Strengthening teachers' abilities to implement a vision health program in Taiwanese schools.

We designed a school-based, nationwide program called the 'New Era in Eye Health' to strengthen teacher training and to examine whether the existence of a government vision care policy influenced teachers' vision care knowledge and students' behavior. Baseline data and 3-month follow-up data were compared. A random sample of teachers (n = 660) from school vision health clusters in 22 cities/counties in Taiwan were invited to participate in our study and 436 agreed to participate (response rate = 66.1%). The mean age of participant teachers was 41.2 years, while the length of service mean was 14.6 years. For monitoring teacher outcomes, five cities/counties were selected as the intensely monitored group based on certain criteria. Sunlight diaries (n = 5434) were distributed and 3342 (61.5%) were returned. Teachers showed significant improvements in knowledge and behavior on the school vision health questionnaire. At the 3-month follow-up, the number of recesses as recorded by students' 'sunlight diary' increased. When teachers had better knowledge and behavior, recesses also increased. This study provided valuable insights to guide dissemination efforts for school vision health interventions and to help teachers implement research into their school vision health activities.

Improved Search for a Light Sterile Neutrino with the Full Configuration of the Daya Bay Experiment.

This Letter reports an improved search for light sterile neutrino mixing in the electron antineutrino disappearance channel with the full configuration of the Daya Bay Reactor Neutrino Experiment. With an additional 404 days of data collected in eight antineutrino detectors, this search benefits from 3.6 times the statistics available to the previous publication, as well as from improvements in energy calibration and background reduction. A relative comparison of the rate and energy spectrum of reactor antineutrinos in the three experimental halls yields no evidence of sterile neutrino mixing in the 2×10^{-4}≲|Δm_{41}^{2}|≲0.3 eV^{2} mass range. The resulting limits on sin^{2}2θ_{14} are improved by approx imately a factor of 2 over previous results and constitute the most stringent constraints to date in the |Δm_{41}^{2}|≲0.2 eV^{2} region.

Limits on Active to Sterile Neutrino Oscillations from Disappearance Searches in the MINOS, Daya Bay, and Bugey-3 Experiments.

Searches for a light sterile neutrino have been performed independently by the MINOS and the Daya Bay experiments using the muon (anti)neutrino and electron antineutrino disappearance channels, respectively. In this Letter, results from both experiments are combined with those from the Bugey-3 reactor neutrino experiment to constrain oscillations into light sterile neutrinos. The three experiments are sensitive to complementary regions of parameter space, enabling the combined analysis to probe regions allowed by the Liquid Scintillator Neutrino Detector (LSND) and MiniBooNE experiments in a minimally extended four-neutrino flavor framework. Stringent limits on sin^{2}2θ_{µe} are set over 6 orders of magnitude in the sterile mass-squared splitting Δm_{41}^{2}. The sterile-neutrino mixing phase space allowed by the LSND and MiniBooNE experiments is excluded for Δm_{41}^{2}<0.8 eV^{2} at 95% CL_{s}.

Measurement of the Reactor Antineutrino Flux and Spectrum at Daya Bay.

This Letter reports a measurement of the flux and energy spectrum of electron antineutrinos from six 2.9 GWth nuclear reactors with six detectors deployed in two near (effective baselines 512 and 561 m) and one far (1579 m) underground experimental halls in the Daya Bay experiment. Using 217 days of data, 296 721 and 41 589 inverse ß decay (IBD) candidates were detected in the near and far halls, respectively. The measured IBD yield is (1.55±0.04) ×10(-18) cm(2) GW(-1) day(-1) or (5.92±0.14) ×10(-43) cm(2) fission(-1). This flux measurement is consistent with previous short-baseline reactor antineutrino experiments and is 0.946±0.022 (0.991±0.023) relative to the flux predicted with the Huber-Mueller (ILL-Vogel) fissile antineutrino model. The measured IBD positron energy spectrum deviates from both spectral predictions by more than 2σ over the full energy range with a local significance of up to ∼4σ between 4-6 MeV. A reactor antineutrino spectrum of IBD reactions is extracted from the measured positron energy spectrum for model-independent predictions.

