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1.
Braz. j. biol ; 83: e240118, 2023. tab, graf
Artículo en Inglés | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1278559

RESUMEN

Abstract For many centuries human populations have been suffering and trying to fight with disease-bearing mosquitoes. Emerging and reemerging diseases such as Dengue, Zika, and Chikungunya affect billions of people around the world and recently has been appealing to control with chemical pesticides. Malathion (MT) is one of the main pesticides used against mosquitoes, the vectors of these diseases. This study aimed to assess cytotoxicity and mutagenicity of the malathion for the bioindicator Allium cepa L. using a multivariate and integrative approach. Moreover, an appendix table was compiled with all available literature of insecticides assessed by the Allium cepa system to support our discussion. Exposures during 48h to 0.5 mg mL-1 and 1.0 mg mL-1 MT were compared to the negative control (distilled water) and positive control (MMS solution at 10 mg L-1). The presence of chromosomal aberrations, micronuclei frequency, and mitotic index abnormalities was evaluated. Anaphase bridges were the alterations with higher incidence and presented a significantly elevated rate in the concentration of 0.5 mg mL-1, including when compared to the positive control. The integrative discriminant analysis summarizes that MT in assessed concentrations presented effects like the positive control, corroborating its potential of toxicity to DNA. Therefore, it is concluded that MT in its pure composition and in realistic concentrations used, has genotoxic potential in the biological assessment of A. cepa cells. The multivariate integrative analysis was fundamental to show a whole response of all data, providing a global view of the effect of MT on DNA.


Resumo Por muitos séculos, as populações humanas sofrem e tentam combater os mosquitos transmissores de doenças. Doenças emergentes e reemergentes como Dengue, Zika e Chikungunya afetam bilhões de pessoas em todo o mundo e, recentemente, vem apelando ao controle com pesticidas químicos. O Malation (MT) é um dos principais pesticidas usados ​​contra mosquitos, vetores dessas doenças. O objetivo deste estudo foi avaliar a citotoxicidade e a mutagenicidade do MT para o bioindicador Allium cepa L. usando uma abordagem multivariada e integrativa. Além disso, uma tabela suplementar foi compilada com toda a literatura disponível de inseticidas avaliada pelo sistema Allium cepa para apoiar nossa discussão. Exposições ao MT durante 48h a 0,5 mg mL-1 e 1,0 mg mL-1 foram comparadas a um controle negativo (água destilada) e um controle positivo (10 mg L-1 de MMS). Foram avaliadas a presença de aberrações cromossômicas, frequência de micronúcleos e anormalidades no índice mitótico. As pontes anafásicas foram as alterações com maior incidência e apresentaram uma taxa significativamente elevada na concentração de 0,5 mg mL-1, inclusive quando comparadas ao controle positivo. A análise discriminante integrativa resume que o MT nas concentrações avaliadas apresentou efeitos semelhantes ao controle positivo, corroborando seu potencial de toxicidade para o DNA. Portanto, conclui-se que o MT, em sua composição pura e nas concentrações realistas utilizadas, possui potencial genotóxico na avaliação biológica de células de A. cepa. A análise integrativa multivariada foi fundamental para mostrar uma resposta completa de todos os dados, fornecendo uma visão global do efeito da MT no DNA.

2.
Braz. j. biol ; 83: e246230, 2023. tab, graf
Artículo en Inglés | LILACS-Express | MEDLINE, LILACSEXPRESS | ID: biblio-1339369

RESUMEN

Abstract Dengue fever vectored by the mosquito Aedes aegypti is one of the most rapidly spreading insect-borne diseases. Current reliance of dengue vector control is mostly on chemical insecticides. Growing insecticide resistance in the primary mosquito vector, Aedes aegypti, limits the effectiveness of vector control through chemical insecticides. These chemical insecticides also have negative environmental impacts on animals, plants and human health. Myco-biocontrol agents are naturally occurring organisms and are found to be less damaging to the environment as compared to chemical insecticides. In the present study, entomopathogenic potential of local strains of fungi isolated from soil was assessed for the control of dengue vector. Local fungal isolates presents better alternative to introducing a foreign biocontrol strain, as they may be better adapted to environmental conditions of the area to survive and may have more entomopathogenic efficacy against target organism. Larvicidal efficacy of Fusarium equiseti and Fusarium proliferatum was evaluated against Aedes aegypti. Local strains of F. equiseti (MK371718) and F. proliferatum (MK371715) were isolated from the soil of Changa Manga Forest, Pakistan by using insect bait method. Larvicidal activity of two Fusarium spp. was tested against forth instar larvae of A. aegypti in the laboratory, using concentrations 105, 106, 107 and 108 conidia /ml. LC50 values for F. equiseti after 24h, 48h, 72h and 96h of exposure were recorded as 3.8x 108, 2.9x107, 2.0x107, and 7.1x106 conidia /ml respectively while LC50 values for F. proliferatum were recorded as 1.21x108, 9.6x107, 4.2x107, 2.6x107 conidia /ml respectively after 24h, 48h, 72h and 96h of exposure. The results indicate that among two fungal strains F. equiseti was found to be more effective in terms of its larvicidal activity than F. proliferatum against larvae of A. aegypti.


