73 research outputs found
Trichlorophenyl-benzoxime induces apoptosis in human colon carcinoma cells via activation of mitochondria dependent pathway
Purpose: To determine the apoptotic effect of trichlorophenyl-benzoxime (TCPB) on colorectal cancer (CRC) cells, and to elucidate the mechanism of action.
Methods: Colon carcinoma cell lines (DLD-1 and HT-29) were used in this study. The cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10 % fetal bovine serum (FBS) and 1 % penicillin/streptomycin at 37 ˚C in an atmosphere of 5 % CO2 and 95 % air. When the cells attained 60 - 70 % confluency, they were treated with serum-free medium and graded concentrations of TCPB (1.0 – 6.0 μM) for 24 h. Cell viability and apoptosis were assessed using 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide (MTT) and flow cytometric assays, respectively. Western blotting and 2', 7' dichlorofluorescein diacetate (DCFH DA) assays were used for the determination of expression levels of apoptotic proteins, and levels of reactive oxygen species (ROS), respectively.
Results: Treatment of DLD-1 and HT-29 cells with TCPB led to significant and dose-dependent reductions in their viability, as well as significant and dose-dependent increases in the number of apoptotic cells (p < 0.05). Treatment of HT-29 cells with TCPB led to significant increases in the population of cells in the G0/G1 phase, but significant reduction of cell proportion in S and G2/M phases (p < 0.05). It also significantly and dose-dependently upregulated the expressions of caspase-3 and bax, down-regulation of the expression of bcl-2 (p < 0.05). TCPB treatment upregulated the expressions of p53, cytochrome c (cyt c), procaspase-3, and procaspase-9, but down-regulated the expression of pAkt dose-dependently (p < 0.05). The expression of Akt in HT-29 cells was not significantly affected by TCPB (p > 0.05). However, TCPB significantly enhanced the cleavage of PARP1, and significantly and dose-dependently increased the levels of ROS in HT-29 cells (p < 0.05).
Conclusion: These results suggest that TCPB exerts apoptotic effect on CRC cells via activation of mitochondria-dependent pathway, and thus can be suitably developed for the management of colon cancer
Cross-Architecture Knowledge Distillation
Transformer attracts much attention because of its ability to learn global
relations and superior performance. In order to achieve higher performance, it
is natural to distill complementary knowledge from Transformer to convolutional
neural network (CNN). However, most existing knowledge distillation methods
only consider homologous-architecture distillation, such as distilling
knowledge from CNN to CNN. They may not be suitable when applying to
cross-architecture scenarios, such as from Transformer to CNN. To deal with
this problem, a novel cross-architecture knowledge distillation method is
proposed. Specifically, instead of directly mimicking output/intermediate
features of the teacher, a partially cross attention projector and a group-wise
linear projector are introduced to align the student features with the
teacher's in two projected feature spaces. And a multi-view robust training
scheme is further presented to improve the robustness and stability of the
framework. Extensive experiments show that the proposed method outperforms 14
state-of-the-arts on both small-scale and large-scale datasets
Post-stroke experiences and health information needs among Chinese elderly ischemic stroke survivors in the internet environment: a qualitative study
BackgroundElderly stroke survivors are encouraged to receive appropriate health information to prevent recurrences. After discharge, older patients seek health information in everyday contexts, examining aspects that facilitate or impair healthy behavior.ObjectivesTo explore the experiences of older stroke patients when searching for health information, focusing on search methods, identification of health information, and difficulties faced during the search process.MethodsUsing the qualitative descriptive methodology, semi-structured interviews were conducted with fifteen participants.ResultsParticipants associated the health information they sought with concerns about future life prospects triggered by perceived intrusive changes in their living conditions. Based on the participants’ descriptions, four themes were refined: participants’ motivation to engage in health information acquisition behavior, basic patterns of health information search, source preferences for health information, and difficulties and obstacles in health information search, and two search motivation subthemes, two search pattern subthemes, four search pathway subthemes, and four search difficulty subthemes were further refined.ConclusionOlder stroke patients face significant challenges in searching for health information online. Healthcare professionals should assess survivors’ health information-seeking skills, develop training programs, provide multichannel online access to health resources, and promote secondary prevention for patients by improving survivors’ health behaviors and self-efficacy
Polysaccharide-based nanomedicines for cancer immunotherapy: a review
Cancer immunotherapy is an effective antitumor approach through activating immune systems to eradicate
tumors by immunotherapeutics. However, direct administration of “naked” immunotherapeutic agents (such as
nucleic acids, cytokines, adjuvants or antigens without delivery vehicles) often results in: (1) an unsatisfactory
efficacy due to suboptimal pharmacokinetics; (2) strong toxic and side effects due to low targeting (or off-target)
efficiency. To overcome these shortcomings, a series of polysaccharide-based nanoparticles have been developed
to carry immunotherapeutics to enhance antitumor immune responses with reduced toxicity and side effects.
