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1.
Epidemiol Rev ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38778757

RESUMO

The incidences of invasive fungal infection (IFI) are increasing especially in patients diagnosed with haematological malignancies due to their immunocompromised nature. Risk factors include advanced age, exposure to immunosuppressants, neutropenia and catheter usage. Some of the most common organisms reported are Candida and Aspergillus species while other fungal species including Scedosporium, Ttrichosporon, Cryptococcus and Fusarium have also increasingly been reported in the past years. However, the epidemiological data on IFI amongst patients with haematological malignancies in Asian countries are lacking and therefore, we aim to investigate published epidemiological data on such cases in the last 10 years (2011-2021) and to discuss the challenges faced in the diagnosis and management of IFI.

2.
Molecules ; 28(9)2023 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-37175283

RESUMO

This review identifies terpenes isolated from the medicinal Angiosperms of Asia and the Pacific with antibacterial and/or antifungal activities and analyses their distribution, molecular mass, solubility, and modes of action. All data in this review were compiled from Google Scholar, PubMed, Science Direct, Web of Science, ChemSpider, PubChem, and library searches from 1968 to 2022. About 300 antibacterial and/or antifungal terpenes were identified during this period. Terpenes with a MIC ≤ 2 µg/mL are mostly amphiphilic and active against Gram-positive bacteria, with a molecular mass ranging from about 150 to 550 g/mol, and a polar surface area around 20 Ų. Carvacrol, celastrol, cuminol, dysoxyhainic acid I, ent-1ß,14ß-diacetoxy-7α-hydroxykaur-16-en-15-one, ergosterol-5,8-endoperoxide, geranylgeraniol, gossypol, 16α-hydroxy-cleroda-3,13 (14)Z-diene-15,16-olide, 7-hydroxycadalene, 17-hydroxyjolkinolide B, (20R)-3ß-hydroxy-24,25,26,27-tetranor-5α cycloartan-23,21-olide, mansonone F, (+)-6,6'-methoxygossypol, polygodial, pristimerin, terpinen-4-ol, and α-terpineol are chemical frameworks that could be candidates for the further development of lead antibacterial or antifungal drugs.


Assuntos
Antifúngicos , Magnoliopsida , Antibacterianos/farmacologia , Antifúngicos/farmacologia , Ásia , Terpenos/farmacologia
3.
J Infect Dis ; 226(11): 1964-1973, 2022 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-35767283

RESUMO

BACKGROUND: The resolution or aggravation of dengue infection depends on the patient's immune response during the critical phase. Cytokines released by immune cells increase with the worsening severity of dengue infections. Cytokines activate the kynurenine pathway (KP) and the extent of KP activation then influences disease severity. METHODS: KP metabolites and cytokines in plasma samples of patients with dengue infection (dengue without warning signs [DWS-], dengue with warning signs [DWS+], or severe dengue) were analyzed. Cytokines (interferon gamma [IFN-É£], tumor necrosis factor, interleukin 6, CXCL10/interferon-inducile protein 10 [IP-10], interleukin 18 [IL-18], CCL2/monocyte chemoattractant protein-1 [MCP-1], and CCL4/macrophage inflammatory protein-1beta [MIP-1ß] were assessed by a Human Luminex Screening Assay, while KP metabolites (tryptophan, kynurenine, anthranilic acid [AA], picolinic acid, and quinolinic acid) were assessed by ultra-high-performance liquid chromatography and Gas Chromatography Mass Spectrophotometry [GCMS] assays. RESULTS: Patients with DWS+ had increased activation of the KP where kynurenine-tryptophan ratio, anthranilic acid, and picolinic acid were elevated. These patients also had higher levels of the cytokines IFN-É£, CXCL10, CCL4, and IL-18 than those with DWS-. Further receiver operating characteristic analysis identified 3 prognostic biomarker candidates, CXCL10, CCL2, and AA, which predicted patients with higher risks of developing DWS+ with an accuracy of 97%. CONCLUSIONS: The data suggest a unique biochemical signature in patients with DWS+. CXCL10 and CCL2 together with AA are potential prognostic biomarkers that discern patients with higher risk of developing DWS+ at earlier stages of infection.


