Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 49
Filter
1.
Biol Reprod ; 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39135547

ABSTRACT

The gestation period in captive Yangtze finless porpoise (YFP) is a well-coordinated and dynamic process that involves both systemic and local alterations. The gut microbiota and its connection to fecal metabolites are crucial in supporting fetal development and ensuring maternal health during reproductive stages. This study evaluates changes in the gut microbiota and their correlation with fecal metabolites in captive YFPs during different reproductive stages. The results reveal that microbial community structure changed significantly during reproductive stages, while gut microbial diversity remained stable. The genus unclassified Peptostrptococcaceae, Corynebacterium, and norank KD4-96 were significantly greater in non-pregnancy (NP), Terrisporobacter was significantly greater in lactating (LL), and Clostridium was significantly higher in early-pregnancy (EP) compared to the other groups. The host fecal metabolome exhibited significant alterations during the reproductive stages. Indoxyl sulfate, octadecatrienoic acid, and methionyl-methionine were significantly higher in the NP; galactosylglycerol, chondroitin 6-sulfate, and lumichrome were significantly higher in the EP and mid-pregnancy (MP); and valylleucine and butyryl-l-carnitine were significantly higher in the LL. The altered metabolites were mostly concentrated in pathways associated with arachidonic acid metabolism (significantly altered in NP), leucine, valine, and isoleucine biosynthesis (significantly altered in EP and MP), and glycerophospholipid metabolism (significantly altered in LL compared to others stages). Additionally, we found a strong link between variations in the host metabolism and alterations in the fecal bacteria of captive YFP. In conclusion, this study provides detailed insights into host metabolic and fecal bacterial changes in captive YFP during reproduction stages, providing important knowledge for improving the reproductive management in the captive YFP.

2.
Int Immunopharmacol ; 140: 112785, 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39088915

ABSTRACT

OBJECTIVE: To observe the effects and mechanisms of Maresin2 on the function of DCs(Dendritic cells). METHOD: The levels of IL-6, IL-12, TNF-α and IL-1ß secreted by BMDCs (Bone marrow-derived Dendritic cells) after Maresin2 treatment were detected by ELISA. At the same time, the expressions of costimulatory molecules CD40 and CD86 on the surface, the ability of phagocytosis of ovalbumin(OVA) antigen, and antigen presentation function in BMDCs were analyzed by flow cytometry. Finally, MAPK and NF-κB pathway signaling phosphorylation in Maresin2-treated BMDCs were detected by western blot. RESULTS: The secretion levels of IL-6, IL-12, TNF-α and IL-1ß were significantly decreased in the Maresin2 treatment group after LPS treatment (P < 0.05). The expression levels of CD86 and CD40 were significantly decreased after Maresin2 treatment (P < 0.05). Maresin2 enhanced the phagocytosis ability of ovalbumin(OVA) (P < 0.05), but the ability of antigen presentation of BMDCs with the treatment of Maresin2 changed slightly (P > 0.05). Phosphorylation of p38, JNK, p65, ikka/ß and ERK peaked at 15 min in the LPS group, while phosphorylation of p-p38 and p-ERK weakened 30 min and 60 min after treatment with Maresin2. CONCLUSIONS: Maresin2 inhibits inflammatory cytokine secretion but enhances phagocytosis via the MAPK/NF-κB pathway in BMDCs, which may contribute to negatively regulating inflammation.

3.
Angew Chem Int Ed Engl ; : e202410885, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39087846

ABSTRACT

To access degradable polyolefin plastic, non-alternating copolymerization of ethylene (E) and carbon monoxide (CO) for producing polyethylene (PE) with in-chain ketones is particularly appealing; however, it still presents significant challenges such as molecular weight modulation (hydrogen response) and chain endgroup control (functional terminal). In this study, we achieved hydrogen-controlled E/CO non-alternating copolymerization using late transition metal catalysts. This process results in linear PEs containing the desired non-alternating in-chain keto groups (1.0-9.3 mol%) and with tunable molecular weights ranging from 43 to 195 kDa. In this reaction, H2 serves as a chain transfer agent, modulating the polymer's molecular weight, forming unique aldehyde endgroups and eliminating usual olefinic endgroups; CO undergoes non-alternating insertion into the PE chain, resulting in a strictly non-alternating structure (> 99%) for the keto-PE. The dispersed incorporation of in-chain keto groups retains bulk properties of PE and makes PE susceptible to photodegradation, which produces significantly lower molecular weight polymers and oligomers with unambiguous vinyl and acetyl terminals.

