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1.
Gerontology ; : 1-16, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38636462

RESUMO

INTRODUCTION: Footcare is an important component of wellbeing in older adults and the promotion of appropriate footcare interventions is imperative for health professionals working with this population. In this scoping review, we describe the health promotion models informing footcare interventions for older adults. The objectives were to (i) understand the context(s) where health promotion models have informed footcare interventions; (ii) identify the health promotion models informing interventions; and (iii) document the effectiveness of theoretically informed health promotion interventions for improving footcare in older adults. METHODS: Footcare interventions developed using health promotion models worldwide and published in English before July 2023 were searched using MEDLINE, Embase, CINAHL, Cochrane Library, and Google Scholar. RESULTS: A total of 2,078 articles were identified, of which 31 were retrieved and assessed for eligibility. Eight articles met the eligibility criteria, with most interventions delivered in Asia (n = 5) and using self-efficacy theory as their theoretical framework (n = 6). Most of the studies included people with diabetes (n = 6) and outcomes were measured using foot health outcomes, knowledge of foot health, and footcare behaviors and self-efficacy. CONCLUSION: This scoping review has identified a range of footcare interventions, with evidence of promising outcomes on improving footcare in older adults. Approaches toward methods and dosage of intervention varied across the studies and more broadly, we identified that few studies report the health promotion model informing the design of intervention(s). Further research is required to ascertain which health promotion model, modality of promotion, and implementation approach are the most effective for improving footcare in older adults.

2.
Int Urol Nephrol ; 55(8): 2059-2066, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36811817

RESUMO

BACKGROUND: Although methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization is common among end-stage kidney disease patients undergoing haemodialysis, few studies were focused on MRSA nasal carriers among haemodialysis patients with central venous catheters (CVCs). The aim of this study is to evaluate the risk factors, various clinical outcomes and effect of decolonization for MRSA nasal colonization among patients on haemodialysis via CVCs. METHODS: This was a single-centre non-concurrent cohort study of 676 patients who had new haemodialysis CVCs inserted. They were all screened for MRSA colonization via nasal swabs and were categorized into two groups: MRSA carriers and MRSA noncarriers. Potential risk factors and clinical outcomes were analysed in both groups. All MRSA carriers were given decolonization therapy and the effect of decolonization on subsequent MRSA infection was also performed. RESULTS: Eighty-two patients (12.1%) were MRSA carriers. Multivariate analysis showed that MRSA carrier (OR 5.44; 95% CI 3.02-9.79), long-term care facility resident (OR 4.08; 95% CI 2.07-8.05), history of Staphylococcus aureus infection (OR 3.20; 95% CI 1.42-7.20) and CVC in situ > 21 days (OR 2.12; 95% CI 1.15-3.93) were independent risk factors for MRSA infection. There was no significant difference in all-cause mortality between MRSA carriers and noncarriers. The MRSA infection rates were similar between MRSA carriers with successful decolonization and those who had failed/incomplete decolonization in our subgroup analysis. CONCLUSION: MRSA nasal colonization is an important cause of MRSA infection among haemodialysis patients with CVCs. However, decolonization therapy may not be effective in reducing MRSA infection.


Assuntos
Cateteres Venosos Centrais , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Estudos de Coortes , Cateteres Venosos Centrais/efeitos adversos , Diálise Renal/efeitos adversos , Infecções Estafilocócicas/tratamento farmacológico , Portador Sadio/tratamento farmacológico
3.
Artigo em Inglês | MEDLINE | ID: mdl-36310622

RESUMO

The beneficial effects of Tai Chi on the cardiovascular risk profile and the migraine trigger factors among female migraineurs remain unknown. This study aimed to evaluate the effectiveness of a 12-week Tai Chi training on blood pressure (BP) and migraine-related trigger factors, including stress, fatigue, and sleep quality among Chinese women with episodic migraine. In this study, eligible Hong Kong Chinese women aged 18-65 years were randomly assigned to the Tai Chi group adopting a modified 33-short form of Yang style Tai Chi training for 12 weeks, followed by additional 12 weeks of self-practice or the waiting list control group that maintained the usual lifestyle for 24 weeks. The primary outcome was the changes in BP from the baseline to 12 and 24 weeks. The secondary outcomes included the stress level, fatigue, and sleep quality measured by the perceived stress scale (PSS), the numeric rating scale-fatigue (NRS-fatigue), and the Pittsburgh sleep quality index (PSQI), respectively. Significant between-group differences were found in systolic BP (-6.8 mmHg at 24 weeks, P=0.02), and a decreasing trend was significant across baseline, 12 weeks, and 24 weeks between groups (P < 0.05). The 12-week Tai Chi training significantly reduced the BP level and moderately improved stress level, fatigue status, and sleep quality among Chinese women with episodic migraine. Therefore, Tai Chi could be considered a promising mind-body exercise with good feasibility for migraineurs in the future. This trial is registered with registration number NCT03015753.