Assuntos
Cinurenina , Dengue Grave , Humanos , Cinurenina/metabolismo , Citocinas , Triptofano/metabolismo , Interleucina-18 , Quimiocina CCL2 , Interferon gama , Quimiocina CXCL10
4.
Cell Mol Biol (Noisy-le-grand) ; 68(8): 22-26, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36800845

RESUMO

Genetic alterations in the homologous recombination repair (HRR) genes are associated with an increased risk of prostate cancer development, and patients harboring these mutations can benefit from targeted therapy. The main aim of this study is to identify genetic alterations in HRR genes as a potential target for targeted treatment. In this study, targeted next generation sequencing (NGS) is used to analyze mutations in the protein-coding regions of the 27 genes involved in HRR and mutations in hotspots of 5 cancer-associated genes in four FFPE samples and three blood samples from prostate cancer patients. We identified two mutations in TP53 and KRAS. We also identified four conflicting interpretations of pathogenicity variants in BRCA2, STK11 genes and one variant of uncertain significance in the RAD51B gene. In addition, we detected one drug response variant in TP53, and two novel variants in CDK12 and ATM. Our results revealed some actionable pathogenic and potential pathogenic variants that may be associated with response to the Poly (ADP-ribose) polymerase (PARP) inhibitor treatment. More studies in a larger cohort are needed to evaluate and determine the association of HRR mutations with prostate cancer.


Assuntos
Neoplasias da Próstata , Reparo de DNA por Recombinação , Masculino , Humanos , Reparo de DNA por Recombinação/genética , Neoplasias da Próstata/genética , Mutação
5.
Intervirology ; 61(4): 193-203, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30541013

RESUMO

OBJECTIVE: Herpes simplex virus infection through the neuronal route is the most well-studied mode of viral encephalitis that can persists in a human host for a lifetime. However, the involvement of other possible infection mechanisms by the virus remains underexplored. Therefore, this study aims to determine the temporal effects and mechanisms by which the virus breaches the human brain micro-vascular endothelial cells of the blood-brain barrier. METHOD: An electrical cell-substrate impedance-sensing tool was utilized to study the real-time cell-cell barrier or morphological changes in response to the virus infection. RESULTS: Herpes simplex virus, regardless of type (i.e., 1 or 2), reduced the cell-cell barrier resistance almost immediately after virus addition to endothelial cells, with negligible involvement of cell-matrix adhesion changes. There is no exclusivity in the infection ability of endothelial cells. From 30 h after HSV infection, there was an increase in cell membrane capacitance with a subsequent loss of cell-matrix adhesion capability, indicating a viability loss of the infected endothelial cells. CONCLUSION: This study shows for the first time that destruction of human brain micro-vascular endothelial cells as an in vitro model of the blood-brain barrier could be an alternative invasion mechanism during herpes simplex virus infection.


Assuntos
Barreira Hematoencefálica/fisiologia , Barreira Hematoencefálica/virologia , Células Endoteliais/fisiologia , Células Endoteliais/virologia , Simplexvirus/crescimento & desenvolvimento , Sobrevivência Celular , Impedância Elétrica , Humanos , Modelos Biológicos
6.
Exp Parasitol ; 194: 67-78, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30268422