Resumo A dengue transmitida pelo mosquito Aedes aegypti é uma das doenças transmitidas por insetos de propagação mais rápida. A dependência atual do controle do vetor da dengue é principalmente de inseticidas químicos. O aumento da resistência a inseticidas no principal vetor do mosquito, Aedes aegypti, limita a eficácia do controle do vetor por meio de inseticidas químicos. Esses inseticidas químicos também têm impactos ambientais negativos sobre os animais, plantas e saúde humana. Os agentes de micobiocontrole são organismos que ocorrem naturalmente e são menos prejudiciais ao meio ambiente em comparação com os inseticidas químicos. No presente estudo, avaliou-se o potencial entomopatogênico de cepas locais de fungos isolados do solo para o controle do vetor da dengue. Isolados de fungos locais apresentam melhor alternativa para a introdução de uma cepa de biocontrole estrangeira, pois podem ser mais bem adaptados às condições ambientais da área para sobreviver e podem ter maior eficácia entomopatogênica contra o organismo-alvo. A eficácia larvicida de Fusarium equiseti e Fusarium proliferatum foi avaliada contra Aedes aegypti. Cepas locais de F. equiseti (MK371718) e F. proliferatum (MK371715) foram isoladas do solo de Changa Manga Forest, Paquistão, usando o método de isca para insetos. Atividade larvicida de dois Fusarium spp. foi testado contra larvas de quarto ínstar de A. aegypti em laboratório, nas concentrações 105, 106, 107 e 108 conídios / ml. Os valores de LC50 para F. equiseti após 24 h, 48 h, 72 h e 96 h de exposição foram registrados como 3,8x 108, 2,9x107, 2,0x107 e 7,1x106 conídios / ml, respectivamente, enquanto os valores de LC50 para F. proliferatum foram registrados como 1,21x108, 9,6 x107, 4,2x107, 2,6x107 conídios / ml, respectivamente, após 24 h, 48 h, 72 h e 96 h de exposição. Os resultados indicam que entre duas cepas de fungos F. equiseti se mostrou mais eficaz em termos de atividade larvicida do que F. proliferatum contra larvas de A. aegypti.

3.
J Ethnopharmacol ; 282: 114627, 2022 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-34509603

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Dengue virus (DENV) is a re-emerging mosquito-borne flavivirus that has recently engendered large epidemics around the world. Consequently antivirals with effective anti-DENV therapeutic activity are urgently required. In the 18th century, Europeans, as well as native inhabitants of North America, were known to adapt the medicinal property of the common perennial plant Eupatorium perfoliatum L. to treat fever and infections. Previous studies have shown that Eupatorium perfoliatum L. possesses anti-inflammatory, anti-oxidative, anti-plasmodial, anti-bacterial and antiviral activities. However, to the best of our knowledge, no anti-DENV activity of E. perfoliatum L. has been investigated at the molecular level so far. AIM OF STUDY: Here, for the first time we have attempted to study the action of E. perfoliatum extract and its few bioactive components i.e., quercetin, caffeic acid and eupafolin against wild primary clinical isolate of DENV-2 infection in an in vitro model. MATERIALS AND METHODS: The presence of the bioactive components in the E. perfoliatum extract, were analyzed by HPLC- DAD. Then, CC50 as well as IC50 values of the extract and its bioactive components were measured against DENV in HepG2 cell line. After that, the antiviral activity was studied by Time of addition assay using qRT-PCR. Further, the downstream signalling action of E. perfoliatum extract, was studied by Human phosphorylation MAPK antibody array, followed by immunofluorescence microscopy. Moreover, a molecular docking analysis was done to study the binding affinity of bioactive components of E. perfoliatum extract with TIM-1 transmembrane receptor protein, which is known for viral internalization. RESULT: We found that E. perfoliatum extract has marked antiviral activity during pre-treatment against DENV infection in HepG2 cell line. The extract also significantly reduced the DENV induced autophagy in HepG2 cell line as detected by LC3 II localization. The presence of different bioactive compounds in E. perfoliatum extract were confirmed by HPLC-DAD. In the bioactive components, in parallel to earlier studies, quercetin showed the most significant preventive action against DENV infection. Further, in molecular docking analysis also, quercetin showed the strongest binding affinity towards DENV membrane receptor TIM-1 protein. CONCLUSION: Our findings suggests that E. perfoliatum extract has significant potential to be an anti-DENV therapeutic agent. Moreover, among the bioactive components, quercetin may have a prophylaxis role in executing the antiviral activity of E. perfoliatum extract against DENV infection.

