Lung cancer tumorigenicity and drug resistance are maintained through ALDH(hi)CD44(hi) tumor initiating cells

published_or_final_versio

Klotho-beta overexpression as a novel target for suppressing proliferation and fibroblast growth factor receptor-4 signaling in hepatocellular carcinoma

<p>Abstract</p> <p>Background</p> <p>We had previously demonstrated overexpression of fibroblast growth factor receptor-4 (FGFR4) in hepatocellular carcinoma (HCC). However, additional molecular mechanisms resulting in amplified FGFR4 signaling in HCC remain under-studied. Here, we studied the mechanistic role of its co-receptor klotho-beta (KLB) in driving elevated FGFR4 activity in HCC progression.</p> <p>Results</p> <p>Quantitative real-time PCR analysis identified frequent elevation of KLB gene expression in HCC tumors relative to matched non-tumor tissue, with a more than two-fold increase correlating with development of multiple tumors in patients. KLB-silencing in Huh7 cells decreased cell proliferation and suppressed FGFR4 downstream signaling. While transient repression of KLB-FGFR4 signaling decreased protein expression of alpha-fetoprotein (AFP), a HCC diagnostic marker, prolonged inhibition enriched for resistant HCC cells exhibiting increased liver stemness.</p> <p>Conclusions</p> <p>Elevated KLB expression in HCC tissues provides further credence to the oncogenic role of increased FGFR4 signaling in HCC progression and represents a novel biomarker to identify additional patients amenable to anti-FGFR4 therapy. The restricted tissue expression profile of KLB, together with the anti-proliferative effect observed with KLB-silencing, also qualifies it as a specific and potent therapeutic target for HCC patients. The enrichment of a liver stem cell-like population in response to extended KLB-FGFR4 repression necessitates further investigation to target the development of drug resistance.</p

Intellectual ability in tuberous sclerosis complex correlates with predicted effects of mutations on TSC1 and TSC2 proteins.

BACKGROUND: Tuberous sclerosis complex is a multisystem genetic disease, caused by mutation in the TSC1 or TSC2 genes, associated with many features, including intellectual disability (ID). We examined psychometric profiles of patients with TSC1 or TSC2 mutations and tested whether different mutation types were associated with different degrees of intellectual ability. METHODS: One hundred subjects with known TSC1/TSC2 mutations were assessed using a range of IQ or developmental quotient (DQ) measures. Effects of mutations on TSC1/TSC2 proteins were inferred from sequence data and published biochemical studies. RESULTS: Most individuals with TSC1 mutations fell on a normal distribution identical to the general population, with ∼10% showing profound ID. Of individuals with TSC2 mutations, 34% showed profound ID, and the remainder a pattern of IQ/DQ more variable and shifted to the left than in TSC1 or the general population. Truncating TSC1 mutations were all predicted to be subject to nonsense-mediated mRNA decay. Mutations predicted to result in unstable protein were associated with less severe effects on IQ/DQ. There was a statistically significant negative correlation between length of predicted aberrant C-terminal tails arising from frameshift mutations in TSC1 and IQ/DQ; for TSC2 a positive but not statistically significant correlation was observed. CONCLUSION: We propose a model where (i) IQ/DQ correlates inversely with predicted levels and/or deleterious biochemical effects of mutant TSC1 or TSC2 protein, and (ii) longer aberrant C-terminal tails arising from frameshift mutations are more detrimental for TSC1 and less for TSC2. Predictions of the model require replication and biochemical testing.We thank the Tuberous Sclerosis Association, the Wales Gene Park, the National Research Foundation of South Africa and the Struengmann Fund for financial support. We thank Prof Chris Smith for helpful comments on the manuscript.This is the author accepted manuscript. The final version is available from the British Medical Journal via http://dx.doi.org/10.1136/jmedgenet-2015-10315

Chemical composition of essential oil of exudates of Dryobalanops aromatica

Purpose: To identify the chemical composition of essential oil from the exudates of Dryobalanops aromatica from Malaysia.Methods: Exudate was collected from D. aromatica and subjected to fractional  distillation to obtain essential oil. Gas chromatography-mass spectrometry  (GC-MS) was used to characterize the composition of the isolated essential oil.Results: The yield of essential oil was 7.58 %, with the highest yield (3.24 %) within the first 2 h of fractional distillation. Thirty compounds which accounted for 97.56 % of essential oil composition were identified. These include sesquiterpenes (46.87 %), monoterpenes (31.05 %), oxygenated monoterpenes (16.76 %) and oxygenated  sesquiterpenes (2.13 %). Borneol accounted for 0.74 % of the essential oil.Conclusion: Essential oil from the exudates of D. aromatica contains terpenoid  compounds and borneol.Keywords: Dryobalanops aromatica, exudate, fractional distillation, essential oil, GS-MS, borneo

