Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
4,515
result(s) for
"Lo, Steven"
Sort by:
China's new united front work in Hong Kong : penetrative politics and its implications
\"This book explores the dynamics of China's new united front work in Hong Kong. Mainland Chinese penetrative politics can be seen in the activities of local pro-Beijing political parties, clans and neighborhood associations, labor unions, women and media organizations, district federations, and some religious groups. However, united front work in the educational and youth sectors of civil society has encountered strong resistance because many Hong Kong people are post-materialistic and uphold their core values of human rights, the rule of law and transparency. China's new united front work in Hong Kong has been influenced by its domestic turn toward \"hard\" authoritarianism, making Beijing see Hong Kong's democratic activists and radicals as political enemies. Hong Kong's \"one country, two systems\" is drifting toward \"one country, two mixed systems\" with some degree of convergence. Yet, Taiwan and some foreign countries have seen China's united front work as politically destabilizing and penetrative. This book will be of use to scholars, journalists, and observers in other countries seeking to reckon with Chinese influence\"-- Provided by publisher.
Book
ADSCs stimulated by resistin promote breast cancer cell malignancy via CXCL5 in a breast cancer coculture model
The tumor microenvironment represents one of the main obstacles in breast cancer treatment owing to the presence of heterogeneous stromal cells, such as adipose-derived stem cells (ADSCs), that may interact with breast cancer cells and promote cancer development. Resistin is an adipocytokine associated with adverse breast cancer progression; however, its underlying mechanisms in the context of the breast tumor microenvironment remain largely unidentified. Here, we utilized a transwell co-culture model containing patient-derived ADSCs and breast cancer cell lines to investigate their potential interaction, and observed that breast cancer cells co-cultured with resistin-treated ADSCs (R-ADSCs) showed enhanced cancer cell growth and metastatic ability. Screening by proteome arrays revealed that C-X-C motif chemokine ligand 5 (CXCL5) was released in the conditioned medium of the co-culture system, and phosphorylated ERK was increased in breast cancer cells after co-culture with R-ADSCs. Breast cancer cells treated with the recombinant proteins of CXCL5 showed similarly enhanced cell migration and invasion ability as occurred in the co-culture model, whereas application of neutralizing antibodies against CXCL5 reversed these phenomena. The orthotopic xenograft in mice by breast cancer cells after co-culture with R-ADSCs had a larger tumor growth and more CXCL5 expression than control. In addition, clinical analysis revealed a positive correlation between the expression of resistin and CXCL5 in both tumor tissues and serum specimens of breast cancer patients. The current study suggests that resistin-stimulated ADSCs may interact with breast cancer cells in the tumor microenvironment via CXCL5 secretion, leading to breast cancer cell malignancy.
Journal Article
IL-1RA promotes oral squamous cell carcinoma malignancy through mitochondrial metabolism-mediated EGFR/JNK/SOX2 pathway
Background
Interleukin-1 receptor antagonist (IL-1RA), a member of the IL-1 family, has diverse roles in cancer development. However, the role of IL-1RA in oral squamous cell carcinoma (OSCC), in particular the underlying mechanisms, remains to be elucidated.
Methods
Tumor tissues from OSCC patients were assessed for protein expression by immunohistochemistry. Patient survival was evaluated by Kaplan–Meier curve analysis. Impact of differential IL-1RA expression on cultured OSCC cell lines was assessed in vitro by clonogenic survival, tumorsphere formation, soft agar colony formation, and transwell cell migration and invasion assays. Oxygen consumption rate was measured by Seahorse analyzer or multi-mode plate reader. PCR array was applied to screen human cancer stem cell-related genes, proteome array for phosphorylation status of kinases, and Western blot for protein expression in cultured cells. In vivo tumor growth was investigated by orthotopic xenograft in mice, and protein expression in xenograft tumors assessed by immunohistochemistry.
Results
Clinical analysis revealed that elevated IL-1RA expression in OSCC tumor tissues was associated with increased tumor size and cancer stage, and reduced survival in the patient group receiving adjuvant radiotherapy compared to the patient group without adjuvant radiotherapy. In vitro data supported these observations, showing that overexpression of IL-1RA increased OSCC cell growth, migration/invasion abilities, and resistance to ionizing radiation, whereas knockdown of IL-1RA had largely the opposite effects. Additionally, we identified that EGFR/JNK activation and SOX2 expression were modulated by differential IL-1RA expression downstream of mitochondrial metabolism, with application of mitochondrial complex inhibitors suppressing these pathways. Furthermore, in vivo data revealed that treatment with cisplatin or metformin—a mitochondrial complex inhibitor and conventional therapy for type 2 diabetes—reduced IL-1RA-associated xenograft tumor growth as well as EGFR/JNK activation and SOX2 expression. This inhibitory effect was further augmented by combination treatment with cisplatin and metformin.
Conclusions
The current study suggests that IL-1RA promoted OSCC malignancy through mitochondrial metabolism-mediated EGFR/JNK activation and SOX2 expression. Inhibition of this mitochondrial metabolic pathway may present a potential therapeutic strategy in OSCC.