4.
J Mol Struct ; 1250: 131756, 2022 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-34690363

RESUMEN

With the arrival of the Covid-19 pandemic, anti-viral agents have regained center stage in the arena of medicine. Out of the various drug targets involved in managing RNA-viral infections, the one that dominates almost all RNA viruses is RdRp (RNA-dependent RNA polymerase). RdRp are proteins that are involved in the replication of RNA-based viruses. Inhibition of RdRps has been an integral approach for managing various viral infections such as dengue, influenza, HCV (Hepatitis), BVDV, etc. Inhibition of the coronavirus RdRp is currently rigorously explored for the treatment of Covid-19 related complications. So, keeping in view the importance and current relevance of this drug target, we have discussed the importance of RdRp in developing anti-viral agents against various viral diseases. Different reported inhibitors have also been discussed, and emphasis has been laid on highlighting the inhibitor's pharmacophoric features and SAR profile.

5.
Univ. salud ; 23(3): 272-283, sep.-dic. 2021. tab, graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1341774

RESUMEN

Resumen Introducción: La prevalencia del dengue en la región de las Américas, amerita intervenciones integrales y contextualizadas que permitan mayor participación, responsabilidad y toma de conciencia de los actores involucrados. Objetivo: Documentar la evidencia científica sobre el lugar de la familia como entorno constructor de capacidades en la prevención y control del dengue. Materiales y métodos: Se realizó una revisión integrativa de literatura mediante la búsqueda, selección, organización y análisis de textos científicos publicados en las bases de datos Jstor, Scopus, Sciencedirect, Scielo y Pubmed, en el periodo 2015 y 2020. Los criterios de inclusión permitieron seleccionar 20 artículos. Resultados: La familia es reconocida como un entorno importante en el cuidado de la salud humana cuya participación, compromiso y empoderamiento se constituyen en elementos de interés para el diseño, implementación y evaluación de programas de prevención y control de enfermedades como el dengue. Paralelo se identificó, la necesidad de incorporar enfoques integrales y contextualizados. Conclusiones: Las familias son fundamentales para la construcción de capacidades humanas, sin embargo, requieren de acompañamiento, motivación, mejoramiento de las condiciones de vida y visibilización de sus formas naturales de aprender y enseñar como estrategia integrativa en los enfoques sociales que buscan prevenir y controlar el dengue.


Abstract Introduction: Dengue prevalence in Central and South America requires comprehensive and contextualized interventions that ensure greater participation, responsibility, and awareness of the involved key players. Objective: To document scientific evidence on the role of family as a capacity-building environment in the prevention and control of dengue. Materials and methods: An integrative literature review was conducted through the search, selection, organization, and analysis of scientific articles published in Jstor, Scopus, Sciencedirect, Scielo and Pubmed databases during the 2015-2020 time period. The inclusion criteria were useful to select 20 articles. Results: The family is recognized as an important environment for human health care. Family's participation, commitment, and empowerment constitute elements of interest for the design, implementation, and assessment of programs for the prevention and control of diseases such as dengue. Likewise, the need to incorporate comprehensive and contextualized approaches was identified. Conclusions: Families are fundamental for the construction of human capacities. Thus, they require support, motivation, improvement of living conditions, and acknowledegement of their natural ways of learning and teaching as an integrative strategy in social approaches to prevent and control dengue.

