19/BAFFR and validated by expression pattern, literature and patent information. This study provides novel support for target profiling of CAR-T from the perspective of clinical trials and also provides a reference for researchers and developers to select new targets or target pairs of CAR-T cell therapy.


Assuntos
Receptores de Antígenos Quiméricos , Receptores de Antígenos Quiméricos/genética , Imunoterapia Adotiva , Antígenos CD19 , Terapia Baseada em Transplante de Células e Tecidos
17.
J Ethnopharmacol ; 319(Pt 3): 117276, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37866464

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Natural products, particularly medicinal plants, have been utilized in traditional medicine for millennia to treat various diseases. The genus Balanophora (Balanophoraceae) consists of 23 accepted species. These species are the most controversial flowering plants, with highly reduced morphologies and are found parasitizing on the roots of their host. They have been used in traditional medicine as a remedy for stomach pain, detumescence, uterine prolapse, wounds, syphilis, gonorrhea, treating injuries from falls, and other conditions. However, there is no review of this genus on its traditional uses, phytochemistry, and pharmacology. AIM: The present narrative review discusses the scientific data supporting the traditional uses of Balanophora species. The available information on its botanical properties, traditional uses, chemical contents, pharmacological activities, and toxicity was summarized to help comprehend current research and offer a foundation for future research. MATERIALS AND METHODS: The materials used in combining data on the genus Balanophora comprises online sources such as Web of Science, Google Scholar, Science Direct, and Chinese National Knowledge Infrastructure (CNKI) for Chinese-related materials. World Flora online was used in validating the scientific names of this genus while ChemBio Draw Ultra Version 22.2 software was employed in drawing the phytochemical compounds. RESULTS: Nine Balanophora species including B. harlandii, B. japonica, B. polyandra, B. fungosa, B. fungosa subsp. indica, B. laxiflora, B. abbreviata, B. tobiracola, and B. involucrata have been documented as vital sources of traditional medicines in different parts of Asia. A total of 159 secondary metabolites have been isolated and identified from the ten species of this genus comprising tannins, flavonoids, sterols, lignans, chalcones, terpenes, and phenylpropanoids. Among these compounds, tannins, lignans, terpenoids, chalcones and phenolic acids contribute to the pharmacological activities of the species in this genus with several biological activities both in vitro and in vivo such as anti-inflammatory, anti-oxidant, hypoglycemic activity, cytotoxicity, anti-microbial, melanin synthesis etc. CONCLUSION: This review summarizes the available literature on the traditional uses, pharmacological properties, and phytoconstituents of Balanophora species indicating that they contain fascinating chemical compounds with diverse biological activities. The traditional uses of the species in this genus have been confirmed by scientific data such as antimicrobial, hemostatic effect, gastroprotective activity and others. However, many species in this genus are yet unknown in terms of their botanical uses, chemical composition and biological activities. Thus, more research into the scientific connections between traditional medicinal uses and pharmacological activities, mode of action of the isolated bioactive constituents, and toxicity of other Balanophora species is needed to determine their efficacy and therapeutic potential for safe clinical application.


Assuntos
Balanophoraceae , Chalconas , Lignanas , Medicina Tradicional , Taninos
18.
Appl Microbiol Biotechnol ; 108(1): 22, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38159121

RESUMO

Three new strains of dissimilatory perchlorate-reducing bacteria (DPRB), QD19-16, QD1-5, and P3-1, were isolated from an active sludge. Phylogenetic trees based on 16S rRNA genes indicated that QD19-16, QD1-5, and P3-1 belonged to Brucella, Acidovorax, and Citrobacter, respectively, expanding the distribution of DPRB in the Proteobacteria. The three strains were gram-negative and facultative anaerobes with rod-shaped cells without flagella, which were 1.0-1.6 µm long and 0.5-0.6 µm wide. The three DPRB strains utilized similar broad spectrum of electron donors and acceptors and demonstrated a similar capability to reduce perchlorate within 6 days. The enzyme activity of perchlorate reductase in QD19-16 toward chlorate was higher than that toward perchlorate. The high sequence similarity of the perchlorate reductase operon and chlorite dismutase genes in the perchlorate reduction genomic islands (PRI) of the three strains implied that they were monophyletic origin from a common ancestral PRI. Two transposase genes (tnp1 and tnp2) were found in the PRIs of strain QD19-16 and QD1-5, but were absent in the strain P3-1 PRI. The presence of fragments of IR sequences in the P3-1 PRI suggested that P3-1 PRI had previously contained these two tnp genes. Therefore, it is plausible to suggest that a common ancestral PRI transferred across the strains Brucella sp. QD19-16, Acidovorax sp. QD1-5, and Citrobacter sp. P3-1 through horizontal gene transfer, facilitated by transposases. These results provided a direct evidence of horizontal gene transfer of PRI that could jump across phylogenetically unrelated bacteria through transposase. KEY POINTS: • Three new DPRB strains can effectively remove high concentration of perchlorate. • The PRIs of three DPRB strains are acquired from a single ancestral PRI. • PRIs are incorporated into different bacteria genome through HGT by transposase.