RESUMO

Treatment of drug resistant protozoa, bacteria, and viruses requires new drugs with alternative chemotypes. Such compounds could be found from Southeast Asian medicinal plants. The present study examines the cytotoxic, antileishmanial, and antiplasmodial effects of 11 ethnopharmacologically important plant species in Malaysia. Chloroform extracts were tested for their toxicity against MRC-5 cells and Leishmania donovani by MTT, and chloroquine-resistant Plasmodium falciparum K1 strain by Histidine-Rich Protein II ELISA assays. None of the extract tested was cytotoxic to MRC-5 cells. Extracts of Uvaria grandiflora, Chilocarpus costatus, Tabernaemontana peduncularis, and Leuconotis eugenifolius had good activities against L. donovani with IC50 < 50 µg/mL. Extracts of U. grandiflora, C. costatus, T. peduncularis, L. eugenifolius, A. subulatum, and C. aeruginosa had good activities against P. falciparum K1 with IC50 < 10 µg/mL. Pinoresinol isolated from C. costatus was inactive against L. donovani and P. falciparum. C. costatus extract and pinoresinol increased the sensitivity of Staphylococcus epidermidis to cefotaxime. Pinoresinol demonstrated moderate activity against influenza virus (IC50 = 30.4 ±â€¯11 µg/mL) and was active against Coxsackie virus B3 (IC50 = 7.1 ±â€¯3.0 µg/mL). ß-Amyrin from L. eugenifolius inhibited L. donovani with IC50 value of 15.4 ±â€¯0.01 µM. Furanodienone from C. aeruginosa inhibited L. donovani and P. falciparum K1 with IC50 value of 39.5 ±â€¯0.2 and 17.0 ±â€¯0.05 µM, respectively. Furanodienone also inhibited the replication of influenza and Coxsackie virus B3 with IC50 value of 4.0 ±â€¯0.5 and 7.2 ±â€¯1.4 µg/mL (Ribavirin: IC50: 15.6 ±â€¯2.0 µg/mL), respectively. Our study provides evidence that medicinal plants in Malaysia have potentials as a source of chemotypes for the development of anti-infective leads.


Assuntos
Anti-Infecciosos/farmacologia , Leishmania donovani/efeitos dos fármacos , Medicina Tradicional do Leste Asiático/métodos , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Plasmodium falciparum/efeitos dos fármacos , Anti-Infecciosos/toxicidade , Apocynaceae/química , Linhagem Celular , Sinergismo Farmacológico , Enterovirus Humano B/efeitos dos fármacos , Etnofarmacologia/métodos , Furanos/química , Furanos/isolamento & purificação , Furanos/farmacologia , Furanos/toxicidade , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Concentração Inibidora 50 , Lignanas/química , Lignanas/isolamento & purificação , Lignanas/farmacologia , Lignanas/toxicidade , Malásia , Extratos Vegetais/química , Extratos Vegetais/toxicidade , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Sesquiterpenos/toxicidade , Tabernaemontana/química , Uvaria/química
7.
Sci Rep ; 14(1): 385, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172146

RESUMO

The aetiology of schizophrenia is multifactorial, and the identification of its risk factors are scarce and highly variable. A cross-sectional study was conducted to investigate the risk factors associated with schizophrenia among Malaysian sub-population. A total of 120 individuals diagnosed with schizophrenia (SZ) and 180 non-schizophrenic (NS) individuals participated in a questionnaire-based survey. Data of complete questionnaire responses obtained from 91 SZ and 120 NS participants were used in statistical analyses. Stool samples were obtained from the participants and screened for gut parasites and fungi using conventional polymerase chain reaction (PCR). The median age were 46 years (interquartile range (IQR) 37 to 60 years) and 35 years (IQR 24 to 47.75 years) for SZ and NS respectively. Multivariable binary logistic regression showed that the factors associated with increased risk of SZ were age, sex, unemployment, presence of other chronic ailment, smoking, and high dairy consumption per week. These factors, except sex, were positively associated with the severity of SZ. Breastfed at infancy as well as vitamin and supplement consumption showed a protective effect against SZ. After data clean-up, fungal or parasitic infections were found in 98% (39/42). of SZ participants and 6.1% (3/49) of NS participants. Our findings identified non-modifiable risk factors (age and sex) and modifiable lifestyle-related risk factors (unemployment, presence of other chronic ailment, smoking, and high dairy consumption per week) associated with SZ and implicate the need for medical attention in preventing fungal and parasitic infections in SZ.