6.
San Salvador; MINSAL; oct. 05, 2021. 23 p. ilus, graf, tab, mapas.
No convencional en Español | LILACS, BISSAL | ID: biblio-1293157

RESUMEN

Resumen de eventos de notificación hasta SE 38/2021. Alertas internacionales. Situación epidemiológica de dengue. Situación epidemiológica de zika y chikungunya. Infección respiratoria aguda. Neumonías. Situación mundial del 2019-nCov (OMS. Vigilancia centinela de influenza y otros virus respiratorios. Vigilancia centinela de rotavirus. Enfermedad diarreica aguda


Summary of notification events up to SE 38/2021. International alerts. Epidemiological situation of dengue. Epidemiological situation of Zika and Chikungunya. Acute respiratory infection. Pneumonia Global situation 2019-nCov (WHO. Sentinel surveillance of influenza and other respiratory viruses. Sentinel surveillance for rotavirus. Acute diarrheal Disease


Asunto(s)
Epidemiología , Publicaciones Electrónicas , COVID-19
7.
Hum Vaccin Immunother ; : 1-5, 2021 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-34612165

RESUMEN

Background: Vaccination has been known to reduce morbidity and mortality of infectious diseases since the emergence of the 1st vaccine in the 18th century. That's why global efforts are directed toward finding a vaccine for COVID-19 in order to eliminate its threat.The current pandemic of COVID-19 has changed the world affecting all fields significantly as a result of the preventive measures including locking down, social distancing, obligatory mask wearing, stopping flights, etc. The medical field is clearly the most significantly affected starting from altering most of the research efforts toward the new virus passing through the inadequate number of physicians as well as unavailable intensive care unit (ICU) beds. In order to break the restricted preventive measures, we need to minimize the newly infected cases which can be achieved by reaching adequate herd immunity. Moreover, calculating the basic reproduction number (R0) of COVID-19 is crucial to estimate the herd immunity threshold (Ic).Methods: In this review, we searched PubMed for studies that mentioned the R0 of COVID_19, SARS, and MERS as well as measles, Zika and dengue virus to calculate the herd immunity threshold and the minimal vaccination coverage.Results: The value of R0 could vary for the same disease and consequently the herd immunity threshold as well as the vaccination coverage. The R0 of COVID-19 ranged widely through various articles from 1.4 to 6.68. As a result, the herd immunity threshold would range from 28.57% to 85.03%. However, the vaccination coverage depends also on the effectiveness of the vaccine which is still unknown.Conclusion: The calculations of vaccination coverage include many variables such as the R0 of the disease, Ic that depends on that value as well as sensitivity and specificity of the vaccine itself.

8.
Sci Rep ; 11(1): 19567, 2021 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-34599250

RESUMEN

Mosquitoes are a great menace for humankind since they transmit pathogenic organisms causing Malaria, Dengue, Chikungunya, Elephantiasis and Japanese encephalitis. There is an urgent need to discover new and novel biological tools to mitigate mosquito-borne diseases. To develop bioinsecticides through newly developed nanotechnology is another option in the present research scenario. In this study we synthesize and characterize sardine fish scales with silver nitrate by adopting various instrumental techniques such as UV- and FTIR-spectroscopy, energy-dispersive X-ray (EDAX), X-ray diffraction analyses (XRD) and scanning electron microscopy (SEM). Toxicity bioassays were conducted with young developmental stages of mosquito vectors. Significant mortality appeared after different life stages of mosquito vectors (young larval and pupal instars were exposed to the nanomaterials). LC50 values were 13.261 ppm for young first instar larvae and 32.182 ppm for pupae. Feeding and predatory potential of G. affinis, before and after exposure to nanoparticles against mosquito larval (I & II) instars of the mosquitoes showed promising results in laboratory experiments. Feeding potential of mosquito fish without nanoparticle treatment was 79.7% and 70.55% for the first and second instar larval populations respectively. At the nanoparticle-exposed situation the predatory efficiency of mosquitofish was 94.15% and 84.3%, respectively. Antioxidant enzymes like (SOD), (CAT), and (LPO) were estimated in the gill region of sardine fish in control and experimental waters. A significant reduction of egg hatchability was evident after nanoparticle application. It became evident from this study that the nano-fabricated materials provide suitable tools to control the malaria vector Anopheles stephensi in the aquatic phase of its life cycle. This finding suggests an effective novel approach to mosquito control.

