Measuring resilience for Chinese-speaking populations: a systematic review of Chinese resilience scales.

Introduction: Despite the rapid growth of interdisciplinary resilience research in Chinese contexts, no study has systematically reviewed individual-level measurement scales for Chinese-speaking populations. We report a systematic review of scales developed for or translated/adapted to Chinese-speaking contexts, where we assessed how widely used scales fare in terms of their psychometric qualities. Methods: Studies included in this review must have been published in peer-reviewed English or Chinese journals between 2015-2020 and included self-reported resilience scales in Chinese-speaking populations. Searches were conducted in PsycINFO, CNKI (completed in May 2021), and PubMed (completed in January 2024). We developed coding schemes for extracting relevant data and adapted and applied an existing evaluation framework to assess the most frequently used resilience scales by seven methodological criteria. Results: Analyses of 963 qualified studies suggested that Chinese resilience scales were used in a diverse range of study contexts. Among 85 unique kinds of resilience measures, we highlighted and evaluated the three most frequently used translated scales and three locally developed scales (nine scales in total including variations such as short forms). In short, resilience studies in Chinese contexts relied heavily on the translated 25-item Connor-Davidson Resilience Scale, which scored moderately on the overall quality. The locally developed Resilience Scale for Chinese Adolescents and Essential Resilience Scale received the best ratings but could use further development. Discussion: We discussed how future work may advance widely used scales, and specified seven methodological recommendations for future resilience scale development with existing and new scales in and beyond the Chinese study contexts. We further addressed issues and challenges in measuring resilience as a process and called on researchers to further develop/evaluate process measures for Chinese-speaking populations.

Examining the Role of Memorable Messages in the Process of Communication about Aging.

Given that individuals have (some) agency to influence their own experiences of aging via communication, it is important to better understand factors that may play a role in these processes. Specifically, this study examined whether and how themes of aging-related memorable messages (e.g. aging involves physical or mental health struggles; age is merely a subjective state) and the extent to which a message offered a sense of positivity and efficacy predicted individuals' efficacy assessments (coping, target, communication) and intention to seek additional information about aging processes. Analyses of responses from a sample of 232 older adults from the United States revealed that memorable message: (a) themes about aging predicted participants' reports of memorable message positivity and efficacy, (b) valence predicted memorable message positivity and efficacy, and (c) characteristics (positivity and efficacy) predicted individuals' efficacy assessments and, ultimately, intention to seek information about aging processes (both directly and indirectly). Results offer theoretical and practical implications.

Multilineage differentiation potential in the infant adipose- and umbilical cord-derived mesenchymal stem cells.

BACKGROUND: This study aims to compare the biological properties of infant adipose-derived mesenchymal stem cells (infant ADSCs) from excised polydactyly fat tissue and umbilical cord-derived mesenchymal stem cells (UCSCs) in terms of proliferation and differentiation capabilities. The proliferation of infant ADSCs and UCSCs was analyzed by determining the fold changes of cell numbers and doubling time periods. METHODS: The state of senescence and replicative stress was compared by analyzing the expression of age-related genes, senescence-associated ß-galactosidase (SA-ß-gal) staining, and phosphorylated histone variant H2AX (γH2AX) immunofluorescence staining. The expression levels of superoxide dismutase ( SODs ) and genes related to multilineage differentiation were analyzed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Differentiation levels were determined using histochemical staining, immunohistochemical staining, and immunofluorescence staining. RESULTS: Infant ADSCs exhibited higher proliferation rates and expression levels of SOD1 , SOD2 , and SOD3 at passages 3-5 compared with UCSCs. Senescence related genes ( p16 , p21 , and p53 ), SA-ß-gal staining, and replicative stress analysis were reduced in infant ADSCs. The expression levels of chondrogenic genes ( COL2 and COL10 ), osteogenic genes ( RUNX2 and ALP ), adipogenic genes ( LPL ), and hepatogenic genes ( ALB and TAT ) in infant ADSC-differentiated cells were significantly higher than those in UCSCs. Histochemical and immunofluorescence staining confirmed these results. Only the expression levels of tenogenic genes ( MMP3 , DCN , and COL3 ) in infant ADSC-differentiated cells were lower than those in UCSCs. CONCLUSION: Infant ADSCs exhibit higher proliferation rates, reduced cellular senescence and replicative stress, better antioxidative activity, and higher differentiation potential toward chondrogenic, osteogenic, adipogenic and hepatogenic lineages than UCSCs.

