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BACKGROUND: Many studies have shown that the COVID-19 pandemic has increased the risk of suicidal tendencies among the public. However, there is limited research reporting on the changing trends in suicidal ideation after 2020 in the context of the long-term normalization of COVID-19 prevention and control measures in China. METHODS: The self-administered online questionnaire was adopted to collect 12-month suicidal ideation, depressive symptoms, anxiety symptoms, stress, and some demographic information from university students by convenient cluster sampling in Shandong, Shaanxi, and Jilin Provinces, China. Multivariate logistic regressions were performed to assess the association between different factors and suicidal ideation. RESULTS: The prevalence of 12-month suicidal ideation from 2021 to 2023 among university students was 3.89 %, 5.81 %, and 4.33 %, respectively, showing a trend of first increasing and then decreasing. The trends presented a similar tendency in the subgroups according to gender, majors, and grades, except among urban freshman-year students. The associated factors of suicidal ideation were different among university students in different surveys. However, female gender, poor mental health, and depressive symptoms were linked to a higher risk of suicidal ideation. LIMITATIONS: More representative large-scale longitudinal studies should be used to monitor the suicidal behavior of university students. CONCLUSIONS: The prevalence of 12-month suicidal ideation among Chinese university students exhibited a pattern of initial increase followed by a subsequent decrease from 2021 to 2023. Despite the complete lifting of COVID-19 prevention and control measures in China, the prolonged three-year epidemic may have enduring adverse effects on university students, underscoring the ongoing importance of providing continuous mental health services to this population.

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Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver condition worldwide, demanding further investigation into its pathogenesis. Circular RNAs (circRNAs) are emerging as pivotal regulators in MASLD processes, yet their pathological implications in MASLD remain poorly understood. This study focused on elucidating the role of circular RNA ribonucleotide reductase subunit M2 (circRRM2) in MASLD progression. In this study, we used both in vitro and in vivo MASLD models using long-chain-free fatty acid (FFA)-treated hepatocytes and high-fat diet (HFD)-induced MASLD in mice, respectively. We determined the expression patterns of circRRM2, microRNA-142-5p (miR-142-5p), and neuregulin 1 (NRG1) in livers of MASLD-afflicted mice and MASLD hepatocytes by RT-qPCR. Dual-luciferase reporter assays verified the binding relationships among circRRM2, miR-142-5p, and NRG1. We conducted further analyses of their roles in MASLD hepatocytes and modulated circRRM2, miR-142-5p, and NRG1 expression in vitro by transfection. Our findings were validated in vivo. The results demonstrated reduced levels of circRRM2 and NRG1, along with elevated miR-142-5p expression in MASLD livers and hepatocytes. Overexpression of circRRM2 downregulated lipogenesis-related genes and decreased triglycerides accumulation in livers of MASLD mice. MiR-142-5p, which interacts with circRRM2, effectively counteracted the effects of circRRM2 in MASLD hepatocytes. Furthermore, NRG1 was identified as a miR-142-5p target, and its overexpression mitigated the regulatory impact of miR-142-5p on MASLD hepatocytes. In conclusion, circRRM2, via its role as a miR-142-5p sponge, upregulating NRG1, possibly influenced triglycerides accumulation in both in vitro and in vivo MASLD models.NEW & NOTEWORTHY CircRRM2 expression was downregulated in free fatty acid (FFA)-challenged hepatocytes and high-fat diet (HFD) fed mice. Overexpressed circular RNA ribonucleotide reductase subunit M2 (circRRM2) attenuated metabolic dysfunction-associated steatotic liver disease (MASLD) development by suppressing FFA-induced triglycerides accumulation. CircRRM2 targeted microRNA-142-5p (miR-142-5p), which served as an upstream inhibitor of neuregulin 1 (NRG1) and collaboratively regulated MASLD progression.