4.
Sci Rep ; 14(1): 15162, 2024 07 02.
Article in English | MEDLINE | ID: mdl-38956440

ABSTRACT

Prolonged ventricular repolarization has been associated with cardiovascular disease. We sought to investigate the association of prolonged ventricular repolarization with mild cognitive impairment (MCI) and the potential underlying neuropathological mechanisms in older adults. This cross-sectional study included 4328 dementia-free participants (age ≥ 65 years; 56.8% female) in the baseline examination of the Multidomain INterventions to delay dementia and Disability in rural China; of these, 989 undertook structural brain magnetic resonance imaging (MRI) scans. QT, QTc, JT, JTc, and QRS intervals were derived from 12-lead electrocardiograph. MCI, amnestic MCI (aMCI), and non-amnestic MCI (naMCI) were defined following the Petersen's criteria. Volumes of gray matter (GM), white matter, cerebrospinal fluid, total white matter hyperintensities (WMH), periventricular WMH (PWMH), and deep WMH (DWMH) were automatically estimated. Data were analyzed using logistic and general linear regression models. Prolonged QT, QTc, JT, and JTc intervals were significantly associated with an increased likelihood of MCI and aMCI, but not naMCI (p < 0.05). In the MRI subsample, QT, QTc, JT, and JTc intervals were significantly associated with larger total WMH and PWMH volumes (p < 0.05), but not with DWMH volume. Statistical interactions were detected, such that prolonged QT and JT intervals were significantly associated with reduced GM volume only among participants with coronary heart disease or without APOE ε4 allele (p < 0.05). Prolonged ventricular repolarization is associated with MCI and cerebral microvascular lesions in a general population of older adults. This underlies the importance of cognitive assessments and brain MRI examination among older adults with prolonged QT interval.


Subject(s)
Cognitive Dysfunction , Magnetic Resonance Imaging , White Matter , Humans , Cognitive Dysfunction/physiopathology , Cognitive Dysfunction/diagnostic imaging , Cognitive Dysfunction/pathology , Female , Male , Aged , Cross-Sectional Studies , White Matter/diagnostic imaging , White Matter/pathology , White Matter/physiopathology , Magnetic Resonance Imaging/methods , Electrocardiography , Aged, 80 and over , Gray Matter/diagnostic imaging , Gray Matter/pathology , Gray Matter/physiopathology , China
6.
J Drug Target ; : 1-15, 2024 Aug 05.
Article in English | MEDLINE | ID: mdl-39073439

ABSTRACT

Phototherapy can cause autophagy while killing tumour cells, leading to tumour recurrence and metastasis. Here, we constructed a laser and enzyme dual responsive nanodrug delivery system Tf-Te@CTSL-HCQ (TT@CH) to precisely regulate autophagy in synergy with phototherapy to inhibit the proliferation and metastasis of melanoma. Firstly, transferrin (Tf) was used as a nanoreactor to synthesise phototherapy agent Tf-Te by the biological template mineralisation method. Then, the thermosensitive liposome modified with FAP-α-responsive peptide (CAP) was used as a carrier to encapsulate autophagy inhibitor hydroxychloroquine (HCQ) and Tf-Te, to obtain an intelligent TT@CH delivery system. Once arriving at the tumour site, TT@CH can be cleaved by FAP-α overexpressed on cancer-associated fibroblasts (CAFs), and release Tf-Te and HCQ. Then Tf-Te can target melanoma cells and exert PTT/PDT anti-tumour effect. What's more, hyperpyrexia induced by PTT can further promote drugs release from TT@CH. Meanwhile, HCQ simultaneously inhibited autophagy of CAFs and melanoma cells, and down-regulated IL-6 and HMGB1 secretion, thus effectively inhibiting melanoma metastasis. Pharmacodynamic results exhibited the best anti-tumour effect of TT@CH with the highest tumour inhibition rate of 91.3%. Meanwhile, lung metastatic nodules of TT@CH treated mice reduced by 124.33 compared with that of mice in control group. Overall, TT@CH provided an effective therapy strategy for melanoma.