9.
Bioinformation ; 17(4): 506-513, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34602778

RESUMEN

Host genetic factors are known to determine disease susceptibility in dengue virus infection. Therefore, in this study association of gene polymorphisms of Vitamin D Receptor [rs731236 (Taq) and rs7975232 (Apa1)], Toll-like receptor 2 [rs5743708 (Arg735Gln) and rs5743704 (Pro631His)] and Toll-like receptor 4 [rs4986790A/G(Asp299Gly13843) and rs4986791 C/T(Thr399Ile)] were studied in cases with dengue as compared to controls. Total 98 cases of confirmed dengue virus infection and 98 age, sex and geographically matched healthy controls were enrolled and their genetic polymorphisms for the above mentioned regions were studied by Sanger sequencing. Mutant genotypes CC of VDR rs731236 (Taq1) [(OR 3.808, p value =0.02, CI 1.160-12.498)], GG of VDR rs7975232 (Apa1) [(OR 3.485, p value =0.02, CI 1.162-10.45)] and heterozygous genotypes of TLR4 rs4986790 A/G Asp299Gly [OR 2.40, p value= 0.02, CI 1.12-5.14], TLR4 rs4986791 C/T Thr399Ile [OR 2.09, p value=0.02, CI 1.12-5.14] were found to be significantly more in cases with dengue virus infection as compared to the controls. Also, at these positions mutant alleles were observed in significantly higher number of cases than controls. The values for C allele at VDR rs731236 (Taq1) were OR 1.86, p value 0.009, CI 1.162-3.001; for allele G at rs7975232( Apa1) were OR 2.71, p value 0.006, CI 1.196-2.98 for allele G at TLR4s rs4986790 A/G Asp299Gly were OR 2.35, p value 0.009, CI 1.23-4.50 and for allele T at rs4986791 C/T Thr399Ile were OR 2.36, p value=0.006, CI 1.28-4.38. VDR and TLR4 but not TLR2 gene polymorphisms were found to be associated with dengue susceptibility in Indian population.

10.
Int J Pept Res Ther ; : 1-18, 2021 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-34602919

RESUMEN

An immunoinformatics technique was used to predict a monovalent amide immunogen candidate capable of producing therapeutic antibodies as well as a potent immunogen candidate capable of acting as a universal vaccination against all dengue fever virus serotypes. The capsid protein is an attractive goal for anti-DENV due to its position in the dengue existence cycle. The widely accessible immunological data, advances in antigenic peptide prediction using reverse vaccinology, and the introduction of molecular docking in immunoinformatics have directed vaccine manufacturing. The C-proteins of DENV-1-4 serotypes were known as antigens to assist with logical design. Binding epitopes for TC cells, TH cells, and B cells is predicted from structural dengue virus capsid proteins. Each T cell epitope of C-protein integrated with a B cell as a templet was used as a vaccine and produce antibodies in contrast to serotype of the dengue virus. A chimeric tetravalent vaccine was created by combining four vaccines, each representing four dengue serotypes, to serve as a standard vaccine candidate for all four Sero groups. The LKRARNRVS, RGFRKEIGR, KNGAIKVLR, and KAINVLRGF from dengue 1, dengue 2, dengue 3, and dengue 4 epitopes may be essential immunotherapeutic representatives for controlling outbreaks.

11.
Clin Infect Dis ; 2021 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-34606595

RESUMEN

BACKGROUND: Takeda's live attenuated tetravalent dengue vaccine candidate (TAK-003) is under evaluation in a long-term clinical trial across eight dengue-endemic countries. Previously, we have reported its efficacy and safety in both seronegative and seropositive participants and that its performance varies by serotype, with some decline in efficacy from first to second year post-vaccination. This exploratory analysis provides an update with cumulative and third year data. METHODS: Healthy 4-16 year-olds (n=20,099) were randomized 2:1 to receive TAK-003 or placebo (0, 3 month schedule). The protocol included baseline serostatus testing of all participants and detection of all symptomatic dengue throughout the trial with a serotype specific RT-PCR. RESULTS: Cumulative efficacy after three years was 62.0% (95% confidence interval: 56.6%, 66.7%) against virologically-confirmed dengue (VCD) and 83.6% (76.8%, 88.4%) against hospitalized VCD. Efficacy was 54.3% (41.9%, 64.1%) against VCD and 77.1% (58.6%, 87.3%) against hospitalized VCD in baseline seronegatives, and 65.0% (58.9%, 70.1%) against VCD and 86.0% (78.4%, 91.0%) against hospitalized VCD in seropositives. Efficacy against VCD during the third year declined to 44.7% (32.5%, 54.7%), while efficacy against hospitalized VCD was sustained at 70.8% (49.6%, 83.0%). Rates of serious adverse events were 2.9% in TAK-003 group and 3.5% in placebo group during the ongoing long-term follow-up (i.e. second half of the three years following vaccination), but none were related. No important safety risks were identified. CONCLUSIONS: TAK-003 was efficacious against symptomatic dengue over three years. Efficacy declined over time but remained robust against hospitalized dengue. A booster dose evaluation is planned.

