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1.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 59(7): 653-662, 2024 Jul 09.
Artigo em Chinês | MEDLINE | ID: mdl-38949133

RESUMO

Objective: To investigate the regulatory effect and mechanism of interleukin-22 (IL-22) on the gingival epithelial barrier in the context of periodontal inflammation. Methods: IL-22 knockout (IL-22 KO) mice were constructed, and periodontitis mice models were established through oral gavage with polymicrobial inoculation. DNAs were extracted from the oral plaques of IL-22 KO periodontitis mice group (n=7) and their wild-type littermates periodontitis group (n=7) to establish a periodontitis-related oral microbiota database"PD-RiskMicroDB", determining the relationship between changes in oral microbiota and microbial function in two groups using 16S rRNA sequencing results. Gingival epithelial cells (GEC) were cultured by modified trypsinization method, and were stimulated with 100 µg/L IL-22, Porphyromonas gingivalis (Pg) (multiplicity of infection:100), separately or together for 3 and 12 hours. The experimental groups were as follows: control group (no stimulation), IL-22 group, Pg group and Pg+IL-22 group. The expression of barrier protein E-cadherin in each group at 3 h was detected by immunofluorescence, real-time fluorescence quantitative PCR (RT-qPCR) and Western blotting. Fluorescein isothiocyanate-dextran-mediated epithelial cell permeability experiment was conducted to clarify the changes in permeability of GEC in each group at 3 and 12 h. The mRNA expressions of E-cadherin in the gingival epithelium of wild-type littermates periodontitis group and IL-22 KO periodontitis group were detected by RT-qPCR. Fifteen C57BL/6 wild-type mice were randomly divided into control group (n=5), periodontitis group (n=5) and periodontitis+IL-22 treatment group (n=5). RT-qPCR and immunohistochemistry (IHC) staining were used to detect the expression level of E-cadherin in the gingival epithelium of each group. Results: 16S rRNA sequencing results showed that the composition of oral microbiota changed in IL-22 KO periodontitis group, of which the abundance of bacterial genera related to periodontal tissue invasion was significantly increased (linear discriminant analysis score: 2.22, P=0.009), compared with wild-type littermates periodontitis group. In vitro cell experiments showed that after Pg infection for 3 hours, the cell connections of GEC in Pg group were interrupted, and the fluorescence intensity of E-cadherin was reduced in Pg group compared with the control group. Meanwhile, the mRNA and protein expression levels of E-cadherin (mRNA: 0.69±0.12; protein: 0.60±0.12) were downregulated compared with the control group [mRNA: 1.00±0.00 (P=0.043); protein: 1.04±0.08 (P=0.003)], respectively. The fluorescence intensity of E-cadherin in the Pg+IL-22 group was enhanced compared with Pg group, and expression levels of E-cadherin mRNA (1.16±0.10) and protein (0.98±0.07) in Pg+IL-22 group showed a significant increase compared with Pg group [mRNA: 0.69±0.12 (P=0.005); protein: 0.60±0.12 (P=0.007)]. The result of epithelial permeability test showed that there was no statistical difference in epithelial permeability among control group, Pg group, IL-22 group and Pg+IL-22 group with treatment for 3 hours (F=0.20, P=0.893). While when the treatment time turned to be 12 hours, the epithelial barrier permeability showed a significant increase in Pg group (1.39±0.15) compared with control group (1.00±0.00, P=0.027), and a decrease in Pg+IL-22 group (1.02±0.18) compared with Pg group (1.39±0.15, P=0.034). In vivo, the mRNA expression of E-cadherin in the gingival epithelium of IL-22 KO periodontitis group decreased significantly (0.32±0.21) compared with wild-type littermates periodontitis group (1.01±0.01) (t=5.70, P=0.005). Moreover, RT-qPCR and IHC staining results showed that the mRNA expression level of E-cadherin (0.40±0.07) and absorbance value of E-cadherin positive expression (0.02±0.00) in gingival epithelial tissue of periodontitis group were both significantly down-regulated compared with control group [mRNA: 1.00±0.00 (P=0.005); absorbance value of E-cadherin positive expression: 0.04±0.01 (P=0.006)]. Meanwhile, the mRNA expression level of E-cadherin (1.06±0.24) and the absorbance value of E-cadherin positive expression (0.03±0.01) were both observed increase in periodontitis+IL-22 treatment group compared with periodontitis group (P=0.003, P=0.039). Conclusions: IL-22 may exert a protective effect on the gingival epithelial barrier in an inflammatory environment by regulating the invasiveness of oral microbiota and the expression of host barrier protein.