7.
Article in English | MEDLINE | ID: mdl-39046653

ABSTRACT

Endothelial-to-mesenchymal transition (EndoMT) is associated with neointimal hyperplasia and vein graft failure, and heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) has emerged as a major modulator of EMT. We aimed to investigate the functional consequence of EndoMT in neointimal hyperplasia and the precise role of hnRNPA1 in the regulation of EndoMT and neointimal hyperplasia. We investigated the spatial and temporal distribution characteristics of EndoMT cells in a mouse model of vein graft transplantation. In vitro, we studied the interaction between EndoMT cells and VSMCs, and the underlying mechanism was investigated by cytokine antibody assays. In cultured HUVECs, we studied the effect of hnRNPA1 on EndoMT and the cellular interactions by using siRNA-mediated knockdown and adenovirus-mediated overexpression. We further investigated the role of hnRNPA1 in EndoMT and neointimal hyperplasia in vivo with an AAV-mediated EC-specific hnRNPA1 overexpression murine model. We demonstrated the presence of EndoMT cells during the initial stage of neointimal formation, and that EndoMT cells promoted the proliferation and migration of VSMCs in vitro. Mechanistic studies revealed that EndoMT cells express and secrete a higher level of PDGF-B. Furthermore, we found a regulatory role for hnRNPA1 in EndoMT in vitro and in vivo. Similarly, we found that hnRNPA1 overexpression in ECs reduced the expression and secretion of PDGF-B during EndoMT, effectively inhibiting EndoMT cell-mediated activation of VSMCs in vitro and neointimal formation in vivo. Taken together, these findings indicate that EndoMT cells can activate VSMCs through a paracrine mechanism mediated by hnRNPA1 and lead to neointimal hyperplasia.

8.
Sci Rep ; 14(1): 16359, 2024 07 16.
Article in English | MEDLINE | ID: mdl-39014187

ABSTRACT

The 3.5 mm diameter or thicker Steinmann pins were commonly used in skeletal traction, which are so highly invasive that may result in severe complications such as pin tract infection and iatrogenic calcaneus fractures. Accordingly, Xirui Wu designed a new type of tension traction bow that can be assembled with 2.0 mm diameter Kirschner wires, but its effectiveness is unclear. We aim to evaluate the effectiveness of 2.0 mm diameter Kirschner wires assembled with Wu's Tension Traction Bows in calcaneal skeletal traction. Data of 65 patients who were admitted to our department with tibia fractures from January 2021 to June 2022 and underwent preoperative calcaneal skeletal traction were collected retrospectively. 36 patients treated with 2.0 mm diameter Kirschner wires assembled with Wu's Tension Traction Bows were assigned into Group 1, and 29 patients treated with 3.5 mm diameter Steinmann pins assembled with Bohler's traction bows were assigned into Group 2. Pins loosening, breakage, and calcaneus fractures occurred in neither group. No statistical differences were observed in traction weight, swelling reduction efficacy, and traction duration (P > 0.05). Statistically significant differences were found between the two groups in term of post-traction bleeding incidence, average bleeding duration, and mean size and healing time of traction wounds (P < 0.05). Though VAS pain score before traction and on the first two days after traction in Group 1 didn't differ from Group 2 (P > 0.05), it was significantly lower in Group 1 compared to Group 2 on the third day after traction (P = 0.030). This study demonstrates that 2.0 mm diameter Kirschner wires assembled with Wu's Tension Traction Bows produce satisfied traction outcomes with less invasion and are recommended in calcaneal skeletal traction.