Predictors and Outcomes of Help-Seeking Behaviors: A Longitudinal Investigation in Mental Illness.

Millions of people around the world are affected by mental illness, yet a substantive portion of individuals with mental illness do not regularly seek help from medical professionals or utilize mental health services. Help-seeking involves an individual's communicative intention and behaviors to solicit advice and/or treatment and thus is essentially a communicative process. This manuscript reports a longitudinal study that examined predictors and outcomes of help-seeking in mental illness contexts. Three-wave data from 223 participants clinically diagnosed with one or more mental illness conditions were collected and analyzed. Results indicated that expected outcomes of help-seeking from counselors were significantly associated with participants' communication efficacy and target efficacy at Wave 1, which subsequently influenced motivation to seek help and actual help-seeking behaviors at Wave 2. Actual help-seeking behaviors predicted post-traumatic growth and cognitive reappraisal at Wave 3. Importantly, communication efficacy and target efficacy interacted in their effects on help-seeking motivation and behaviors. Theoretical implications for help-seeking communication processes and practical implications for mental health help-seeking are discussed.

Osimertinib Induces the Opposite Effect of Proliferation and Migration in the Drug Resistance of EGFR-T790M Non-small Cell Lung Cancer Cells.

BACKGROUND: Lung cancer has become one of the leading causes of cancer incidence and mortality worldwide. Non-small cell lung carcinoma (NSCLC) is the most common type among all lung cancer cases. NSCLC patients contained high levels of activating epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletion, L858R and T790M. Osimertinib, a third-generation of EGFR tyrosine kinase inhibitor (EGFR-TKI), has therapeutic efficacy on the EGFR-T790M mutation of NSCLC patients; however, treatment of osimertinib still can induce drug resistance in lung cancer patients. Therefore, investigation of the drug resistance mechanisms of osimertinib will provide novel strategies for lung cancer therapy. METHODS: The H1975OR osimertinib-resistant cell line was established by prolonged exposure with osimertinib derived from the H1975 cells. The cell proliferation ability was evaluated by the cell viability and cell growth assays. The cell migration ability was determined by the Boyden chamber assays. The differential gene expression profile was analyzed by genome-wide RNA sequencing. The protein expression and location were analyzed by western blot and confocal microscopy. RESULTS: In this study, we established the osimertinib-resistant H1975 (T790M/L858R) cancer cells, named the H1975OR cell line. The cell growth ability was decreased in the H1975OR cells by comparison with the H1975 parental cells. Conversely, the cell migration ability was elevated in the H1975OR cells. We found the differential gene expression profile of cell proliferation and migration pathways between the H1975OR and H1975 parental cells. Interestingly, the protein levels of phospho-EGFR, PD-L1, E-cadherin and ß-catenin were decreased, but the survivin and N-cadherin proteins were increased in the H1975OR drug-resistant cells. CONCLUSION: Osimertinib induces the opposite effect of proliferation and migration in the drug resistance of EGFRT790M lung cancer cells. We suggest that differential gene and protein expressions in the cell proliferation and migration pathways may mediate the drug resistance of osimertinib in lung cancer cells. Understanding the molecular drugresistant mechanisms of proliferation and migration pathways of osimertinib may provide novel targets and strategies for the clinical treatment of EGFR-TKIs in lung cancer patients.

Memorable Messages as Anticipatory Resilience: Examining Associations among Memorable Messages, Communication Resilience Processes, and Mental Health.

Memorable messages oftentimes are associated with hope, can foster anticipatory resilience prior to the experience of disruptive events, and can buffer the negative impact of adverse experiences on mental health. However, associations among memorable messages, engagement in resilience processes, and mental health have not been examined. Drawing from the communication theory of resilience (CTR), analyses of data from 262 Chinese adults suggested that memorable messages provided a sense of agency and pathways - two interrelated but distinct components of dispositional hope - and functioned as a form of anticipatory resilience that was positively associated with outcomes of coping with disruptive life events including mental health, posttraumatic growth, and meaning in life. These associations were mediated by the extent to which individuals engaged in change- and continuity-related resilience processes as outlined in CTR. Findings offer theoretical implications for memorable message and resilience research as well as practical implications for communicative strategies that can cultivate anticipatory resilience, promote positive adaptation, learning, and reflection, and mitigate the negative effects that disruptive events can have on mental health.

