Displaying publications 1 - 20 of 39 in total

Abstract:
Sort:
  1. Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, et al.
    Autophagy, 2016;12(1):1-222.
    PMID: 26799652 DOI: 10.1080/15548627.2015.1100356
  2. Chen YH, Chen HJ, Yang CY, Shiu JH, Hoh DZ, Chiang PW, et al.
    Environ Microbiol, 2021 Oct 27.
    PMID: 34708512 DOI: 10.1111/1462-2920.15824
    Terpios hoshinota is an aggressive, space-competing sponge that kills various stony corals. Outbreaks of this species have led to intense damage to coral reefs in many locations. Here, the first large-scale 16S rRNA gene survey across three oceans revealed that bacteria related to the taxa Prochloron, Endozoicomonas, SAR116, Ruegeria, and unclassified Proteobacteria were prevalent in T. hoshinota. A Prochloron-related bacterium was the most dominant and prevalent cyanobacterium in T. hoshinota. The complete genome of this uncultivated cyanobacterium and pigment analysis demonstrated that it has phycobiliproteins and lacks chlorophyll b, which is inconsistent with the definition of Prochloron. Furthermore, the cyanobacterium was phylogenetically distinct from Prochloron, strongly suggesting that it should be a sister taxon to Prochloron. Therefore, we proposed this symbiotic cyanobacterium as a novel species under the new genus Candidatus Paraprochloron terpiosi. Comparative genomic analyses revealed that 'Paraprochloron' and Prochloron exhibit distinct genomic features and DNA replication machinery. We also characterized the metabolic potentials of 'Paraprochloron terpiosi' in carbon and nitrogen cycling and propose a model for interactions between it and T. hoshinota. This study builds a foundation for the study of the T. hoshinota microbiome and paves the way for better understanding of ecosystems involving this coral-killing sponge.
  3. Howson JMM, Zhao W, Barnes DR, Ho WK, Young R, Paul DS, et al.
    Nat Genet, 2017 Jul;49(7):1113-1119.
    PMID: 28530674 DOI: 10.1038/ng.3874
    Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10-8, in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms.
  4. Duraisamy M, Elancheziyan M, Eswaran M, Ganesan S, Ansari AA, Rajamanickam G, et al.
    Int J Biol Macromol, 2023 Jul 31;244:125329.
    PMID: 37307970 DOI: 10.1016/j.ijbiomac.2023.125329
    The use of advanced electroactive catalysts enhances the performance of electrochemical biosensors in real-time biomonitoring and has received much attention owing to its excellent physicochemical and electrochemical possessions. In this work, a novel biosensor was developed based on the electrocatalytic activity of functionalized vanadium carbide (VC) material, including VC@ruthenium (Ru), VC@Ru-polyaniline nanoparticles (VC@Ru-PANI-NPs) as non-enzymatic nanocarriers for the fabrication of modified screen-printed electrode (SPE) to detect acetaminophen in human blood. As-prepared materials were characterized using SEM, TEM, XRD, and XPS techniques. Biosensing was carried out using cyclic voltammetry and differential pulse voltammetry techniques and has revealed imperative electrocatalytic activity. A quasi-reversible redox method of the over-potential of acetaminophen increased considerably compared with that at the modified electrode and the bare SPE. The excellent electrocatalytic behaviour of VC@Ru-PANI-NPs/SPE is attributed to its distinctive chemical and physical properties, including rapid electron transfer, striking ᴫ-ᴫ interface, and strong adsorptive capability. This electrochemical biosensor exhibits a detection limit of 0.024 μM, in a linear range of 0.1-382.72 μM with a reproducibility of 2.45 % relative standard deviation, and a good recovery from 96.69 % to 105.59 %, the acquired results ensure a better performance compared with previous reports. The enriched electrocatalytic activity of this developed biosensor is mainly credited to its high surface area, better electrical conductivity, synergistic effect, and abundant electroactive sites. The real-world utility of the VC@Ru-PANI-NPs/SPE-based sensor was ensured via the investigation of biomonitoring of acetaminophen in human blood samples with satisfactory recoveries.
  5. Mari E, Duraisamy M, Eswaran M, Sellappan S, Won K, Chandra P, et al.
    Mikrochim Acta, 2024 Mar 20;191(4):212.
    PMID: 38509344 DOI: 10.1007/s00604-024-06273-9
    The facile fabrication is reported of highly electrochemically active Ti3C2Tx MXene/MWCNT (3D/1D)-modified screen-printed carbon electrode (SPE) for the efficient simultaneous electrochemical detection of paracetamol, theophylline, and caffeine in human blood samples. 3D/1D Ti3C2Tx MXene/MWCNT nanocomposite was synthesized using microwave irradiation and ultrasonication processes. Then, the Ti3C2Tx/MWCNT-modified SPE electrode was fabricated and thoroughly characterized towards its physicochemical and electrochemical properties using XPS, TEM, FESEM, XRD, electrochemical impedance spectroscopy, cyclic voltammetry, and differential pulse voltammetry techniques. As-constructed Ti3C2Tx-MWCNT/SPE offers excellent electrochemical sensing performance with good detection limits (0.23, 0.57, and 0.43 µM) and wide linear ranges (1.0 ~ 90.1, 2.0 ~ 62.0, and 2.0-90.9 µM) for paracetamol, caffeine, and theophylline, respectively,  in the human samples. Notably, the non-enzymatic electroactive nanocomposite-modified electrode has depicted a semicircle Nyquist plot with low charge transfer resistance (Rct∼95 Ω), leading to high ionic diffusion and facilitating an excellent electron transfer path. All the above results in efficient stability, reproducibility, repeatability, and sensitivity compared with other reported works, and thus, it claims its practical utilization in realistic clinical applications.
  6. Connelly K, Kandane-Rathnayake R, Hoi A, Louthrenoo W, Hamijoyo L, Luo SF, et al.
    Arthritis Rheumatol, 2023 Mar;75(3):401-410.
    PMID: 36122172 DOI: 10.1002/art.42350
    OBJECTIVE: In trials of systemic lupus erythematosus (SLE), the SLE Responder Index (SRI) is the most commonly used primary efficacy end point but has limited validation against long-term outcomes. We aimed to investigate associations of attainment of a modified version of the SRI (mSRI) with key clinical outcomes in SLE patients with up to 5 years of follow-up.