Subject(s)
Bone Wires , Calcaneus , Traction , Humans , Calcaneus/surgery , Male , Female , Traction/methods , Middle Aged , Adult , Retrospective Studies , Fractures, Bone/surgery , Fractures, Bone/therapy , Aged , Bone Nails , Treatment Outcome , Fracture Fixation, Internal/methods , Fracture Fixation, Internal/instrumentation
9.
Rev Sci Instrum ; 95(6)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38832852

ABSTRACT

Electromagnetic ultrasonic detection technology utilizes the electromagnetic coupling method to generate and receive ultrasonic waves without a couplant, which is suitable for rapid detection. However, the detection can be affected by the spatial distribution of the acoustic field and the polarization direction of the shear wave, which can result in suboptimal detection performance. The acoustic field directivity of the shear wave generated by the butterfly coil electromagnetic acoustic transducer was measured using the transmission method. The data indicate that the acoustic pressure amplitude of the shear wave is maximized along the axis of the acoustic field, thereby meeting the requirements of synthetic aperture focusing technique imaging. We used the reflection method to detect the through-hole defects and investigated the effect of shear wave polarization direction. By comparing the experimental data and imaging results, it can be concluded that higher echo amplitudes are obtained when the polarization direction of the shear wave is perpendicular to the axis of the through-hole defects. Based on the explosive reflection model, the frequency domain phase shift migration (PSM) method converts the time-domain signal to the frequency domain for processing and uses a phase-shift factor for layer-by-layer imaging. We used the PSM method to process the experimental data, which not only produced high-resolution images but also had a high computational speed.

10.
Acta Pharm Sin B ; 14(6): 2554-2566, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38828147

ABSTRACT

Oncolytic viruses (OVs), a group of replication-competent viruses that can selectively infect and kill cancer cells while leaving healthy cells intact, are emerging as promising living anticancer agents. Unlike traditional drugs composed of non-replicating compounds or biomolecules, the replicative nature of viruses confer unique pharmacokinetic properties that require further studies. Despite some pharmacokinetics studies of OVs, mechanistic insights into the connection between OV pharmacokinetics and antitumor efficacy remain vague. Here, we characterized the pharmacokinetic profile of oncolytic virus M1 (OVM) in immunocompetent mouse tumor models and identified the JAK‒STAT pathway as a key modulator of OVM pharmacokinetics. By suppressing the JAK‒STAT pathway, early OVM pharmacokinetics are ameliorated, leading to enhanced tumor-specific viral accumulation, increased AUC and Cmax, and improved antitumor efficacy. Rather than compromising antitumor immunity after JAK‒STAT inhibition, the improved pharmacokinetics of OVM promotes T cell recruitment and activation in the tumor microenvironment, providing an optimal opportunity for the therapeutic outcome of immune checkpoint blockade, such as anti-PD-L1. Taken together, this study advances our understanding of the pharmacokinetic-pharmacodynamic relationship in OV therapy.

12.
Glob Chang Biol ; 30(6): e17349, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38822665

ABSTRACT

Priming of soil organic matter (SOM) decomposition by microorganisms is a key phenomenon of global carbon (C) cycling. Soil pH is a main factor defining priming effects (PEs) because it (i) controls microbial community composition and activities, including enzyme activities, (ii) defines SOM stabilization and destabilization mechanisms, and (iii) regulates intensities of many biogeochemical processes. In this critical review, we focus on prerequisites and mechanisms of PE depending on pH and assess the global change consequences for PE. The highest PEs were common in soils with pH between 5.5 and 7.5, whereas low molecular weight organic compounds triggered PE mainly in slightly acidic soils. Positive PEs up to 20 times of SOM decomposition before C input were common at pH around 6.5. Negative PEs were common at soil pH below 4.5 or above 7 reflecting a suboptimal environment for microorganisms and specific SOM stabilization mechanisms at low and high pH. Short-term soil acidification (in rhizosphere, after fertilizer application) affects PE by: mineral-SOM complexation, SOM oxidation by iron reduction, enzymatic depolymerization, and pH-dependent changes in nutrient availability. Biological processes of microbial metabolism shift over the short-term, whereas long-term microbial community adaptations to slow acidification are common. The nitrogen fertilization induced soil acidification and land use intensification strongly decrease pH and thus boost the PE. Concluding, soil pH is one of the strongest but up to now disregarded factors of PE, defining SOM decomposition through short-term metabolic adaptation of microbial groups and long-term shift of microbial communities.