Structural transitions during the cooperative assembly of baculovirus single-stranded DNA-binding protein on ssDNA.

Single-stranded DNA-binding proteins (SSBs) interact with single-stranded DNA (ssDNA) to form filamentous structures with various degrees of cooperativity, as a result of intermolecular interactions between neighboring SSB subunits on ssDNA. However, it is still challenging to perform structural studies on SSB-ssDNA filaments at high resolution using the most studied SSB models, largely due to the intrinsic flexibility of these nucleoprotein complexes. In this study, HaLEF-3, an SSB protein from Helicoverpa armigera nucleopolyhedrovirus, was used for in vitro assembly of SSB-ssDNA filaments, which were structurally studied at atomic resolution using cryo-electron microscopy. Combined with the crystal structure of ssDNA-free HaLEF-3 octamers, our results revealed that the three-dimensional rearrangement of HaLEF-3 induced by an internal hinge-bending movement is essential for the formation of helical SSB-ssDNA complexes, while the contacting interface between adjacent HaLEF-3 subunits remains basically intact. We proposed a local cooperative SSB-ssDNA binding model, in which, triggered by exposure to oligonucleotides, HaLEF-3 molecules undergo ring-to-helix transition to initiate continuous SSB-SSB interactions along ssDNA. Unique structural features revealed by the assembly of HaLEF-3 on ssDNA suggest that HaLEF-3 may represent a new class of SSB.

From Offline to Online: Understanding Chinese Single Mothers' Uncertainty Management in Interpersonal and Online Contexts.

Divorced and unwed single motherhood is heavily stigmatized in Chinese cultural context, preventing Chinese single mothers from actively seeking the information and support needed and negatively impacting their wellbeing. Drawing on the theory of motivated information management (TMIM), this study tested how perceived stigma and cultural norms influenced Chinese single mothers' search for information and social support from families, friends as well as from online communities. Using two-wave data collected from 226 single mothers, findings support the utility of the TMIM in explaining information management and support seeking behaviors and contribute to situating the TMIM process within larger socio-cultural contexts. Practical implications regarding how to facilitate more effective uncertainty management and enhance Chinese single mothers' wellbeing in interpersonal vs. online contexts are discussed.

Artificial Intelligence Algorithm-Based Differential Diagnosis of Crohn's Disease and Ulcerative Colitis by CT Image.

The aim of this study was to investigate the effect of low-dose CT enterography (CTE) based on modified guided image filtering (GIF) algorithm in the differential diagnosis of ulcerative colitis (UC) and Crohn's disease (CD). Methods. One hundred and twenty patients with suspected diagnosis of IBD were studied. They were randomly divided into control group (routine CT examination) and observation group (low-dose CTE examination based on improved GIF algorithm), with 60 cases in each group. Comprehensive diagnosis was used as the standard to assess the diagnostic effect. Results. (1) The peak signal-to-noise ratio (PSNR) (26.02 dB) and structural similarity (SSIM) (0.8921) of the algorithm were higher than those of GIF (17.22 dB/0.8491), weighted guided image filtering (WGIF) (23.78 dB/0.8489), and gradient domain guided image filtering (GGIF) (23.77 dB/0.7567) (P < 0.05); (2) the diagnostic sensitivity (91.49%), specificity (92.31%), accuracy (91.67%), positive predictive value (97.73%), and negative predictive value (75%) of the observation group were higher than those of the control group (P < 0.05); the sensitivity and specificity of CTE in the diagnosis of UD and CD were 96.77% and 81.25% and 98.33% and 93.33%, respectively (P < 0.05); there were significant differences in symmetrical intestinal wall thickening and smooth serosal surface between UD and CD (P < 0.05). Conclusion. (1) The improved GIF algorithm has a more effective application value in the denoising processing of low-dose CT images and can better improve the image quality; (2) the accuracy of CTE in the diagnosis of IBD is high, and CTE is of great value in the differential diagnosis of UD and CD.