4.
J Pain Res ; 15: 701-713, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35300404

RESUMO

Objective: This study aimed to examine the prevalence and features of migraine and explore the possible migraine triggers in a sample of university nursing students in Hong Kong. Methods: A cross-sectional study using self-administered questionnaires was conducted in the Hong Kong Polytechnic University in 2016. The questionnaire included ID Migraine™ for migraine screening and items measuring the frequency, duration, severity, associated symptoms, and trigger factors of migraine. Years 2-5 undergraduate nursing students from the university completed the questionnaires. Binary logistic regression was conducted to examine the migraine-associated factors. Results: A total of 702 nursing students, including 168 males and 534 females, were successfully screened. Their mean age was 20.8 ± 1.4 years. The overall prevalence of migraine reached 11.8%. Over half (67.5%) of the students with migraine experienced attacks at least once per month. Each attack had a median duration of 3 h (interquartile range: 1-4 h) and the mean pain intensity score of 6.4 ± 1.6. Students with a family history of migraine (adjusted odds ratio [OR]: 1.89; 95% confidence interval [CI]: 1.10, 3.25; p < 0.05) and poor general health status (Adjusted OR: 3.41, 95% CI: 1.05, 11.09; p < 0.05) were more likely to suffer from migraine than those without. The three most common migraine triggers were the lack of sleep (94.0%), change in sleep schedule (83.1%), and noise (81.9%). Female students were more likely to experience fatigue-triggered migraine than male students (85.9% vs 63.2%, p < 0.05). Conclusion: Migraine prevalence was relatively high among undergraduate nursing students in Hong Kong. Sleep problem was the most frequent trigger factor. The students' awareness of migraine attacks should be increased, and migraine management must be improved by avoiding common trigger factors in this population.

5.
Nephrology (Carlton) ; 26(8): 650-658, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33729651

RESUMO

AIM: Direct kidney involvement in B-cell lymphoproliferative disease is a rare disorder with only a few studies reported in Caucasian patients. The clinicopathological characteristics and outcome of this entity remain poorly described. METHODS: We retrospectively studied all adult Chinese patients who had histology-proven renal parenchymal infiltration by malignant B-cells between 1 January 2000 and 31 December 2018 at two tertiary hospitals in Hong Kong. Clinical, pathological and radiological data were collected from 20 patients. Follow-up data were analysed until 31 December 2019. RESULTS: Median follow-up duration was 22 (1-171) months. Only seven patients (35%) had established diagnosis of haematological cancer before kidney biopsy. Diffuse large B-cell lymphoma (DLBCL) was the most common subtype in our cohort (n = 5, 25%). Others included low-grade B-cell lymphoma (n = 11), intravascular large B-cell lymphoma (n = 1), mantle cell lymphoma (n = 1) and multiple myeloma (n = 2). Fourteen patients (70%) presented with AKI while 12 patients (60%) had proteinuria. Seven patients (35%) had unilateral renal mass, one had bilateral renal masses and one had bilateral diffuse nephromegaly in computed tomography. Lymphomatous tubulointerstitial infiltration was the prevalent histological finding. Nine patients (45%) had coexisting renal lesions other than direct tumour infiltration. All but one patient received chemotherapy. Ten patients died and renal responders had a significantly better survival than non-renal responders (p = .03). CONCLUSION: Direct tumour infiltration can occur in a wide variety of B-cell lymphoproliferative disorders. Coexisting immunoglobulin-related nephropathy is frequently found. Renal biopsy is required for early diagnosis which allows timely and appropriate treatment.