Asunto(s)

Dieta Alta en Grasa , Hepatocitos , MicroARNs , Neurregulina-1 , ARN Circular , Animales , MicroARNs/metabolismo , MicroARNs/genética , Ratones , Hepatocitos/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , Masculino , Neurregulina-1/genética , Neurregulina-1/metabolismo , Ratones Endogámicos C57BL , Hígado Graso/metabolismo , Hígado Graso/genética , Humanos , Hígado/metabolismo , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Enfermedad del Hígado Graso no Alcohólico/genética , Ribonucleósido Difosfato Reductasa

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Incorporation of CO into substrates to construct high-value carbonyl compounds is an intensive industrial carbonylation procedure, however, high toxicity and wide explosion limits (12.5-74.0 vol% in air) of CO limit its application in industrial production. The development of a CO-free catalytic system for carbonylation is one of ideal methods, but full of challenge. Herein, this study reports the CO-free aminocarbonylation conversion of terminal alkynes synergistically catalyzed by a unique Co(ІІ)/Ag(І) metal-organic framework (MOF), in which the combination of isocyanides and O2 is employed as safe and green source of aminocarbonyl. This reaction has broad substrate applicability in terminal alkyne and isocyanides components with 100% atom economy. The bimetal MOF catalyst can be recycled at least five times without substantial loss of catalytic activities. Mechanistic investigations demonstrate that the synergistic effect between Ag(I) and Co(II) sites can efficiently activate terminal alkyne and isocyanides, respectively. Free radical capture experiments, FT-IR analysis and theoretical explorations further reveal that terminal alkynes and isocyanides can be catalytically transformed into an anionic intermediate through heterolysis pathways. This work provides secure and practical access to carbonylation as well as a new approach to aminocarbonylation of terminal alkynes.

RESUMEN

The fruits of Alpinia oxyphylla (Alpiniae Oxyphyllae Fructus, AOF) are one of the "Four Famous South Medicines" in China. In this study, beta-site amyloid protein precursor cleaving enzyme 1 (BACE1) was applied to explore the active components in AOF responsible for type 2 diabetes mellitus (T2DM)-related cognitive disorder. As a result, 24 compounds including three unreported ones (1, 3, 4) were isolated from AOF. Compound 1 is an unusual carbon­carbon linked diarylheptanoid dimer, and compound 4 is the first case of 3,4-seco-eudesmane sesquiterpenoid with a 5/6-bicyclic skeleton. Four diarylheptanoids (3, 5-7), one flavonoid (9) and two sesquiterpenoids (14 and 20) showed BACE1 inhibitory activity, of which the most active 6 was revealed to be a non-competitive and anti-competitive mixed inhibitor. Docking simulation suggested that OH-4' of 6 played important roles in maintaining activity by forming hydrogen bonds with Ser36 and Ile126 residues. Compounds 3, 5, 9 and 20 displayed neuroprotective effects against amyloid ß (Aß)-induced damage in BV2 cells. Mechanism study revealed that compounds 5 and 20 downregulated the expression of BACE1 and upregulated the expression of Lamp2 to exert effects. Thus, the characteristic diarylheptanoids and sesquiterpenoids in AOF had the efficacy to alleviate T2DM-related cognitive disorder by inhibiting BACE1 activity and reversing Aß-induced neuronal damage.

RESUMEN

Bisphenol A (BPA), a prominent endocrine-disrupting compound, has garnered considerable attention due to its urgent need for rapid removal from water. Herein, we first used a novel reactive phosphine oxide containing tertiary amines as crosslinker to prepare water-insoluble crosslinked ß-cyclodextrin (ß-CD) adsorbent via radical-mediated thiol-ene polymerization. Owing to the synergistic hydrogen-bond (H-bond) interactions of functional groups (tertiary amine and PO groups) toward BPA, the resulted adsorbents showed fast adsorption kinetics to BPA with an adsorption equilibrium time of 5 min. After six adsorption-desorption cycles, the removal efficiency of BPA was 92.5 %, indicating its excellent reusability. Due to the presence of the CS bonds, the ß-CD -derived bio-adsorbents offered binding sites for Cu2+ ions, resulting in a maximum adsorption capacity of 113.89 mg g-1.