Assuntos
Micoses , Doenças Parasitárias , Esquizofrenia , Adulto , Humanos , Pessoa de Meia-Idade , Estudos Transversais , Doenças Parasitárias/complicações , Doenças Parasitárias/epidemiologia , Fatores de Risco , Esquizofrenia/diagnóstico , Esquizofrenia/epidemiologia , Micoses/complicações , Micoses/epidemiologia
8.
medRxiv ; 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38883728

RESUMO

Background: Dengue is a vector-borne viral disease impacting millions across the globe. Nevertheless, akin to many other diseases, reports indicated a decline in dengue incidence and seroprevalence during the COVID-19 pandemic (2020-22). This presumably could be attributed to reduced treatment-seeking rates, under-reporting, misdiagnosis, disrupted health services and reduced exposure to vectors due to lockdowns. Scientific evidence on dengue virus (DENV) disease during the COVID-19 pandemic is limited globally. Methods: A cross-sectional, randomized cluster sampling community-based survey was carried out to assess anti-dengue IgM and IgG and SARS-CoV-2 IgG seroprevalence across all 38 districts of Tamil Nadu, India. The prevalence of DENV in the Aedes mosquito pools during 2021 was analyzed and compared with previous and following years of vector surveillance for DENV by real-time PCR. Findings: Results implicate that both DENV-IgM and IgG seroprevalence and mosquito viral positivity were reduced across all the districts. A total of 13464 mosquito pools and 5577 human serum samples from 186 clusters were collected. Of these, 3·76% of mosquito pools were positive for DENV. In the human sera, 4·12% were positive for DENV IgM and 6·4% were positive for DENV IgG. The anti-SARS-CoV-2 antibody titres correlated with dengue seropositivity with a significant association whereas vaccination status significantly correlated with dengue IgM levels. Interpretation: Continuous monitoring of DENV seroprevalence, especially with the evolving variants of the SARS-CoV-2 virus and surge in COVID-19 cases will shed light on the transmission and therapeutic attributes of dengue infection.

9.
Microorganisms ; 12(1)2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38257848

RESUMO

The emergence of disease in shrimp has governed much concern in food safety and security among consumers with the recent reports on hepatopancreatic microsporidiosis (HPM) caused by Enterocytozoon hepatopenaei (EHP). The microsporidians present in shrimp remain a silent pathogen that prevents optimal shrimp growth. However, the biggest threat is in its food safety concerns, which is the primary focus in ensuring food biosecurity and biosafety. Hence, the objective of this review is to summarise the current knowledge of EHP and its infection in shrimp with food safety concerns. This paper provides an analysis of the diagnostic methods for detecting EHP infections in shrimp aquaculture. Interventions with current molecular biology and biotechnology would be the second approach to addressing EHP diseases. Finally, a systematic guideline for shrimp food safety using diagnostic and intervention is proposed. Thus, this review was aimed to shed light on effective methods for the diagnosis and prevention of EHP infection in shrimp. We also include information on molecular and genomics tools as well as innate immune biomolecules as future targets in the intervention strategies on the microsporidsosis life cycle in shrimp and its environment. Overall, this will result in reduced disease outbreaks in shrimp aquaculture, ensuring the shrimp food safety in the future.

10.
Adv Med Sci ; 68(2): 359-365, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37757663

RESUMO

Prostate cancer (PC) is the second most common cancer in men worldwide. Homologous recombination repair (HRR) gene defects have been identified in a significant proportion of metastatic castration-resistant PC (mCRPC) and are associated with an increased risk of PC and more aggressive PC. Importantly, it has been well-documented that poly ADP-ribose polymerase (PARP) inhibition in cells with HR deficiency (HRD) can cause cell death. This has been exploited for the targeted treatment of PC patients with HRD by PARP inhibitors. Moreover, it has been shown that platinum-based chemotherapy is more effective in mCRPC patients with HRR gene alterations. This review highlights the prognosis and therapeutic implications of HRR gene alterations in PC.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Reparo de DNA por Recombinação , Masculino , Humanos , Reparo de DNA por Recombinação/genética , Prognóstico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia
11.
medRxiv ; 2023 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-37609153

RESUMO

Background: Early detection of latent tuberculosis infection (LTBI) is critical to TB elimination in the current WHO vision of End Tuberculosis Strategy. Methods: We investigated whether detecting plasma cytokines could aid in diagnosing LTBI across household contacts (HHCs) positive for IGRA, HHCs negative for IGRA, and healthy controls. We also measured the plasma cytokines using a commercial Bio-Plex Pro Human Cytokine 17-plex assay. Results: Increased plasma CXCL8 and decreased MCP-1, TNF-α, and IFN-γ were associated with LTBI. Regression analysis showed that a combination of CXCL8 and MCP-1 increased the risk of LTBI among HHCs to 14-fold. Conclusions: We postulated that CXCL8 and MCP-1 could be the surrogate biomarkers of LTBI, especially in resource-limited settings.

