Reenvisioning Traditional to Regenerative Therapeutic Advances in Managing Nonalcoholic Fatty Liver Disease in Diabetes Mellitus.

Reports indicate the increasing prevalence of liver disorders in diabetes mellitus (DM) patients. Clinically, it has also been revealed that the existence of nonalcoholic fatty liver disease (NAFLD) enhances the incidence of type 2 diabetes mellitus (T2DM), while T2DM exacerbates NAFLD to extremely severe forms of steatohepatitis, cirrhosis, and hepatocellular carcinoma. This implies the coexistence and bidirectional nature of NAFLD and T2DM, which function synergistically to drive adverse consequences in clinical practice. For treatment of such comorbid state, though the existing practices such as lifestyle management, traditional Chinese medicines (TCM), and pharmaceuticals have offered somewhat relief, the debate continues about the optimal therapeutic impacts. Recent developments in the field of tissue engineering have led to a renewed interest in novel biomaterial alternatives such as stem cells. This might be attributable to their differentiation potential towards hepatic and pancreatic lineage. These cellular therapies could be further complemented by platelet-derived biomaterials, TCM formulations, or any specific drug. Based on these abovementioned approaches, we aimed to comprehensively analyze various preclinical and clinical studies from traditional to regenerative therapeutic approaches in managing concomitant NAFLD and T2DM.

Psychometric properties of the Chinese mainland version of the Palliative Care Spiritual Care Competency Scale (PCSCCS-M) in nursing: a cross-sectional study.

BACKGROUND: Spiritual care competencies are among the primary professional skills that enable best practices in nursing. Assessing these competencies and identifying those that are insufficient are important tasks. The traditional Chinese version of the Palliative Care Spiritual Care Competency Scale (PCSCCS) used in Taiwan is a well-validated tool to measure palliative caregivers' competencies in providing spiritual care. However, whether this scale is valid and reliable for use with nurses in other health-care contexts is unknown. The purpose of this study is to determine this version's validity and reliability for use with nurses in mainland China. METHODS: The PCSCCS was first converted into a simplified Chinese version (PCSCCS-M) from the traditional Chinese version used in Taiwan such that mainland nurses could read and understand it easily. Then, the validity and reliability of the PCSCCS-M was evaluated with 400 Chinese nurses recruited using convenience sampling from three university-affiliated comprehensive hospitals, two cancer hospitals, one psychiatric hospital, two traditional Chinese medicine hospitals, one marital and child service care center, and one community health service center. Concurrent validity was assessed using Pearson's correlation coefficients of the PCSCCS-M and the Chinese version of the Spiritual Care-Giving Scale (C-SCGS). Exploratory factor analysis (EFA) was performed to determine the construct validity. Confirmatory factor analysis (CFA) was conducted using another sample of 351 nurses to verify the quality of the factor structures of the PCSCCS-M. An internal consistency test based on Cronbach's alpha coefficient and a stability test based on the Guttman split-half coefficient were also conducted. RESULTS: Useful data were obtained from 356 participants (response rate: 89%). EFA confirmed a three-dimensional structure of the scale after one item was deleted, and the three factors explained 63.839% of the total variance. Cronbach's alpha coefficients of the three subscales were 0.811, 0.889 and 0.896, and the Guttman split-half coefficient for the PCSCCS-M was 0.862. Modified CFA indicated a well-fitting model. The correlation between the PCSCCS-M and C-SCGS was 0.340 (p < 0.01). CONCLUSIONS: The PCSCCS-M is a brief, easy-to-understand, and psychometrically sound measurement tool to evaluate spiritual care competencies in nurses from mainland China.

Preclinical investigation of ibrutinib, a Bruton's kinase tyrosine (Btk) inhibitor, in suppressing glioma tumorigenesis and stem cell phenotypes.