Assuntos
Ilhas Genômicas , Percloratos , Filogenia , Oxirredução , Transferência Genética Horizontal , RNA Ribossômico 16S/genética , Bactérias/genética , Oxirredutases/genética , Ecossistema , Transposases/genética
19.
Rev Sci Instrum ; 94(8)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38065158

RESUMO

A digital holographic interferometry based on Fresnel biprism has been developed to measure the electron density profile of laser-produced collisionless shocks in laboratory, which used the Fourier transform method to solve the wrapped phase. The discontinuous surfaces of shocks will produce the break and split of the interference fringes, which cannot be processed by the conventional path-following phase unwrapping algorithm when reconstructing the real phase of the plasma. Therefore, we used a least-squares method to extract the real phase, which is proportional to the line-integrated electron density. We obtained fine density profiles of collisionless shocks in the line-integrated density region around 1018 cm-2 with a density resolution of 3.38 × 1016 cm-2. The shock structure is in well agreement with that measured by the dark-field schlieren methods and that predicted by shock jump condition. Synthetic holograms are used to confirm the effectiveness of our algorithm, and it is shown that correct results can still be obtained even if part of the diagnostic light is refracted out of the optical system by the shock.

20.
Front Immunol ; 14: 1280007, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38143760

RESUMO

Background: Anaplastic Large Cell Lymphoma (ALCL) is one of the most common subtypes of T-cell lymphoma. Among these, refractory and relapsed (r/r) ALK positive ALCL lacks effective therapies. The chimeric antigen receptor-modified T (CAR-T) cell therapy holds great promise as a therapeutic strategy for this disease. However, it is not known yet whether anti-CD5 CAR-T cells are sufficient for the definitive treatment of relapsed ALK+ ALCL, nor the role of accurate laboratory-based diagnoses during CAR-T treatment. Case presentation: The adolescent patient received autologous T cells containing sequences encoding VH domains specific to CD5. Following the infusion, there was an increase in both the copy number and proportion of CAR-T cells in peripheral blood. IL-6 and ferritin levels in the patient exhibited significant fluctuations, with increases of 13 and 70 folds respectively, compared to baseline after the treatment. Additionally, adverse effects were observed, including grade 4 rash, grade 1 headache, nausea, and neck-pain. Surprisingly, a relapsed disease phenotype was identified based on the results of PET/CT and histopathological analysis of the inguinal lymph node biopsy. After conducting a thorough diagnostic assessment, which included flow cytometry, next-generation sequencing (NGS), examination of immune-related gene rearrangements, and analysis of the immune repertoire of T-cell receptors (TCR), we conclusively determined that the hyperplastic T cells identified in the lymph node were the result of an expansion of CAR-T cells. Ultimately, the patient has attained complete remission (CR) and has sustained a disease-free survival state for 815 days as of the cutoff date on August 30, 2023. Conclusion: Taken together, the results demonstrate that anti-CD5 CAR-T cells can induce a clinical response in r/r ALK+ ALCL patient. Furthermore, this case underscores the importance of utilizing advanced technologies with high sensitivity and accuracy for biological detection in clinical laboratory diagnosis and prognosis in CAR-T cell treatment. Trial registration number: NCT04767308.


Assuntos
Linfoma Anaplásico de Células Grandes , Receptores de Antígenos Quiméricos , Adolescente , Humanos , Diagnóstico Diferencial , Linfoma Anaplásico de Células Grandes/terapia , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Receptores Proteína Tirosina Quinases/genética , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos Quiméricos/genética , Receptores de Antígenos Quiméricos/uso terapêutico , Linfócitos T/patologia
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