12.
Lancet Reg Health Southeast Asia ; 19: 100272, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38076717

RESUMO

Background: Despite the continued vaccination efforts, there had been a surge in breakthrough infections, and the emergence of the B.1.1.529 omicron variant of SARS-CoV-2 in India. There is a paucity of information globally on the role of newer XBB variants in community transmission. Here, we investigated the mutational patterns among hospitalised patients infected with the XBB omicron sub-variant, and checked if there was any association between the rise in the number of COVID-19 cases and the observed novel mutations in Tamil Nadu, India. Methods: Nasopharyngeal and oropharyngeal swabs, collected from symptomatic and asymptomatic COVID-19 patients were subjected to real-time PCR followed by Next Generation Sequencing (NGS) to rule out the ambiguity of mutations in viruses isolated from the patients (n = 98). Using the phylogenetic association, the mutational patterns were used to corroborate clinico-demographic characteristics and disease severity among the patients. Findings: Overall, we identified 43 mutations in the S gene across 98 sequences, of which two were novel mutations (A27S and T747I) that have not been reported previously with XBB sub-variants in the available literature. Additionally, the XBB sequences from our cohort had more mutations than omicron B.1.1.529. The phylogenetic analysis comprising six major branches clearly showed convergent evolution of XBB. Our data suggests that age, and underlying conditions (e.g., diabetes, hypertension, and cardiovascular disease) or secondary complications confers increased susceptibility to infection rather than vaccination status or prior exposure. Many vaccinated individuals showed evidence of a breakthrough infection, with XBB.3 being the predominant variant identified in the study population. Interpretation: Our study indicates that the XBB variant is highly evasive from available vaccines and may be more transmissible, and potentially could emerge as the 'next' predominant variant, which likely could overwhelm the existing variants of SARS-CoV-2 omicron variants. Funding: National Health Mission (India), SIDASARC, VINNMER (Sweden), ORIP/NIH (USA).

13.
PLOS Glob Public Health ; 3(11): e0002327, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37992019

RESUMO

Early detection of latent tuberculosis infection (LTBI) is critical to TB elimination in the current WHO vision of End Tuberculosis Strategy. The study investigates whether detecting plasma cytokines could aid in diagnosing LTBI across household contacts (HHCs) positive for IGRA, HHCs negative for IGRA, and healthy controls. The plasma cytokines were measured using a commercial Bio-Plex Pro Human Cytokine 17-plex assay. Increased plasma CXCL8 and decreased MCP-1, TNF-α, and IFN-γ were associated with LTBI. Regression analysis showed that a combination of CXCL8 and MCP-1 increased the risk of LTBI among HHCs to 14-fold. Our study suggests that CXCL-8 and MCP-1 could serve as the surrogate biomarkers of LTBI, particularly in resource-limited settings. Further laboratory investigations are warranted before extrapolating CXCL8 and MCP-1 for their usefulness as surrogate biomarkers of LTBI in resource-limited settings.