Standard interventions for glioma include surgery, radiation and chemotherapies but the prognosis for malignant cases such as glioblastoma multiforme remain grim. Even with targeted therapeutic agent, bevacitumab, malignant glioma often develops resistance and recurrence. Thus, developing alternative interventions (therapeutic targets, biomarkers) is urgently required. Bruton's tyrosine kinase (Btk) has been long implicated in B cell malignancies but surprisingly it has recently been shown to also play a tumorigenic role in solid tumors such as ovarian and prostate cancer. Bioinformatics data indicates that Btk is significantly higher in clinical glioma samples as compared to normal brain cells and Btk expression level is associated with stage progression. This prompts us to investigate the potential role of Btk as a therapeutic target for glioma. Here, we demonstrate Btk expression is associated with GBM tumorigenesis. Down-regulation of Btk in GBM cell lines showed a significantly reduced abilities in colony formation, migration and GBM sphere-forming potential. Mechanistically, Btk-silenced cells showed a concomitant reduction in the expression of CD133 and Akt/mTOR signaling. In parallel, Ibrutinib (a Btk inhibitor) treatment led to a similar anti-tumorigenic response. Using xenograft mouse model, tumorigenesis was significantly reduced in Btk-silenced or ibrutinib-treated mice as compared to control counterparts. Finally, our glioma tissue microarray analysis indicated a higher Btk staining in the malignant tumors than less malignant and normal brain tissues. Collectively, Btk may represent a novel therapeutic target for glioma and ibrunitib may be used as an adjuvant treatment for malignant GBM.

Phase 2 study of combined sorafenib and radiation therapy in patients with advanced hepatocellular carcinoma.

PURPOSE: This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). METHODS AND MATERIALS: Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. RESULTS: Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal. CONCLUSIONS: When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation.

BlueBerry Isolate, Pterostilbene, Functions as a Potential Anticancer Stem Cell Agent in Suppressing Irradiation-Mediated Enrichment of Hepatoma Stem Cells.

For many malignancies, radiation therapy remains the second option only to surgery in terms of its curative potential. However, radiation-induced tumor cell death is limited by a number of factors, including the adverse response of the tumor microenvironment to the treatment and either intrinsic or acquired mechanisms of evasive resistance, and the existence of cancer stem cells (CSCs). In this study, we demonstrated that using different doses of irradiation led to the enrichment of CD133(+) Mahlavu cells using flow cytometric method. Subsequently, CD133(+) Mahlavu cells enriched by irradiation were characterized for their stemness gene expression, self-renewal, migration/invasion abilities, and radiation resistance. Having established irradiation-enriched CD133(+) Mahlavu cells with CSC properties, we evaluated a phytochemical, pterostilbene (PT), found abundantly in blueberries, against irradiation-enriched CSCs. It was shown that PT treatment dose-dependently reduced the enrichment of CD133(+) Mahlavu cells upon irradiation; PT treatment also prevented tumor sphere formation, reduced stemness gene expression, and suppressed invasion and migration abilities as well as increasing apoptosis of CD133(+) Mahlavu CSCs. Based on our experimental data, pterostilbene could be used to prevent the enrichment of CD133(+) hepatoma CSCs and should be considered for future clinical testing as a combined agent for HCC patients.

Effectiveness of 3-week intervention of Shi Quan Da Bu Tang for alleviating hematotoxicity among patients with breast carcinoma receiving chemotherapy.

PURPOSE: Although Shi Quan Da Bu Tang (SQDBT) has been used to treat cancer patients clinically, very few studies evaluating the effectiveness of SQDBT using objective indicators have been published. The study objectives were to examine the effectiveness of SQDBT for alleviating hematotoxicity, as indicated by white blood cell (WBC) counts and hemoglobin (Hb) levels, among patients with breast carcinoma receiving chemotherapy. METHODS: The authors identified patients with breast carcinoma who received chemotherapy in a teaching hospital in Taipei in 2008 through a chart review process. Only patients with initial WBC counts of <4000/µL were included. The case group was composed of 47 chemotherapy courses treated with SQDBT, whereas the comparison group included 257 courses without SQDBT. The complete blood count test was done before start of a chemotherapy course and 1 week after chemotherapeutic drugs were given. RESULTS: Age, cancer stage, cancer status, use of granulocyte colony-stimulating factor, and chemotherapy drugs were controlled in the model. Patients who took SQDBT had significantly increased WBC counts, especially neutrophils, and Hb after chemotherapy (adjusted ß = 1202.51, 95% confidence interval [CI] 440.45-1964.57 for WBC; ß = 834.83, 95% CI = 197.35-1472.31 for neutrophils; ß = 0.34, 95% CI = 0.05-0.63 for Hb). There were no significant differences in tumor markers CEA and CA153 between patients given SQDBT or not after chemotherapy. CONCLUSION: SQDBT is effective in alleviating hematotoxicity among patients with breast carcinoma receiving chemotherapy, without affecting the presentation of tumor markers in the short term. More study is needed to determine long-term outcomes such as recurrence and survival.

Is the blood donated by habitual nut quid chewers suitable for use in transfusion?

