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1.
Pharmaceutics ; 16(6)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38931841

RESUMO

Gastric acid secretion is closely associated with the development and treatment of chronic gastritis, gastric ulcers, and reflux esophagitis. However, gastric acid secretion is affected by complex physiological and pathological factors, and real-time detection and control are complicated and expensive. A gastric delivery system for antacids and therapeutics in response to low pH in the stomach holds promise for smart and personalized treatment of stomach diseases. In this study, pH-responsive modular units were used to assemble various modular devices for self-regulation of pH and drug delivery to the stomach. The modular unit with a release window of 50 mm2 could respond to pH and self-regulate within 10 min, which is related to its downward floatation and internal gas production. The assembled devices could stably float downward in the medium and detach sequentially at specific times. The assembled devices loaded with antacids exhibited smart pH self-regulation under complex physiological and pathological conditions. In addition, the assembled devices loaded with antacids and acid suppressors could multi-pulse or prolong drug release after rapid neutralization of gastric acid. Compared with traditional coating technology, 3D printing can print the shell layer by layer, flexibly adjust the internal and external structure and composition, and assemble it into a multi-level drug release system. Compared with traditional coating, 3D-printed shells have the advantage of the flexible adjustment of internal and external structure and composition, and are easy to assemble into a complex drug delivery system. This provides a universal and flexible strategy for the personalized treatment of diseases with abnormal gastric acid secretion, especially for delivering acid-unstable drugs.

2.
Sheng Li Xue Bao ; 76(3): 394-406, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38939934

RESUMO

Spinal cord injury (SCI) is a serious central nervous system disease with high disability and mortality rates and complex pathophysiologic mechanisms. MicroRNA (miRNA), as a kind of non-coding RNA, plays an important role in SCI. miRNA is involved in the regulation of inflammatory response, oxidative stress, axonal regeneration, and apoptosis after SCI, and interacts with long non-coding RNA (lncRNA) and circular RNA (circRNA) to regulate the pathophysiological process of SCI. This paper summarizes the changes in miRNA expression after SCI, and reviews the targeting mechanism of miRNA in SCI and the current research status of miRNA-targeted drugs to provide new targets and new horizons for basic and clinical research on SCI.


Assuntos
MicroRNAs , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , MicroRNAs/genética , MicroRNAs/metabolismo , MicroRNAs/fisiologia , Humanos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Longo não Codificante/fisiologia , RNA Circular/genética , RNA Circular/fisiologia , RNA Circular/metabolismo , Estresse Oxidativo , Apoptose/genética
3.
Trop Med Infect Dis ; 9(6)2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38922050

RESUMO

BACKGROUND: This study aimed to examine the epidemiological characteristics of imported infections and assess the effectiveness of border health screening in detecting imported diseases. METHODS: We obtained infection data for 2016 to 2019 from the Fuzhou Changle International Airport Infection Reporting System. The demographic, temporal, and spatial characteristics of travel-related infections were analyzed using r×c contingency tables, the Cochran-Armitage trend test, and seasonal-trend decomposition using LOESS (STL). Detection rates were used as a proxy for the effectiveness of border health-screening measures. RESULTS: Overall, 559 travel-related infections were identified during the study period, with 94.3% being imported infections. Airport health screening demonstrated an overall effectiveness of 23.7% in identifying travel-associated infections. Imported infections were predominantly identified in males, with 55.8% of cases occurring in individuals aged 20-49. The peak periods of infection importation were from January to February and from May to August. The infectious diseases identified were imported from 25 different countries and regions. All dengue fever cases were imported from Southeast Asia. Most notifiable infections (76.0%) were identified through fever screening at the airport. CONCLUSION: The increasing number of imported infections poses a growing challenge for public health systems. Multifaceted efforts including surveillance, vaccination, international collaboration, and public awareness are required to mitigate the importation and spread of infectious diseases from overseas sources.