New measurement of antineutrino oscillation with the full detector configuration at Daya Bay.

We report a new measurement of electron antineutrino disappearance using the fully constructed Daya Bay Reactor Neutrino Experiment. The final two of eight antineutrino detectors were installed in the summer of 2012. Including the 404 days of data collected from October 2012 to November 2013 resulted in a total exposure of 6.9×10^{5} GW_{th} ton days, a 3.6 times increase over our previous results. Improvements in energy calibration limited variations between detectors to 0.2%. Removal of six ^{241}Am-^{13}C radioactive calibration sources reduced the background by a factor of 2 for the detectors in the experimental hall furthest from the reactors. Direct prediction of the antineutrino signal in the far detectors based on the measurements in the near detectors explicitly minimized the dependence of the measurement on models of reactor antineutrino emission. The uncertainties in our estimates of sin^{2}2θ_{13} and |Δm_{ee}^{2}| were halved as a result of these improvements. An analysis of the relative antineutrino rates and energy spectra between detectors gave sin^{2}2θ_{13}=0.084±0.005 and |Δm_{ee}^{2}|=(2.42±0.11)×10^{-3} eV^{2} in the three-neutrino framework.

Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression.

Ketamine produces rapid antidepressant effects in treatment-resistant depression (TRD), but the magnitude of response varies considerably between individual patients. Brain-derived neurotrophic factor (BDNF) has been investigated as a biomarker of treatment response in depression and has been implicated in the mechanism of action of ketamine. We evaluated plasma BDNF and associations with symptoms in 22 patients with TRD enrolled in a randomized controlled trial of ketamine compared to an anaesthetic control (midazolam). Ketamine significantly increased plasma BDNF levels in responders compared to non-responders 240 min post-infusion, and Montgomery-Åsberg Depression Rating Scale (MADRS) scores were negatively correlated with BDNF (r=-0.701, p = 0.008). Plasma BDNF levels at 240 min post-infusion were highly negatively associated with MADRS scores at 240 min (r = -0.897, p=.002), 24 h (r = -0.791, p = 0.038), 48 h (r = -0.944, p = 0.001) and 72 h (r = -0.977, p = 0.010). No associations with BDNF were found for patients receiving midazolam. These data support plasma BDNF as a peripheral biomarker relevant to ketamine antidepressant response.

Search for a light sterile neutrino at Daya Bay.

A search for light sterile neutrino mixing was performed with the first 217 days of data from the Daya Bay Reactor Antineutrino Experiment. The experiment's unique configuration of multiple baselines from six 2.9 GW(th) nuclear reactors to six antineutrino detectors deployed in two near (effective baselines 512 m and 561 m) and one far (1579 m) underground experimental halls makes it possible to test for oscillations to a fourth (sterile) neutrino in the 10(-3) eV(2)<|Δm(41)(2) |< 0.3 eV(2) range. The relative spectral distortion due to the disappearance of electron antineutrinos was found to be consistent with that of the three-flavor oscillation model. The derived limits on sin(2) 2θ(14) cover the 10(-3) eV(2) ≲ |Δm(41)(2)| ≲ 0.1 eV(2) region, which was largely unexplored.

Use of independent component analysis to improve signal-to-noise ratio in multi-probe fluorescence microscopy.