12.
J Clin Lab Anal ; : e24035, 2021 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-34606646

RESUMEN

BACKGROUND: Humoral immunity is thought to play a central role in mediating the immunopathogenesis of dengue virus (DENV) infection; however, the B-cell responses elicited by primary DENV2 infection are incompletely understood. Follicular helper T cells (Tfh) are important to promote B-cell activation and differentiation. METHODS: The present study analyzed the detailed dynamic changes of circulating B-cell subsets and Tfh (cTfh) using flow cytometry to explore their responses to DENV2 infection. RESULTS: Thirty-six patients with DENV2 and 21 healthy individuals were included. The results showed that CD27+ CD38+ plasmablasts emerged after DENV2 infection, and correlated with CXCR5+ PD-1+ or CXCR5+ ICOS+ PD-1+ cTfh, which increased after DENV2 infection, and correlated with DENV2 RNA viral loads. Significantly low levels of CD27- naïve B cells, and CD24hi CD27hi and CD24hi CD38hi regulatory B cells (Breg) were observed after DENV2 infection, which correlated negatively with CXCR5+ PD-1+ or CXCR5+ ICOS+ PD-1+ cTfh cells. CONCLUSION: Overall, these results provide insights into the DENV2-elicited B-cell response and revealed previously unidentified CD24hi CD27hi and CD24hi CD38hi Breg responses to DENV2 infection.

13.
J Biol Chem ; : 101272, 2021 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-34606827

RESUMEN

Mammalian cells acquire fatty acids from dietary sources or via de novo palmitate production by fatty acid synthase (FASN). Although most cells express FASN at low levels, it is upregulated in cancers of the breast, prostate, and liver, among others, and is required during the replication of many viruses, such as Dengue virus, Hepatitis C, HIV-1, Hepatitis B, and SARS-CoV-2, among others. The precise role of FASN in disease pathogenesis is poorly understood, and whether de novo fatty acid synthesis contributes to host or viral protein acylation has been traditionally difficult to study. Here we describe a cell permeable, click-chemistry compatible alkynyl-acetate analog (Alk-4) that functions as a reporter of FASN-dependent protein acylation. In a FASN-dependent manner, Alk-4 selectively labels the cellular protein interferon-induced transmembrane protein 3 (IFITM3) at its known palmitoylation sites, a process that is essential for the antiviral activity of the protein, and the HIV-1 matrix protein at its known myristoylation site, a process that is required for membrane targeting and particle assembly. Alk-4 metabolic labeling also enabled biotin-based purification and identification of more than 200 FASN-dependent acylated cellular proteins. Thus, Alk-4 is a useful bioorthogonal tool to selectively probe FASN-mediated protein acylation in normal and diseased states.

14.
Am J Trop Med Hyg ; 2021 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-34607306

RESUMEN

Dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV) are arboviruses that can affect maternal and fetal outcome if acquired during pregnancy. This study was done to estimate the positivity of DENV, CHIKV, and ZIKV in febrile pregnant women attending a tertiary care hospital in north India. Symptomatic pregnant women were tested for these viruses by IgM ELISA and/or by Trioplex real-time polymerase chain reaction. Their symptoms and laboratory parameters were recorded and were followed up till delivery to know their immediate delivery outcome. Of 104 women tested, 50 (48.1%) were positive for viral markers. Of these, evidence of infection by DENV, CHIKV, and both was found in 34 (32.7%), 10 (9.6%), and 6 (5.8%), respectively. ZIKV was not detected in any woman. Maximum DENV positivity occurred in the third trimester of pregnancy and in women residing in urban than rural areas. Chills and rigors, arthralgia, retro-orbital pain, anemia, and vaginal bleeding were more commonly associated with DENV positivity. Backache, arthralgia, jaundice, and vaginal bleeding were more common in CHIKV positives but the difference between positives and nonpositives regarding these symptoms was not statistically significant. Dengue infections were associated with more frequent hospitalizations (OR = 8.38, 95% confidence intervals [CI] = 3.29-21.30) and mortality (OR = 19.0, 95% CI = 1.01-357.10). Hence, to conclude, in India wherever possible, all symptomatic pregnant women should be screened for DENV, CHIKV, and ZIKV as part of sentinel surveillance for ZIKV.