    METHODS: We used data from a large multicenter, longitudinal SLE cohort in which patients received standard of care. The first visit with active disease (defined as SLE Disease Activity Index 2000 [SLEDAI-2K] score ≥6) was designated as baseline, and mSRI attainment (defined as a reduction in SLEDAI-2K ≥4 points with no worsening in physician global assessment ≥0.3 points) was determined at annual intervals from baseline up to 5 years. Associations between mSRI attainment and outcomes including disease activity, glucocorticoid dose, flare, damage accrual, Lupus Low Disease Activity State (LLDAS), and remission were studied.

    RESULTS: We included 2,060 patients, with a median baseline SLEDAI-2K score of 8. An mSRI response was attained by 56% of patients at 1 year, with similar responder rates seen at subsequent annual time points. Compared to nonresponders, mSRI responders had significantly lower disease activity and prednisolone dose and higher proportions of LLDAS and remission attainment at each year, and less damage accrual at years 2 and 3. Furthermore, mSRI responder status at 1 year predicted clinical benefit at subsequent years across most outcomes, including damage accrual (odds ratio [OR] range 0.58-0.69, P 

  7. Tsai IH, Chen YH, Wang YM, Liau MY, Lu PJ
    Arch Biochem Biophys, 2001 Mar 15;387(2):257-64.
    PMID: 11370849
    To investigate the geographic variations in venoms of two medically important pitvipers, we have purified and characterized the phospholipases A2 (PLA2s) from the pooled venoms of Calloselasma rhodostoma from Malaysia, Thailand, Indonesia, and Vietnam, as well as the individual venom of Trimeresurus mucrosquamatus collected from both North and South Taiwan. Enzymatic and pharmacological activities of the purified PLA2s were also investigated. The complete amino acid sequences of the purified PLA2s were determined by sequencing the corresponding cDNAs from the venom gland and shown to be consistent with their molecular weight data and the N-terminal sequences. All the geographic venom samples of C. rhodostoma contain a major noncatalytic basic PLA2-homolog and two or three acidic PLA2s in different proportions. These acidic PLA2s contain Glu6-substitutions and show distinct inhibiting specificities toward the platelets from human and rabbit. We also found that the T. mucrosquamatus venoms from North Taiwan but not those from South Taiwan contain an Arg6-PLA2 designated as TmPL-III. Its amino acid sequence is reported for the first time. This enzyme is structurally almost identical to the low- or nonexpressed Arg6-PLA2 from C. rhodostoma venom gland, and thus appears to be a regressing venom component in both of the Asian pitvipers.
  8. Chang H, Ho CD, Chen YH, Chen L, Hsu TH, Lim JW, et al.
    Membranes (Basel), 2021 Apr 07;11(4).
    PMID: 33916991 DOI: 10.3390/membranes11040266
    Two geometric shape turbulence promoters (circular and square of same areas) of different array patterns using three-dimensional (3D) printing technology were designed for direct contact membrane distillation (DCMD) modules in the present study. The DCMD device was performed at middle temperature operation (about 45 °C to 60 °C) of hot inlet saline water associated with a constant temperature of inlet cold stream. Attempts to reduce the disadvantageous temperature polarization effect were made inserting the 3D turbulence promoters to promote both the mass and heat transfer characteristics in improving pure water productivity. The additive manufacturing 3D turbulence promoters acting as eddy promoters could not only strengthen the membrane stability by preventing vibration but also enhance the permeate flux with lessening temperature polarization effect. Therefore, the 3D turbulence promoters were individually inserted into the flow channel of the DCMD device to create vortices in the flow stream and increase turbulent intensity. The modeling equations for predicting the permeate flux in DCMD modules by inserting the manufacturing 3D turbulence promoter were investigated theoretically and experimentally. The effects of the operating conditions under various geometric shapes and array patterns of turbulence promoters on the permeate flux with hot inlet saline temperatures and flow rates as parameters were studied. The distributions of the fluid velocities were examined using computational fluid dynamics (CFD). Experimental study has demonstrated a great potential to significantly accomplish permeate flux enhancement in such new design of the DCMD system. The permeate flux enhancement for the DCMD module by inserting 3D turbulence promoters in the flow channel could provide a maximum relative increment of up to 61.7% as compared to that in the empty channel device. The temperature polarization coefficient (τtemp) was found in this study for various geometric shapes and flow patterns. A larger τtemp value (the less thermal resistance) was achieved in the countercurrent-flow operation than that in the concurrent-flow operation. An optimal design of the module with inserting turbulence promoters was also delineated when considering both permeate flux enhancement and energy utilization effectiveness.
  9. Cutiongco-de la Paz EM, Chung BH, Faradz SMH, Thong MK, David-Padilla C, Lai PS, et al.
    Am J Med Genet C Semin Med Genet, 2019 06;181(2):177-186.
    PMID: 31037827 DOI: 10.1002/ajmg.c.31703
    The status of training in clinical genetics and genetic counseling in Asia is at diverse stages of development and maturity. Most of the training programs are in academic training centers where exposure to patients in the clinics or in the hospital is a major component. This setting provides trainees with knowledge and skills to be competent geneticists and genetic counselors in a variety of patient care interactions. Majority of the training programs combine clinical and research training which provide trainees a broad and integrated approach in the diagnosis and management of patients while providing opportunities for research discoveries that can be translated to better patient care. The background on how the training programs in clinical genetics and genetic counseling in Asia evolved to their current status are described. Each of these countries can learn from each other through sharing of best practices and resources.
  10. Chen YH, Leong WS, Lin MS, Huang CC, Hung CS, Li HY, et al.
    JACC Cardiovasc Interv, 2016 09 12;9(17):1825-32.
    PMID: 27609258 DOI: 10.1016/j.jcin.2016.06.015
    OBJECTIVES: This study sought to determine predictors for successful endovascular treatment in patients with chronic carotid artery occlusion (CAO).