Assuntos
Linfócitos B , Nefropatias/etiologia , Nefropatias/patologia , Transtornos Linfoproliferativos/complicações , Transtornos Linfoproliferativos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Estudos de Coortes , Feminino , Hong Kong , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
Nat Commun ; 11(1): 5263, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067430

RESUMO

Global emergence of Gram-negative bacteria carrying the plasmid-borne resistance genes, blaMBL and mcr, raises a significant challenge to the treatment of life-threatening infections by the antibiotics, carbapenem and colistin (COL). Here, we identify an antirheumatic drug, auranofin (AUR) as a dual inhibitor of metallo-ß-lactamases (MBLs) and mobilized colistin resistance (MCRs), two resistance enzymes that have distinct structures and substrates. We demonstrate that AUR irreversibly abrogates both enzyme activity via the displacement of Zn(II) cofactors from their active sites. We further show that AUR synergizes with antibiotics on killing a broad spectrum of carbapenem and/or COL resistant bacterial strains, and slows down the development of ß-lactam and COL resistance. Combination of AUR and COL rescues all mice infected by Escherichia coli co-expressing MCR-1 and New Delhi metallo-ß-lactamase 5 (NDM-5). Our findings provide potential therapeutic strategy to combine AUR with antibiotics for combating superbugs co-producing MBLs and MCRs.


Assuntos
Antibacterianos/administração & dosagem , Auranofina/administração & dosagem , Carbapenêmicos/farmacologia , Colistina/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Inibidores de beta-Lactamases/administração & dosagem , Animais , Farmacorresistência Bacteriana Múltipla , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/antagonistas & inibidores , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Testes de Sensibilidade Microbiana , beta-Lactamases/genética , beta-Lactamases/metabolismo
7.
Prog Transplant ; 30(3): 249-253, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32552577

RESUMO

INTRODUCTION: Although the association between CYP3A5 gene polymorphism and tacrolimus dosing requirements was well established, the impact on how CYP3A5 genotype affects the acute rejection and long-term renal function in patients who received kidney transplants and were treated with tacrolimus remained controversial. DESIGN: Sixty-seven Chinese patients with kidney transplants receiving de novo tacrolimus-based immunosuppressive therapy with known CYP3A5 genotype were divided into 2 groups. Those with at least 1 CYP3A5*1 allele were CYP3A5 expressers while homozygotes for the mutant allele CYP3A5*3 were nonexpressers. Instead of trough level, our center used abbreviated area under the curve for tacrolimus monitoring. Primary outcome was the long-term renal function between both groups while secondary outcomes included the weight-adjusted daily tacrolimus dose, graft survival, incidence of biopsy-proven acute rejection (BPAR), opportunistic infection, and cancer. RESULTS: Thirty-five (52.2%) patients were CYP3A5 expressers while 32 were nonexpressers. Mean daily tacrolimus dose in the CYP3A5 expressers and nonexpressers was 0.08 (0.03) and 0.05 (0.02) mg/kg, respectively (P < .01). Starting from 1-month posttransplant, the renal function was comparable between both groups, which persisted up to 10-year. Ten patients experienced BPAR rejection and there was no significant difference in the rejection-free survival between both groups (P = .87). There was also no significant difference in the death-censored graft survival between both groups (P = .86). Finally, the incidence of opportunistic infection and posttransplant cancer was similar between them. DISCUSSION: There was no significant difference in renal function, graft survival, and acute rejection between CYP3A5 expressers and nonexpressers.


Assuntos
Citocromo P-450 CYP3A/genética , Rejeição de Enxerto/genética , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/genética , Transplante de Rim/efeitos adversos , Polimorfismo Genético , Tacrolimo/uso terapêutico , Transplantados , Adulto , Área Sob a Curva , Povo Asiático/genética , Feminino , Genótipo , Rejeição de Enxerto/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Testes de Função Renal , Masculino , Pessoa de Meia-Idade
9.
Adv Healthc Mater ; 8(18): e1900575, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31386308

RESUMO

With large anti-Stokes shifts and background-free signals, upconversion luminescent (UCL) screening assays have been a promising method to reduce the transmission of influenza epidemic, which can critically alleviate the disease burden and extra annual deaths. In this work, a luminescent resonance energy transfer sandwich assay is developed, which utilizes core-shell upconversion nanoparticles and gold nanoparticles as the donor and acceptor, respectively. The influenza H7 gene of H7N9 virus is used as the target for optimization of the assay. Importantly, the hybridization time of the assay is ≈40 min and the specificity test indicates the probes are specific toward the H7 target. The limit of detection of the system is ≈134 × 10-12 m (≈3.22 × 1010 molecules). Moreover, the assay is tested with the use of polymerase chain reaction validated samples from human isolates. The results are promising for implanting future on-site rapid influenza screening application.