15.
Epidemiol Health ; : e2021070, 2021 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-34607402

RESUMEN

The countries of the Association of Southeast Asian Nations (ASEAN) have been dealing with dengue outbreaks for decades, being one of the regions with high dengue infection cases globally. These outbreaks are happening on top of the COVID-19 pandemic that is causing havoc among these ten countries. Both infectious diseases have caused a tremendous burden for the countries in the region-from infection control to the economic impact. This increasing number of cases happened with the contribution of the disruption in the pathogen-host-vector relationship, caused by the change of human behaviour during the pandemic period, and aggravated by the implementation of lockdowns and social distancing policies. These had several consequences, including limiting the coverage of dengue preventive programs and delaying the medical management of both diseases due to co-infection and misdiagnosis. It is of utmost importance to maintain the awareness of the population of both diseases and to devise strategies on dengue vector control to properly address the infection with digitalization and remote surveillance. Similarly, critical triage algorithms and further research are also needed to address co-infection and misdiagnosis. Management of COVID-19 using vaccination also should be optimized to subside the pandemic.

16.
Trop Biomed ; 38(3): 396-402, 2021 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-34608113

RESUMEN

Dengue shock syndrome (DSS) is a potentially critical and life-threatening concern, especially in children of tropical countries. The serum cortisol levels in severe DSS or later stages of DSS are limited references. We prospectively studied an association between of serum cortisol as well as interleukin levels and the severity of DSS in pediatric patients. A prospective cross-sectional study of 35 consecutive DSS cases (3 months to 16 years old) admitted to our institution from July 1, 2019, to June 30, 2020 was conducted. Serum cortisol, IL-6, and IL-10 were measured at T0 (shock recognition) and T12 (12 hours after T0); their values were presented as median and interquartile ranges (25%-75%). Severe DSS included patients with impalpable pulses or systolic blood pressure < 70 mmHg, recurrent shock, and prolonged shock. In contrast, non-severe DSS presented circulatory failure without any features of severe DSS. A total of 8 (22.8%) severe DSS patients expressed the cortisol (T0) significantly lower compared to the non-severe DSS group (7.3 µg/dl versus 14.3 µg/dl, p=0.008). In severe DSS, there was a minimal change in cortisol levels between T0 and T12 (7.3 µg/dl and 4.7 µg/dl p>0.05), whereas the decrease is significant in their counterparts (14.3 µg/dl to 5.6 µg/dl, p<0.005). Additionally, there were moderate correlations between IL-6 (T0), IL-10 (T0), IL-10 (T12) and total fluid requirement (Spearman's rho = 0.47, 0.4, and 0.36, respectively; p<0.05). Our study demonstrated that adrenal dysfunction was present in patients with severe and non-severe DSS, as noted by cortisol level at T12. In addition, IL-6 and IL-10 levels are correlated with the total fluid requirement, which is a marker of DSS severity. Further studies could reveal how adrenal dysfunction in pediatric patients with DSS can affect outcomes and the potential roles of interleukin levels in fluid management strategy.

17.
Trop Biomed ; 38(3): 446-452, 2021 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-34608118

RESUMEN

Inundated with escalating dengue outbreaks, there is an urgent call to find alternate potential vector control methods as the currently employed method fails to curb the expanding of dengue virus transmission in Malaysia. Supported by this aim, we are interested in exploiting the potential of Ipomoea cairica leaves extract towards primary and secondary vectors of dengue fever, Aedes aegypti and Aedes albopictus. To assess the effectiveness of this plant extracts towards Aedes larvae, we carried out two complementary analyses. First, we observed the comparative effectiveness of larvicidal activity I. cairica extract against the laboratory and field strains of Ae. aegypti and Ae. albopictus. Then, we determined the effective lethal dose of this plant extract against Aedes larvae using log-probit regression analysis of the SPSS 20.0 programme. Results from bioassay demonstrated that I. cairica leaves extract was highly effective to induce larvicidal mortality of Ae. albopictus and Ae. aegypti within 24 and 48 hours post-treatment. Results from the factorial analysis of variance (ANOVA) also indicated that there were significant differences in larvicidal activity between species and strains used (P<0.05). It is interesting to notify that the sequence of effectiveness for the larvicidal activities of I. cairica acethonilic leaves extract is in the manner; Ae. albopictus field strain > Ae. aegypti laboratory strain > Ae. aegypti field strain > Ae. albopictus laboratory strain. The I. cairica leaves extract displayed high larvicidal activity against Ae. albopictus as compared to Ae. aegypti. This is the first evaluation involving the comparison of I. cairica leaves extract effects for the laboratory strain and field strain of Ae. albopictus and Ae. Aegypti.