    BACKGROUND: Endovascular recanalization in patients with chronic CAO has been reported to be feasible, but technically challenging.

    METHODS: Endovascular attempts in 138 consecutive chronic CAO patients with impaired ipsilateral hemisphere perfusion were reviewed. We analyzed potential variables including epidemiology, symptomatology, angiographic morphology, and interventional techniques in relation to the technical success.

    RESULTS: The technical success rate was 61.6%. Multivariate analysis showed absence of prior neurologic event (odds ratio [OR]: 0.27; 95% confidence interval [CI]: 0.10 to 0.76), nontapered stump (OR: 0.18; 95% CI: 0.05 to 0.67), distal internal carotid artery (ICA) reconstitution via contralateral injection (OR: 0.19; 95% CI: 0.05 to 0.75), and distal ICA reconstitution at communicating or ophthalmic segments (OR:0.12; 95% CI: 0.04 to 0.36) to be independent factors associated with lower technical success. Point scores were assigned proportional to model coefficients, and technical success rates were >80% and <40% in patients with scores of ≤1 and ≥4, respectively. The c-indexes for this score system in predicting technical success was 0.820 (95% CI: 0.748 to 0.892; p < 0.001) with a sensitivity of 84.7% and a specificity of 67.9%.

    CONCLUSIONS: Absence of prior neurologic event, nontapered stump, distal ICA reconstitution via contralateral injection, and distal ICA reconstitution at communicating or ophthalmic segments were identified as independent negative predictors for technical success in endovascular recanalization for CAO.

  11. Chang YT, Coombs G, Ling T, Balaji V, Rodrigues C, Mikamo H, et al.
    Int J Antimicrob Agents, 2017 Jun;49(6):734-739.
    PMID: 28435019 DOI: 10.1016/j.ijantimicag.2017.01.030
    This study was conducted to investigate the epidemiology and antimicrobial susceptibility patterns of Gram-negative bacilli (GNB) isolated from intra-abdominal infections (IAIs) in the Asia-Pacific region (APR) from 2010-2013. A total of 17 350 isolates were collected from 54 centres in 13 countries in the APR. The three most commonly isolated GNB were Escherichia coli (46.1%), Klebsiella pneumoniae (19.3%) and Pseudomonas aeruginosa (9.8%). Overall, the rates of extended-spectrum β-lactamase (ESBL)-producing E. coli and K. pneumoniae were 38.2% and 24.3%, respectively, and they were highest in China (66.6% and 38.7%, respectively), Thailand (49.8% and 36.5%, respectively) and Vietnam (47.9% and 30.4%, respectively). During 2010-2013, the rates of ESBL-producing E. coli and K. pneumoniae isolates causing community-associated (CA) IAIs (collected <48 h after admission) were 26.0% and 13.5%, respectively, and those causing hospital-associated (HA) IAIs were 48.0% and 30.6%, respectively. Amikacin, ertapenem and imipenem were the most effective agents against ESBL-producing isolates. Piperacillin/tazobactam displayed good in vitro activity (91.4%) against CA ESBL-producing E. coli. For other commonly isolated Enterobacteriaceae, fluoroquinolones, cefepime and carbapenems exhibited better in vitro activities than third-generation cephalosporins. Amikacin possessed high in vitro activity against all GNB isolates (>80%) causing IAIs, except for Acinetobacter calcoaceticus-baumannii (ACB) complex (30.9% for HA-IAI isolates). All of the antimicrobial agents tested exhibited <45% in vitro activity against ACB complex. Antimicrobial resistance is a persistent threat in the APR and continuous monitoring of evolutionary trends in the susceptibility patterns of GNB causing IAIs in this region is mandatory.
  12. Zarzeczna N, Hanel PHP, Rutjens BT, Bono SA, Chen YH, Haddock G
    J Exp Psychol Appl, 2023 Oct 30.
    PMID: 37902696 DOI: 10.1037/xap0000500
    We examined how different types of communication influence people's responses to health advice. We tested whether presenting COVID-19 prevention advice (e.g., washing hands/distancing) as either originating from a government or scientific source would affect people's trust in and intentions to comply with the advice. We also manipulated uncertainty in communicating the advice effectiveness. To achieve this, we conducted an experiment using large samples of participants (N = 4,561) from the United Kingdom, the United States, Canada, Malaysia, and Taiwan. Across countries, participants found messages more trustworthy when the purported source was science rather than the government. This effect was moderated by political orientation in all countries except for Canada, while religiosity moderated the source effect in the United States. Although source did not directly affect intentions to act upon the advice, we found an indirect effect via trust, such that a more trusted source (i.e., science) was predictive of higher intentions to comply. However, the uncertainty manipulation was not effective. Together, our findings suggest that despite prominence of science skepticism in public discourse, people trust scientists more than governments when it comes to practical health advice. It is therefore beneficial to communicate health messages by stressing their scientific bases. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
  13. Taylor EJ, Pariñas S, Mamier I, Atarhim MA, Angeles L, Aslan H, et al.
    J Clin Nurs, 2023 Feb;32(3-4):597-609.
    PMID: 36039033 DOI: 10.1111/jocn.16497
    AIMS AND OBJECTIVES: To compare the frequency of nurse-provided spiritual care across diverse cultures.