Assuntos
Bioensaio/métodos , Subtipo H7N9 do Vírus da Influenza A/isolamento & purificação , Luminescência , Humanos , Limite de Detecção , Nanopartículas Metálicas/ultraestrutura , Reação em Cadeia da Polimerase , Reprodutibilidade dos Testes , Propriedades de Superfície
10.
Transplant Proc ; 51(6): 1754-1757, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31255354

RESUMO

BACKGROUND: Although high tacrolimus (FK) intrapatient variability (IPV) was shown to be associated with poor graft outcome in kidney transplant recipients (KTRs), it is uncertain whether there is any association between the CYP3A5 genotype and IPV of FK concentrations. Instead of trough level, we use calculated abbreviated AUC0-12 to investigate the impact of CYP3A5 genetic polymorphism on IPV of FK pharmacokinetics. METHODS: We conducted a retrospective, single-center study of 86 adult Chinese KTRs with known CYP3A5 genotype. Coefficient of variation (CV) was used for the quantification of FK IPV. CV of dose-normalized FK AUC0-12 was calculated and was compared between the CYP3A5 expresser group and nonexpresser group. RESULTS: Forty-one patients (47.7%) were classified as CYP3A5 expressers while 45 were nonexpressers. No significant differences in the baseline characteristics were found between expressers and nonexpressers. CYP3A5 expressers required 1.8 times higher FK dose compared with the nonexpressers. There was no significant difference in the FK CV between CYP3A5 expressers (18.2 ± 7.5%) and nonexpressers (16.7 ± 5.7%) (P = .31). CONCLUSION: The IPV of FK exposure was not associated with CYP3A5 genotype in stable KTRs. Further studies should focus on other factors such as medication nonadherence, which may explain FK IPV.


Assuntos
Citocromo P-450 CYP3A/genética , Imunossupressores/farmacocinética , Transplante de Rim , Variantes Farmacogenômicos/genética , Tacrolimo/farmacocinética , Adulto , Povo Asiático , Feminino , Genótipo , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Estudos Retrospectivos , Tacrolimo/uso terapêutico , Transplantados
11.
J Am Chem Soc ; 141(24): 9610-9616, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31117483

RESUMO

Two-dimensional MXenes are promising for various energy-related applications such as energy storage devices and electrocatalysis of water-splitting. MXenes prepared from hydrofluoric (HF) acid etching have been widely reported. Nonetheless, the acute toxicity of HF acid impedes the large-scale fabrication of MXenes and their wide utilization in energy-related applications. It is thus greatly encouraging to explore a more innocuous protocol for MXenes synthesis. Thereby, a universal strategy based on thermal-assisted electrochemical etching route is developed to synthesize MXenes (e.g., Ti2CT x, Cr2CT x, and V2CT x). Furthermore, the cobalt ion doped MXenes show an exceptionally enhanced capability of hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) activity, demonstrating their multifunctionalities, which is comparable to the commercialized catalysts. Moreover, we successfully exploited our MXenes as cathodes for the novel aqueous rechargeable battery, with proficient retention and excellent electrical output performance. This work paves a nontoxic and HF-free route to prepare various MXenes and demonstrates practical applications of the materials.

12.
Nanoscale Adv ; 1(1): 265-272, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36132455

RESUMO

Heavy metal contamination in water can pose lethal threats to public health; therefore it is highly desired to develop a rapid and sensitive sensor for monitoring water quality. Owing to their superior optical features, upconversion nanoparticles (UCNPs) are widely explored to detect metal ions based on resonance energy transfer to dye quenchers. However, these schemes heavily rely on the optical properties of the molecules, which limits the flexibility of the probe design. Herein, a flexible carbon fiber cloth/UCNP composite probe was fabricated for sensing copper(ii) (Cu2+) ions and an electrochemical (E-chem) technique was implemented for the first time to enhance its sensing performance. By applying 0.3 V on the composite probe, Cu2+ ions can be effectively accumulated through oxidation, yielding a remarkable improvement in the selectivity and sensitivity. A more outstanding detection limit of the sensor was achieved at 82 ppb under the E-chem assistance, with 300-fold enhancement compared to the detection without the E-chem effect. This sensing approach can be an alternative to molecular quenchers and open up new possibilities for simple, rapid and portable sensing of metal ions.