In conventional multi-probe fluorescence microscopy, narrow bandwidth filters on detectors are used to avoid bleed-through artefacts between probes. The limited bandwidth reduces the signal-to-noise ratio of the detection, often severely compromising one or more channels. Herein, we describe a process of using independent component analysis to discriminate the position of different probes using only a dichroic mirror to differentiate the signals directed to the detectors. Independent component analysis was particularly effective in samples where the spatial overlap between the probes is minimal, a very common case in cellular microscopy. This imaging scheme collects nearly all of the emitted light, significantly improving the image signal-to-noise ratio. In this study, we focused on the detection of two fluorescence probes used in vivo, NAD(P)H and ANEPPS. The optimal dichroic mirror cutoff frequency was determined with simulations using the probes spectral emissions. A quality factor, defined as the cross-channel contrast-to-noise ratio, was optimized to maximize signals while maintaining spatial discrimination between the probes after independent component analysis post-processing. Simulations indicate that a ∼3 fold increase in signal-to-noise ratio using the independent component analysis approach can be achieved over the conventional narrow-band filtering approach without loss of spatial discrimination. We confirmed this predicted performance from experimental imaging of NAD(P)H and ANEPPS in mouse skeletal muscle, in vivo. For many multi-probe studies, the increased sensitivity of this 'full bandwidth' approach will lead to improved image quality and/or reduced excitation power requirements.

Neurocognitive effects following an overnight call shift on faculty anesthesiologists.

BACKGROUND: The impact of sleep deprivation on neurocognitive performance is a significant concern to both the health of patients and to the physicians caring for them, as demonstrated by the Accreditation Council for Graduate Medical Education enforced resident work hours. This study examined the effects of an overnight call at a level 1 trauma hospital on neurocognitive performance of faculty anesthesiologists. METHODS: Eleven faculty anesthesiologists completed a series of computerized tests that were designed to evaluate different areas of neurocognition, such as working memory, verbal learning, and concentration. The anesthesiologists completed the tests following an overnight call in the morning at 6:30 and again following a normal night's rest at 6:30 on a different date. RESULTS: Within-subjects, repeated measures analysis of variance revealed a significant difference on post-call vs. control performance on measures of learning and memory (P = 0.04). However, there were no significant differences on performance on measures of working memory or sustained attention and vigilance. Pre-call vs. control performances were also evaluated, but no significant differences were detected. CONCLUSIONS: Following a night call shift, performance on learning and memory was significantly reduced. Other areas were not significantly affected, which may have been due to certain possibilities, such as practice effect or variability in the call shifts. The real-world relevance of the decline in performance on these measures remains unclear.

Risk assessment of malignant transformation of oral leukoplakia in patients with previous oral squamous cell carcinoma.

The aim of this study was to identify the risk factors associated with developing oral squamous cell carcinoma (OSCC) from surgically excised oral leukoplakia (OL) in patients with previous oral cavity cancer. Clinicopathological data of 84 patients who were treated for OL between July 2002 and July 2020 and who had previously received treatment for OSCC were reviewed retrospectively. The follow-up time ranged from 0.69 to 17.99 years (mean 6.78 ± 4.25 years). The overall cumulative malignant transformation rate was 25% and the annual transformation rate was 5.73%. Kaplan-Meier survival analysis and the log-rank test showed that Candida infection (P = 0.010) was a risk factor associated with malignant transformation. In the multivariate Cox regression analysis, tongue and floor of the mouth as the location of the leukoplakia (P = 0.039), multifocal lesions of OL (P = 0.047), and Candida infection (P = 0.018) were the three independent prognostic factors related to the development of OSCC from the treated OL. A cautious approach to OL of the tongue with Candida infection or multifocal disease in this group of patients would be appropriate.

Host Genetic Associations with Salivary Microbiome in Oral Cancer.

Despite the growing recognition of a host genetic effect on shaping gut microbiota composition, the genetic determinants of oral microbiota remain largely unexplored, especially in the context of oral diseases. Here, we performed a microbiome genome-wide association study in 2 independent cohorts of patients with oral squamous cell carcinoma (OSCC, n = 144 and 67) and an additional group of noncancer individuals (n = 104). Besides oral bacterial dysbiosis and signatures observed in OSCC, associations of 3 loci with the abundance of genus-level taxa and 4 loci with ß diversity measures were detected (q < 0.05) at the discovery stage. The most significant hit (rs10906082 with the genus Lachnoanaerobaculum, P = 3.55 × 10-9 at discovery stage) was replicated in a second OSCC cohort. Moreover, the other 2 taxonomical associations, rs10973953 with the genus Kingella (P = 1.38 × 10-9) and rs4721629 with the genus Parvimonas (P = 3.53 × 10-8), were suggestive in the meta-analysis combining 2 OSCC cohorts. Further pathway analysis revealed that these loci were enriched for genes in regulation of oncogenic and angiogenic responses, implicating a genetic anchor to the oral microbiome in estimation of casual relationships with OSCC. Our findings delineate the role of host genotypes in influencing the structure of oral microbial communities.