Assuntos
Caderinas , Gengiva , Interleucina 22 , Interleucinas , Camundongos Knockout , Microbiota , Periodontite , Porphyromonas gingivalis , Animais , Interleucinas/metabolismo , Caderinas/metabolismo , Gengiva/citologia , Gengiva/metabolismo , Gengiva/microbiologia , Camundongos , Periodontite/microbiologia , Periodontite/metabolismo , Células Epiteliais/metabolismo , RNA Ribossômico 16S
2.
Trop Biomed ; 40(3): 273-280, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37897158

RESUMO

Most of the public health importance coronaviruses, such as Severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV-2 are likely originated from bats and spread to humans through intermediate hosts; civet cats, dromedary camel and Malayan pangolin, respectively. SARS-CoV-2-like coronaviruses were detected in Thailand, which is neighbouring with Kelantan in East Coast Malaysia. To date, there is no report on the presence of public health concerns (SARS-CoV, SARS-CoV-2 and MERS-CoV) coronaviruses in bats from Malaysia. This study was aimed to elucidate the presence of these coronaviruses in bat samples from East Coast, Malaysia. A total of hundred seventy oropharyngeal swab samples were collected from three states of East Coast Malaysia. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was conducted based on partial 3' Untranslated region (3'UTR) or ORF10 gene and the products were sequenced. The sequences were compared with all coronavirus sequences from the National Center for Biotechnology Information-GenBank (NCBI-GenBank) using NCBI-Basic Local Alignment Search Tool (NCBI-BLAST) software. A phylogenetic tree was constructed to determine the genetic relationship among the detected coronaviruses with the reference coronaviruses from the NCBI-GenBank. Our results showed that SARSCoV-2-like viruses were present in 3% (5/170) of the bats from East Coast Malaysia that have 98-99% sequence identities and are genetically related to SARS-CoV-2 from humans. This finding indicates the presence of SARS-CoV-2-like viruses in bats from East Coast Malaysia that may become a public health concern in the future.


Assuntos
COVID-19 , Quirópteros , Animais , Humanos , SARS-CoV-2 , Filogenia , Malásia/epidemiologia
3.
Tropical Biomedicine ; : 273-280, 2023.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-1006824

RESUMO

@#Most of the public health importance coronaviruses, such as Severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and SARS-CoV-2 are likely originated from bats and spread to humans through intermediate hosts; civet cats, dromedary camel and Malayan pangolin, respectively. SARS-CoV-2-like coronaviruses were detected in Thailand, which is neighbouring with Kelantan in East Coast Malaysia. To date, there is no report on the presence of public health concerns (SARS-CoV, SARS-CoV-2 and MERS-CoV) coronaviruses in bats from Malaysia. This study was aimed to elucidate the presence of these coronaviruses in bat samples from East Coast, Malaysia. A total of hundred seventy oropharyngeal swab samples were collected from three states of East Coast Malaysia. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was conducted based on partial 3’ Untranslated region (3’UTR) or ORF10 gene and the products were sequenced. The sequences were compared with all coronavirus sequences from the National Center for Biotechnology Information-GenBank (NCBI-GenBank) using NCBI-Basic Local Alignment Search Tool (NCBI-BLAST) software. A phylogenetic tree was constructed to determine the genetic relationship among the detected coronaviruses with the reference coronaviruses from the NCBI-GenBank. Our results showed that SARSCoV-2-like viruses were present in 3% (5/170) of the bats from East Coast Malaysia that have 98-99% sequence identities and are genetically related to SARS-CoV-2 from humans. This finding indicates the presence of SARS-CoV-2-like viruses in bats from East Coast Malaysia that may become a public health concern in the future.