4.
Toxics ; 12(6)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38922059

RESUMO

Electronic waste (e-waste) dismantling facilities are well-known bisphenol chemical (BP) sources. In this study, non-targeted screening combined with targeted analysis of BPs in surface soil from e-waste dismantling facilities and their surroundings revealed their presence, distribution, and exposure risk. A total of 14 BPs were identified including bisphenol A (BPA) and its novel structural analogs and halogenated BPs. The total concentrations of BPs ranged from 963 to 47,160 ng/g (median: 6970 ng/g) in e-waste soil, higher than those measured in surface soil from surrounding areas, i.e., 10-7750 ng/g (median 197 ng/g). BPA, tetrabromobisphenol A (TBBPA), and bisphenol F (BPF) were the dominant ones from the two areas. Concentrations of TBBPA and its debromination product from the surrounding area significantly decreased with increasing distances from the e-waste dismantling facilities. Estimation of daily intake via oral ingestion of soil suggests that current contamination scenarios are unlikely to pose health risks for e-waste dismantling workers and adults and toddlers living in the surrounding areas, with their intakes generally well below the tolerable daily intakes proposed for several BPs. However, the BPA intakes of workers exceeded the more strict tolerable daily intake for BPA established recently, which merits continuous environmental surveillance.

5.
Sci Total Environ ; 946: 173947, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880148

RESUMO

Mine fires caused by spontaneous coal combustion are major disasters in coal mines. The staged oxidation kinetic parameters of various coal samples at oxygen concentrations of 21 %, 15 %, 10 %, 5 %, and 3 % were analyzed using a programmed temperature testing system. Herein, the temperature increase rate of coal, the temperature difference between the furnace and coal, and the oxygen consumption characteristics were obtained. Based on the amount of CO produced and the temperature sensitivity coefficient, three characteristic temperatures and four stages of low-temperature oxidation (LTO) were identified. The results showed that at a critical temperature (TC), the amount of CO gas released from the coal samples increased with increasing oxygen concentration, and the difference in the oxygen consumption rate increased. After the limit temperature (Tu), the amount of CO gas increased steadily, and the increase in the oxygen consumption rate stagnated. CO production, the maximum heating rate, and the maximum heat release rate were positively correlated with the oxygen concentration. As the oxygen concentration increased, the activation energy during the oxygen absorption stage gradually decreased. The average reaction enthalpy (ΔH) of pre-oxidized water-immersed coal was 19.37 kJ/kg greater than that of raw coal. The equation for the conservation of energy of the coal oxidation warming process was normalized. The theoretical values of the awakening stage and the stable stage were τν and τν (1-B), respectively. When B was >1, pre-oxidized water-immersed coal at a low oxygen concentration was prone to crossover points during the oxygen absorption stage, which increased the risk of coal spontaneous combustion (CSC). The research results could provide a theoretical basis for the staged control of the spontaneous combustion of water-immersed coal in goaf areas.

6.
Adv Sci (Weinh) ; : e2400238, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38923264

RESUMO

The placenta links feto-maternal circulation for exchanges of nutrients, gases, and metabolic wastes between the fetus and mother, being essential for pregnancy process and maintenance. The allantois and mesodermal components of amnion, chorion, and yolk sac are derived from extraembryonic mesoderm (Ex-Mes), however, the mechanisms contributing to distinct components of the placenta and regulation the interactions between allantois and epithelium during chorioallantoic fusion and labyrinth formation remains unclear. Isl1 is expressed in progenitors of the Ex-Mes and allantois the Isl1 mut mouse line is analyzed to investigate contribution of Isl1+ Ex-Mes / allantoic progenitors to cells of the allantois and placenta. This study shows that Isl1 identifies the Ex-Mes progenitors for endothelial and vascular smooth muscle cells, and most of the mesenchymal cells of the placenta and umbilical cord. Deletion of Isl1 causes defects in allantois growth, chorioallantoic fusion, and placenta vessel morphogenesis. RNA-seq and CUT&Tag analyses revealed that Isl1 promotes allantoic endothelial, inhibits mesenchymal cell differentiation, and allantoic signals regulated by Isl1 mediating the inductive interactions between the allantois and chorion critical for chorionic epithelium differentiation, villous formation, and labyrinth angiogenesis. This study above reveals that Isl1 plays roles in regulating multiple genetic and epigenetic pathways of vascular morphogenesis, provides the insight into the mechanisms for placental formation, highlighting the necessity of Isl1 for placenta formation/pregnant maintenance.