18.
Sci Rep ; 11(1): 19713, 2021 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-34611200

RESUMEN

The novel coronavirus disease 2019 (COVID-19) presents with non-specific clinical features. This may result in misdiagnosis or delayed diagnosis, and lead to further transmission in the community. We aimed to derive early predictors to differentiate COVID-19 from influenza and dengue. The study comprised 126 patients with COVID-19, 171 with influenza and 180 with dengue, who presented within 5 days of symptom onset. All cases were confirmed by reverse transcriptase polymerase chain reaction tests. We used logistic regression models to identify demographics, clinical characteristics and laboratory markers in classifying COVID-19 versus influenza, and COVID-19 versus dengue. The performance of each model was evaluated using receiver operating characteristic (ROC) curves. Shortness of breath was the strongest predictor in the models for differentiating between COVID-19 and influenza, followed by diarrhoea. Higher lymphocyte count was predictive of COVID-19 versus influenza and versus dengue. In the model for differentiating between COVID-19 and dengue, patients with cough and higher platelet count were at increased odds of COVID-19, while headache, joint pain, skin rash and vomiting/nausea were indicative of dengue. The cross-validated area under the ROC curve for all four models was above 0.85. Clinical features and simple laboratory markers for differentiating COVID-19 from influenza and dengue are identified in this study which can be used by primary care physicians in resource limited settings to determine if further investigations or referrals would be required.


Asunto(s)
COVID-19/patología , Dengue/patología , Gripe Humana/patología , Adulto , Área Bajo la Curva , COVID-19/complicaciones , COVID-19/virología , Estudios de Cohortes , Dengue/complicaciones , Dengue/virología , Diagnóstico Diferencial , Diarrea/etiología , Femenino , Fiebre/etiología , Humanos , Gripe Humana/complicaciones , Gripe Humana/virología , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , ARN Viral/análisis , ARN Viral/metabolismo , Curva ROC , SARS-CoV-2/genética , SARS-CoV-2/aislamiento & purificación , Vómitos/etiología , Adulto Joven
19.
mBio ; : e0156321, 2021 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-34634928

RESUMEN

Wolbachia are endosymbiont bacteria known to infect arthropods causing different effects, such as cytoplasmic incompatibility and pathogen blocking in Aedes aegypti. Although several Wolbachia strains have been studied, there is little knowledge regarding the relationship between this bacterium and their hosts, particularly on their obligate endosymbiont nature and its pathogen blocking ability. Motivated by the potential applications on disease control, we developed a genome-scale model of two Wolbachia strains: wMel and the strongest Dengue blocking strain known to date: wMelPop. The obtained metabolic reconstructions exhibit an energy metabolism relying mainly on amino acids and lipid transport to support cell growth that is consistent with altered lipid and cholesterol metabolism in Wolbachia-infected mosquitoes. The obtained metabolic reconstruction was then coupled with a reconstructed mosquito model to retrieve a symbiotic genome-scale model accounting for 1,636 genes and 6,408 reactions of the Aedes aegypti-Wolbachia interaction system. Simulation of an arboviral infection in the obtained novel symbiotic model represents a metabolic scenario characterized by pathogen blocking in higher titer Wolbachia strains, showing that pathogen blocking by Wolbachia infection is consistent with competition for lipid and amino acid resources between arbovirus and this endosymbiotic bacteria. IMPORTANCE Arboviral diseases such as Zika and Dengue have been on the rise mainly due to climate change, and the development of new treatments and strategies to limit their spreading is needed. The use of Wolbachia as an approach for disease control has motivated new research related to the characterization of the mechanisms that underlie its pathogen-blocking properties. In this work, we propose a new approach for studying the metabolic interactions between Aedes aegypti and Wolbachia using genome-scale models, finding that pathogen blocking is mainly influenced by competition for the resources required for Wolbachia and viral replication.

20.
Cell Rep ; 37(2): 109801, 2021 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-34644578

RESUMEN

Uncovering vulnerable steps in the life cycle of viruses supports the rational design of antiviral treatments. However, information on viral replication dynamics obtained from traditional bulk assays with host cell populations is inherently limited as the data represent averages over a multitude of unsynchronized replication cycles. Here, we use time-lapse imaging of virus replication in thousands of single cells, combined with computational inference, to identify rate-limiting steps for dengue virus (DENV), a widespread human pathogen. Comparing wild-type DENV with a vaccine candidate mutant, we show that the viral spread in the mutant is greatly attenuated by delayed onset of productive replication, whereas wild-type and mutant virus have identical replication rates. Single-cell analysis done after applying the broad-spectrum antiviral drug, ribavirin, at clinically relevant concentrations revealed the same mechanism of attenuating viral spread. We conclude that the initial steps of infection, rather than the rate of established replication, are quantitatively limiting DENV spread.

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