    BACKGROUND: Given an ethical imperative to respect patient spirituality and religiosity, nurses are increasingly taught and expected to provide spiritual care. Although nurses report positive attitudes toward spiritual care, they typically self-report providing it infrequently. Evidence about the reported frequency of spiritual care is constrained by substantial variation in its measurement.

    DESIGN: This cross-sectional, descriptive study involved secondary analysis of data collected in multiple sites globally using one quantitative instrument.

    METHODS: Data were collected from practicing nurses using the Nurse Spiritual Care Therapeutics Scale and analysed using descriptive statistics and a meta-analysis procedure with random-effect modelling. Datasets from 16 studies completed in Indonesia, Iran, Malaysia, Philippines, Portugal, Taiwan, Turkey and the United States contributed to a pooled sample (n = 4062). STROBE guidelines for cross-sectional observational studies were observed.

    RESULTS: Spiritual care varied between countries and within countries. It was slightly more frequent within Islamic cultures compared with predominantly Christian cultures. Likewise, frequency of spiritual care differed between nurses in palliative care, predominantly hospital/inpatient settings, and skilled nursing homes. Overall, "Remaining present…" was the most frequent therapeutic, whereas documenting spiritual care and making arrangements for the patient's clergy or a chaplain to visit were among the most infrequent therapeutics.

    CONCLUSIONS: In widely varying degrees of frequency, nurses around the world provide care that is cognisant of the spiritual and religious responses to living with health challenges. Future research should be designed to adjust for the multiple factors that may contribute to nurses providing spiritual care.

    RELEVANCE TO CLINICAL PRACTICE: Findings offer a benchmark and begin to inform nurse leaders about what may be normative in practice. They also encourage nurses providing direct patient care that they are not alone and inform educators about what instruction future nurses require.

