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1.
Microbiol Resour Announc ; 12(11): e0071323, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37889012

RESUMO

This study announces the sequence of a multidrug-resistant Escherichia coli MAHK_SCM_BAU_30A strain isolated from bovine subclinical mastitis milk in 2022 in Bangladesh. Our assembled genome had a length of 4,884,948 bp, three plasmids, two CRISPR arrays, five prophages, 51 predicted antibiotic resistance, and 72 predicted virulence factor genes.

2.
Glob Med Genet ; 10(3): 199-204, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37565062

RESUMO

Hepatitis C virus (HCV) is a causative agent that causes chronic liver diseases worldwide. It is a little, enclosed, single-stranded ribonucleic acid (RNA) virus. The recognition of the pathogenic HCV genotype is critical for the remedy of its sufferers. The aim of this study was to identify the HCV RNA genotype to decide the correct treatment of hepatitis C positive sufferers in Bangladesh. Blood samples were collected from 390 individuals and isolated RNA (60 µg) from blood plasma. Extracted RNA was used for quantitative HCV RNA, and complementary DNA (cDNA) was prepared by polymerase chain reaction (PCR) conducted by reverse transcriptase enzyme. This cDNA amplified in multiplex by RT-PCR, which was performed with specific set of primers. The HCV RNA genotype was detected 297 of 390 patients. Of the 390 test samples, 200 (51.28%) samples were from males and 190 (48.71%) were from females, with age ranging from 5 to 78 years. In all, 166 of 200 male samples and 131/190 female samples were found positive for HCV. Of these 390 participants included in the study, 213 (54.61%) were identified as genotype 3 positive, 78 (20%) as genotype 1 positive, 6 (1.53%) as genotype 6 positive, and the remaining 93 (23.85%) samples were unclassified due to low/undetected viral load. In this study, we detected the highest percentage (30.89%) of genotype 3 HCV in patients aged 51 to 60 years. The results suggested that genotype 3 HCV is frequently present in Bangladesh and it is usually responses better to interferon therapy. However, genotype 1 and 6 HCV have also been found circulating in this country, which demands longer treatments and effective control measures.

3.
Ecohealth ; 20(2): 167-177, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37455270

RESUMO

In 2015, human influenza surveillance identified a human infection with A/H9N2 in Dhaka, Bangladesh with evidence of exposure to a sick quail. We conducted in-depth interviews with household quail caregivers, pet bird retail shop owners, and mobile vendors, key informant interviews with pet bird wholesale shop owners, one group discussion with pet bird retail shop workers and unstructured observations in households, pet bird wholesale and retail markets, and mobile bird vendor's travelling areas to explore quail rearing and selling practices among households, mobile vendors, and retail pet bird and wholesale bird markets in Dhaka. Every day, quail were supplied from 23 districts to two wholesale markets, and then sold to households and restaurants directly, or through bird shops and mobile vendors. All respondents (67) reported keeping quail with other birds in cages, feeding quail, cleaning feeding pots, removing quail faeces, slaughtering sick quail, and discarding dead quail. Children played with quail and assisted in slaughtering of quail. Most respondents (94%) reported rinsing hands with water only after slaughtering and disposing of wastes and dead quail. No personal protective equipment was used during any activities. Frequent unprotected contact with quail and their by-products potentially increased the risk of cross-species avian influenza virus transmission. Avian influenza surveillance in retail pet bird and wholesale bird markets, mobile vendors, and households may identify cases promptly and reduce the risk of virus transmission.