14.
Parasitol Res ; 110(6): 2475-80, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22278727

RESUMO

The pathogenesis of Blastocystis hominis in human hosts has always been a matter of debate as it is present in both symptomatic and asymptomatic individuals. A recent report showed that B. hominis isolated from an asymptomatic individual could facilitate the proliferation and growth of existing cancer cells while having the potential to downregulate the host immune response. The present study investigated the differences between the effects of symptomatic and asymptomatic derived solubilized antigen of B. hominis (Blasto-Ag) on the cell viability and proliferation of colorectal cancer cells. Besides that, the gene expression of cytokine and nuclear transcriptional factors in response to the symptomatic and asymptomatic B. hominis antigen in HCT116 was also compared. In the current study, an increase in cell proliferation was observed in HCT116 cells which led to the speculation that B. hominis infection could facilitate the growth of colorectal cancer cells. In addition, a more significant upregulation of Th2 cytokines observed in HCT116 may lead to the postulation that symptomatic Blasto-Ag may have the potential in weakening the cellular immune response, allowing the progression of existing tumor cells. The upregulation of nuclear factor kappa light chain enhancer of activated B cells (NF-κB) was observed in HCT116 exposed to symptomatic Blasto-Ag, while asymptomatic Blasto-Ag exhibited an insignificant effect on NF-κB gene expression in HCT116. HCT116 cells exposed to symptomatic and asymptomatic Blasto-Ag caused a significant upregulation of CTSB which lead to the postulation that the Blasto-Ag may enhance the invasive and metastasis properties of colorectal cancer. In conclusion, antigen isolated from a symptomatic individual is more pathogenic as compared to asymptomatic isolates as it caused a more extensive inflammatory reaction as well as more enhanced proliferation of cancer cells.


Assuntos
Antígenos de Protozoários/metabolismo , Infecções por Blastocystis/parasitologia , Blastocystis hominis/patogenicidade , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/parasitologia , Antígenos de Protozoários/isolamento & purificação , Doenças Assintomáticas , Blastocystis hominis/química , Blastocystis hominis/isolamento & purificação , Linhagem Celular Tumoral , Citocinas/biossíntese , Perfilação da Expressão Gênica , Humanos , Regulação para Cima
15.
J Fungi (Basel) ; 8(11)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36354893

RESUMO

Candida auris, a newly emerging healthcare-associated yeast pathogen from the Metschnikowiaceae family, was first described in the ear canal of an elderly Japanese patient in 2009. The yeast is one of the causative agents of candidemia, which has been linked with nosocomial outbreaks and high mortality rates in healthcare facilities worldwide. Since its first isolation, the occurrence of C. auris in six continents has becomes a grave concern for the healthcare professionals and scientific community. Recent reports showed the identification of five geographically distinct clades and high rates of antifungal resistance associated with C. auris. Till date, there are no effective treatment options, and standardized measures for prevention and control of C. auris infection in healthcare facilities. This leads to frequent therapeutic failures and complicates the eradication of C. auris infection in healthcare facilities. Thus, this review focuses on the recent understanding of the epidemiology, risk factors, diagnosis, transmission and prevention and control strategies of C. auris infection in healthcare facilities in Asia.

16.
Front Cell Infect Microbiol ; 12: 975222, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36159640

RESUMO

Dengue is a major public health concern, affecting almost 400 million people worldwide, with about 70% of the global burden of disease in Asia. Despite revised clinical classifications of dengue infections by the World Health Organization, the wide spectrum of the manifestations of dengue illness continues to pose challenges in diagnosis and patient management for clinicians. When the Zika epidemic spread through the American continent and then later to Africa and Asia in 2015, researchers compared the characteristics of the Zika infection to Dengue, considering both these viruses were transmitted primarily through the same vector, the Aedes aegypti female mosquitoes. An important difference to note, however, was that the Zika epidemic diffused in a shorter time span compared to the persisting feature of Dengue infections, which is endemic in many Asian countries. As the pathogenesis of viral illnesses is affected by host immune responses, various immune modulators have been proposed as biomarkers to predict the risk of the disease progression to a severe form, at a much earlier stage of the illness. However, the findings for most biomarkers are highly discrepant between studies. Meanwhile, the cross-reactivity of CD8+ and CD4+ T cells response to Dengue and Zika viruses provide important clues for further development of potential treatments. This review discusses similarities between Dengue and Zika infections, comparing their disease transmissions and vectors involved, and both the innate and adaptive immune responses in these infections. Consideration of the genetic identity of both the Dengue and Zika flaviviruses as well as the cross-reactivity of relevant T cells along with the actions of CD4+ cytotoxic cells in these infections are also presented. Finally, a summary of the immune biomarkers that have been reported for dengue and Zika viral infections are discussed which may be useful indicators for future anti-viral targets or predictors for disease severity. Together, this information appraises the current understanding of both Zika and Dengue infections, providing insights for future vaccine design approaches against both viruses.