Polysaccharides are a family of natural polymers that hold unique physicochemical and biological properties, as
they could interact with immune system to stimulate an enhanced immune response. Their structures offer
versatility in synthesizing multifunctional nanocomposites, which could be chemically modified to achieve high
stability and bioavailability for delivering therapeutics into tumor tissues. This review aims to highlight recent
advances in polysaccharide-based nanomedicines for cancer immunotherapy and propose new perspectives on
the use of polysaccharide-based immunotherapeutics.info:eu-repo/semantics/publishedVersio
Present and Future: Crosstalks Between Polycystic Ovary Syndrome and Gut Metabolites Relating to Gut Microbiota
Polycystic ovary syndrome (PCOS) is a common disease, affecting 8%–13% of the females of reproductive age, thereby compromising their fertility and long-term health. However, the pathogenesis of PCOS is still unclear. It is not only a reproductive endocrine disease, dominated by hyperandrogenemia, but also is accompanied by different degrees of metabolic abnormalities and insulin resistance. With a deeper understanding of its pathogenesis, more small metabolic molecules, such as bile acids, amino acids, and short-chain fatty acids, have been reported to be involved in the pathological process of PCOS. Recently, the critical role of gut microbiota in metabolism has been focused on. The gut microbiota-related metabolic pathways can significantly affect inflammation levels, insulin signaling, glucose metabolism, lipid metabolism, and hormonal secretions. Although the abnormalities in gut microbiota and metabolites might not be the initial factors of PCOS, they may have a significant role in the pathological process of PCOS. The dysbiosis of gut microbiota and disturbance of gut metabolites can affect the progression of PCOS. Meanwhile, PCOS itself can adversely affect the function of gut, thereby contributing to the aggravation of the disease. Inhibiting this vicious cycle might alleviate the symptoms of PCOS. However, the role of gut microbiota in PCOS has not been fully explored yet. This review aims to summarize the potential effects and modulative mechanisms of the gut metabolites on PCOS and suggests its potential intervention targets, thus providing more possible treatment options for PCOS in the future
Cost-effectiveness analysis of dostarlimab plus carboplatin-paclitaxel as first-line treatment for advanced endometrial cancer
BackgroundA recent phase III clinical trial (NCT03981796) evaluated the efficacy and safety of dostarlimab combined with carboplatin-paclitaxel (DOS-CP) compared to placebo combined with carboplatin-paclitaxel (PLB-CP) as a first-line treatment for advanced endometrial cancer (EC). The NCT03981796 trial demonstrated that DOS-CP significantly improved progression-free survival and overall survival of patients with advanced EC while maintaining an acceptable safety profile. However, DOS-CP is expensive and its cost-effectiveness has not been evaluated. This study aims to evaluate the cost-effectiveness of DOS-CP compared to PLB-CP as a first-line treatment for advanced EC from the perspective of the Chinese healthcare system.MethodsA Markov model with three health states was developed to evaluate the cost-effectiveness of DOS-CP as a first-line treatment for advanced EC. Clinical efficacy data were derived from the NCT03981796 trial, and drug costs were determined based on national tender prices. Other costs and utility values were obtained from published literature. The outcomes assessed included total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The robustness of the model was assessed through one-way sensitivity analysis and probabilistic sensitivity analysis.ResultsIn comparison to PLB-CP, the ICER of DOS-CP was 53,063.61/QALY for the dMMR subgroup, and 38,201 per QALY. The most important variable that affected the results of the model was the discount rate, the cost of dostarlimab, and the utility value for progressive disease.ConclusionFrom the perspective of the Chinese healthcare system, DOS-CP is unlikely to be a cost-effective first-line treatment option for advanced EC
Toxicity of microplastics and nanoplastics: invisible killers of female fertility and offspring health
Microplastics (MPs) and nanoplastics (NPs) are emergent pollutants, which have sparked widespread concern. They can infiltrate the body via ingestion, inhalation, and cutaneous contact. As such, there is a general worry that MPs/NPs may have an impact on human health in addition to the environmental issues they engender. The threat of MPs/NPs to the liver, gastrointestinal system, and inflammatory levels have been thoroughly documented in the previous research. With the detection of MPs/NPs in fetal compartment and the prevalence of infertility, an increasing number of studies have put an emphasis on their reproductive toxicity in female. Moreover, MPs/NPs have the potential to interact with other contaminants, thus enhancing or diminishing the combined toxicity. This review summarizes the deleterious effects of MPs/NPs and co-exposure with other pollutants on female throughout the reproduction period of various species, spanning from reproductive failure to cross-generational developmental disorders in progenies. Although these impacts may not be directly extrapolated to humans, they do provide a framework for evaluating the potential mechanisms underlying the reproductive toxicity of MPs/NPs
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