Assuntos
Vírus da Influenza A Subtipo H9N2 , Influenza Aviária , Influenza Humana , Animais , Criança , Humanos , Influenza Aviária/epidemiologia , Codorniz , Bangladesh/epidemiologia , Influenza Humana/epidemiologia , Aves Domésticas , Galinhas
4.
Sci Rep ; 13(1): 7734, 2023 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-37173392

RESUMO

Thalassemia is one of the most common autosomal recessive hereditary blood disorders worldwide, especially in developing countries, including Bangladesh. Thus, this study aimed to determine HRQoL and its determinants of thalassemia patients (TP) in Bangladesh. A cross-sectional survey was performed on 356 randomly selected thalassemia patients. Participants were invited to face-to-face interviews. Descriptive statistics (frequencies and percentages), independent t-test, ANOVA, and multivariate (linear and logistic regression) analysis was performed to analyze the data. Our demographic data showed that among 356 patients, 54% and 46% were male and female, respectively, with an average age of 19.75 (SD = 8.02) years. Most were transfusion-dependent (91%), 26% had comorbidities, and 52% were from low-income families. In the case of HRQoL, male patients showed significantly higher scores of bodily pains and physical health summaries than female patients. Lower income, high blood transfusion status, disease severity, comorbidities, and medical expenses (p < 0.05; CI 95%) are significantly associated with lower SF-36 scores. This study found an association between lower income, blood transfusion, disease severity, comorbidities, as well as medical expenses, and the deterioration of HRQoL among TP. Male patients experienced poorer HRQoL than females. National action plans are required to guarantee the holistic welfare of thalassemia patients.


Assuntos
Qualidade de Vida , Talassemia , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Estudos Transversais , Bangladesh/epidemiologia , Talassemia/epidemiologia , Talassemia/terapia , Inquéritos e Questionários
5.
J Immunol Res ; 2023: 2274415, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36874624

RESUMO

Background: Although the monkeypox virus-associated illness was previously confined to Africa, recently, it has started to spread across the globe and become a significant threat to human lives. Hence, this study was designed to identify the B and T cell epitopes and develop an epitope-based peptide vaccine against this virus's cell surface binding protein through an in silico approach to combat monkeypox-associated diseases. Results: The analysis revealed that the cell surface binding protein of the monkeypox virus contains 30 B cell and 19 T cell epitopes within the given parameter. Among the T cell epitopes, epitope "ILFLMSQRY" was found to be one of the most potential peptide vaccine candidates. The docking analysis revealed an excellent binding affinity of this epitope with the human receptor HLA-B∗15:01 with a very low binding energy (-7.5 kcal/mol). Conclusion: The outcome of this research will aid the development of a T cell epitope-based peptide vaccine, and the discovered B and T cell epitopes will facilitate the creation of other epitope and multi-epitope-based vaccines in the future. This research will also serve as a basis for further in vitro and in vivo analysis to develop a vaccine that is effective against the monkeypox virus.


Assuntos
Epitopos de Linfócito T , Monkeypox virus , Humanos , Proteínas de Membrana , Vacinas de Subunidades Antigênicas , Linfócitos B
6.
PLoS One ; 18(2): e0280879, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36735692

RESUMO

BACKGROUND: Physical activity is important for the control of high blood pressure (hypertension). We aimed to investigate the associations of current physical activity levels, sedentary time, knowledge of and attitude towards physical activity with blood pressure in people with hypertension in a rural area in Bangladesh. METHODS: A total of 307 adults aged 30 to 75 years with hypertension were recruited from the Banshgram Union of Narial district as part of a cluster-randomized control trial. Current blood pressure was measured as the outcome variable. Associated variables included physical activity at work, travel to and from places, recreational activity, metabolic equivalent task (MET)-min, sedentary time, and awareness of and attitudes towards physical activity. Rasch analysis was used to compute a combined score from the five awareness of and attitudes towards physical activity items and categorized into 0-40 (towards negative attitude), 41-60 score (mixed attitude) and 61-100 (positive attitude). We used a generalised linear model to analyze the data. RESULTS: Participants (n = 68, 22.1%) who engaged in vigorous-intensity physical activity that causes large increases in breathing or heart rate like carrying or lifting heavy loads, digging or construction work for at least 10 minutes continuously had lower systolic blood pressure (SBP) (mean (95% confidence interval (CI)), 143.6 (140.1, 147.2)) compared to those who did not take part in a vigorous-intensity physical activity (mean (95% CI), 150 (147.6, 152.3)). MET-min less than 600 min/week was significantly associated with higher SBP 153.8 (148.1, 159.6) than MET-min 600-2999 min/week 148.0 (143.0, 152.9) and MET-min>3000 min/week 146.9 (144.5, 149.3), p = 0.001 for trend. Sitting time more than four hours a day was associated with higher DBP 91.4 (89.7, 93.0) compared to those who had sitting time less than fours a day 88.6 (87.1, 90.1). People with positive attitudes were associated with a reduced SBP of 10.6 (0.36, 20.8) mmHg and DBP 5.88 (0.47, 11.3) compared to the people who had a negative attitude towards taking part in physical activity. CONCLUSIONS: Participating in high physical activity and positive attitudes towards physical activity were associated with lower blood pressure levels. Physical activity awareness programs should be implemented to increase awareness of health benefits and increase participation in high physical activity.