4.
Int J Infect Dis ; 94: 125-127, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32304822

RESUMO

OBJECTIVE: This is a brief report of 4 paediatric cases of COVID-19 infection in Malaysia BACKGROUND: COVID-19, a coronavirus, first detected in Wuhan, China has now spread rapidly to over 60 countries and territories around the world, infecting more than 85000 individuals. As the case count amongst children is low, there is need to report COVID-19 in children to better understand the virus and the disease. CASES: In Malaysia, until end of February 2020, there were four COVID-19 paediatric cases with ages ranging from 20 months to 11 years. All four cases were likely to have contracted the virus in China. The children had no symptoms or mild flu-like illness. The cases were managed symptomatically. None required antiviral therapy. DISCUSSION: There were 2 major issues regarding the care of infected children. Firstly, the quarantine of an infected child with a parent who tested negative was an ethical dilemma. Secondly, oropharyngeal and nasal swabs in children were at risk of false negative results. These issues have implications for infection control. Consequently, there is a need for clearer guidelines for child quarantine and testing methods in the management of COVID-19 in children.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Betacoronavirus/isolamento & purificação , COVID-19 , Criança , Pré-Escolar , Infecções por Coronavirus/virologia , Feminino , Humanos , Lactente , Malásia , Masculino , Pneumonia Viral/virologia , SARS-CoV-2
5.
Trop Biomed ; 37(3): 542-550, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33612769

RESUMO

Toxoplasma gondii, a zoonotic protozoan that has a worldwide distribution, is known to infect many warm-blooded vertebrates. The feline species including domestic cats are the definitive hosts for Toxoplama gondii and shed the infective oocyst. There is lack of information on the prevalence of Toxoplasma gondii in cats in Malaysia. The objective of this study was to determine both the seroprevalence of T. gondii and the prevalence of T. gondii DNA in cats' feces in Klang Valley, Malaysia. 198 blood and 201 fecal samples were collected from pet and stray cats from the local council, Dewan Bandaraya Kuala Lumpur (DBKL) and University Veterinary Hospital, Universiti Putra Malaysia respectively. The overall seroprevalence of Toxoplasma gondii in cats in the Klang Valley was found to be 5.5%. There was a high prevalence (10.5%) of T. gondii DNA detected in the cat fecal samples in both pet and stray cats suggestive of T. gondii oocyst shedding. Stray cats showed a higher seroprevalence and molecular prevalence of T. gondii than the pet cats. However, comparative analysis using Chi-square test showed no significant difference between both groups (P>0.05). Higher prevalence (10.5%) of cats shedding T. gondii DNA as compared to the seroprevalence (5.5%) was found in the cat population in the Klang Valley. The high prevalence of cats shedding T. gondii DNA is alarming as this may directly reflect the number of oocysts excreted into the environment posing a significant public health hazard.


Assuntos
Gatos/parasitologia , Toxoplasma/isolamento & purificação , Toxoplasmose Animal/epidemiologia , Animais , Animais Selvagens , Doenças do Gato/epidemiologia , Doenças do Gato/parasitologia , Estudos Transversais , DNA de Protozoário/isolamento & purificação , Fezes/parasitologia , Malásia/epidemiologia , Animais de Estimação , Prevalência , Estudos Soroepidemiológicos
6.
Trop Biomed ; 37(3): 756-762, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33612788

RESUMO

Tritrichomonas foetus is known to cause chronic diarrhea in the feline species in many different regions of the world. However, there is a paucity of information on T. foetus among cats in Malaysia. This study was conducted to determine the prevalence of Tritrichomonas foetus in the pet and stray cat population in Klang Valley, Malaysia. A total of 201 pet and stray cats' fecal samples were collected in Klang Valley. 24 samples were cultured in the InPouch® TF Feline to observe for motile trophozoites. A nested PCR protocol was used to screen for T. foetus in the collected samples. The prevalence of T. foetus in the cat population in Klang Valley was 33%. There was no association between Tritrichomonas infection and age, sex, breed or management of the cats. However, statistical analysis revealed that stray cats were more likely to be infected with T. foetus compared to pet cats. This study confirmed for the first time the presence of T. foetus among the cat population in Klang Valley, Malaysia.