AMP-activated protein kinase mediates lipopolysaccharide-induced proinflammatory responses and elevated bone resorption in differentiated osteoclasts.

Systemic and intracellular metabolic states are critical factors affecting immune cell functions. The metabolic regulator AMP-activated protein kinase (AMPK) senses AMP levels and mediates cellular responses to energy-restrained conditions. The ubiquitously expressed AMPK participates in various biological functions in numerous cell types, including innate immune cell macrophages and osteoclasts, which are their specialized derivatives in bone tissues. Previous studies have demonstrated that the activation of AMPK promotes macrophage polarization toward anti-inflammatory M2 status. Additionally, AMPK acts as a negative regulator of osteoclastogenesis, and upregulation of AMPK disrupts the differentiation of osteoclasts. However, the regulation and roles of AMPK in differentiated osteoclasts have not been characterized. Here, we report that inflammatory stimuli-regulated-AMPK activation of differentiated and undifferentiated osteoclasts in opposite ways. Lipopolysaccharide (LPS) inhibited the phosphorylation of AMPK in macrophages and undifferentiated osteoclasts, but it activated AMPK in differentiated osteoclasts. Inactivating AMPK decreased cellular responses against the activation of toll-like receptor signaling, including the transcriptional activation of proinflammatory cytokines and the bone resorption genes TRAP, and MMP9. The elevation of bone resorption by LPS stimulation was disrupted by AMPK inhibitor, indicating the pivotal roles of AMPK in inflammation-induced activities in differentiated osteoclasts. The AMPK activator metformin did not increase proinflammatory responses, possibly because other factors are also required for this regulation. Notably, changing the activation status of AMPK did not alter the expression levels of bone resorption genes in unstimulated osteoclasts, indicating the essential roles of AMPK in cellular responses to inflammatory stimuli but not in the maintenance of basal levels. Unlike its M2-polarizing roles in macrophages, AMPK was not responsive to the M2 stimulus of interleukin-4. Our observations revealed differences in the cellular properties of macrophages and osteoclasts as well as the complexity of regulatory mechanisms for osteoclast functions.

Targeting EGFR and Monitoring Tumorigenesis of Human Lung Cancer Cells In Vitro and In Vivo Using Nanodiamond-Conjugated Specific EGFR Antibody.

Nanoprobes provide advantages for real-time monitoring of tumor markers and tumorigenesis during cancer progression and development. Epidermal growth factor receptor (EGFR) is a key protein that plays crucial roles for tumorigenesis and cancer therapy of lung cancers. Here, we show a carbon-based nanoprobe, nanodiamond (ND), which can be applied for targeting EGFR and monitoring tumorigenesis of human lung cancer cells in vitro and in vivo. The optimal fluorescent intensities of ND particles were observed in the human lung cancer cells and nude mice under in vivo imaging system. The fluorescence signal of ND particles can be real-time detected in the xenografted human lung tumor formation of nude mice. Moreover, the ND-conjugated specific EGFR antibody cetuximab (Cet) can track the location and distribution of EGFR proteins of lung cancer cells in vitro and in vivo. ND-Cet treatment increased cellular uptake ability of nanocomposites in the EGFR-expressed cells but not in the EGFR-negative lung cancer cells. Interestingly, single ND-Cet complex can be directly observed on the protein G bead by immunoprecipitation and confocal microscopy. Besides, the EGFR proteins were transported to lysosomes for degradation. Together, this study demonstrates that ND-conjugated Cet can apply for targeting EGFR and monitoring tumorigenesis during lung cancer progression and therapy.

A novel EGFR inhibitor suppresses survivin expression and tumor growth in human gefitinib-resistant EGFR-wild type and -T790M non-small cell lung cancer.