  14. Liao TZ, Chen YH, Tsai JN, Chao C, Huang TP, Hong CF, et al.
    Plant Dis, 2023 Jul;107(7):2039-2053.
    PMID: 36428260 DOI: 10.1094/PDIS-06-22-1285-RE
    Brown root rot disease (BRRD), caused by Phellinus noxius, is an important tree disease in tropical and subtropical areas. To improve chemical control of BRRD and deter emergence of fungicide resistance in P. noxius, this study investigated control efficacies and systemic activities of fungicides with different modes of action. Fourteen fungicides with 11 different modes of action were tested for inhibitory effects in vitro on 39 P. noxius isolates from Taiwan, Hong Kong, Malaysia, Australia, and Pacific Islands. Cyproconazole, epoxiconazole, and tebuconazole (Fungicide Resistance Action Committee [FRAC] 3, target-site G1) inhibited colony growth of P. noxius by 99.9 to 100% at 10 ppm and 97.7 to 99.8% at 1 ppm. The other effective fungicide was cyprodinil + fludioxonil (FRAC 9 + 12, target-site D1 + E2), which showed growth inhibition of 96.9% at 10 ppm and 88.6% at 1 ppm. Acropetal translocation of six selected fungicides was evaluated in bishop wood (Bischofia javanica) seedlings by immersion of the root tips in each fungicide at 100 ppm, followed by liquid or gas chromatography tandem mass spectrometry analyses of consecutive segments of root, stem, and leaf tissues at 7 and 21 days posttreatment. Bidirectional translocation of the fungicides was also evaluated by stem injection of fungicide stock solutions. Cyproconazole and tebuconazole were the most readily absorbed by roots and efficiently transported acropetally. Greenhouse experiments suggested that cyproconazole, tebuconazole, and epoxiconazole have a slightly higher potential for controlling BRRD than mepronil, prochloraz, and cyprodinil + fludioxonil. Because all tested fungicides lacked basipetal translocation, soil drenching should be considered instead of trunk injection for their use in BRRD control.
  15. Chen KJ, Lai CC, Chen HC, Chong YJ, Sun MH, Chen YP, et al.
    Microorganisms, 2021 Apr 24;9(5).
    PMID: 33923356 DOI: 10.3390/microorganisms9050918
    Enterococcus faecalis is known to cause severe acute endophthalmitis and often leads to poor visual outcomes in most ophthalmic infections. This retrospective study is to report the clinical settings, antimicrobial susceptibility patterns, and visual outcome of E. faecalis endophthalmitis at a tertiary referral institution in Taoyuan, Taiwan. E. faecalis endophthalmitis was diagnosed in 37 eyes of 37 patients. Post-cataract surgery was the most common cause (n = 27, 73%), followed by bleb-associated (n = 3, 8%), endogenous (n = 2, 5%), corneal ulcer-related (n = 2, 5%), post-vitrectomy (n = 1, 3%), post-pterygium excision (n = 1, 3%), and trauma (n = 1, 3%). Visual acuities upon presentation ranged from counting fingers to no light perception. Pars plana vitrectomy with intravitreal antibiotics were performed in 23 eyes (76%) as primary or secondary treatment. All isolates (37/37, 100%) were sensitive to vancomycin, penicillin, ampicillin, and teicoplanin. Six of 22 eyes (27%) were resistant to high-level gentamicin (minimum inhibitory concentration > 500 mg/L). Final visual acuities were better than 20/400 in 11 eyes (30%), 5/200 to hand motions in 4 eyes (11%), and light perception to no light perception in 22 eyes (59%). Three eyes were treated with evisceration. Compared with non-cataract subgroups, the post-cataract subgroup showed a significant difference of better visual prognosis (p = 0.016).