7.
Phytochem Anal ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38924240

RESUMO

INTRODUCTION: The identification of active dietary flavonoids in food is promising for novel drug discovery. The active ingredients of duckweed (a widely recognized food and herb with abundant flavonoids) that are associated with acute myeloid leukemia (AML) have yet to be identified, and their underlying mechanisms have not been elucidated. OBJECTIVES: The objective of this study was to identify novel constituents exhibiting antileukemia activity in duckweed through the integration of chemical profiling, network pharmacology, and experimental validation. METHODS: First, high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to characterize the primary constituents of duckweed. Subsequently, AML cell-xenograft tumor models were used to validate the anticancer effect of duckweed extract. Furthermore, network pharmacology analysis was conducted to predict the potential active compounds and drug targets against AML. Lastly, based on these findings, two monomers (apiin and luteoloside) were selected for experimental validation. RESULTS: A total of 17 compounds, all of which are apigenin and luteolin derivatives, were identified in duckweed. The duckweed extract significantly inhibited AML cell growth in vivo. Furthermore, a total of 88 targets for duckweed against AML were predicted, with key targets including PTGS2, MYC, MDM2, VEGFA, CTNNB1, CASP3, EGFR, TP53, HSP90AA1, CCND1, MMP9, TNF, and MAPK1. GO and KEGG pathway enrichment analyses indicated that these targets were primarily involved in the apoptotic signaling pathway. Lastly, both apiin and luteoloside effectively induced apoptosis through CASP3 activation, and this effect could be partially reversed by a caspase inhibitor (Z-VAD). CONCLUSION: Duckweed extract has an antileukemic effect, and apiin derived from duckweed shows potential as a treatment for AML.

8.
Ren Fail ; 46(2): 2346267, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38905298

RESUMO

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes mellitus (T2DM) patients. Shrunken pore syndrome (SPS) is defined as eGFRcystatin C/eGFRcreatinine ratio <0.70 and predicts high CVD mortality. The Framingham Risk Score (FRS) is used to estimate an individual's 10-year CVD risk. This study investigated the association between FRS and eGFRcystatin C/eGFRcreatinine ratio in T2DM patients. METHODS: Patients aged 18-80 years who were newly diagnosed with T2DM were included in this retrospective study. Ordinal logistic regression analysis was used to investigate the association between risk factors of T2DM and FRS. A Generalized Linear Model was used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: There were 270 patients included in the study. Only 27 patients (10%) met the diagnostic criteria of SPS. Ordinal logistic regression analysis showed that SPS was not correlated with FRS risk (OR = 1.99, 95%CI = 0.94-4.23, p = 0.07), whereas eGFRcystatin C/eGFRcreatinine (OR = 0.86, 95%CI = 0.77-0.97, p = 0.01) showed a significant negative association with FRS risk. Compared with eGFRcystatin C/eGFRcreatinine>0.85, eGFRcystatin C/eGFRcreatinine≤0.85 increased FRS risk (OR = 1.95, 95%CI = 1.18-3.21, p < 0.01). After adjustment for confounding factors, increased eGFRcystatin C/eGFRcreatinine ratio was associated with decreased FRS risk when considered as a continuous variable (OR = 0.87, 95%CI = 0.77-0.99, p = 0.03). The FRS risk in patients with eGFRcystatin C/eGFRcreatinine≤0.85 is 1.86 times higher than that in patients with eGFRcystatin C/eGFRcreatinine>0.85 (OR = 1.86, 95%CI = 1.08-3.21, p = 0.03). CONCLUSIONS: In the current study, no significant association between SPS and FRS was identified. However, lower eGFRcystatin C/eGFRcreatinine and eGFRcystatin C/eGFRcreatinine≤0.85 were associated with a significantly increased CVD risk in T2DM.