Determination of borneol and other chemical compounds of essential oil of Dryobalanops aromatica exudate from Malaysia

Purpose: To determine borneol and other chemical compounds of essential oil derived from the exudate of Dryobalanops aromatica in Malaysia.Methods: Exudate was collected from D. aromatica and subjected to fractional distillation to obtain essential oil. Gas chromatography-mass spectrometry (GC-MS) was performed to characterize the composition of the isolated essential oil.Results: Essential oil (7.58 %) was obtained with the highest yield (3.24 %) in the first 2 h of fractional distillation. Thirty compounds which accounted for 97.56 % of total essential oil composition were identified by GC-MS, and they include sesquiterpenes (46.87 %), monoterpenes (31.05 %), oxygenated monoterpenes (16.76 %) and oxygenated sesquiterpenes (2.13 %). Borneol (0.74 %) was also detected in the essential oil.Conclusion: Borneol and other terpenoid compounds are present in the essential oil of the exudate of D. aromatica.Keywords: Exudate, Dryobalanops Aromatica, Fractional distillation, Essential oil, Gaschromatography-mass spectrometry, Borneo

Hong Kong dentists' preparedness for medical emergency in dental clinics

Aim: The aim of this study was to investigate the Hong Kong dentists’ and dental clinics’ preparedness for medical emergency in the dental clinic. Methods: Two custom designed questionnaires were developed, one for dentists and another for dental clinics, to collect the required information. The sampling frame for participants was the list of registered dentists published by the Hong Kong Dental Council on its website in January 2016. A total of 434 dentists and 143 dental clinics were selected from the list by systematic random sampling. The latter sample was supplemented by 10 randomly selected government dental clinics. The questionnaires were mailed the selected dentists together with a cover letter and a stamped return envelope. A reminder letter and another copy of the questionnaire were sent out two weeks after the first mailing. Results: 167 (38%) completed dentist questionnaires and 53 (35%) clinic questionnaires were collected. Most of the respondent dentists had some deficient knowledge on basic life support (BLS), their mean score was 3.5 out of a maximum of 5. Most (>60%) of the respondents thought they were competent in performing medical emergency procedures except giving intravenous injection. Moreover, most (>60%) of them held positive attitude towards having immediate availability of essential medical emergency equipment and drugs in their clinic. Dentists who were more recent graduates, those with postgraduate qualifications, and those who work with accompaniment generally had higher mean BLS knowledge scores. In the dental clinics, the most commonly kept medical emergency equipment/drug was instant glucose (70%) and followed by antihistamine (62%). Only a quarter of the clinics were equipped with AED, and 45% were equipped with oxygen cylinder. For 8 out of the 11 items, a higher proportion of the bigger clinics (>2 dental chairs) than the smaller clinics had the medical emergency equipment/drug available (Chi-square test, p<0.05). Conclusion: Hong Kong dentists have a moderate level of knowledge on BLS which should be enhanced through regular attendance at CE courses. Their knowledge level is affected by a number of their background and professional activities factors. Most dental clinics in Hong Kong have only few of the essential medical emergency equipment and drugs while the larger clinics are better equipped than the smaller clinics.published_or_final_versio

Antibody stabilization for thermally accelerated deep immunostaining

Antibodies have diverse applications due to their high reaction specificities but are sensitive to denaturation when a higher working temperature is required. We have developed a simple, highly scalable and generalizable chemical approach for stabilizing off-the-shelf antibodies against thermal and chemical denaturation. We demonstrate that the stabilized antibodies (termed SPEARs) can withstand up to 4 weeks of continuous heating at 55 °C and harsh denaturants, and apply our method to 33 tested antibodies. SPEARs enable flexible applications of thermocycling and denaturants to dynamically modulate their binding kinetics, reaction equilibrium, macromolecular diffusivity and aggregation propensity. In particular, we show that SPEARs permit the use of a thermally facilitated three-dimensional immunolabeling strategy (termed ThICK staining), achieving whole mouse brain immunolabeling within 72 h, as well as nearly fourfold deeper penetration with threefold less antibodies in human brain tissue. With faster deep-tissue immunolabeling and broad compatibility with tissue processing and clearing methods without the need for any specialized equipment, we anticipate the wide applicability of ThICK staining with SPEARs for deep immunostaining

PHIL and Squid Embolization of Cerebral Arteriovenous Malformation: A Retrospective Case Series of 23 Patients