Assuntos
Gatos/parasitologia , Infecções Protozoárias em Animais/epidemiologia , Tritrichomonas foetus/isolamento & purificação , Animais , Animais Selvagens , Doenças do Gato/epidemiologia , Doenças do Gato/parasitologia , Diarreia/parasitologia , Diarreia/veterinária , Fezes/parasitologia , Feminino , Malásia , Masculino , Animais de Estimação , Prevalência
7.
Tropical Biomedicine ; : 756-762, 2020.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-825606

RESUMO

@#Tritrichomonas foetus is known to cause chronic diarrhea in the feline species in many different regions of the world. However, there is a paucity of information on T. foetus among cats in Malaysia. This study was conducted to determine the prevalence of Tritrichomonas foetus in the pet and stray cat population in Klang Valley, Malaysia. A total of 201 pet and stray cats’ fecal samples were collected in Klang Valley. 24 samples were cultured in the InPouch® TF Feline to observe for motile trophozoites. A nested PCR protocol was used to screen for T. foetus in the collected samples. The prevalence of T. foetus in the cat population in Klang Valley was 33%. There was no association between Tritrichomonas infection and age, sex, breed or management of the cats. However, statistical analysis revealed that stray cats were more likely to be infected with T. foetus compared to pet cats. This study confirmed for the first time the presence of T. foetus among the cat population in Klang Valley, Malaysia.

8.
Tropical Biomedicine ; : 542-550, 2020.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-825510

RESUMO

@#Toxoplasma gondii, a zoonotic protozoan that has a worldwide distribution, is known to infect many warm-blooded vertebrates. The feline species including domestic cats are the definitive hosts for Toxoplama gondii and shed the infective oocyst. There is lack of information on the prevalence of Toxoplasma gondii in cats in Malaysia. The objective of this study was to determine both the seroprevalence of T. gondii and the prevalence of T. gondii DNA in cats’ feces in Klang Valley, Malaysia. 198 blood and 201 fecal samples were collected from pet and stray cats from the local council, Dewan Bandaraya Kuala Lumpur (DBKL) and University Veterinary Hospital, Universiti Putra Malaysia respectively. The overall seroprevalence of Toxoplasma gondii in cats in the Klang Valley was found to be 5.5%. There was a high prevalence (10.5%) of T. gondii DNA detected in the cat fecal samples in both pet and stray cats suggestive of T. gondii oocyst shedding. Stray cats showed a higher seroprevalence and molecular prevalence of T. gondii than the pet cats. However, comparative analysis using Chi-square test showed no significant difference between both groups (P>0.05). Higher prevalence (10.5%) of cats shedding T. gondii DNA as compared to the seroprevalence (5.5%) was found in the cat population in the Klang Valley. The high prevalence of cats shedding T. gondii DNA is alarming as this may directly reflect the number of oocysts excreted into the environment posing a significant public health hazard.

9.
Med J Malaysia ; 73(5): 334-335, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30350818

RESUMO

Amebiasis is one of the major causes of diarrhea in the developing countries and it can present with a wide range of gastrointestinal symptoms depending on the phase of infection. We described a case of 50 year-old male patient who presented with abdominal pain, diarrhea and vomiting. After right hemicolectomy for appendicular abscess with tumour over the ileum, histopathological examinations revealed numerous trophozoites of Entamoeba histolytica in a background of inflammations (Figure 1). Following resection of the ameboma, he received intravenous metronidazole treatment for total of two weeks duration.


Assuntos
Abscesso Abdominal/diagnóstico , Amebíase/diagnóstico , Neoplasias do Colo/diagnóstico , Entamebíase/diagnóstico , Abscesso Abdominal/parasitologia , Diagnóstico Diferencial , Entamoeba histolytica , Entamebíase/parasitologia , Humanos , Masculino , Pessoa de Meia-Idade
10.
Artigo em Chinês | MEDLINE | ID: mdl-29798210