13.
Prim Health Care Res Dev ; 20: e102, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32800020

RESUMO

BACKGROUND: Peer-led school-based anti-smoking programs have been shown to affect the smoking behaviors of students. The aim of this study was to examine the effectiveness of a school-based peer-led live theater production advocating a smoke-free life. METHODS: This is a cross-section design study. Students from the drama club were recruited as School Health Ambassadors (SHAs). The SHAs were to involve in a theater production in advocating a smoke-free life, and were provided a health education workshop from the project team on facts relating to smoking and smoke-free life. All the students in the school were to watch the theater production as school peer audience members (SPAs). Comparison will be made between the two groups of students in their attitude and decision towards living a smoke-free life after being involved in the theater production or in watching the drama. RESULTS: A total of 409 students, 21 SHAs, and 388 SPAs were included in the project. Both the SHAs and the SPAs reported confidently about their ability to resist offers or temptation to smoke, and were determined to live a smoke-free life and refrain from smoking the first cigarette. CONCLUSIONS: A peer-led theater production advocating a smoke-free life shows some effects on students' attitude and decision to resist offers and the temptation to smoke, and to come to the decision to live a smoke-free life and refrain from smoking the first cigarette.


Assuntos
Drama , Educação em Saúde/métodos , Prevenção do Hábito de Fumar/métodos , Estudantes/psicologia , Adolescente , Estudos Transversais , Feminino , Humanos , Masculino , Grupo Associado
14.
J Prim Care Community Health ; 8(4): 349-362, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29161946

RESUMO

BACKGROUND: The purpose of this review was to explore the uptake of the human papillomavirus (HPV) vaccination, its associated factors, and the facilitators of and barriers to HPV vaccination among adolescents. METHODS: A comprehensive literature search was conducted through 5 electronic databases, including PubMed, CINAHL, Cochrane Library, Medline, and PsycInfo from January 2006 to March 2015 for studies examining the uptake, awareness, knowledge, acceptability, and intention of adolescents with regard to HPV vaccination. RESULTS: Twenty-eight studies were identified and included. The HPV vaccination uptake rate (at least 1 dose) varied significantly among countries, ranging from 2.4% to 94.4%. Scotland achieved the highest uptake of all the studies included in this review, while Hong Kong had the lowest, at 2.4% to 9.1%. This review also showed that adolescents had limited awareness and knowledge of HPV infections and vaccines, even 10 years after the vaccine had become available. CONCLUSIONS: It is recommended that barriers to the uptake of the vaccine should be addressed, and that school-based sexual health education of HPV infection and vaccine promotion should be reinforced.


Assuntos
Neoplasias do Ânus/prevenção & controle , Neoplasias Orofaríngeas/prevenção & controle , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Neoplasias do Colo do Útero/prevenção & controle , Cobertura Vacinal/estatística & dados numéricos , Adolescente , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Hong Kong , Humanos , Intenção , Masculino , Aceitação pelo Paciente de Cuidados de Saúde , Fatores de Risco , Escócia
15.
BMC Res Notes ; 10(1): 390, 2017 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-28797277

RESUMO

BACKGROUND: The aim of this study is to examine knowledge and attitude as facilitators and barriers to the acceptance of HPV vaccination for adolescent girls by mothers and adolescent girls. METHODS: A cross-sectional survey conducted in Hong Kong in January 2010. Adolescent girls aged 12-18, together with their mothers, were recruited to complete two separate questionnaires with similar questions. RESULTS: A total of 170 mother-adolescent girl dyads were recruited. When the daughters and mothers were compared, the mothers were found to be more aware of "the risk of becoming infected with HPV through early sexual intercourse," while more daughters than mothers knew that "the HPV virus cannot be cured with antibiotics." Significantly more daughters perceived that they had a "chance of being infected with HPV and getting cervical cancer without the vaccine," while more mothers were concerned that "vaccinating for HPV will cause a girl to be stigmatized as promiscuous" and thought that their "adolescent daughters are too young to receive the HPV vaccine." The major predictive factor for the acceptance of the HPV vaccine among mothers was "The HPV vaccine is safe" (OR = 10.126, 95% CI 2.47-41.54). Among daughters who accepted the vaccine, the predictive factor was "The HPV vaccine can prevent most HPV infections" (OR = 6.274, 95% CI 1.93-20.42). CONCLUSIONS: The findings provide healthcare professionals with a better understanding of the differences between mothers and adolescent girls in knowledge, attitude, and potential factors associated with acceptance of the HPV vaccine. Health professionals should promote the early prevention of HPV infection and eliminate the stigma surrounding HPV vaccination to increase its acceptance. The government should provide financial support for adolescent girls to receive the vaccination in school.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde/etnologia , Vacinas contra Papillomavirus , Aceitação pelo Paciente de Cuidados de Saúde/etnologia , Adolescente , Adulto , Criança , Feminino , Hong Kong/etnologia , Humanos , Mães , Núcleo Familiar
16.
Biochim Biophys Acta ; 1840(3): 958-63, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24246953