Assuntos
Hipertensão , Adulto , Humanos , Pressão Sanguínea , Bangladesh , Hipertensão/epidemiologia , Exercício Físico , Comportamento Sedentário
7.
Virus Res ; 319: 198859, 2022 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-35809696

RESUMO

Hepatitis B virus (HBV) is a major public health concern worldwide. Co-infection of hepatitis B patients with other pathogens intensifies the severity of the disease. We report a novel variant of hepatitis B virus (HBV) in Bangladesh isolated from a patient co-infected with hepatitis C virus (HCV) who exhibited liver cirrhosis. From 150 collected plasma samples, we sequenced HBV complete genome from one HBV-HCV co-infected patient. The complete genome was analysed using bioinformatics tools, NCBI BLAST, Geno2Pheno, and SnapGene software. The strain belongs to genotype A and subgenotype A1. Upon analysing the complete genome of this strain, we found a frameshift deletion of 54 nucleotides at the pre-S2 region, a functional regulator of HBV surface protein. Furthermore, we observed a Y126H mutation in the polymerase protein of this strain. This is the first report with such an unusual pre-S deletion event of the HBV genome in an HCV-co-infected patient associated with liver cirrhosis. These findings may inform scientists about genomic modifications in the HBV genome associated with HCV co-infection.


Assuntos
Coinfecção , Hepatite B Crônica , Hepatite B , Hepatite C , DNA Viral/genética , Genótipo , Hepacivirus/genética , Hepatite B/complicações , Antígenos de Superfície da Hepatite B/genética , Vírus da Hepatite B/genética , Hepatite C/complicações , Humanos , Cirrose Hepática/complicações
8.
Can J Neurol Sci ; 49(5): 662-671, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-34321129

RESUMO

BACKGROUND: To investigate the relative contributions of cerebral cortex and basal ganglia to movement stopping, we tested the optimum combination Stop Signal Reaction Time (ocSSRT) and median visual reaction time (RT) in patients with Alzheimer's disease (AD) and Parkinson's disease (PD) and compared values with data from healthy controls. METHODS: Thirty-five PD patients, 22 AD patients, and 29 healthy controls were recruited to this study. RT and ocSSRT were measured using a hand-held battery-operated electronic box through a stop signal paradigm. RESULT: The mean ocSSRT was found to be 309 ms, 368 ms, and 265 ms in AD, PD, and healthy controls, respectively, and significantly prolonged in PD compared to healthy controls (p = 0.001). The ocSSRT but not RT could separate AD from PD patients (p = 0.022). CONCLUSION: Our data suggest that subcortical networks encompassing dopaminergic pathways in the basal ganglia play a more important role than cortical networks in movement-stopping. Combining ocSSRT with other putative indices or biomarkers of AD (and other dementias) could increase the accuracy of early diagnosis.