Tyrosine kinase inhibitors of epidermal growth factor receptor (EGFR-TKIs) are currently used therapy for non-small cell lung cancer (NSCLC) patients; however, drug resistance during cancer treatment is a critical problem. Survivin is an anti-apoptosis protein, which promotes cell proliferation and tumor growth that highly expressed in various human cancers. Here, we show a novel synthetic compound derived from gefitinib, do-decyl-4-(4-(3-(4-(3-chloro-4-fluorophenylamino)-7-methoxyquinazolin-6-yloxy)propyl) piper-azin-1-yl)-4-oxobutanoate, which is named as SP101 that inhibits survivin expression and tumor growth in both the EGFR-wild type and -T790M of NSCLC. SP101 blocked EGFR kinase activity and induced apoptosis in the A549 (EGFR-wild type) and H1975 (EGFR-T790M) lung cancer cells. SP101 reduced survivin proteins and increased active caspase 3 for inducing apoptosis. Ectopic expression of survivin by a survivin-expressed vector attenuated the SP101-induced cell death in lung cancer cells. Moreover, SP101 inhibited the gefitinib-resistant tumor growth in the xenograft human H1975 lung tumors of nude mice. SP101 substantially reduced survivin proteins but conversely elicited active caspase 3 proteins in tumor tissues. Besides, SP101 exerted anticancer abilities in the gefitinib resistant cancer cells separated from pleural effusion of a clinical lung cancer patient. Consistently, SP101 decreased the survivin proteins and the patient-derived xenografted lung tumor growth in nude mice. Anti-tumor ability of SP101 was also confirmed in the murine lung cancer model harboring EGFR T790M-L858R. Together, SP101 is a new EGFR inhibitor with inhibiting survivin that can be developed for treating EGFR wild-type and EGFR-mutational gefitinib-resistance in human lung cancers.

Influential factors of surgical decompression for ulnar nerve neuropathy in Guyon's canal.

BACKGROUND: Guyon's canal syndrome is nerve compressive pathology which can lead to sensory and/or motor function deficits. This problem is usually difficult to distinguish from cubital tunnel syndrome and relatively less common than cubital tunnel syndrome. This study evaluated the functional results and patient-reported outcomes following decompression of the ulnar nerve in Guyon's canal. METHODS: Patients who were diagnosed with Guyon's canal syndrome confirmed by electrodiagnostic studies and underwent nerve decompression surgery were included in this study. The functional improvement by examining the Froment's sign, Wartenberg's sign, static two-point discrimination, and Semmes Weinstein monofilament examination as physical examination scores was evaluated. The visual analogue scale of satisfaction and the disabilities of the arm, shoulder, and hand questionnaire were used for the postoperative patient-reported outcome evaluation. RESULTS: From 2003 to 2019, 38 cases had been enrolled with a mean age of 53 years, ranging from 19 to 85 years. There were seven patients with comorbidity of diabetes mellitus and 28 patients who received additional neurolysis combined with the Guyon's release procedure. There were 19 patients with a good response to surgery and 10 patients with a poor surgical outcome due to persistent paresthesia or weakness. After statistical analysis, it was revealed that several influential factors could have been related to a compromised functional outcome, including a symptom duration of more than 3 months, combination with additional neurolysis of ipsilateral extremity, and/or comorbidity with diabetes mellitus. CONCLUSION: It was concluded that promising functional outcomes after surgical release of ulnar neuropathy in Guyon's canal could be achieved if the patients did not need additional neurolysis or the symptom duration was within 3 months.

Adipose-Derived Mesenchymal Stem Cells From a Hypoxic Culture Improve Neuronal Differentiation and Nerve Repair.

Hypoxic expansion has been demonstrated to enhance in vitro neuronal differentiation of bone-marrow derived mesenchymal stem cells (BMSCs). Whether adipose-derived mesenchymal stem cells (ADSCs) increase their neuronal differentiation potential following hypoxic expansion has been examined in the study. Real-time quantitative reverse transcription-polymerase chain reaction and immunofluorescence staining were employed to detect the expression of neuronal markers and compare the differentiation efficiency of hypoxic and normoxic ADSCs. A sciatic nerve injury animal model was used to analyze the gastrocnemius muscle weights as the outcomes of hypoxic and normoxic ADSC treatments, and sections of the regenerated nerve fibers taken from the conduits were analyzed by histological staining and immunohistochemical staining. Comparisons of the treatment effects of ADSCs and BMSCs following hypoxic expansion were also conducted in vitro and in vivo. Hypoxic expansion prior to the differentiation procedure promoted the expression of the neuronal markers in ADSC differentiated neuron-like cells. Moreover, the conduit connecting the sciatic nerve gap injected with hypoxic ADSCs showed the highest recovery rate of the gastrocnemius muscle weights in the animal model, suggesting a conceivable treatment for hypoxic ADSCs. The percentages of the regenerated myelinated fibers from the hypoxic ADSCs detected by toluidine blue staining and myelin basic protein (MBP) immunostaining were higher than those of the normoxic ones. On the other hand, hypoxic expansion increased the neuronal differentiation potential of ADSCs compared with that of the hypoxic BMSCs in vitro. The outcomes of animals treated with hypoxic ADSCs and hypoxic BMSCs showed similar results, confirming that hypoxic expansion enhances the neuronal differentiation potential of ADSCs in vitro and improves in vivo therapeutic potential.