RESUMO

BACKGROUND: Ricin is a type II ribosome-inactivating protein (RIP) that potently inactivates eukaryotic ribosomes by removing a specific adenine residue at the conserved α-sarcin/ricin loop of 28S ribosomal RNA (rRNA). Here, we try to increase the specificity of the enzymatically active ricin A chain (RTA) towards human immunodeficiency virus type 1 (HIV-1) by adding a loop with HIV protease recognition site to RTA. METHODS: HIV-specific RTA variants were constructed by inserting a peptide with HIV-protease recognition site either internally or at the C-terminal region of wild type RTA. Cleavability of variants by viral protease was tested in vitro and in HIV-infected cells. The production of viral p24 antigen and syncytium in the presence of C-terminal variants was measured to examine the anti-HIV activities of the variants. RESULTS: C-terminal RTA variants were specifically cleaved by HIV-1 protease both in vitro and in HIV-infected cells. Upon proteolysis, the processed variants showed enhanced antiviral effect with low cytotoxicity towards uninfected cells. CONCLUSIONS: RTA variants with HIV protease recognition sequence engineered at the C-terminus were cleaved and the products mediated specific inhibitory effect towards HIV replication. GENERAL SIGNIFICANCE: Current cocktail treatment of HIV infection fails to eradicate the virus from patients. Here we illustrate the feasibility of targeting an RIP towards HIV-infected cells by incorporation of HIV protease cleavage sequence. This approach may be generalized to other RIPs and is promising in drug design for combating HIV.


Assuntos
Fármacos Anti-HIV/farmacologia , Ricina/farmacologia , Sequência de Aminoácidos , Sequência de Bases , Linhagem Celular , Humanos , Dados de Sequência Molecular , Engenharia de Proteínas , Estrutura Terciária de Proteína , Ricina/química
17.
Food Chem ; 141(3): 2522-5, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-23870990

RESUMO

Hedyotis diffusa Willd. (Baihuasheshecao) is an ingredient of herbal teas commonly consumed in the Orient and tropical Asia for cancer treatment and health maintenance. In the market, this ingredient is frequently adulterated by the related species Hedyotis corymbosa (L.) Lam. The objective of this study is to develop a novel loop-mediated isothermal amplification (LAMP) technique to differentiate H. diffusa from its adulterant H. corymbosa. A set of four internal control primers (F3, FIP, BIP and B3) were designed based on six loci in the internal transcribed spacer (ITS) for LAMP of both H. diffusa and H. corymbosa. Two specific primers (S_F3 and S_FIP) were designed for specific LAMP detection of H. diffusa only. Our data showed that LAMP was successful for both H. diffusa and H. corymbosa in internal control. In contrast, only H. diffusa was detected in specific LAMP using the specific primers S_F3 and S_FIP. This study showed that LAMP was useful to differentiate H. diffusa from its adulterant H. corymbosa. This study is significant for the verification of the authenticity for better quality control of this common herbal tea ingredient. The strategy of including an internal control assures the quality of the concerned DNA region for LAMP.


Assuntos
Bebidas/análise , Hedyotis/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Primers do DNA/genética , DNA Intergênico/genética , DNA de Plantas/genética , Controle de Qualidade
18.
PLoS One ; 7(12): e49608, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23251345

RESUMO

Ribosome-inactivating proteins (RIPs) inactivate prokaryotic or eukaryotic ribosomes by removing a single adenine in the large ribosomal RNA. Here we show maize RIP (MOD), an atypical RIP with an internal inactivation loop, interacts with the ribosomal stalk protein P2 via Lys158-Lys161, which is located in the N-terminal domain and at the base of its internal loop. Due to subtle differences in the structure of maize RIP, hydrophobic interaction with the 'FGLFD' motif of P2 is not as evidenced in MOD-P2 interaction. As a result, interaction of P2 with MOD was weaker than those with trichosanthin and shiga toxin A as reflected by the dissociation constants (K(D)) of their interaction, which are 1037.50 ± 65.75 µM, 611.70 ± 28.13 µM and 194.84 ± 9.47 µM respectively.Despite MOD and TCS target at the same ribosomal protein P2, MOD was found 48 and 10 folds less potent than trichosanthin in ribosome depurination and cytotoxicity to 293T cells respectively, implicating the strength of interaction between RIPs and ribosomal proteins is important for the biological activity of RIPs. Our work illustrates the flexibility on the docking of RIPs on ribosomal proteins for targeting the sarcin-ricin loop and the importance of protein-protein interaction for ribosome-inactivating activity.