Asunto(s)

Compuestos Bicíclicos Heterocíclicos con Puentes , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Puntaje de Propensión , Sulfonamidas , Humanos , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Leucemia Mieloide Aguda/tratamiento farmacológico , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/diagnóstico , Sulfonamidas/uso terapéutico , Sulfonamidas/administración & dosificación , Masculino , Anciano , Femenino , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Adulto , Anciano de 80 o más Años

RESUMEN

The Pd(0)-mediated umpolung reaction of an alkyne to achieve trans-difunctionalization is a potential synthetic methodology, but its insightful activation mechanism of Pd(0)-alkyne interaction has yet to be established. Here, a Pd(0)-π-Lewis base activation mode is proposed and investigated by combining theoretical and experimental studies. In this activation mode, the Pd(0) coordinates to the alkyne group and enhances its nucleophilicity through π-back-donation, facilitating the nucleophilic attack on the aldehyde to generate a trans-Pd(ii)-vinyl complex. Ligand-effect studies reveal that the more electron-donating one would accelerate the reaction, and the cyclization of the challenging flexible C- or O-tethered substrates has been realized. The origin of regioselectivities is also explicated by the newly proposed metal π-Lewis base activation mode.

RESUMEN

Estuaries are significant contributors to greenhouse gases (GHGs) in waterways. However, the effects of human activities and ecological variables on GHG emissions in estuaries remain poorly understood. This study examines the patterns and causes of GHG emissions in the Scheldt Estuary, focusing on the roles of salinity, water contamination, and land use. The findings indicate that salinity negatively impacts the release of carbon dioxide (CO2) and nitrous oxide (N2O), likely due to reduced salt levels and cleaner water upstream. Water contamination's influence on GHG emissions was more pronounced in cleaner, upriver sites compared to saltier downstream locations. Specifically, CO2 emissions quadrupled, and N2O emissions tripled as water conditions worsened from healthy (near the mouth, bordered by agricultural land) to polluted (farther downstream, bordered by urban areas). Methane (CH4) emissions were significantly higher in aquatic locations than in salty sites. The reduced impact of contamination from downstream to the river mouth may be due to increasing population density. Urban sites emitted about twice as much CO2 and N2O as those in natural and industrial areas. Machine learning analysis also showed that fertilizers and organic enrichment, along with salinity, significantly increased GHG emissions. These results highlight the importance of understanding the interplay of salinity, water contamination, and land use in influencing GHG emissions in coastal ecosystems.

RESUMEN

Fusarium rot on melon fruit has become an important postharvest disease for producers worldwide, typically involving multiple Fusarium pathogens (Khuna et al. 2022; Medeiros Araújo et al. 2021). In 2022, Fusarium fruit rot of muskmelon (Cucumis melo var. conomon) occurred sporadically in a field at Huainan Academy of Agricultural Sciences (32.658193º N, 117.064922º E) with an incidence of about 10%. Among these diseased muskmelons, a fruit exhibiting a white to yellowish colony athe intersection of the diseased and healthy tissues was collected and labeled TGGF22-17. The streak plate method was employed to isolate fungal spores on Bengal Red PDA (potato dextrose agar), which were then incubated at 25℃ in darkness. Following isolation and purification, a single-spore strain, TGGF22-17, was obtained and analyzed using morphological characters on PDA, synthetic nutrient agar (SNA) and carnation leaf agar (CLA) (Leslie and Summerell 2006), along with molecular identification. Colours were rated according to the color charts of Kornerup and Wanscher (1978). Based on the colony morphology on PDA, the isolate displayed a rosy buff or buff color with a white to buff margin. The colony margin was undulate, with the reverse transitioning from amber-yellow to honey-yellow. Aerial macroconidia on SNA were thin-walled, hyaline, mostly 3-5 septate, falcate, and measured 18.5-46.4 (x̄=34.2) × 2.9-4.8 (x̄ =3.9) µm in size (n =50). Sporodochial macroconidia on CLA were mostly five-septate with long apical and basal cells, exhibiting dorsiventral curvature. They were hyaline, with the apical cell hooked to tapering and the basal cell foot-shaped, measuring 46.5-89.6 (x̄ =72.3) × 3.5-5.0 (x̄ =4.3) µm in size (n = 100). Portions of three loci (TEF-1α, RPB1 and RPB2) were amplified and sequenced as described by Wang et al. (2019). Sequences were deposited in GenBank with accession number PP196583 to PP196585. The three gene sequences (TEF-1α, RPB1 and RPB2) of strain TGGF2022-17 shared 99.5% (629/632bp), 97.9% (1508/1540 bp) and 99.9% (1608/1609 bp) identity to the ex-type strain F. ipomoeae LC12165 respectively by pairwise DNA alignments on the FUSARIOID-ID database (https://www.fusarium.org). Phylogenetic analysis of the partial TEF-1α and RPB2 sequences with PhyloSuite (Zhang et al. 2020) showed the isolated fungus clustered with F. ipomoeae. Based on the morphological and phylogenetic analyses, TGGF22-17 was identified as F. ipomoeae. Pathogenicity tests were performed on healthy melons, which were surface-sterilized with 75% alcohol and wounded using a sterilized inoculation needle. A 4-mm diameter plug from a 7-day-old SNA culture of TGGF22-17 was aseptically inserted in the middle of the wound, sealed with plastic bag after absorbent cotton was included to maintain moisture. Five melons were each inoculated at three points. Noncolonized PDA agar plugs served as the negative control. The inoculated and uninoculated plugs were removed approximately 48 hours after inoculation. The melon inoculated with TGGF22-17 exhibited water-soaked black lesions 48h post-inoculation, resulting in a 100% infection rate (15/15). After 7 days, mycelium was obseved on the inoculated melons. No disease symptoms were observed on the uninoculated melons. To fulfill Koch's postulates, fungi were isolated from the inoculated fruit and confirmed as F. ipomoeae by morphological observation. Fusarium ipomoeae has been reported to cause fruit rot on winter squash (Cucurbita maxima) in Japan (Kitabayashi et al. 2023). To our knowledge, this is the first report of fruit rot on muskmelon caused by F. ipomoeae in China and this report will be valuable for monitoring and management of fruit rot disease on muskmelons.