Interactions among Actual Uncertainty, Desired Uncertainty, and Uncertainty Discrepancy on Anxiety and Information Seeking.

This study investigated the role of uncertainty in information management processes by integrating insights from uncertainty management theory and the theory of motivated information management. Specifically, we examined the extent to which uncertainty appraisals moderated the effects of uncertainty on anxiety and information seeking about family health history (FHH) from spouses. Data from 626 married individuals suggested that desired uncertainty moderated uncertainty's effect on anxiety such that uncertainty led to more anxiety when individuals wanted to be more certain. Uncertainty also exerted stronger effects on anxiety and information seeking when one's actual uncertainty was low. Efficacy remained a predictor of information seeking, consistent with the literature. Findings offer theoretical implications about the interaction effects among different conceptualizations of uncertainty (i.e., actual, desired, and uncertainty discrepancy) and practical applications for encouraging information seeking about FHH.

Uncertainty Management in Sexual Communication: Testing the Moderating Role of Marital Quality, Relational Closeness, and Communal Coping.

Romantic partners' communication about sex has been shown to enhance marital satisfaction and well-being, yet is often associated with high levels of uncertainty due to the challenging and potentially face-threatening topics involved in such discussion. While much literature focuses on sexual health information seeking, relational partners' uncertainty management related to sexual satisfaction has not been examined. This study focused on married couples' discussion of sexual satisfaction, tested the theory of motivated information management (TMIM; Afifi & Weiner, 2004) within this context, and examined relational moderators that could influence relational partners' communication about sexual satisfaction. Data from 248 married participants suggested that TMIM effectively predicted five different information management strategies, including direct and indirect information seeking, avoidance, cognitive reappraisal, and disclosure, although the processes through which uncertainty discrepancy influenced information management differed depending on the information management strategy. Furthermore, results indicated relational factors such as marital quality, relational closeness, and communal coping moderated TMIM paths in distinct ways. Theoretical and practical implications for relational partners' uncertainty management about sexual satisfaction are discussed.

Extending Communication Campaign from Health to Peacebuilding: A Locally Driven Communication Campaign Approach as Part of A Peacebuilding Initiative in Liberia.

A vast amount of literature exists on communication campaign design, implementation, and evaluation, especially in health contexts. Despite recent calls to center the role of local citizens in designing and implementing campaign initiatives, limited literature exists on how to integrate local expertise with the expertise of those external to the local context. Drawing on health communication campaigns literature, peacebuilding literature, and our experiences collaborating on a multi-year communication campaign for peacebuilding and health promotion in Liberia, West Africa, we advance a locally driven communication campaign approach that integrates expertise of local citizens, campaign researchers, and campaign practitioners. We make a critical linkage between health communication and peacebuilding to discuss implications about how a locally driven communication campaign approach can contribute to communication campaigns in general, as well as health and peacebuilding specifically.

Targeting EGFR of triple-negative breast cancer enhances the therapeutic efficacy of paclitaxel- and cetuximab-conjugated nanodiamond nanocomposite.