Assuntos
Doenças Cardiovasculares , Creatinina , Cistatina C , Diabetes Mellitus Tipo 2 , Taxa de Filtração Glomerular , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/complicações , Estudos Retrospectivos , Idoso , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Adulto , Creatinina/sangue , Creatinina/urina , China/epidemiologia , Cistatina C/sangue , Modelos Logísticos , Adulto Jovem , Idoso de 80 Anos ou mais , Medição de Risco/métodos , Adolescente , Fatores de Risco , Fatores de Risco de Doenças Cardíacas , População do Leste Asiático
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 685-692, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38926954

RESUMO

OBJECTIVE: To analyze the characteristics and prognosis of patients with mucormycosis after chemotherapy for acute leukemia, and to strengthen understanding of the disease. METHODS: 7 cases of acute leukemia (AL) patients diagnosed with mucormycosis by metagenomic next generation sequencing (mNGS) after chemotherapy at the First Affiliated Hospital of Bengbu Medical College from October 2021 to June 2022 were collected, and their clinical data, including clinical characteristics, diagnosis, treatment, and prognosis, were retrospectively analyzed. RESULTS: Among the 7 patients with AL complicated with mucormycosis, there were 3 males and 4 females, with a median age of 52(20-59) years. There were 6 cases of acute myeloid leukemia (AML) and 1 case of acute lymphocytic leukemia (ALL). Extrapulmonary involvement in 4 cases, including 1 case suspected of central nervous system involvement. The median time for the occurrence of mucor infection was 16(6-69) days after chemotherapy and 19(14-154) days after agranulocytosis. The main clinical manifestations of mucormycosis were fever (7/7), cough (3/7), chest pain (3/7) and dyspnea (1/7). The most common chest CT imaging findings were nodules, patchy or mass consolidation (6/7). All patients were treated with posaconazole or voriconazole prophylaxis during neutropenia phase. 5 patients died within 8 months, and the median time from diagnosis to death was 1 month. CONCLUSION: Although prophylactic antifungal therapy is adopted, patients with acute leukemia still have a risk of mucor infection during the neutropenia phase. Fever is the main manifestation in the early stage of mucor infection. The use of intravenous antifungal drugs alone is ineffective and there is a high mortality rate in acute leukemia patients with mucormycosis.


Assuntos
Leucemia Mieloide Aguda , Mucormicose , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Mucormicose/diagnóstico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Antifúngicos/uso terapêutico , Adulto Jovem , Leucemia/complicações , Leucemia/tratamento farmacológico
10.
IEEE Trans Med Imaging ; PP2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861436

RESUMO

Medical image reporting focused on automatically generating the diagnostic reports from medical images has garnered growing research attention. In this task, learning cross-modal alignment between images and reports is crucial. However, the exposure bias problem in autoregressive text generation poses a notable challenge, as the model is optimized by a word-level loss function using the teacher-forcing strategy. To this end, we propose a novel Token-Mixer framework that learns to bind image and text in one embedding space for medical image reporting. Concretely, Token-Mixer enhances the cross-modal alignment by matching image-to-text generation with text-to-text generation that suffers less from exposure bias. The framework contains an image encoder, a text encoder and a text decoder. In training, images and paired reports are first encoded into image tokens and text tokens, and these tokens are randomly mixed to form the mixed tokens. Then, the text decoder accepts image tokens, text tokens or mixed tokens as prompt tokens and conducts text generation for network optimization. Furthermore, we introduce a tailored text decoder and an alternative training strategy that well integrate with our Token-Mixer framework. Extensive experiments across three publicly available datasets demonstrate Token-Mixer successfully enhances the image-text alignment and thereby attains a state-of-the-art performance. Related codes are available at https://github.com/yangyan22/Token-Mixer.