  16. Hung TH, Li YH, Tseng CP, Lan YW, Hsu SC, Chen YH, et al.
    Cancer Gene Ther, 2015 May;22(5):262-70.
    PMID: 25908454 DOI: 10.1038/cgt.2015.15
    Inappropriate c-MET signaling in cancer can enhance tumor cell proliferation, survival, motility, and invasion. Inhibition of c-MET signaling induces apoptosis in a variety of cancers. It has also been recognized as a novel anticancer therapy approach. Furthermore, reports have also indicated that constitutive expression of P-glycoprotein (ABCB1) is involved in the HGF/c-MET-related pathway of multidrug resistance ABCB1-positive human hepatocellular carcinoma cell lines. We previously reported that elevated expression levels of PKCδ and AP-1 downstream genes, and HGF receptor (c-MET) and ABCB1, in the drug-resistant MES-SA/Dx5 cells. Moreover, leukemia cell lines overexpressing ABCB1 have also been shown to be more resistant to the tyrosine kinase inhibitor imatinib mesylate. These findings suggest that chemoresistant cancer cells may also develop a similar mechanism against chemotherapy agents. To circumvent clinical complications arising from drug resistance during cancer therapy, the present study was designed to investigate apoptosis induction in ABCB1-overexpressed cancer cells using c-MET-targeted RNA interference technology in vitro and in vivo. The results showed that cell viability decreased and apoptosis rate increased in c-MET shRNA-transfected HGF/c-MET pathway-positive MES-SA/Dx5 and MCF-7/ADR2 cell lines in a dose-dependent manner. In vivo reduction of tumor volume in mice harboring c-MET shRNA-knockdown MES-SA/Dx5 cells was clearly demonstrated. Our study demonstrated that downregulation of c-MET by shRNA-induced apoptosis in a multidrug resistance cell line.
  17. Lee MT, Chen YH, Mackie K, Chiou LC
    J Pain, 2021 03;22(3):300-312.
    PMID: 33069869 DOI: 10.1016/j.jpain.2020.09.003
    Analgesic tolerance to opioids contributes to the opioid crisis by increasing the quantity of opioids prescribed and consumed. Thus, there is a need to develop non-opioid-based pain-relieving regimens as well as strategies to circumvent opioid tolerance. Previously, we revealed a non-opioid analgesic mechanism induced by median nerve electrostimulation at the overlaying PC6 (Neiguan) acupoint (MNS-PC6). Here, we further examined the efficacy of MNS-PC6 in morphine-tolerant mice with neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. Daily treatments of MNS-PC6 (2 Hz, 2 mA), but not electrostimulation at a nonmedian nerve-innervated location, for a week post-CCI induction significantly suppressed established mechanical allodynia in CCI-mice in an orexin-1 (OX1) and cannabinoid-1 (CB1) receptor-dependent fashion. This antiallodynic effect induced by repeated MNS-PC6 was comparable to that induced by repeated gabapentin (50 mg/kg, i.p.) or single morphine (10 mg/kg, i.p.) treatments, but without tolerance, unlike repeated morphine-induced analgesia. Furthermore, single and repeated MNS-PC6 treatments remained fully effective in morphine-tolerant CCI-mice, also in an OX1 and CB1 receptor-dependent