Subject(s)
Soil Microbiology , Soil , Soil/chemistry , Hydrogen-Ion Concentration , Carbon Cycle , Carbon/analysis , Carbon/metabolism
14.
Exp Neurol ; 378: 114845, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38838802

ABSTRACT

BACKGROUND: Research in the areas of inflammation and mitochondrial stress in ischemic stroke is rapidly expanding, but a comprehensive overview that integrates bibliometric trends with an in-depth review of molecular mechanisms is lacking. OBJECTIVE: To map the evolving landscape of research using bibliometric analysis and to detail the molecular mechanisms that underpin these trends, emphasizing their implications in ischemic stroke. METHODS: We conducted a bibliometric analysis to identify key trends, top contributors, and focal research themes. In addition, we review recent research advances in mitochondrial stress and inflammation in ischemic stroke to gain a detailed understanding of the pathophysiological processes involved. CONCLUSION: Our integrative approach not only highlights the growing research interest and collaborations but also provides a detailed exploration of the molecular mechanisms that are central to the pathology of ischemic stroke. This synthesis offers valuable insights for researchers and paves the way for targeted therapeutic interventions.


Subject(s)
Bibliometrics , Inflammation , Ischemic Stroke , Mitochondria , Humans , Ischemic Stroke/metabolism , Ischemic Stroke/pathology , Mitochondria/metabolism , Inflammation/metabolism , Inflammation/pathology , Animals
15.
Exp Mol Med ; 56(6): 1412-1425, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38825640

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most common fatal cancers worldwide, and the identification of novel treatment targets and prognostic biomarkers is urgently needed because of its unsatisfactory prognosis. Regulator of G-protein signaling 19 (RGS19) is a multifunctional protein that regulates the progression of various cancers. However, the specific function of RGS19 in HCC remains unclear. The expression of RGS19 was determined in clinical HCC samples. Functional and molecular biology experiments involving RGS19 were performed to explore the potential mechanisms of RGS19 in HCC. The results showed that the expression of RGS19 is upregulated in HCC tissues and is significantly associated with poor prognosis in HCC patients. RGS19 promotes the proliferation and metastasis of HCC cells in vitro and in vivo. Mechanistically, RGS19, via its RGS domain, stabilizes the MYH9 protein by directly inhibiting the interaction of MYH9 with STUB1, which has been identified as an E3 ligase of MYH9. Moreover, RGS19 activates ß-catenin/c-Myc signaling via MYH9, and RGS19 is also a transcriptional target gene of c-Myc. A positive feedback loop formed by RGS19, MYH9, and the ß-catenin/c-Myc axis was found in HCC. In conclusion, our research revealed that competition between RGS19 and STUB1 is a critical mechanism of MYH9 regulation and that the RGS19/MYH9/ß-catenin/c-Myc feedback loop may represent a promising strategy for HCC therapy.


Subject(s)
Carcinoma, Hepatocellular , Gene Expression Regulation, Neoplastic , Liver Neoplasms , Myosin Heavy Chains , Proto-Oncogene Proteins c-myc , RGS Proteins , beta Catenin , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , beta Catenin/metabolism , RGS Proteins/metabolism , RGS Proteins/genetics , Proto-Oncogene Proteins c-myc/metabolism , Proto-Oncogene Proteins c-myc/genetics , Animals , Myosin Heavy Chains/metabolism , Myosin Heavy Chains/genetics , Cell Line, Tumor , Mice , Signal Transduction , Cell Proliferation , Male , Prognosis , Feedback, Physiological , Female
16.
Heliyon ; 10(9): e30424, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38765104

ABSTRACT

Stroke is the fifth leading cause of death worldwide, and the functional status of the gut plays a key role in patients' prognosis. Recent publications have explored the gut association with stroke, but few articles have been published that specifically address a comprehensive bibliometric analysis of the gut microbiota and its association with stroke. To address this gap, we used bibliometric methods to examine the landscape of research concerning the gut and stroke over approximately two decades, utilizing the Web of Science Core Collection (WoSCC). On November 1, 2022, a search was conducted for English-language articles published between 2002 and 2022, with only including original articles. Visual and statistical analyses were performed using CiteSpace, VOSviewer, and Bibliometrix 4.1.0 Package. After screening relevant articles, the results revealed that the number of articles published in this field has progressively increased during the last two decades. In particular, the total number of publications rapidly increased year by year from 2014. Among them, China ranked first in the world with a total of 227 publications. Authorship analysis highlighted Wang Z as the most prolific author, with 18 publications and an H-index of 14, highlighting significant contributions to this field. Meanwhile, the Southern Medical University of China was identified as the most productive institution. Moreover, analysis of keywords revealed that 'cerebral ischemia', 'intestinal microbiota', 'gut microbiota', and 'trimethylamine N-oxide' were popular topics searched, and research on the relationship between stroke and the gut continues to be a research hotspot. In summary, this study presents an overview of the progress and emerging trends in research on the relationship between stroke and gut health over the past two decades, providing a valuable resource for researchers aiming to understand the current state of the field and identify potential directions for future studies.