11.
Signal Transduct Target Ther ; 9(1): 143, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38844468

RESUMO

Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine (PAAG) in patients with first-line mPC (NCT05493995). The primary endpoints included the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety. In 66 patients analysed for efficacy, the best response, indicated by the ORR, was recorded at 50.0% (33/66) (95% CI, 37.4-62.6%), with 33 patients achieving partial response (PR). Notably, the DCR was 95.5% (63/66, 95% CI, 87.3-99.1%). The median PFS (mPFS) and OS (mOS) were 8.8 (95% CI, 8.1-11.6), and 13.7 (95% CI, 12.4 to not reached) months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 39.4% of patients (26/66). In prespecified exploratory analysis, patients with altered SWI/SNF complex had a poorer PFS. Additionally, low serum CA724 level, high T-cell recruitment, low Th17 cell recruitment, and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efficacy. In conclusion, PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for mPC. The biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.


Assuntos
Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina , Gencitabina , Indóis , Paclitaxel , Neoplasias Pancreáticas , Quinolinas , Humanos , Masculino , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Feminino , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paclitaxel/farmacologia , Pessoa de Meia-Idade , Idoso , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Indóis/administração & dosagem , Indóis/uso terapêutico , Albuminas/administração & dosagem , Albuminas/efeitos adversos , Quinolinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos Prospectivos , Adulto , Metástase Neoplásica , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/farmacologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia
12.
Medicine (Baltimore) ; 103(23): e38416, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847724

RESUMO

To investigate the expression of Inhibin B between various clinical stages, Chinese medicine dialectic typing, and in nasopharyngeal carcinoma (NPC) tissues and serum, and to evaluate the potential of Inhibin B as a new biomarker for NPC. Paraffin specimens of pathologically confirmed NPC tissues and paracancerous tissues were retrospectively collected, and the expression of Inhibin α (INHA) and Inhibin ßB (INHBB) was detected by SP method, and their relationship with clinicopathological indexes was analyzed; in addition, patients with NPC who had received radiotherapy were included as the study subjects, and Epstein-Barr virus DNA (EBV-DNA), INHA, and INHBB in patients were detected by using the fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and chemiluminescent immuno-sandwiching method, respectively. EBV-DNA, EBV-viral capsid antigen-immunoglobulin A (VCA IgA), INHA, and INHBB were detected in the patients, respectively, and their relationships with traditional Chinese medicine (TCM) patterns were also analyzed. The expression of INHA and INHBB in NPC tissues was lower than that in paracancerous tissues, and the expression of INHA in NPC patients was correlated with lymphatic metastasis, clinical staging, and TCM staging; the levels of EBV-DNA and VCA IgA were higher than that of healthy populations in NPC patients and were higher than that of patients with stage III + IV than that of patients with stage I + II, and the levels of INHA and INHBB were lower than those of healthy populations and were lower than those of patients with stage III + IV than that of patients with stage I + II. The levels of INHA and INHBB in nasopharyngeal cancer patients were lower than those in healthy people, and the levels in stage III + IV patients were lower than those in stage I + II patients. The levels of EBV-DNA and VCA IgA in nasopharyngeal cancer patients were correlated with the Chinese medicine patterns, and had different patterns. The expression of Inhibin B may be related to the progression of NPC, and it has certain typing significance for different TCM syndromes of NPC, which is helpful for TCM typing diagnosis.