First Report of Association of Mucor circinelloides on Noni (Morinda citrifolia) in Hawaii.

Noni (Morinda citrifolia) is a popular medicinal plant found in tropical or subtropical regions of the world. The fruit and juice extracts have properties that are reportedly therapeutic for diabetes, high blood pressure, and certain types of cancer (1,4). In our studies on noni juice produced from fruit collected from the Kohala and Puna districts of the island of Hawaii from 2008 to 2010, Mucor circinelloides f. sp. circinelloides was isolated from 85% of 157 juice samples and observed with up to 75% incidence on fruit surfaces during fermentation processing in glass jars. Fungal growth, appearing 14 to 21 days in storage at 22°C, was pale yellow to tan brown and was associated with wounded surfaces. Single-spore strains, KN 06-2 (2006; ripe fruit puree) and KN 08-08 (2008; fermented juice; CBS 124110), identified by Centraalbureau voor Schimmelcultures by molecular methods were 97.3% similar in internal transcribed spacer sequence to the type strain (CBS 195.68). M. circinelloides f. sp. circinelloides strains (KN 08-08, KN 09-06, or KN 10-02) (2008 to 2010; fermented juice) were inoculated by pipetting an aliquot of 100 µl of fungus strain spore suspension (1 × 105 to 1.33 × 106 spores/ml) onto firm, yellow maturity noni fruit that were washed, surface disinfected, and either wounded (surface cuts) or nonwounded. Controls consisted of no inoculation and sterile distilled water (SDW) inoculation treatments. Ten to twenty each of wounded and nonwounded fruit comprised each inoculation treatment. Fruit were incubated in acrylic bins with a layer of distilled water at the bottom, and sealed with snap-on lids. The bins were incubated on a lab bench at 22 to 23°C under fluorescent lights. Fruits were evaluated for presence of fungal growth and severity of symptoms. To determine viability of spores on inoculated fruit without symptoms, surfaces were swabbed with sterile cotton swabs dipped in SDW, streaked on potato dextrose agar (PDA) plates, and incubated at 22°C under fluorescent lights. The inoculation experiment was conducted twice. Nonwounded fruit inoculated with M. circinelloides f. sp. circinelloides strains did not result in infections (KN 09-06 and KN 10-02) or produced slight mycelial growth (0 to 20%; KN 08-08). Wounded fruit inoculated with any of the three strains resulted in 85 to 100% infection of moderate severity. There were no infections in noninoculated or SDW treatments of nonwounded or wounded fruit. Koch's postulates were fulfilled with the reisolation of M. circinelloides f. sp. circinelloides from selected fruit exhibiting soft tissue, discoloration, and sporulating yellowish green mycelial growth. Swab washes from asymptomatic surfaces of inoculated nonwounded fruit resulted in the growth of M. circinelloides f. sp. circinelloides on PDA, proving viability of the spores and confirmed that the fungus is primarily pathogenic only on wounded fruit surfaces. To our knowledge, this is the first report of M. circinelloides as a wound pathogen of noni fruit. The quality of fermented noni juice may be affected by the presence of M. circinelloides f. sp. circinelloides but can be remedied by pasteurization that does not affect antitumor properties (unpublished data). This fungus is also a reported pathogen of mango (2) and peach (3). References: (1) J. Li et al. Oncol. Rep. 20:1505, 2008. (2) K. Pernezny and G. W. Simone. Phytopathol. News 34:25, 2000. (3) C. Restuccia et al. J. Food Prot. 69:2465, 2006. (4) M. Y. Wang et al. Acta Pharmacol. Sin. 23:1127, 2002.