RESUMEN

Not available.

RESUMEN

The MEF2D rearrangement is a recurrent chromosomal abnormality detected in approximately 2.4-5.3% of patients with acute B-cell lymphoblastic leukemia (B-ALL). Currently, MEF2D-rearranged B-ALL is not classified as an independent subtype in the WHO classification. Consequently, the clinical significance of MEF2D rearrangement in B-ALL remains largely unexplored. In this study, we retrospectively screened 260 B-ALL patients with RNA sequencing data collected between November 2018 and December 2022. Among these, 10 patients were identified with MEF2D rearrangements (4 with MEF2D::HNRNPUL1, 3 with MEF2D::BCL9, 1 with MEF2D::ARID1B, 1 with MEF2D::DAZAP1 and 1 with MEF2D::HNRNPM). Notably, HNRNPM and ARID1B are reported as MEF2D fusion partners for the first time. The patient with the MEF2D::HNRNPM fusion was resistant to chemotherapy and chimeric antigen receptor T-cell therapy and relapsed early after allogenic stem cell transplantation. The patient with MEF2D::ARID1B experienced early extramedullary relapse after diagnosis. All 10 patients achieved complete remission after induction chemotherapy. However, 9/10 (90%) of whom experienced relapse. Three of the 9 patients relapsed with aberrant expression of myeloid antigens. The median overall survival of these patients was only 11 months. This small cohort showed a high incidence of early relapse and short survival in patients with MEF2D rearrangements.

RESUMEN

Glucagon-like peptide-1 (GLP-1) secretagogues are fascinating pharmacotherapies to overcome the defects of GLP-1 analogs and dipeptidyl peptidase-4 (DPP-4) inhibitors in treating diabetes and obesity. To discover new GLP-1 secretagogues from natural sources, alpigalangols A-Q (1-17), 17 new labdane diterpenoids including four unusual nor-labdane and N-containing ones, were isolated from the fruits of Alpinia galanga. Most of the isolates showed GLP-1 promotive effects in NCl-H716 cells, of which compounds 3, 4, 12, and 14-17 were revealed with high promoting rates of 246.0%-413.8% at 50 µM. A mechanistic study manifested that the most effective compound 12 upregulated the mRNA expression of Gcg and Pcsk1, and the protein phosphorylation of PKA, CREB, and GSK3ß, but was inactive on GPBAR and GPR119 receptors. Network pharmacology analysis indicated that the PI3K-Akt pathway was involved in the GLP-1 stimulation of 12, which was highly associated with AKT1, CASP3, PPARG, and ICAM1 proteins. This study suggests that A. galanga is rich in diverse labdane diterpenoids with GLP-1 promoting effects, representing a new type of antidiabetic candidates from natural sources.