Assuntos
Aedes , Vírus da Dengue , Dengue , Vacinas , Infecção por Zika virus , Zika virus , Animais , Reações Cruzadas , Feminino , Humanos , Imunidade Humoral , Mosquitos Vetores
17.
Parasit Vectors ; 15(1): 313, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064639

RESUMO

BACKGROUND: Blastocystis sp. is one of the most common colonisers of the intestinal tract that demonstrate strong interaction with accompanying gut bacteria. Previously, the protozoan isolated from individuals with irritable bowel syndrome (IBS) showed altered phenotypic features suggesting that it can be triggered to become pathogenic. Previous studies reported altered gut microbiota and high prevalence of Blastocystis sp. in schizophrenia patients. However, the phenotypic characteristics of Blastocystis sp. isolated from individuals with SZ have yet to be described. METHODS: In this study, faecal samples from 50 patients with severe schizophrenia (SZ) and 100 non-schizophrenic (NS) individuals were screened for Blastocystis sp. INFECTION: Positive isolates were subjected to genotypic and phenotypic characterization. RESULTS: We found that 12 out of 50 (24%) SZ and 5 out of 100 (5%) NS individuals were detected Blastocystis sp. positive using both in vitro culture and PCR method with no significant association to age and gender. Out of the 15 sequenced isolates, ST3 was the most prevalent subtype (66.7%) followed by ST1 (20%) and ST6 (13.3%). The isolates from SZ individuals demonstrated significant slower growth rate (34.9 ± 15.6 h) and larger range of cell diameter (3.3-140 µm). We detected higher amoebic forms and metronidazole resistance among SZ isolates with variation in cell surface glycoprotein where 98% of cells from SZ showed consistent medium to high binding affinity (+ 2 to + 3) to Concavalin A staining compared to NS isolates that demonstrated only 76% high lectin (+ 3) binding affinity. Cysteine and serine protease levels were predominantly found among SZ isolates. We also demonstrate the presence of metalloprotease in Blastocystis sp. especially among NS isolates. Introduction of solubilised antigens from SZ isolates increased the cell proliferation of HCT116 cells by two fold when compared to NS isolates. CONCLUSION: Our findings demonstrated Blastocystis sp. isolated from SZ individuals showed variation in phenotype specifically in morphology and drug resistance. The findings indicate that the gut environment (SZ and NS) and treatment of SZ could have influenced the phenotype of Blastocystis sp.


Assuntos
Infecções por Blastocystis , Blastocystis , Síndrome do Intestino Irritável , Blastocystis/genética , Infecções por Blastocystis/epidemiologia , Fezes , Humanos , Síndrome do Intestino Irritável/epidemiologia , Metronidazol/farmacologia , Metronidazol/uso terapêutico
18.
Front Cell Infect Microbiol ; 12: 975398, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36189346

RESUMO

The Flavivirus genus is made up of viruses that are either mosquito-borne or tick-borne and other viruses transmitted by unknown vectors. Flaviviruses present a significant threat to global health and infect up to 400 million of people annually. As the climate continues to change throughout the world, these viruses have become prominent infections, with increasing number of infections being detected beyond tropical borders. These include dengue virus (DENV), West Nile virus (WNV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV). Several highly conserved epitopes of flaviviruses had been identified and reported to interact with antibodies, which lead to cross-reactivity results. The major interest of this review paper is mainly focused on the serological cross-reactivity between DENV serotypes, ZIKV, WNV, and JEV. Direct and molecular techniques are required in the diagnosis of Flavivirus-associated human disease. In this review, the serological assays such as neutralization tests, enzyme-linked immunosorbent assay, hemagglutination-inhibition test, Western blot test, and immunofluorescence test will be discussed. Serological assays that have been developed are able to detect different immunoglobulin isotypes (IgM, IgG, and IgA); however, it is challenging when interpreting the serological results due to the broad antigenic cross-reactivity of antibodies to these viruses. However, the neutralization tests are still considered as the gold standard to differentiate these flaviviruses.