RESUMO

Objective:We sought to compare clinical characteristics between eosinophilic and non-eosinophilic chronic rhinosinusitis with nasal polyps (CRSwNP) and asthma, and explored the association of chronic rhinosinusitis inflammation subtypewith bronchial inflammation phenotype in CRSwNP with asthma. Method:Fifty-one consecutive patients suffering from CRSwNP with asthma undergoing endoscopic sinus surgery (ESS) were recruited. Preoperative computed tomography (CT), skin-prick test, bronchial provocation test, lung function, and oral fractional exhaled nitric oxide (FeNO) measurements were conducted. Venous blood was taken within 1 week before ESS. Nasal polyps (NPs) specimens were obtained from each patient during ESS, and stained with hematoxylin and eosin. According to the pathologic characteristics of NP samples, fifty-one patients suffering from CRSwNP with asthma were grouped as eosinophilic CRSwNP (ECRSwNP) and non-ECRSwNP and three levels of eosinophil infiltration were recognized. Result:Fifty-one patients suffering from CRSwNP with asthma were grouped as ECRSwNP (n=33) and non-ECRSwNP (n=18). History of surgery, history of allergy, Lund-Mackay scores, duration of asthma, frequency of severity asthma, numbers of asthma exacerbation in the last year, FeNO, blood eosinophil percentage and absolute count were all significantly higher in the ECRSwNP with asthma group compared with the non-ECRSwNP with asthma group (P<0.05). Blood eosinophil percentage had a significant correlation with degree of eosinophil infiltration in NPs (r=0.459, P<0.01) and FeNO (r=0.591, P<0.01). There was a correlation between degree of eosinophil infiltration in NPs and FeNO (r=0.556, P<0.01). Furthermore, Lund-Mackay scores had a positive correlation with blood eosinophil percentage (r=0.327, P<0.05) and degree of eosinophil infiltration in NPs (r=0.412, P<0.01) and FeNO (r=0.691, P<0.01). Conclusion:There is different clinical characteristics between ECRSwNP with asthma and non-ECRSwNP with asthma. These data suggest that CRSwNP inflammation subtype is significantly correlated with bronchial inflammation phenotype in patients suffering from CRSwNP with asthma.


Assuntos
Asma/imunologia , Inflamação/imunologia , Pneumopatias/imunologia , Fenótipo , Rinite/imunologia , Doença Crônica , Eosinófilos , Humanos , Pólipos Nasais/imunologia , Sinusite
12.
J Helminthol ; 90(4): 392-7, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26123649

RESUMO

Ancylostoma ceylanicum is a common zoonotic nematode. Cats act as natural reservoirs of the hookworm and are involved in transmitting infection to humans, thus posing a potential risk to public health. The prevalence of feline A. ceylanicum in Guangzhou (South China) was surveyed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In total, 112 faecal samples were examined; 34.8% (39/112) and 43.8% (49/112) samples were positive with hookworms by microscopy and PCR method, respectively. Among them, 40.8% of samples harboured A. ceylanicum. Twelve positive A. ceylanicum samples were selected randomly and used for cox 1 sequence analysis. Sequencing results revealed that they had 97-99% similarity with A. ceylanicum cox 1 gene sequences deposited in GenBank. A phylogenetic tree showed that A. ceylanicum isolates were divided into two groups: one comprising four isolates from Guangzhou (South China), and the other comprising those from Malaysia, Cambodia and Guangzhou. In the latter group, all A. ceylanicum isolates from Guangzhou were clustered into a minor group again. The results indicate that the high prevalence of A. ceylanicum in stray cats in South China poses a potential risk of hookworm transmission from pet cats to humans, and that A. ceylanicum may be a species complex worldwide.


Assuntos
Ancylostoma/classificação , Ancilostomíase/veterinária , Doenças do Gato/parasitologia , Ciclo-Oxigenase 1/genética , Fezes/parasitologia , Variação Genética , Filogenia , Ancylostoma/genética , Ancylostoma/isolamento & purificação , Ancilostomíase/epidemiologia , Ancilostomíase/parasitologia , Animais , Doenças do Gato/epidemiologia , Gatos , China/epidemiologia , Análise por Conglomerados , Genótipo , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Prevalência , Análise de Sequência de DNA
13.
ScientificWorldJournal ; 2014: 205703, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24578624