17.
ISME J ; 18(1)2024 Jan 08.
Article in English | MEDLINE | ID: mdl-38691428

ABSTRACT

Elucidating complex interactions between bacteria and fungi that determine microbial community structure, composition, and functions in soil, as well as regulate carbon (C) and nutrient fluxes, is crucial to understand biogeochemical cycles. Among the various interactions, competition for resources is the main factor determining the adaptation and niche differentiation between these two big microbial groups in soil. This is because C and energy limitations for microbial growth are a rule rather than an exception. Here, we review the C and energy demands of bacteria and fungi-the two major kingdoms in soil-the mechanisms of their competition for these and other resources, leading to niche differentiation, and the global change impacts on this competition. The normalized microbial utilization preference showed that bacteria are 1.4-5 times more efficient in the uptake of simple organic compounds as substrates, whereas fungi are 1.1-4.1 times more effective in utilizing complex compounds. Accordingly, bacteria strongly outcompete fungi for simple substrates, while fungi take advantage of complex compounds. Bacteria also compete with fungi for the products released during the degradation of complex substrates. Based on these specifics, we differentiated spatial, temporal, and chemical niches for these two groups in soil. The competition will increase under the main five global changes including elevated CO2, N deposition, soil acidification, global warming, and drought. Elevated CO2, N deposition, and warming increase bacterial dominance, whereas soil acidification and drought increase fungal competitiveness.


Subject(s)
Bacteria , Fungi , Soil Microbiology , Fungi/metabolism , Fungi/growth & development , Bacteria/metabolism , Bacteria/classification , Bacteria/genetics , Soil/chemistry , Carbon/metabolism , Microbial Interactions
18.
Sci Rep ; 14(1): 10049, 2024 05 02.
Article in English | MEDLINE | ID: mdl-38698008

ABSTRACT

Although some studies have reported on the expression and clinical significance of Fascin-1 (FSCN1) in liver cancer, the clinical application and differential diagnosis value of FSCN1 in liver cancer are still unclear. The aim of this study was to analyze the expression level of FSCN1 protein in liver cancer tissues and explore its diagnostic and application value in differentiating between hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The immunehistochemical analysis was used to detect the expression of FSCN1 in 108 cases of HCC, 26 cases of ICC, 23 cases of liver cirrhosis, and 11 cases of normal liver tissues. The differences in the positive expression rate and strong positive expression rate of FSCN1 among different groups were analyzed. The positive rate of FSCN1 in normal liver tissues, liver cirrhosis, HCC, and ICC tissues was 0.0% (0/11), 0.0% (0/23), 13.9% (15/108), and 92.3% (24/26), respectively, while the strong positive rate was 0.0% (0/11), 0.0% (0/23), 0.9% (1/108), and 69.2% (18/26), respectively. Both the positive rate and strong positive rate of FSCN1 in ICC tissues were significantly higher than those in HCC, liver cirrhosis, and normal liver tissues. Additionally, the positive rate of FSCN1 in moderately to poorly differentiated HCC tissues was 18.8% (15/80), significantly higher than in well-differentiated HCC (0.0%, 0/28) (P = 0.031). In liver cancer, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FSCN1 positive prediction for ICC were 92.3%, 86.1%, 61.5%, and 97.9%, respectively, whereas the sensitivity, specificity, PPV, and NPV of FSCN1 strong positive prediction for ICC were 69.2%, 99.1%, 94.7%, and 93.0%, respectively. These results suggest that FSCN1 may play an important role in the occurrence and progression of liver cancer, and it can be used as a novel diagnostic marker for ICC.