Assuntos
Vírus da Dengue , Vírus da Encefalite Japonesa (Espécie) , Flavivirus , Vírus do Nilo Ocidental , Infecção por Zika virus , Zika virus , Animais , Anticorpos Antivirais , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Epitopos , Humanos , Imunoglobulina A , Imunoglobulina G , Imunoglobulina M , Mosquitos Vetores , Infecção por Zika virus/diagnóstico
19.
Biosensors (Basel) ; 11(5)2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33921935

RESUMO

Dengue is a major threat to public health globally. While point-of-care diagnosis of acute/recent dengue is available to reduce its mortality, a lack of rapid and accurate testing for the detection of previous dengue remains a hurdle in expanding dengue seroepidemiological surveys to inform its prevention, especially vaccination, to reduce dengue morbidity. This study evaluated ViroTrack Dengue Serostate, a biosensors-based semi-quantitative anti-dengue IgG (immunoglobulin G) immuno-magnetic agglutination assay for the diagnosis of previous and recent dengue in a single test. Blood samples were obtained from 484 healthy participants recruited randomly from two communities in Petaling district, Selangor, Malaysia. The reference tests were Panbio Dengue IgG indirect and capture enzyme-linked immunosorbent assays, in-house hemagglutination inhibition assay, and focus reduction neutralization test. Dengue Serostate had a sensitivity and specificity of 91.1% (95%CI 87.8-93.8) and 91.1% (95%CI 83.8-95.8) for the diagnosis of previous dengue, and 90.2% (95%CI 76.9-97.3) and 93.2% (95%CI 90.5-95.4) for the diagnosis of recent dengue, respectively. Its positive predictive value of 97.5% (95%CI 95.3-98.8) would prevent most dengue-naïve individuals from being vaccinated. ViroTrack Dengue Serostate's good point-of-care diagnostic accuracy can ease the conduct of dengue serosurveys to inform dengue vaccination strategy and facilitate pre-vaccination screening to ensure safety.


Assuntos
Técnicas Biossensoriais , Dengue/diagnóstico , Testes Imediatos , Adulto , Anticorpos Antivirais/sangue , Dengue/sangue , Testes Diagnósticos de Rotina , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G , Malásia , Sistemas Automatizados de Assistência Junto ao Leito , Sensibilidade e Especificidade , Adulto Jovem
20.
Parasitol Res ; 106(4): 941-5, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20165878

RESUMO

Blastocystis hominis is one of the most common intestinal protozoan parasites in humans, and reports have shown that blastocystosis is coupled with intestinal disorders. In the past, researchers have developed an in vitro model using B. hominis culture filtrates to investigate its ability in triggering inflammatory cytokine responses and transcription factors in human colonic epithelial cells. Studies have also correlated the inflammation by parasitic infection with cancer. The present study provides evidence of the parasite facilitating cancer cell growth through observing the cytopathic effect, cellular immunomodulation, and apoptotic responses of B. hominis, especially in malignancy. Here we investigated the effect of solubilized antigen from B. hominis on cell viability, using peripheral blood mononuclear cells (PBMCs) and human colorectal carcinoma cells (HCT116). The gene expressions of cytokines namely interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha, interferon gamma, nuclear factor kappa light-chain enhancer of activated B cells (a gene transcription factor), and proapoptotic genes namely protein 53 and cathepsin B were also studied. Results exhibited favor the fact that antigen from B. hominis, at a certain concentration, could facilitate the growth of HCT116 while having the ability to downregulate immune cell responses (PBMCs). Therefore, there is a vital need to screen colorectal cancer patients for B. hominis infection as it possesses the ability to enhance the tumor growth.


Assuntos
Antígenos de Protozoários/farmacologia , Blastocystis hominis/química , Neoplasias Colorretais/parasitologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Animais , Apoptose , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/biossíntese , Citocinas/genética , Perfilação da Expressão Gênica , Células HCT116 , Humanos
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