BACKGROUND/PURPOSE: Betel quid (BQ) chewing is a popular oral masticatory activity, and there are approximately 600 million BQ chewers worldwide. Although chewing BQ has been linked to the patho-genesis of oral cancer, leukoplakia, and oral submucous fibrosis. The question whether the mixed constituents present in areca nut, which may exert cytotoxic effects on red blood cells (RBCs), has never been addressed. METHODS: Heparinized blood specimens were obtained with informed consent from healthy laboratory personnel. RBCs were separated with the standard procedure and adjusted to 10% hematocrit with PBS. Various concentrations of areca nut extract (ANE; 100-800 microg/mL) were added to these RBC preparations and incubated at 37 degrees C for 4 hours. Two portions (0.4 mL each) of the incubated RBCs were then used for measuring osmotic deformability index and for observing RBC morphology with scanning electron microscopy. The remaining RBCs were used for determining membrane sulfhydryl groups and protein profiles by sodium dodecyl sulfate polyacrylamide gel electrophoresis. RESULTS: Blood incubated with various concentrations of ANE showed concentration-dependent decreases in osmotic deformability index and membrane sulfhydryl groups. Membrane protein profiles revealed a significant loss of the band 3 fraction, with the concomitant appearance of several new protein bands in the electropheretogram. Finally, drastic morphological changes of ANE-treated RBCs were observed. CONCLUSION: We suggest that to assure the quality of transfusion, the blood donated by a habitual BQ chewer should be used with caution because of its possible contamination with areca nut ingredients that may be cytotoxic to RBCs.

The lived experiences of spiritual suffering and the healing process among Taiwanese patients with terminal cancer.

AIMS AND OBJECTIVES: The purposes of this study were to explore the lived experiences of spiritual suffering and the change mechanism in healing processes among Taiwanese patients with terminal cancer. METHODS: The approach to this study was phenomenological-hermeneutic. Twenty-one patients with terminal cancer were invited to participate in a semi-structured interview that dealt with their experiences of spiritual suffering and the healing process. This study was conducted in the inpatient unit of the oncology department in two general hospitals. The interviews were recorded, transcribed and later analysed using the approach of narrative analysis. RESULTS: According to the results of case narration, the causes of spiritual suffering included cancer, known as a life-threatening illness, physical pain, treatment complications, uncertain illness progression, disability problems and lack of support. Patients turned to internal resources (including regarding the suffering as a life challenge, volunteering to help other cancer patients and searching for life wisdoms) and external resources (including peer support groups and family support) as they endured spiritual suffering. Taiwanese patients turned to Eastern and Western philosophies of Taoism, Confucianism, Buddhism and Christianity as methods to interpret their spiritual suffering. CONCLUSION: Patients' positive views of misfortune because of cancer and sufficient social supports were the key elements of the healing process to alleviate spiritual suffering. RELEVANCE TO CLINICAL PRACTICE: Nurses who learn to participate in suffering assessment are better able to understand spiritual needs of cancer patients. Cancer patients' views on the change mechanism in healing processes could provide essential information for nurses in developing an effective intervention programme. If nurses consider cultural factors that shape patients' experiences of spiritual suffering and the healing process, they could learn how to meet the needs of patients better from different cultural backgrounds.

Development of probe-based ultraweak chemiluminescence technique for the detection of a panel of four oxygen-derived free radicals and their applications in the assessment of radical-scavenging abilities of extracts and purified compounds from food and herbal preparations.

We report here the development of a probe-based ultraweak chemiluminescence (uwCL) method capable of detecting a panel of four oxygen-derived free radicals (ODFRs) including superoxide (O2-), hydrogen peroxide (H2O2), hydroxyl radical (*OH), and peroxyl radical (ROO*) using different probes specific for these radicals performed by the same uwCL analyzer. The selected radical-generating systems and their corresponding uwCL-probing emitters were validated. These ODFR-detecting systems were subsequently utilized by us to assess the radical-scavenging ability (RSA) of a variety of extracts and purified constituents derived from foods and herbal preparations. Our approach for assessing RSA for these constituents is based on the suppression of uwCL generated by each ODFR, and the degrees of inhibition have been shown to be dose-dependent. For this reason, the estimation of IC50 for each testing compound can be obtained from the curve constructed based on the percent of inhibitions of uwCL versus the concentrations of the compound tested. To illustrate the practical applications of our devised methodology, data for comparative studies of RSA activities of fermented extracts of Cordeceps sinensis, purified methylgallate isolated from Toona sinesis, resveratrol purified from grape seeds, plus epimedin C from the aerial part of the Epimedium plant (yinyanghuo) are to be presented.