RESUMO

Lipid nanoparticles are colloidal carrier systems that have extensively been investigated for controlled drug delivery, cosmetic and pharmaceutical applications. In this work, a cost effective stearic acid-oleic acid nanoparticles (SONs) with high loading of salicylic acid, was prepared by melt emulsification method combined with ultrasonication technique. The physicochemical properties, thermal analysis and encapsulation efficiency of SONs were studied. TEM micrographs revealed that incorporation of oleic acid induces the formation of elongated spherical particles. This observation is in agreement with particle size analysis which also showed that the mean particle size of SONs varied with the amount of OA in the mixture but with no effect on their zeta potential values. Differential scanning calorimetry analysis showed that the SONs prepared in this method have lower crystallinity as compared to pure stearic acid. Different amount of oleic acid incorporated gave different degree of perturbation to the crystalline matrix of SONs and hence resulted in lower degrees of crystallinity, thereby improving their encapsulation efficiencies. The optimized SON was further incorporated in cream and its in vitro release study showed a gradual release for 24 hours, denoting the incorporation of salicylic acid in solid matrix of SON and prolonging the in vitro release.


Assuntos
Anti-Infecciosos/química , Nanopartículas/química , Ácido Oleico/química , Ácido Salicílico/química , Creme para a Pele/química , Ácidos Esteáricos/química , Administração Tópica , Preparações de Ação Retardada , Tamanho da Partícula
14.
Cell Death Dis ; 4: e848, 2013 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-24113182

RESUMO

Epithelial-mesenchymal transition (EMT) is a crucial step in tumor progression, and the TGFß-SMAD signaling pathway as an inductor of EMT in many tumor types is well recognized. However, the role of non-canonical TGFß-TAK1 signaling in EMT remains unclear. Herein, we show that TAK1 deficiency drives metastatic skin squamous cell carcinoma earlier into EMT that is conditional on the elevated cellular ROS level. The expression of TAK1 is consistently reduced in invasive squamous cell carcinoma biopsies. Tumors derived from TAK1-deficient cells also exhibited pronounced invasive morphology. TAK1-deficient cancer cells adopt a more mesenchymal morphology characterized by higher number of focal adhesions, increase surface expression of integrin α5ß1 and active Rac1. Notably, these mutant cells exert an increased cell traction force, an early cellular response during TGFß1-induced EMT. The mRNA level of ZEB1 and SNAIL, transcription factors associated with mesenchymal phenotype is also upregulated in TAK1-deficient cancer cells compared with control cancer cells. We further show that TAK1 modulates Rac1 and RhoA GTPases activities via a redox-dependent downregulation of RhoA by Rac1, which involves the oxidative modification of low-molecular weight protein tyrosine phosphatase. Importantly, the treatment of TAK1-deficient cancer cells with Y27632, a selective inhibitor of Rho-associated protein kinase and antioxidant N-acetylcysteine augment and hinders EMT, respectively. Our findings suggest that a dysregulated balance in the activation of TGFß-TAK1 and TGFß-SMAD pathways is pivotal for TGFß1-induced EMT. Thus, TAK1 deficiency in metastatic cancer cells increases integrin:Rac-induced ROS, which negatively regulated Rho by LMW-PTP to accelerate EMT.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , MAP Quinase Quinase Quinases/metabolismo , Neoplasias de Células Escamosas/enzimologia , Neoplasias de Células Escamosas/patologia , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Cutâneas/patologia , Animais , Fenômenos Biomecânicos/efeitos dos fármacos , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Células HEK293 , Humanos , Integrina beta1/metabolismo , Integrina beta3/metabolismo , MAP Quinase Quinase Quinases/deficiência , Camundongos , Modelos Biológicos , Invasividade Neoplásica , Oxirredução/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Neoplasias Cutâneas/enzimologia , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta1/farmacologia , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo
15.
Clin Genet ; 84(5): 501-4, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23083294

RESUMO

A variant (rs3129882) in the genome-wide association study (GWAS)-linked variant [in the human leukocyte antigen (HLA) gene region] has been reported to associate with an increased risk of Parkinson's disease (PD) in Caucasian population. Studies among Chinese are limited. To address this, we analysed rs3129882 in a total of 1312 subjects of Chinese ethnicity from independent Asian centers comprising of 675 controls and 637 PD cases. The rs3129882 variant was associated with a decreased risk in our ethnic Chinese PD patients. Logistic regression analysis taking into consideration variables of age, gender and race showed that allele A reduced the risk of PD via a dominant model [odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.62, 0.96, p = 0.018]. As HLA is a highly polymorphic region, it is possible that ethnic-specific effect or environmental agents may modulate the effect of this GWAS-linked locus in influencing the risk of PD.