Journal Article
Investigating the mediating role of self-efficacy on work stress and job insecurity among Indonesian startup employees
Type of the article: Research Article AbstractThe wave of layoffs in Indonesia’s startups has increased employees’ concerns about job insecurity, raising the need for a deeper understanding of its determinants. This study examines the associations between work stress, self-efficacy, and job insecurity in Indonesia’s startup ecosystem. Specifically, it investigates direct and indirect effects of work stress on job insecurity through self-efficacy. Data were collected from 262 digital startup employees in Jakarta using an online survey at the beginning of 2024 and analyzed using covariance-based structural equation modeling with LISREL software. The findings suggest that work stress does not directly influence job insecurity (T-value of 0.79 < 1.967), indicating that startup employees may perceive stress as a regular aspect of their dynamic and high-pressure work environment. However, work stress significantly and positively impacts self-efficacy (T-value of 11.32> 1.967), implying that stress can enhance employees’ confidence in their abilities when managed effectively. Self-efficacy has a significant and positive effect on job insecurity (T-value of 9.98 > 1.967), highlighting its pivotal role in shaping perceptions of job stability. Furthermore, work stress indirectly influences job insecurity through self-efficacy (Indirect effect 0.7392 > direct effect 0.045), emphasizing the mediating role of self-belief in mitigating the adverse effects of workplace stress. The findings emphasize the importance of fostering self-efficacy through supportive management, training programs, and clear communication to lessen job insecurity and promote resilience. These insights provide practical implications for enhancing employee well-being and organizational sustainability in the rapidly evolving startup environment.
Journal Article
MRE11 promotes oral cancer progression through RUNX2/CXCR4/AKT/FOXA2 signaling in a nuclease-independent manner
MRE11, the nuclease component of RAD50/MRE11/NBS1 DNA repair complex which is essential for repair of DNA double-strand-breaks in normal cells, has recently garnered attention as a critical factor in solid tumor development. Herein we report the crucial role of MRE11 in oral cancer progression in a nuclease-independent manner and delineate its key downstream effectors including CXCR4. MRE11 expression in oral cancer samples was positively associated with tumor size, cancer stage and lymph node metastasis, and was predictive of poorer patient survival and radiotherapy resistance. MRE11 promoted cell proliferation/migration/invasion in a nuclease-independent manner but enhanced radioresistance via a nuclease-dependent pathway. The nuclease independent promotion of EMT and metastasis was mediated by RUNX2, CXCR4, AKT, and FOXA2, while CXCR4 neutralizing antibody mitigated these effects in vitro and in vivo. Collectively, MRE11 may serve as a crucial prognostic factor and therapeutic target in oral cancer, displaying dual nuclease dependent and independent roles that permit separate targeting of tumor vulnerabilities in oral cancer treatment.
Journal Article
Areca nut-induced metabolic reprogramming and M2 differentiation promote OPMD malignant transformation
Background
Betel quid and its major ingredient, areca nut, are recognized by IARC as major risk factors in oral cancer development. Areca nut extract (ANE) exposure has been linked to OPMD progression and malignant transformation to OSCC. However, the detailed mechanism through which ANE acts on other cell types in the oral microenvironment to promote oral carcinogenesis remains elusive.
Methods
Immunoprofiling of macrophages associated with OPMD and OSCC was carried out by immunohistochemical and immunofluorescence staining. Phosphokinase and cytokine arrays and western blotting were performed to determine the underlying mechanisms. Transwell assays were used to evaluate the migration-promoting effect of ANE. Hamster model was finally applied to confirm the in vivo effect of ANE.
Results
We reported that M2 macrophages positively correlated with oral cancer progression. ANE induced M2 macrophage differentiation, CREB phosphorylation and VCAM-1 secretion and increased mitochondrial metabolism. Conditioned medium and VCAM-1 from ANE-treated macrophages promoted migration and mesenchymal phenotypes in oral precancer cells. In vivo studies showed that ANE enhanced M2 polarization and related signaling pathways in the oral buccal tissues of hamsters.
Conclusion
Our study provides novel mechanisms for areca nut-induced oral carcinogenesis, demonstrating that areca nut promotes M2 macrophage differentiation and secretion of oncogenic cytokines that critically activate malignant transformation of oral premalignant cells.