Subject(s)
Biomarkers, Tumor , Carcinoma, Hepatocellular , Carrier Proteins , Cholangiocarcinoma , Liver Neoplasms , Microfilament Proteins , Humans , Liver Neoplasms/diagnosis , Liver Neoplasms/metabolism , Microfilament Proteins/metabolism , Carrier Proteins/metabolism , Male , Female , Middle Aged , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/metabolism , Biomarkers, Tumor/metabolism , Cholangiocarcinoma/diagnosis , Cholangiocarcinoma/metabolism , Aged , Adult , Liver Cirrhosis/diagnosis , Liver Cirrhosis/metabolism , Diagnosis, Differential , Bile Duct Neoplasms/diagnosis , Bile Duct Neoplasms/metabolism , Bile Duct Neoplasms/pathology , Sensitivity and Specificity
19.
Phytochemistry ; 225: 114165, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38815884

ABSTRACT

Ten C-geranylated flavonoids, along with three known analogues, were isolated from the leaves of Artocarpus communis. The chemical structures of these compounds were unambiguously determined via comprehensive spectroscopic analysis, single-crystal X-ray diffraction experiments, and quantum chemical electronic circular dichroism calculations. Structurally, artocarones A-I (1-9) represent a group of unusual, highly modified C-geranylated flavonoids, in which the geranyl chain is cyclised with the ortho-hydroxy group of flavonoids to form various heterocyclic scaffolds. Notably, artocarones E and G-I (5 and 7-9) feature a 6H-benzo[c]chromene core that is hitherto undescribed in C-geranylated flavonoids. Artocarone J (10) is the first example of C-9-C-16 connected C-geranylated aurone. Meanwhile, the plausible biosynthetic pathways for these rare C-geranylated flavonoids were also proposed. Notably, compounds 1, 2, 4, 8, 11, and 12 exhibited promising in vitro inhibitory activities against respiratory syncytial virus and herpes simplex virus type 1.


Subject(s)
Antiviral Agents , Artocarpus , Flavonoids , Flavonoids/chemistry , Flavonoids/isolation & purification , Flavonoids/pharmacology , Artocarpus/chemistry , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Antiviral Agents/isolation & purification , Molecular Structure , Herpesvirus 1, Human/drug effects , Microbial Sensitivity Tests , Respiratory Syncytial Viruses/drug effects , Plant Leaves/chemistry , Structure-Activity Relationship , Models, Molecular
20.
Acta Pharm Sin B ; 14(5): 2317-2332, 2024 May.
Article in English | MEDLINE | ID: mdl-38799627

ABSTRACT

Autophagy is an important factor in reducing the efficacy of tumor phototherapy (including PTT and PDT). Accurate regulation of autophagy in tumor cells is a new strategy to improve the anti-tumor efficiency of PTT/PDT. This project intended to construct a tumor-activated autophagy regulator to efficiently block PTT/PDT-induced autophagy and realize synergistic sensitization to tumor phototherapy. To achieve this goal, we first synthesized TRANSFERRIN (Tf) biomimetic mineralized nano-tellurium (Tf-Te) as photosensitizer and then used disulfide bond reconstruction technology to induce Tf-Te self-assembly. The autophagy inhibitor hydroxychloroquine (HCQ) and iron ions carried by Tf were simultaneously loaded to prepare a tumor-responsive drug reservoir Tf-Te/HCQ. After entering breast cancer cells through the "self-guidance system", Tf-Te/HCQ can generate hyperpyrexia and ROS under NIR laser irradiation, to efficiently induce PTT/PDT effect. Meanwhile, the disulfide bond broke down in response to GSH, and the nanoparticles disintegrated to release Fe2+ and HCQ at fixed points. They simultaneously induce lysosomal alkalinization and increased osmotic pressure, effectively inhibit autophagy, and synergistically enhance the therapeutic effect of phototherapy. In vivo anti-tumor results have proved that the tumor inhibition rate of Tf-Te/HCQ can be as high as 88.6% on 4T1 tumor-bearing mice. This multifunctional drug delivery system might provide a new alternative for more precise and effective tumor phototherapy.

SELECTION OF CITATIONS
SEARCH DETAIL