Precipitating hydrophobic injectable liquid (PHIL; MicroVention, Aliso Viejo, CA, USA) and Squid (Balt, Irvine, CA, USA) are 2 newer liquid embolic agents used in endovascular embolization of cerebral arteriovenous malformation (AVM). This study aims to investigate and compare the effectiveness and safety profile of the 2 newer liquid embolic agents in the embolization of cerebral AVM. This is a retrospective study on all patients diagnosed with cerebral AVM undergoing endovascular embolization with liquid embolic agents PHIL and Squid admitted to the Division of Neurosurgery, Department of Surgery in Prince of Wales Hospital from January 2014 to June 2021. Twenty-three patients with cerebral AVM were treated with 34 sessions of endovascular embolization with either PHIL or Squid (17 sessions each) liquid embolic agents with a male to female ratio of 2.3:1 (male 16; female 7) and mean age of 44.6 (range, 12 to 67). The mean total nidus obliteration rate per session was 57% (range, 5% to 100%). Twenty-one patients (91.3%) received further embolization, stereotactic radiosurgery, or surgical excision after initial endovascular embolization. There were 2 morbidities (1 neurological and 1 non-neurological, 6%) and no mortalities (0%). All patients had static or improvement in modified Rankin Scale at 3 to 6 months at discharge. PHIL and Squid are effective and safe liquid embolic agents for endovascular embolization of cerebral AVM, achieving satisfactory nidal obliteration rates and patient functional outcomes

The psychophysiological effects of Tai-chi and exercise in residential Schizophrenic patients: a 3-arm randomized controlled trial

BACKGROUND: Patients with schizophrenia are characterized by high prevalence rates and chronicity that often leads to long-term institutionalization. Under the traditional medical model, treatment usually emphasizes the management of psychotic symptoms through medication, even though anti-psychotic drugs are associated with severe side effects, which can diminish patients’ physical and psychological well-being. Tai-chi, a mind-body exercise rooted in Eastern health philosophy, emphasizes the motor coordination and relaxation. With these potential benefits, a randomized controlled trial (RCT) is planned to investigate the effects of Tai-chi intervention on the cognitive and motor deficits characteristic of patients with schizophrenia. METHODS/DESIGN: A 3-arm RCT with waitlist control design will be used in this study. One hundred and fifty three participants will be randomized into (i) Tai-chi, (ii) exercise or (iii) waitlist control groups. Participants in both the Tai-chi and exercise groups will receive 12-weeks of specific intervention, in addition to the standard medication and care received by the waitlist control group. The exercise group will serve as a comparison, to delineate any unique benefits of Tai-chi that are independent of moderate aerobic exercise. All three groups will undergo three assessment phases: (i) at baseline, (ii) at 12 weeks (post-intervention), and (iii) at 24 weeks (maintenance). All participants will be assessed in terms of symptom management, motor coordination, memory, daily living function, and stress levels based on self-perceived responses and a physiological marker. DISCUSSION: Based on a promising pilot study conducted prior to this RCT, subjects in the Tai-chi intervention group are expected to be protected against deterioration of motor coordination and interpersonal functioning. They are also expected to have better symptoms management and lower stress level than the other treatment groups. TRIAL REGISTRATION: The trail has been registered in the Clinical Trials Center of the University of Hong Kong (HKCTR-1453)

Transmission dynamics, serial interval and epidemiology of COVID-19 diseases in Hong Kong under different control measures

Background: The outbreak of coronavirus disease 2019 (COVID-19) started in Wuhan, China in late December 2019, and subsequently became a pandemic. Hong Kong had implemented a series of control measures since January 2020, including enhanced surveillance, isolation and quarantine, border control and social distancing. Hong Kong recorded its first case on 23 January 2020, who was a visitor from Wuahn. We analysed the surveillance data of COVID-19 to understand the transmission dynamics and epidemiology in Hong Kong. Methods: Based on cases recorded from 23 January to 6 April 2020, we constructed the epidemic curve of daily COVID-19 incidence and used this data to estimate the time-varying reproduction number ( R t ) with the R package EpiEstim, with serial interval computed from local data. We described the demographic and epidemiological characteristics of reported cases. We computed weekly incidence by age and residential district to understand the spatial and temporal transmission of the disease. Results: COVID-19 disease in Hong Kong was characterised with local cases and clusters detected after two waves of importations, first in late January and the second one in early March. The R t increased to approximately 2 and approximately 1, respectively, following these importations; it decreased to below 1 afterwards, which coincided with the implementation, modification and intensification of different control measures. Compared to local cases, imported cases were younger (mean age: 52 years among local cases vs 35 years among imported cases), had a lower proportion of underlying disease (9% vs 5%) and severe outcome (13% vs 5%). Cases were recorded in all districts but the incidence was highest in those in the Hong Kong Island region. Conclusions: Stringent and sustained public health measures at population level could contain the COVID-19 disease at a relatively low level