Assuntos
Fosfoproteínas/metabolismo , Proteínas Ribossômicas/metabolismo , Proteínas Inativadoras de Ribossomos/metabolismo , Ribossomos/metabolismo , Zea mays/metabolismo , Animais , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fosfoproteínas/genética , RNA Ribossômico/metabolismo , Ratos , Proteínas Ribossômicas/genética , Proteínas Inativadoras de Ribossomos/genética , Proteínas Inativadoras de Ribossomos/farmacologia , Ribossomos/efeitos dos fármacos , Toxina Shiga/genética , Toxina Shiga/metabolismo , Tricosantina/genética , Tricosantina/metabolismo , Zea mays/genética
19.
Nucleic Acids Res ; 37(2): 602-10, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19073700

RESUMO

Ribosome-inactivating proteins (RIPs) inhibit protein synthesis by enzymatically depurinating a specific adenine residue at the sarcin-ricin loop of the 28S rRNA, which thereby prevents the binding of elongation factors to the GTPase activation centre of the ribosome. Here, we present the 2.2 A crystal structure of trichosanthin (TCS) complexed to the peptide SDDDMGFGLFD, which corresponds to the conserved C-terminal elongation factor binding domain of the ribosomal P protein. The N-terminal region of this peptide interacts with Lys173, Arg174 and Lys177 in TCS, while the C-terminal region is inserted into a hydrophobic pocket. The interaction with the P protein contributes to the ribosome-inactivating activity of TCS. This 11-mer C-terminal P peptide can be docked with selected important plant and bacterial RIPs, indicating that a similar interaction may also occur with other RIPs.


Assuntos
Fosfoproteínas/química , Proteínas Ribossômicas/química , Tricosantina/química , Sequência de Aminoácidos , Modelos Moleculares , Dados de Sequência Molecular , Peptídeos/química , Estrutura Terciária de Proteína , Homologia de Sequência de Aminoácidos
20.
Nucleic Acids Res ; 35(18): 6259-67, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17855394

RESUMO

Maize ribosome-inactivating protein is classified as a class III or an atypical RNA N-glycosidase. It is synthesized as an inactive precursor with a 25-amino acid internal inactivation region, which is removed in the active form. As the first structural example of this class of proteins, crystals of the precursor and the active form were diffracted to 2.4 and 2.5 A, respectively. The two proteins are similar, with main chain root mean square deviation (RMSD) of 0.519. In the precursor, the inactivation region is found on the protein surface and consists of a flexible loop followed by a long alpha-helix. This region diminished both the interaction with ribosome and cytotoxicity, but not cellular uptake. Like bacterial ribosome-inactivating proteins, maize ribosome-inactivating protein does not have a back-up glutamate in the active site, which helps the protein to retain some activity if the catalytic glutamate is mutated. The structure reveals that the active site is too small to accommodate two glutamate residues. Our structure suggests that maize ribosome-inactivating protein may represent an intermediate product in the evolution of ribosome-inactivating proteins.


Assuntos
Ácido Glutâmico/química , Proteínas de Plantas/química , Inibidores da Síntese de Proteínas/química , Proteínas Inativadoras de Ribossomos/química , Animais , Sítios de Ligação , Linhagem Celular Tumoral , Cristalografia por Raios X , Ácido Glutâmico/genética , Humanos , Modelos Moleculares , Mutação , Proteínas de Plantas/genética , Proteínas de Plantas/farmacologia , Inibidores da Síntese de Proteínas/metabolismo , Inibidores da Síntese de Proteínas/farmacologia , Ratos , Proteínas Ribossômicas/metabolismo , Proteínas Inativadoras de Ribossomos/genética , Proteínas Inativadoras de Ribossomos/farmacologia , Ribossomos/química , Relação Estrutura-Atividade
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