Breast cancer is the most common malignancy and a leading cause of cancer-related mortality among women worldwide. Triple-negative breast cancer (TNBC) is characterized by the lack of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2). However, epidermal growth factor receptor (EGFR) is highly expressed in most of the TNBCs, which may provide a potential target for EGFR targeting therapy. Nanodiamond (ND) is a carbon-based nanomaterial with several advantages, including fluorescence emission, biocompatibility, and drug delivery applications. In this study, we designed a nanocomposite by using ND conjugated with paclitaxel (PTX) and cetuximab (Cet) for targeting therapy on the EGFR-positive TNBC cells. ND-PTX inhibited cell viability and induced mitotic catastrophe in various human breast cancer cell lines (MDA-MB-231, MCF-7, and BT474); in contrast, ND alone did not induce cell death. ND-PTX inhibited the xenografted human breast tumors in nude mice. We further investigated ND-PTX-Cet drug efficacy on the TNBC of MDA-MB-231 breast cancer cells. ND-PTX-Cet could specifically bind to EGFR and enhanced the anticancer effects including drug uptake levels, mitotic catastrophe, and apoptosis in the EGFR-expressed MDA-MB-231 cells but not in the EGFR-negative MCF-7 cells. In addition, ND-PTX-Cet increased the protein levels of active caspase-3 and phospho-histone H3 (Ser10). Furthermore, ND-PTX-Cet showed more effective on the reduction of TNBC tumor volume by comparison with ND-PTX. Taken together, these results demonstrated that ND-PTX-Cet nanocomposite enhanced mitotic catastrophe and apoptosis by targeting EGFR of TNBC cells, which can provide a feasible strategy for TNBC therapy. STATEMENT OF SIGNIFICANCE: Current TNBC treatment is ineffective against the survival rate of TNBC patients. Therefore, the development of new treatment strategies for TNBC patients is urgently needed. Here, we have designed a nanocomposite by targeting on the EGFR of TNBC to enhance therapeutic efficacy by ND-conjugated PTX and Cet (ND-PTX-Cet). Interestingly, we found that the co-delivery of Cet and PTX by ND enhanced the apoptosis, mitotic catastrophe and tumor inhibition in the EGFR-expressed TNBC in vitro and in vivo. Consequently, this nanocomposite ND-PTX-Cet can be applied for targeting EGFR of human TNBC therapy.

Co-delivery of paclitaxel and cetuximab by nanodiamond enhances mitotic catastrophe and tumor inhibition.

The poor intracellular uptake and non-specific binding of anticancer drugs into cancer cells are the bottlenecks in cancer therapy. Nanocarrier platforms provide the opportunities to improve the drug efficacy. Here we show a carbon-based nanomaterial nanodiamond (ND) that carried paclitaxel (PTX), a microtubule inhibitor, and cetuximab (Cet), a specific monoclonal antibody against epidermal growth factor receptor (EGFR), inducing mitotic catastrophe and tumor inhibition in human colorectal cancer (CRC). ND-PTX blocked the mitotic progression, chromosomal separation, and induced apoptosis in the CRC cells; however, NDs did not induce these effects. Conjugation of ND-PTX with Cet (ND-PTX-Cet) was specifically binding to the EGFR-positive CRC cells and enhanced the mitotic catastrophe and apoptosis induction. Besides, ND-PTX-Cet markedly decreased tumor size in the xenograft EGFR-expressed human CRC tumors of nude mice. Moreover, ND-PTX-Cet induced the mitotic marker protein phospho-histone 3 (Ser10) and apoptotic protein active-caspase 3 for mitotic catastrophe and apoptosis. Taken together, this study demonstrated that the co-delivery of PTX and Cet by ND enhanced the effects of mitotic catastrophe and apoptosis in vitro and in vivo, which may be applied in the human CRC therapy.

Synthesis and biological assay of erlotinib analogues and BSA-conjugated erlotinib analogue.

A series of erlotinib analogues that have structural modification at 6,7-alkoxyl positions is efficiently synthesized. The in vitro anti-tumor activity of synthesized compounds is studied in two non-small cell lung cancer (NSCLC) cell lines (A549 and H1975). Among the synthesized compounds, the iodo compound 6 (ETN-6) exhibits higher anti-cancer activity compared to erlotinib. An efficient method is developed for the conjugation of erlotinib analogue-4, alcohol compound, with protein, bovine serum albumin (BSA), via succinic acid linker. The in vitro anti-tumor activity of the protein attached erlotinib analogue, 8 (ETN-4-Suc-BSA), showed stronger inhibitory activity in both A549 and H1975 NSCLC cell lines.