Assuntos
Medicina Tradicional Chinesa , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Feminino , Neoplasias Nasofaríngeas/virologia , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/patologia , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/virologia , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Medicina Tradicional Chinesa/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , DNA Viral/análise , DNA Viral/sangue , Inibinas/sangue , Herpesvirus Humano 4/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/sangue , Estadiamento de Neoplasias , Subunidades beta de Inibinas/metabolismo , Subunidades beta de Inibinas/sangue , Idoso , Antígenos Virais/sangue , Imunoglobulina A/sangue , Proteínas do Capsídeo
13.
Chem Biol Drug Des ; 103(6): e14557, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38825578

RESUMO

Recently, natural compounds such as quercetin have gained an increasing amount of attention in treating breast cancer. However, the exact mechanisms responsible for the antiproliferative functions of quercetin are not completely understood. Therefore, we aimed to examine quercetin impacts on breast cancer cell proliferation and survival and the involvement of PI3K/Akt/mTOR pathway. Breast cancer MDA-MB-231 and MCF-7 cells were exposed to quercetin, and cell proliferation was assessed by MTT assay. ELISA was applied to evaluate cell apoptosis. The expression levels of apoptotic mediators such as caspase-3, Bcl-2, Bax and PI3K, Akt, mTOR, and PTEN were assessed via qRT-PCR and western blot. We found that quercetin suppressed dose dependently cell growth capacity in MDA-MB-231 and MCF-7 cells. In addition, quercetin treatment increase apoptosis in both cells lines via modulating the pro- and antiapoptotic markers. Quercetin upregulated PTEN and downregulated PI3K, Akt, and mTOR, hence suppressing this signaling pathway in cells. In conclusion, we showed antiproliferative and pro-apoptotic function of quercetin in breast cancer cell lines, which is mediated by targeting and suppressing PI3K/Akt/mTOR signal transduction.


Assuntos
Apoptose , Neoplasias da Mama , Proliferação de Células , Sobrevivência Celular , PTEN Fosfo-Hidrolase , Proteínas Proto-Oncogênicas c-akt , Quercetina , Transdução de Sinais , Serina-Treonina Quinases TOR , Quercetina/farmacologia , Humanos , Serina-Treonina Quinases TOR/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proliferação de Células/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células MCF-7 , Fosfatidilinositol 3-Quinases/metabolismo
14.
Mol Neurobiol ; 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38878116

RESUMO

The amyloid-beta (Aß) aggregation in Alzheimer's disease (AD) triggers neuroinflammation, and neurodegeneration, which lead to cognitive deficits along with other neuropsychiatric symptoms, including depression and anxiety. G protein-coupled receptor 35 (GPR35) is expressed in the brain and is involved in metabolic stresses. However, the role of GPR35 in AD pathogenesis remains unknown. Herein, pharmacological blockade, shRNA-mediated knockdown or knockout of GPR35 was performed to investigate the role and mechanisms of GPR35 in Aß1-42-induced cognitive impairment and emotional alterations in mice. A series of behavioral, histopathological, and biochemical tests were performed in mice. Our results showed that hippocampal GPR35 expression was significantly increased in Aß1-42-induced and APP/PS1 AD mouse models. Pharmacological blockade or knockdown of GPR35 ameliorated cognitive impairment and emotional alterations induced by Aß1-42 in mice. We also found that blockade or knockdown of GPR35 decreased the accumulation of Aß, and improved neuroinflammation, cholinergic system deficiency, and neuronal apoptosis via the RhoA/ROCK2 pathway in Aß1-42-treaed mice. However, activation of GPR35 aggravates Aß1-42-induced cognitive deficits and emotional alterations in mice. In addition, genetic deletion of GPR35 protects against the Aß1-42-induced cognitive deficits and emotional alterations in mice. Moreover, GPR35 could bind to TLR4. These results indicate that GPR35 participates in the pathogenesis of cognitive deficits and emotional alterations induced by Aß1-42 in mice, suggesting that GPR35 could be a potential therapeutic target for AD.

15.
Neurochem Res ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864944

RESUMO

Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disease with a challenging treatment landscape, due to its complex pathogenesis and limited availability of clinical drugs. Ferroptosis, an iron-dependent form of programmed cell death (PCD), stands distinct from apoptosis, necrosis, autophagy, and other cell death mechanisms. Recent studies have increasingly highlighted the role of iron deposition, reactive oxygen species (ROS) accumulation, oxidative stress, as well as systemic Xc- and glutamate accumulation in the antioxidant system in the pathogenesis of amyotrophic lateral sclerosis. Therefore, targeting ferroptosis emerges as a promising strategy for amyotrophic lateral sclerosis treatment. This review introduces the regulatory mechanism of ferroptosis, the relationship between amyotrophic lateral sclerosis and ferroptosis, and the drugs used in the clinic, then discusses the current status of amyotrophic lateral sclerosis treatment, hoping to provide new directions and targets for its treatment.