Assuntos
Cadeias alfa de HLA-DR/genética , Imunidade Inata/genética , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único , Idoso , Povo Asiático , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Loci Gênicos , Humanos , Inflamação/etnologia , Inflamação/genética , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/etnologia
16.
Lupus ; 22(2): 198-204, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23257407

RESUMO

BACKGROUND: Human leukocyte antigen (HLA) antigens and genes have long been reported associated with systemic lupus erythematosus (SLE) susceptibility in many populations. With the advance in technologies such as genome-wide association studies, many newly discovered SLE-associated single-nucleotide polymorphisms (SNPs) have been reported in recent years. These include HLA-DRB1/HLA-DQA1 rs9271366 and HLA-DQB1/HLA-DQA2 rs9275328. Our aim was to investigate these SNPs in a Malaysian SLE cohort. MATERIALS AND METHODS: SNPs rs9271366 and rs9275328 were screened across 790 Malaysian citizens from three ethnic groups (360 patients and 430 healthy volunteers) by Taqman SNP genotyping assays. Allele and genotyping frequencies, Hardy-Weinberg equilibrium, Fisher's exact test and odds ratio were calculated for each SNP and ethnic group. Linkage disequilibrium and interaction between the two SNPs were also evaluated. RESULTS: The minor allele G and its homozygous genotype GG of HLA-DRB1/HLA-DQA1 rs9271366 significantly increased the SLE susceptibility in Malaysian patients, including those of Malay and Chinese ethnicity (odds ratio (OR) > 1, p < 0.05). As for HLA-DQB1/HLA-DQA2 rs9275328, the minor allele T and the heterozygous genotype CT conferred protective effect to SLE in Malaysians, as well as in Malays and Chinese, by having OR < 1 and p value <0.05. Both SNPs did not show associations to SLE in Indians. D' and r (2) values for the two SNPs in LD analysis were 0.941 and 0.065, respectively, with haplotype GC and AT being significantly associated with SLE (p < 5.0 × 10(-4)) after 10,000 permutations were performed. The MDR test clustered the genotype combinations of GG and CC, and AG and CC of rs9271366 and rs9275328, accordingly, as high-risk group, and the two SNPs interacted redundantly by removing 1.96% of the entropy. CONCLUSIONS: Our findings suggest that in addition to some classical HLA variants, rs9271366 and rs9275328 are additional polymorphisms worth considering in the Malaysian and possibly in a larger Asian SLE scenario.


Assuntos
Antígenos HLA-DQ/genética , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/genética , Povo Asiático , Predisposição Genética para Doença , Humanos , Malásia , Polimorfismo de Nucleotídeo Único
17.
Trop Biomed ; 29(2): 270-6, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22735849

RESUMO

Penicilliosis is a rare occurrence among non human immunodeficiency virus (HIV) infected patients. We report here two cases of Penicillium marneffei infection in patients with systemic lupus erythematosus (SLE). Both patients had a recent flare of lupus and were on immunosuppressive drugs when they presented with prolonged fever without an obvious foci of infection, unresponsive to broad-spectrum antibiotics. They were leucopaenic upon admission, with rapid deterioration during the course of the illness. Diagnosis of penicilliosis via fungal isolation from blood culture was delayed resulting in the late initiation of antifungal agents. While both patients ultimately recovered, the delay in diagnosis led to a prolonged hospital stay with increased morbidity. Clinicians should be aware of this uncommon but emerging fungal pathogen in SLE patients and maintain a high index of suspicion in diagnosing this potentially fatal but treatable disease.