Comparison of the once-daily levofloxacin-containing triple therapy with the twice-daily standard triple therapy for first-line Helicobacter pylori eradication: a prospective randomised study.

BACKGROUND/AIMS: Simple compound of Helicobacter pylori eradication therapy may improve drug compliance of patients. The aims of this study were to compare the efficacy and tolerability of a simple combination containing levofloxacin 7-day once-daily with standard twice-daily triple therapy. PATIENTS AND METHODS: This was a prospective, randomised, open-label trial. A total of 189 consecutive patients diagnosed with peptic ulcer and H. pylori infection were enrolled. Patients were randomly divided into two groups: LEC group--levofloxacin 500 mg, esomeprazole 40 mg and clarithromycin 500 mg once daily for 7 days; AEC group--amoxicillin 1 g, esomeprazole 40 mg and clarithromycin 500 mg twice daily for 7 days. RESULTS: There were 90 patients in the LEC group and 99 patients in the AEC group. By intention-to-treat and per-protocol analysis, the H. pylori eradication rate was 78.9% [71/90; 95% confidence interval (CI), 70.3-87.5%] and 83.5% (71/85; 95% CI, 75.5-91.6%) respectively, in the LEC group; and 74.8% (74/99; 95% CI, 66.0-83.5%) and 86.0% (74/86; 95% CI, 78.6-93.5%) respectively, in the AEC group. The incidence and tolerability of side effects were similar between these two groups. CONCLUSION: The efficacy and tolerability of once-daily levofloxacin-containing triple therapy are equal to those of the standard twice-daily triple therapy in this study. However, none of the treatment regimens evaluated achieved enough eradication efficacies to be considered as a recommendable first-line treatment.

Active Volcanism Revealed from a Seismicity Conduit in the Long-resting Tatun Volcano Group of Northern Taiwan.

Abundant earthquakes clustered within a particular zone often reflect an active geological feature, such as clustering seismicity along a fault zone and a huge number of volcanic-earthquakes around the erupting conduit. Herein we perform a double-difference tomographic inversion and relocate the seismicity at the long-resting Tatun volcano group (TVG) in northern Taiwan. A dramatic improvement of the earthquake location model surprisingly show that, from 2014 to 2017, two clustered seismic zones are identified in the TVG. One major group of events (>1000) persistently clustered within a ~500 m diameter vertical conduit with a ~2 km height. The clustering seismicity conduit is just located nearby Dayoukeng, one of the strongest fumaroles in the TVG, and is connected to a fracture zone characterized by low Vp/Vs in the shallow crust. The other group of events is clustered within a sphere-like zone beneath Mt. Chihsin around the depths between 0.5 km and 2 km. Both seismic zones are probably triggered by the significantly volcanic gases and fluids ascending from the deep magma reservoir. Combined with a variety of results from literature, the seismicity conduit near the strong fumarole is the evidence for an active volcano and also identifies a likely pathway for ascending magma if the TVG erupts again in the future. But possibility of developing different magma pathways at other clustered seismic zones such as beneath Mt. Chihsin may not be totally excluded.

Protamine-associated hypotension in patients on hemodialysis: retrospective study and prevalence of antiprotamine antibodies.