fashion. In CCI-mice receiving escalating doses of morphine for 21 days (10, 20 and 50 mg/kg), single and repeated MNS-PC6 treatments remained fully effective. Therefore, repeated MNS-PC6 treatments induce analgesia without tolerance, and retain efficacy in opioid-tolerant mice via a mechanism that involves OX1 and CB1 receptors. This study suggests that MNS-PC6 is an alternative pain management strategy that maybe useful for combatting the opioid epidemic, and opioid-tolerant patients receiving palliative care. PERSPECTIVE: Median nerve stimulation relieves neuropathic pain in mice without tolerance and retains efficacy even in mice with analgesic tolerance to escalating doses of morphine, via an opioid-independent, orexin-endocannabinoid-mediated mechanism. This study provides a proof of concept for utilizing peripheral nerve stimulating devices for pain management in opioid-tolerant patients.
  18. Chen YH, Lee HJ, Lee MT, Wu YT, Lee YH, Hwang LL, et al.
    Proc Natl Acad Sci U S A, 2018 11 06;115(45):E10720-E10729.
    PMID: 30348772 DOI: 10.1073/pnas.1807991115
    Adequate pain management remains an unmet medical need. We previously revealed an opioid-independent analgesic mechanism mediated by orexin 1 receptor (OX1R)-initiated 2-arachidonoylglycerol (2-AG) signaling in the ventrolateral periaqueductal gray (vlPAG). Here, we found that low-frequency median nerve stimulation (MNS) through acupuncture needles at the PC6 (Neiguan) acupoint (MNS-PC6) induced an antinociceptive effect that engaged this mechanism. In mice, MNS-PC6 reduced acute thermal nociceptive responses and neuropathy-induced mechanical allodynia, increased the number of c-Fos-immunoreactive hypothalamic orexin neurons, and led to higher orexin A and lower GABA levels in the vlPAG. Such responses were not seen in mice with PC6 needle insertion only or electrical stimulation of the lateral deltoid, a nonmedian nerve-innervated location. Directly stimulating the surgically exposed median nerve also increased vlPAG orexin A levels. MNS-PC6-induced antinociception (MNS-PC6-IA) was prevented by proximal block of the median nerve with lidocaine as well as by systemic or intravlPAG injection of an antagonist of OX1Rs or cannabinoid 1 receptors (CB1Rs) but not by opioid receptor antagonists. Systemic blockade of OX1Rs or CB1Rs also restored vlPAG GABA levels after MNS-PC6. A cannabinoid (2-AG)-dependent mechanism was also implicated by the observations that MNS-PC6-IA was prevented by intravlPAG inhibition of 2-AG synthesis and was attenuated in Cnr1-/- mice. These findings suggest that PC6-targeting low-frequency MNS activates hypothalamic orexin neurons, releasing orexins to induce analgesia through a CB1R-dependent cascade mediated by OX1R-initiated 2-AG retrograde disinhibition in the vlPAG. The opioid-independent characteristic of MNS-PC6-induced analgesia may provide a strategy for pain management in opioid-tolerant patients.
  19. Chen YJ, Chang JC, Lai EL, Liao TL, Chen HH, Hung WT, et al.
    Semin Arthritis Rheum, 2020 06;50(3):451-457.
    PMID: 32115237 DOI: 10.1016/j.semarthrit.2020.01.014
    OBJECTIVES: Systemic lupus erythematosus (SLE) is an autoimmune disease that develops mainly in women of reproductive age. We aimed to explore the risk of pregnancy complications in Asian patients with SLE.