16.
Plants (Basel) ; 13(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38891268

RESUMO

Symplocos paniculata are reported to exhibit seed dormancy, which impedes its cultivation and widespread adoption. In this study, a comprehensive method was established to overcome seed dormancy by subjecting seeds to scarification in 98% H2SO4 for 10 min, followed by 1000 mg·L-1 GA3 soaking for 48 h and stratification at 4 °C for 100 days. The seed germination percentage has increased significantly, to a peak of 42.67%, though the seeds could not germinate timely by NaOH scarification. Additionally, the dynamic changes of key stored substances (proteins, soluble sugars, starches, and fats), associated enzyme activities (amylases, peroxidase, and catalase), and endogenous hormones (abscisic acid, gibberellic acid, and indole-3-acetic acid) in seeds were investigated. The results demonstrated a continuous degradation of starch and fat in S. paniculata seeds, while the levels of protein and soluble sugar exhibited fluctuations, which probably facilitated seed dormancy breaking through energy supply and transformation. The enzymatic activities underwent rapid changes, accompanied by a gradual decrease in ABA content within the seeds with increasing stratification time. Notably, GA3, GA3/ABA, and (GA3 + IAA)/ABA showed significant increases, indicating their positive regulatory roles in seed germination. This study clarified the dormancy mechanism and established an effective method for the release dormancy of S. paniculata seeds.

17.
Animals (Basel) ; 14(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38891682

RESUMO

Crytosporidium spp., Giardia duodenalis, and Enterocytozoon bieneusi are important diarrheal pathogens with a global distribution that threatens the health of humans and animals. Despite cattle being potential transmission hosts of these protozoans, the associated risks to public health have been neglected. In the present study, a total of 1155 cattle fecal samples were collected from 13 administrative regions of Heilongjiang Province. The prevalence of Cryptosporidium spp., G. duodenalis, and E. bieneusi were 5.5% (64/1155; 95% CI: 4.2-6.9), 3.8% (44/1155; 95% CI: 2.7-4.9), and 6.5% (75/1155; 95% CI: 5.1-7.9), respectively. Among these positive fecal samples, five Cryptosporidium species (C. andersoni, C. bovis, C. ryanae, C. parvum, and C. occultus), two G. duodenalis assemblages (E and A), and eight E. bieneusi genotypes (BEB4, BEB6, BEB8, J, I, CHS7, CHS8, and COS-I) were identified. Phylogenetic analysis showed that all eight genotypes of E. bieneusi identified in the present study belonged to group 2. It is worth noting that some species/genotypes of these intestinal protozoans are zoonotic, suggesting a risk of zoonotic disease transmission in endemic areas. The findings expanded our understanding of the genetic composition and zoonotic potential of Cryptosporidium spp., G. duodenalis, and E. bieneusi in cattle in Heilongjiang Province.

18.
Sci Adv ; 10(25): eadm7569, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38896615

RESUMO

Realizing a multifunctional integrated photonic platform is one of the goals for future optical information processing, which usually requires large size to realize due to multiple integration challenges. Here, we realize a multifunctional integrated photonic platform with ultracompact footprint based on inverse design. The photonic platform is compact with 86 inverse designed-fixed couplers and 91 phase shifters. The footprint of each coupler is 4 µm by 2 µm, while the whole photonic platform is 3 mm by 0.2 mm-one order of magnitude smaller than previous designs. One-dimensional Floquet Su-Schrieffer-Heeger model and Aubry-André-Harper model are performed with measured fidelities of 97.90 (±0.52) % and 99.34 (±0.44) %, respectively. We also demonstrate a handwritten digits classification task with the test accuracy of 87% using on-chip training. Moreover, the scalability of this platform has been proved by demonstrating more complex computing tasks. This work provides an effective method to realize an ultrasmall integrated photonic platform.