Asunto(s)

Apendicectomía , Apendicitis , Colonoscopía , Humanos , Apendicectomía/métodos , Apendicitis/cirugía , Colonoscopía/métodos , Masculino

RESUMEN

A high-nuclear Co-added polyoxometalate (CoAP) was synthesized via a hydrothermal reaction: H14.5K9Na7.5-{[Co8(µ2-OH)(µ3-OH)2(H2O)2(Co(H2O)GeW6O26)(B-α-GeW9O34)2][BO(OH)2][Co12(µ2-OH)(µ3-OH)5(H2O)3(Co(H2O)GeW6O26)(GeW6O26)(B-α-GeW9O34)]}·46H2O (1). The polyoxoanion of 1 contains a large Co20 cluster gathered by lacunary GeW6O26 and GeW9O34 subunits. 1 represents a one-dimensional (1D) chain formed by adjacent polyoxoanions coupling through a CoO6 double bridge, showing the first example of a high-nuclear CoAP-based inorganic chain. 1 served as an efficient electrocatalyst in oxygen evolution reactions (OERs).

RESUMEN

Vascular dementia (VaD) is a cognitive disorder characterized by a decline in cognitive function resulting from cerebrovascular disease. The hippocampus is particularly susceptible to ischemic insults, leading to memory deficits in VaD. Astaxanthin (AST) has shown potential therapeutic effects in neurodegenerative diseases. However, the mechanisms underlying its protective effects in VaD and against hippocampal neuronal death remain unclear. In this study, We used the bilateral common carotid artery occlusion (BCCAO) method to establish a chronic cerebral hypoperfusion (CCH) rat model of VaD and administered a gastric infusion of AST at 25 mg/kg per day for 4 weeks to explore its therapeutic effects. Memory impairments were assessed using Y-maze and Morris water maze tests. We also performed biochemical analyses to evaluate levels of hippocampal neuronal death and apoptosis-related proteins, as well as the impact of astaxanthin on the PI3K/Akt/mTOR pathway and oxidative stress. Our results demonstrated that AST significantly rescued memory impairments in VaD rats. Furthermore, astaxanthin treatment protected against hippocampal neuronal death and attenuated apoptosis. We also observed that AST modulated the PI3K/Akt/mTOR pathway, suggesting its involvement in promoting neuronal survival and synaptic plasticity. Additionally, AST exhibited antioxidant properties, mitigating oxidative stress in the hippocampus. These findings provide valuable insights into the potential therapeutic effects of AST in VaD. By elucidating the mechanisms underlying the actions of AST, this study highlights the importance of protecting hippocampal neurons and suggests potential targets for intervention in VaD. There are still some unanswered questions include long-term effects and optimal dosage of the use in human. Further research is warranted to fully understand the therapeutic potential of AST and its application in the clinical treatment of VaD.

Asunto(s)

Apoptosis , Demencia Vascular , Hipocampo , Trastornos de la Memoria , Neuronas , Fármacos Neuroprotectores , Estrés Oxidativo , Ratas Sprague-Dawley , Xantófilas , Animales , Xantófilas/uso terapéutico , Xantófilas/farmacología , Hipocampo/efectos de los fármacos , Demencia Vascular/tratamiento farmacológico , Ratas , Masculino , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/etiología , Estrés Oxidativo/efectos de los fármacos , Neuronas/efectos de los fármacos , Apoptosis/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Aprendizaje por Laberinto/efectos de los fármacos , Modelos Animales de Enfermedad , Transducción de Señal/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Muerte Celular/efectos de los fármacos , Antioxidantes/uso terapéutico , Antioxidantes/farmacología , Prueba del Laberinto Acuático de Morris/efectos de los fármacos