AIMS: Protamine, when administered to neutralize heparin in cardiovascular surgery, is associated with occasionally severe antigen-antibody reactions associated with substantial morbidity and mortality. The objective of this study is to investigate whether patients on hemodialysis are more susceptible to the protamine adverse effects. METHOD: First, a retrospective analysis of a protamine-associated hypotension episode (PAHE) in 239 patients undergoing coronary artery bypass grafting surgery was performed for the incidence study in the period of 1999 to 2005. Second, an ELISA determination of serum anti-protamine IgG antibody in 255 serum samples from individuals without previous surgical histories was conducted for prevalence survey. In both studies, patients on HD were matched for age with non HD patients. RESULTS: The highest incidence (57%) of PAHE occurred in patients on hemodialysis using of M-insulin (a mixed type of insulin aspart 30%, insulin aspart protamine 70%) formulation, and this group also exhibited a high anti-protamine IgG antibody titer in serum (odds ratio: 18.31). CONCLUSIONS: A substantial proportion of patients on hemodialysis are at high risk of acquiring protamine adverse effects, but definite conclusion about the association between uremia and PAHE, however, still needs to be made with caution.

Altered fibrinolytic activities in gastric cancer and uremic patients after intervention.

INTRODUCTION: Although thromboembolism is the most recognized cause of death in cancer and uremic patients following tumorectomy or hemodialysis, respectively, little data exist concerning its etiologies and treatments in post-intervention settings. In this study, we determined the post-intervention fibrinolytic activities to exploit their implications in gastric cancer and uremic patients. MATERIALS AND METHODS: A small-scale case-control study with totally 56 cases aimed to compare the difference of the post-intervention fibrinolytic activities of two hypercoagulable groups of gastric cancer and uremic patients versus healthy controls was conducted. In-house functional assays for plasma plasminogen (Pg) and plasminogen activators (PA) activities were employed. RESULTS: As compared to the control, both variable-stratified patient groups disclosed reduced Pg activities, synonyms at the "hypofibrinolytic" state, suggesting that the alleged post-intervention hypercoagulability of the two patient groups could be rationalized by the hypofibrinolysis mechanism. On the other hand, cancer patients showed elevated PA activity, concomitantly implicating that there was associated fibrinolytic consumption. Moreover, the altered PA activity could be ascribed to tumor metastasis according to literature review. CONCLUSIONS: Our data suggested that the PA/Pg fibrinolytic activities were altered in gastric cancer and uremic patients post-interventionally. Measurement of the post-intervention fibrinolytic activities could be useful in projection of some potential risks.

DNA methylation and histone modification regulate silencing of epithelial cell adhesion molecule for tumor invasion and progression.

Epithelial cell adhesion molecule (Ep-CAM) is believed to have a critical role in carcinogenesis and cell proliferation. However, the association of Ep-CAM with cancer invasion and progression is less clear. We found that Ep-CAM was highly expressed on low-invasive cells compared with highly invasive cells. Forced expression of Ep-CAM decreased cancer invasiveness, and silencing Ep-CAM expression elevated cancer invasiveness. Ep-CAM expression was associated with promoter methylation. Treatment with a demethylating agent, and/or the histone deacetylase inhibitor reactivated Ep-CAM expression in Ep-CAM-negative cells and inhibited cancer invasiveness. Using a promoter-reporter construct, we demonstrated methylation of the promoter fragment drive Ep-CAM-silenced transcription. Additionally, silenced Ep-CAM gene in cancer cells was enriched for hypermethylated histone 3 lysine 9. When unmethylated and active, this promoter was associated with acetylated histone 3 lysine 9. Furthermore, we observed an increased association of Ep-CAM promoter with repression components as tumor invasiveness increased. In cancer tissues, Ep-CAM expression significantly correlated with tumor progression and associated with promoter methylation. Our data support the idea that modulation of Ep-CAM plays a pivotal role in tumor invasion and progression. Moreover, aberrant DNA methylation of Ep-CAM is implicated in enhancing invasive/metastatic proclivity of tumors.

Patterns of combined prescriptions of aspirin-Ginkgo biloba in Taiwan: a population-based study.