19.
ACS Nano ; 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902594

RESUMO

Although in vitro neuronal network models hold great potential for advancing neuroscience research, with the capacity to provide fundamental insights into mechanisms underlying neuronal functions, the dynamics of cell communication within such networks remain poorly understood. Here, we develop a customizable, polymer modified three-dimensional gold microelectrode array with sufficient stability for high signal-to-noise, long-term, neuronal recording of cultured networks. By using directed spatial and temporal patterns of electrical stimulation of cells to explore synaptic-based communication, we monitored cell network dynamics over 3 weeks, quantifying communication capability using correlation heatmaps and mutual information networks. Analysis of synaptic delay and signal speed between cells enabled us to establish a communication connectivity model. We anticipate that our discoveries of the dynamic changes in communication across the neuronal network will provide a valuable tool for future studies in understanding health and disease as well as in developing effective platforms for evaluating therapies.

20.
J Obstet Gynaecol ; 44(1): 2360547, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38904638

RESUMO

BACKGROUND: MiR-381 can regulate the expression of cyclin A2 (CCNA2) to inhibit the proliferation and migration of bladder cancer cells, but whether miR-381 has the same function in breast cancer is not well know. METHODS: The over express or silence miR-381 expressing cell lines were constructed by lentivirus infection to reveal the biological functions of miR-381 in vitro. The expression of miR-381 and CCNA2 in 162 breast cancer patients were detected to further reveal their impact and predictive value on progression-free survival (PFS) and overall survival (OS). RESULTS: After transfection of MDA-MB-231 and MCF-7 cells with miR-381 mimics, the expression of miR-381 was effectively up-regulated and CCNA2 was effectively down-regulated, while the opposite results were observed in tumour cell which transfected with miR-381 inhibitors. After transfection of cell lines with miR-381 mimics, tumour cell activity was significantly reduced, while the opposite results were observed in tumour cell which transfected with miR-381 inhibitors. The area under curves (AUCs) of miRNA-381 and CCNA2 for predicting PFS and OS were 0.711, 0.695, 0.694 and 0.675 respectively. Cox regression analysis showed that miRNA-381 ≥ 1.65 2-ΔΔCt and CCNA ≥ 2.95 2-ΔΔCt were the influence factors of PFS and OS, the hazard ratio (HR) values were 0.553, 2.075, 0.462 and 2.089, respectively. CONCLUSION: miR-381 inhibitors breast cancer cells proliferation and migration by down-regulating the expression of CCNA2, both of them can predict the prognosis of breast cancer.


miR-381 can regulate the expression of cyclin A2 and inhibit the proliferation and migration of bladder cancer cells, but whether miR-381 has the same function in breast cancer is not well know. We analysed the levels of miR-381 and cyclin A2 in breast cancer patients and breast cancer cells to reveal the mechanism of miR-381 affecting the expression of cyclin A2. We found miRNA-381 affects the proliferation and migration of breast cancer cells by down-regulating the expression of cyclin A2. The expression of serum miR-381 and cyclin A2 have important values in predicting the prognosis of breast cancer. Our findings provide mechanistic insights into how miR-381 regulates the proliferation and migration of breast cancer, as well as a new target for clinical treatment. Future research may focus on how to improve patient prognosis by up-regulating expression of miR-381 and down-regulating the expression of cyclin A2.


Assuntos
Neoplasias da Mama , Proliferação de Células , Ciclina A2 , Regulação Neoplásica da Expressão Gênica , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Proliferação de Células/genética , Ciclina A2/genética , Ciclina A2/metabolismo , Prognóstico , Pessoa de Meia-Idade , Linhagem Celular Tumoral , Células MCF-7 , Adulto
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