Journal Article
Free vascularised medial femoral condyle periosteal flaps in recalcitrant long bone non-union: a systematic review
IntroductionIn adults, treatment of recalcitrant long bone non-union is extremely challenging, with poorly vascularised and atrophic defects unresponsive to standard non-vascularised bone graft treatment. Recent studies have documented the use of free vascularised periosteal flaps to achieve union in refractory long bone fracture non-union, yet its use is not well established. This systematic review aims to assess the evidence for free vascularised periosteal flaps in recalcitrant long bone non-union.Materials and methodsThe MEDLINE®/PubMed® and Embase databases were searched for the Medical Subject Heading (MeSH) terms periosteal flap/vascularised flap/long bone/non-union/non united fracture in accordance with the PRISMA guidelines. Bibliographies were scrutinised for additional articles.ResultsPooled data from 14 studies met the inclusions criteria, comprising 137 cases of non-union, with 117 relating to long bone non-union. Pooled data indicated an overall 99% (116/117) successful union rate. All studies were of mid- to low-level evidence (Level III, IV and V). Only one study directly compared vascularised periosteal flaps to non-vascularised bone grafts, showing union rates of 100% versus 80% and faster time to union (2 versus 5.5 months).ConclusionsFree vascularised periosteal flaps are promising with pooled data showing a 99% success rate in achieving union in refractory long bone non-union. This compares favourably with standard orthopaedic care consisting of revision fixation and non-vascularised bone graft union rates of approximately 80%. However, study design flaws should be addressed by validated outcome measures plus adequate blinding, and further comparative studies with greater patient numbers are required.
Journal Article
T-Cell Autophagy Deficiency Increases Mortality and Suppresses Immune Responses after Sepsis
Although the role of autophagy in sepsis has been characterized in several organs, its role in the adaptive immune system remains to be ascertained. This study aimed to investigate the role of autophagy in sepsis-induced T cell apoptosis and immunosuppression, using knockout mice with T cell specific deletion of autophagy essential gene Atg7.
Sepsis was induced in a cecal ligation and puncture (CLP) model, with T-cell-specific Atg7-knockout mice compared to control mice. Autophagic vacuoles examined by electron microscopy were decreased in the spleen after CLP. Autophagy proteins LC3-II and ATG7, and autophagosomes and autolysosomes stained by Cyto-ID Green and acridine orange were decreased in CD4+ and CD8+ splenocytes at 18 h and 24 h after CLP. This decrease in autophagy was associated with increased apoptosis of CD4+ and CD8+ after CLP. Moreover, mice lacking Atg7 in T lymphocytes showed an increase in sepsis-induced mortality, T cell apoptosis and loss of CD4+ and CD8+ T cells, in comparison to control mice. This was accompanied by suppressed cytokine production of Th1/Th2/Th17 by CD4+ T cells, reduced phagocytosis in macrophages and decreased bacterial clearance in the spleen after sepsis.
These results indicated that sepsis led to down-regulation of autophagy in T lymphocytes, which may result in enhanced apoptosis induction and decreased survival in sepsis. Autophagy may therefore play a protective role against sepsis-induced T lymphocyte apoptosis and immunosuppression.
Journal Article
Visfatin Enhances Breast Cancer Progression through CXCL1 Induction in Tumor-Associated Macrophages
Visfatin, an adipocytokine highly expressed in breast tumor tissues, is associated with breast cancer progression. Recent studies showed that adipocytokines mediate tumor development through adipocytokine tumor-stromal interactions in the tumor microenvironment. This study focused on the interaction between one key stromal constituent—tumor-associated macrophages—and visfatin. Pretreatment of THP-1 and peripheral blood mononuclear cells (PBMCs) with recombinant visfatin resulted in M2-polarization determined by CD163 and CD206 expression. Indirect co-culture with visfatin-treated THP-1 (V-THP-1) promoted the viability, migration, tumorsphere formation, EMT, and stemness of breast cancer cells. Cytokine array identified an increased CXCL1 secretion in V-THP-1 conditioned medium and recombinant CXCL1 enhanced cell migration and invasion, which were abrogated by the CXCL1-neutralizing antibody. Additionally, visfatin induced pERK in THP-1 cells and clinical samples confirmed a positive CXCL1/pERK correlation. In an orthotopic mouse model, the tumor bioluminescent signal of luciferase-expressing MDA-MB-231 (Luc-MDA-MB-231) cells co-cultured with V-THP-1 and the expression of proliferation marker Ki67 were significantly higher than that co-cultured with THP-1. Furthermore, tail vein-injected Luc-MDA-MB-231 pretreated with V-PBMCs conditioned medium metastasized to lungs more frequently compared to control, and this was reversed by CXCL1 blocking antibody. In summary, this study demonstrated that visfatin enhanced breast cancer progression via pERK/CXCL1 induction in macrophages.
Journal Article
Split median superficial sural artery perforator (MSSAP) flap and medial sural artery perforator (MSAP) flap for posterior thigh sarcoma reconstruction
Reconstruction of composite defects of the posterior thigh and knee is challenging. Pedicled medial gastrocnemius flaps are the traditional reconstructive approach, but late contractures related to skin grafted muscle may affect knee function. More recently, the medial sural artery perforator (MSAP) flap has been described for such defects, although may necessitate skin grafting of the donor site. To minimise the drawbacks with these options, we describe a combination of a median superficial sural artery perforator (MSSAP) flap and MSAP flap. This allows both tension free closure of the donor site without skin grafting, and facilitates coverage of a round defect by splitting the flap into two adjacent triangular flaps. This is the first report of posterior thigh defect reconstruction with a combination of MSSAP and MSAP flaps.
Journal Article