Assuntos
Febre/microbiologia , Lúpus Eritematoso Sistêmico/microbiologia , Micoses/diagnóstico , Penicillium/patogenicidade , Adulto , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Diagnóstico Tardio , Feminino , Hospitalização , Humanos , Lúpus Eritematoso Sistêmico/complicações , Masculino , Micoses/tratamento farmacológico , Micoses/microbiologia , Penicillium/isolamento & purificação , Adulto Jovem
18.
Transpl Infect Dis ; 14(4): E23-6, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22551151

RESUMO

Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia (PCP) is a rare but serious infection that usually occurs within a year after solid organ transplantation. PCP may occur after 1 year post transplantation, but the rate is reported to be very low. Studies have shown an association between cytomegalovirus (CMV) infection in solid organ transplant patients and an increased risk of opportunistic infection. This increased risk is thought to be a result of the immunomodulatory effects of the CMV infection. We present a case of PCP infection occurring 13 years after a renal transplantation. This occurred following a recurrent CMV infection while the patient was on low-dose immunosuppressants.


Assuntos
Infecções por Citomegalovirus/imunologia , Transplante de Rim/efeitos adversos , Infecções Oportunistas/imunologia , Pneumocystis carinii , Pneumonia por Pneumocystis/imunologia , Pneumonia por Pneumocystis/microbiologia , Adulto , Citomegalovirus , Infecções por Citomegalovirus/virologia , Feminino , Humanos , Imunossupressores/administração & dosagem , Infecções Oportunistas/microbiologia , Recidiva , Fatores de Risco , Fatores de Tempo
19.
Biotechnol Bioeng ; 109(1): 1-15, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21915849

RESUMO

Treatment of esophageal cancer often requires surgical procedures that involve removal. The current approaches to restore esophageal continuity however, are known to have limitations which may not result in full functional recovery. In theory, using a tissue engineered esophagus developed from the patient's own cells to replace the removed esophageal segment can be the ideal method of reconstruction. One of the key elements involved in the tissue engineering process is the scaffold which acts as a template for organization of cells and tissue development. While a number of scaffolds range from traditional non-biodegradable tubing to bioactive decellularized matrix have been proposed to engineer the esophagus in the past decade, results are still not yet favorable with many challenges relating to tissue quality need to be met improvements. The success of new esophageal tissue formation will ultimately depend on the success of the scaffold being able to meet the essential requirements specific to the esophageal tissue. Here, the design of the scaffold and its fabrication approaches are reviewed. In this paper, we review the current state of development in bioengineering the esophagus with particular emphasis on scaffold design.


Assuntos
Esôfago/citologia , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Humanos
20.
J Pharm Sci ; 100(6): 2379-90, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21491450

RESUMO

This study is to enhance the dissolution rate of a poorly water-soluble drug, quercetin, by fabricating nanocrystals using high-pressure homogenization. The particle size, crystallinity, dissolution, and antioxidant effects of fabricated quercetin nanocrystals have been investigated. Characterization of the original quercetin powder and nanocrystals was carried out by photon correlation spectroscopy (PCS), laser diffraction, scanning electron microscopy, differential scanning calorimetry (DSC), X-ray diffraction, dissolution tester, and so on. A PCS size of about 483 nm was obtained for the nanocrystals after 20 cycles of homogenization at 1500 bar. X-ray diffraction and DSC studies revealed that the lyophilized quercetin nanoparticles were crystalline after high-pressure homogenization. The percent dissolution efficiency, relative dissolution, mean dissolution time, difference factor (f(1)), and similarity factor (f(2)) were calculated for the statistical analysis. It was found that the dissolution of the drug nanocrystals was much higher than that of the pure drug at pH 6.8 and 1.2. The antioxidant activity and reducing power of the quercetin nanocrystals were more effective than the original quercetin.


Assuntos
Antioxidantes/química , Composição de Medicamentos/métodos , Nanopartículas/química , Quercetina/química , Compostos de Bifenilo/química , Varredura Diferencial de Calorimetria , Cristalização , Microscopia Eletrônica de Varredura , Estrutura Molecular , Tamanho da Partícula , Picratos/química , Solubilidade , Propriedades de Superfície , Difração de Raios X
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