    METHODS: From January 2005 to December 2014, we conducted a nationwide case-control study, using Taiwan's National Health Insurance Research Database. Obstetric complications and perinatal outcomes in SLE patients were compared with those without SLE.

    RESULTS: 2059 SLE offspring and 8236 age-matched, maternal healthy controls were enrolled. We found increased obstetric and perinatal complications in SLE population compared with healthy controls. SLE patients exhibited increased risk of preeclampsia/eclampsia (8.98% vs.1.98%, odds ratio [OR]: 3.87, 95% confidence interval [95% CI]: 3.08-4.87, p<0.0001). Their offspring tended to have lower Apgar scores (<7) at both 1 min (10.7% vs. 2.58%, p<0.0001) and 5 min (4.25% vs. 1.17%, p<0.0001), as well as higher rates of intrauterine growth restriction (IUGR, 9.91% vs. 4.12%, OR: 2.24, 95% CI: 1.85-2.71, p<0.0001), preterm birth (23.70% vs 7.56%, OR: 3.00, 95% CI: 2.61-3.45, p<0.0001), and stillbirth (4.23% vs. 0.87%, OR: 3.59, 95% CI: 2.54-5.06, p<0.0001). The risks of preterm birth and stillbirth were markedly increased in SLE patients with concomitant preeclampsia/eclampsia or IUGR. Preterm birth of SLE patients was 1~4 gestational weeks earlier than that of healthy controls and the peak occurrence of stillbirth in SLE population was at 20~30 gestational weeks.

    CONCLUSIONS: Asian SLE patients exhibited increased risks of maternal complications and adverse birth outcomes. Frequent antenatal visits before 20 gestational weeks are recommended in high-risk SLE patients.

Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links