BACKGROUND AND OBJECTIVES: Although interactions between aspirin and Ginkgo biloba extract (GBE) have been documented, the extent to which these two drugs are used in combination remains unclear. The aim of this study was to estimate the extent and utilization patterns of combined prescriptions of aspirin and GBE in Taiwan based on an analysis of a nationwide database. METHODS: A representative nationwide sample of 200 000 National Health Insurance (NHI) beneficiaries in Taiwan was used. The prescription details of ambulatory care claims for this sample of beneficiaries for the period 1997-2003 were analysed. The prevalence of aspirin and GBE prescriptions was evaluated. The extent of co-prescription of the two drugs was assessed together with the associated patient characteristics. RESULTS: There was an increase in the number of aspirin prescriptions (from 29 986 out of 2 454 879 (1.2%) in 1997, to 50 614 out of 2 499 605 (2.0%) in 2003). Aspirin was mostly prescribed to patients over 50 years old. The percentage of prescriptions with aspirin increased rapidly from 57% to 84%, among those over 50 years old. The number of prescriptions with GBE also increased from 3039 to 6171 and 78-84% was prescribed to those 50 years or older. During the study period, combined prescriptions of aspirin and GBE dramatically increased four times. Most prescriptions were longer than 14 days and 42.4% of combined prescriptions were found to be at the same ambulatory care visit. CONCLUSION: The findings of this study suggest that there is an increasing trend in co-prescription of aspirin and GBE for Taiwan's elderly population during 1997-2003. This trend is of concern and worthy of note.

Complete nucleotide and deduced amino acid sequences of human and murine preprocathepsin L. An abundant transcript induced by transformation of fibroblasts.

Transfection of an activated rat oncogene into NIH3T3 fibroblasts leads to transformation and induction of a metastatic phenotype. To identify genes whose activation might mediate these processes, we used a differential screening strategy. A 1.5-kb transcript is induced fiftyfold, constitutes 1% of ras transformed cell messenger RNA (mRNA) and is the most abundantly induced message in these cells. Our sequence data shows that it encodes murine cathepsin L, a potent collagenolytic and elastinolytic lysosomal enzyme. The murine clone was used to isolate human cathepsin L complementary DNA (cDNA) clones. The complete nucleotide and deduced amino acid sequences of human and murine preprocathepsin L are presented and compared to other papain family cysteine proteinases. Northern analysis shows that both human and murine cathepsin L probes hybridize to a 1.5-kb transcript in several tissues, but also to a 4-kb transcript in human kidney. These clones will facilitate studies of the structure, expression, and function of cathepsin L, including its unexpected upregulation in transformation.

Solamargine induces apoptosis and sensitizes breast cancer cells to cisplatin.

Solamargine (SM), a major steroidal alkaloid glycoside, was purified from Solanum incanum plant. SM exhibited the most cytotoxic effect comparing with that of cisplatin (cDDP), methotrexate (MTX), 5-fluorouracil (5-FU), epirubicin (EPI) and cyclophosphamide (CP) against human breast cancer cells. In this study, SM induces apoptosis of the breast cancer cells and the mechanism was characterized. SM up-regulated the expressions of external death receptors, such as tumor necrosis factor receptor I (TNFR-I), Fas receptor (Fas), TNFR-I-associated death domain (TRADD), and Fas-associated death domain (FADD). SM also enhanced the intrinsic ratio of Bax to Bcl-2 by up-regulating Bax and down-regulating Bcl-2 and Bcl-xL expressions. These effects resulted in the release of mitochondrial cytochrome c and activation of caspase-8, -9 and -3 in the cells, indicating that SM triggered extrinsic and intrinsic apoptotic pathways of breast cancer cells. Similar to function way of SM, cDDP causes cancer cell apoptosis though caspase-8/caspase-3 and Bax/cytochrome c pathways, but the resistance to cDDP is correlated with Bcl-2 and Bcl-xL overexpression. However, the overexpression of Bcl-2 and Bcl-xL can be broken through by SM. The combined treatment of SM and cDDP significantly reduced Bcl-2 and Bcl-xL expressions, and enhanced Bax, cytochrome c, caspase-9 and -3 expressions in breast cancer cells. Thus, the combined use of SM and cDDP may be effective in cDDP-resistant breast cancer.