RESUMEN

Background: Accurately assessing the prognosis of patient with large-scale cerebral infarction caused by acute middle cerebral artery (MCA) occlusion in the early stages of onset can help clinicians to actively and effectively intervene, thus reducing mortality and disability rates. This study set out to investigate the predictive value of fluid-attenuated inversion recovery vascular hyperintensity (FVH) on collateral circulation and clinical prognosis. Methods: The clinical data of 70 patients admitted to The First People's Hospital of Lianyungang from January 2018 to December 2021 with acute cerebral infarction due to occlusion of the proximal end of the M1 segment in the MCA were retrospectively collected. All patients had their first onset of disease and did not receive thrombolytic therapy at the time of onset. Subsequently, they underwent endovascular thrombectomy for treatment. The FVH and collateral vessel scores were derived according to patients' fluid-attenuated in version recovery (FLAIR) sequence and time-of-flight magnetic resonance angiography images. Based on the 90-day Modified Rankin Scale (mRS), patients were allocated to a good prognosis group (mRS ≤2) and a poor prognosis group (mRS =3-6). The correlation between the FVH and collateral vessel scores was assessed using the Spearman rank correlation test. Pearson correlation coefficient analysis was used to assess the correlation between FVH and the 90-day mRS together with the infarct size. Univariate analysis, multivariate binary logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were adopted to identify those factors potentially. associated with the prognosis of patients with acute ischemic stroke (AIS). Results: Out of 70 patients with acute unilateral MCA occlusion (MCAO) who met the inclusion criteria, 62 showed positive FVH sign. These 62 patients were divided into a good prognosis group (n=32) and a poor prognosis group (n=30) based on the mRS score 90 days after discharge. The Spearman rank correlation test indicated that FVH was positively correlated with collateral vessel grade (Spearman rho =0.865; P<0.001); meanwhile, Pearson correlation coefficient analysis indicated that FVH score had moderate negative correlation with 90-day mRS score (r=-0.605; P<0.001). The results of multivariate binary logistic regression analysis indicated that collateral vessel grade and FVH score may be associated with the prognosis of patients with AIS, and the area under the curve (AUC) of FVH score was larger than collateral vessel grade (AUC =0.738). Conclusions: There was a positive correlation between FVH score and collateral vessel grade, and FVH score could indicate collateral circulation. FVH score was negatively correlated with 90-day mRS score and infarct volume and thus can predict clinical prognosis.

RESUMEN

Pseudorabies virus (PRV) is recognized as the aetiological agent responsible for Aujeszky's disease, or pseudorabies, in swine populations. Rab6, a member of the small GTPase family, is implicated in various membrane trafficking processes, particularly exocytosis regulation. Its involvement in PRV infection, however, has not been documented previously. In our study, we observed a significant increase in the Rab6 mRNA and protein levels in both PK-15 porcine kidney epithelial cells and porcine alveolar macrophages, as well as in the lungs and spleens of mice infected with PRV. The overexpression of wild-type Rab6 and its GTP-bound mutant facilitated PRV proliferation, whereas the GDP-bound mutant form of Rab6 had no effect on viral propagation. These findings indicated that the GTPase activity of Rab6 was crucial for the successful spread of PRV. Further investigations revealed that the reduction in Rab6 levels through knockdown significantly hampered PRV proliferation and disrupted virus assembly and egress. At the molecular level, Rab6 was found to interact with the PRV glycoproteins gB and gE, both of which are essential for viral assembly and egress. Our results collectively suggest that PRV exploits Rab6 to expedite its assembly and egress and identify Rab6 as a promising novel target for therapeutic treatment for PRV infection.

Asunto(s)

Herpesvirus Suido 1 , Ensamble de Virus , Liberación del Virus , Proteínas de Unión al GTP rab , Animales , Ratones , Línea Celular , Herpesvirus Suido 1/genética , Herpesvirus Suido 1/metabolismo , Seudorrabia/virología , Proteínas de Unión al GTP rab/metabolismo , Proteínas de Unión al GTP rab/genética , Porcinos , Enfermedades de los Porcinos/virología , Ensamble de Virus/genética , Liberación del Virus/genética

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Da-Chai-Hu-Tang (DCHT), a Chinese traditional herbal compound, has been utilized for the treatment of Hepatic diseases in China for over 1800 years. The DCHT formula contains eight herbals: Bupleurum chinense DC. (chaihu), Scutellaria baicalensis Georgi (huangqin), Paeonia lactiflora Pall. (baishao), Pinellia ternata (Thunb.) Makino (banxia), Rheum officinale Baill. (dahuang), Citrus × aurantium L. (zhishi), Zingiber officinale Roscoe (shengjiang), Ziziphus jujuba Mill. (dazao). Clinical studies have demonstrated the effectiveness of DCHT in hepatocellular carcinoma (HCC) and its ability to enhance the immunity of patients with hepatocellular carcinoma. A total of 20 Chinese articles have been published on the use of DCHT in treating HCC. AIM OF THE STUDY: The study aimed to validate the effect of DCHT in HCC cells and to identify related targets (TP53, AKT1, BCL2, STAT3) in treating HCC by DCHT in vitro experiments. MATERIALS AND METHODS: Cell proliferation and migration were investigated in vitro. Flow cytometry analysis was used to evaluate the cell cycle and apoptosis. Apoptotic bodies in HepG2 cells were observed using a confocal microscope. Biochemical detection was employed to analyze LDH release, MDA levels, and SOD levels. Bioinformatics analysis was used to predict core targets between DCHT and HCC, as well as potential signaling pathways. The protein levels of metastasis-associated, apoptosis, and PI3K, AKT, p-AKT, and STAT3 were further determined through Western blotting. RESULTS: Following treatment with DCHT, the inhibition of viability, migration, and G2/M arrest was observed in HepG2 cells. Flow cytometry analysis and Morphological apoptosis studies provided evidence that DCHT could induce apoptosis in HepG2 cells. Biochemical detection revealed that DCHT could increase LDH release and the level of MDA, and inhibit the viability of the SOD. Bioinformatics analysis identified key targets such as TP53, AKT1, BCL2, STAT3. The PI3K/AKT/STAT3 signaling pathway emerged as a critical pathway in the KEGG enrichment analysis. Western blotting results indicated that DCHT could enhance the expression of E-cadherin, p53, and Bax, while reducing the content of N-cadherin, Bcl-2, PI3K, p-AKT, AKT1, and STAT3. CONCLUSIONS: The results proved that DCHT could inhibit the progression and metastasis of HCC by regulating the expression of E-cadherin, N-cadherin, p53, Bax, Bcl-2, PI3K, p-AKT, AKT, and STAT3 through the PI3K/AKT/STAT3 signaling pathway.

Asunto(s)

Apoptosis , Puntos de Control del Ciclo Celular , Medicamentos Herbarios Chinos , Neoplasias Hepáticas , Proteínas Proto-Oncogénicas c-akt , Factor de Transcripción STAT3 , Humanos , Factor de Transcripción STAT3/metabolismo , Apoptosis/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células Hep G2 , Medicamentos Herbarios Chinos/farmacología , Puntos de Control del Ciclo Celular/efectos de los fármacos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Transducción de Señal/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Antineoplásicos Fitogénicos/farmacología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos

RESUMEN

Rhei Radix et Rhizoma is common traditional Chinese medicine with multiple original plants. The content and proportion of the active components in Rhei Radix et Rhizoma from different plant species were compared to accurately evaluate the medicine qua-lity and provide a theoretical basis for precise use of this medicine in clinical practice. In this study, fresh Rhei Radix et Rhizoma samples were collected from the four-year-old plants of Rheum palmatum, R. tanguticum, and R. officinale. The relative content of 220 anthraquinones, anthrones, and tannins in the samples were determined by pseudo-targeted metabolomics, and the differential components were screened by multivariate statistical methods. The principal component analysis classified the samples into three clusters according to the original plants. The orthogonal partial least squares-discriminant analysis(OPLS-DA) screened out 117 differential components, including 8 free anthraquinones, 18 anthraquinone glycosides, 80 anthrones, and 11 tannins. Twenty-eight components had the highest content in R. tanguticum, mainly including sennosides, anthraquinone glycosides, and procyanidins. Thirty-five components showed the highest content in R. officinale, mainly including free anthraquinones and catechines. Fifty-four components showed the highest content in R. palmatum, mainly including dianthrones, while the structures of most of them cannot be determined temporarily. The content distribution of differential components in the three original plants indicates that R. tanguticum has the strongest effect of purging, while R. officinale has the strongest effect of clearing heat and purging fire, and both have stronger effects of resolvong stasis and dredging meridians than R. palmatum.

Asunto(s)

Medicamentos Herbarios Chinos , Metabolómica , Rheum , Rizoma , Rheum/química , Rizoma/química , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/análisis , Antraquinonas/química , Antraquinonas/análisis , Cromatografía Líquida de Alta Presión