Assuntos
Doença de Alzheimer , Doença de Parkinson , Doença de Alzheimer/diagnóstico , Gânglios da Base , Dopamina , Humanos , Doença de Parkinson/diagnóstico , Tempo de Reação
9.
F1000Res ; 10: 655, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34900232

RESUMO

The prevalence of Herpes simplex virus 2 (HSV2) is increasing at an alarming rate in the world. Most of the HSV2 cases are not diagnosed properly, although a range of molecular and serological diagnoses exist. Herein, we have reported a very rapid detection method specific for HSV2 using real-time PCR. The primers specific for HSV2 were designed using the Primer-BLAST tool and 120 base pairs of the polymerase gene were amplified using real-time PCR with SYBR Green dye. The designed primer pair was found highly efficient in detecting only HSV2 DNA, but not HSV1. The threshold cycle (Ct) value for HSV2 reactions by designed primers was found to be an average of 22.55 for a standard copy number of viral DNA that may denote the efficiency of the primers. The melting temperature (Tm) of the amplicon using designed primers (82.6 0C) was also higher than that using reference primers (about 78 0C), indicating the high GC content of the amplified template. The designed primer pair will help clinicians to detect the HSV2 DNA specifically and diagnose the associated disease rapidly.


Assuntos
Herpesvirus Humano 2 , Quinolinas , Benzotiazóis , Diaminas , Herpesvirus Humano 2/genética , Reação em Cadeia da Polimerase em Tempo Real
10.
Artigo em Inglês | MEDLINE | ID: mdl-34574492

RESUMO

This initial investigation aimed to investigate the knowledge of the health benefits of physical activity (PA) and attitudes towards participation in PA. The study recruited 307 people aged 30-75 years with hypertension as part of a cluster randomized controlled trial from a rural area in Bangladesh. Of the 307 participants, 135 participated less than 2.5 h of physical activity per week, from which we collected data on attitudes toward PA. Regression analysis and Rasch analysis were used. More than 85% of homemakers, employees or businesspersons were willing to take part in PA. Based on the combined score from the knowledge and attitude items, 46% of people endorsed PA programs; proportions were higher in men than women (53% vs. 41%). After adjusting for covariates, men (odds ratio, 95% confidence interval (CI) 3.50, 1.72-7.11) compared to women and people with at least primary levels of schooling (OR 3.06, 95% CI, 1.27-7.38) compared with those with no education were more likely to organize or take part in any PA programs. People have positive attitudes towards PA but do not feel obligated to participate in PA programs. Future programs are needed to promote awareness and motivational interventions for PA, especially targeting women and people with low education levels, should be developed and implemented.


Assuntos
Hipertensão , Intenção , Bangladesh , Exercício Físico , Feminino , Humanos , Hipertensão/epidemiologia , Hipertensão/prevenção & controle , Masculino , Motivação
11.
Inorg Chem ; 60(18): 14116-14131, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34477372

RESUMO

The enantiopure Schiff bases (R or S)-N-1-(X-C6H4)ethyl-2-hydroxy-1-naphthaldimine {X = H [(R or S)-HL1], p-CH3O [(R or S)-HL2], and p-Br [(R- or S)-HL3]} react with cobalt(II) acetate to give bis[(R or S)-N-1-(X-C6H4)ethyl-2-oxo-1-naphthaldiminato-κ2N,O]-Λ/Δ-cobalt(II) {X = H [Λ/Δ-Co-(R or S)-L1], p-CH3O [Λ/Δ-Co-(R or S)-L2], and p-Br [Λ/Δ-Co-(R or S)-L3]} (1-3), respectively. Induced Λ and Δ chirality originates at the metal center of the C2-symmetric molecule in pseudotetrahedral geometry. Differential scanning calorimetry analyses explored the thermal stability of the complexes, which undergo reversible phase transformation from crystalline solid to isotropic liquid phase for 1 and 3 but irreversible phase transformation for 2. Like other cobalt(II) complexes, compounds 1-3 exhibit a continuous ensemble of absorption and circular dichroism bands, which span from the UV to IR region and can be collected into a superspectrum. Infrared vibrational circular dichroism (IR-VCD) spectra witness the coupling between Co2+-centered low-lying electronic states and ligand-centered vibrations. The coupling produces enhanced and almost monosignate VCD spectra, with both effects being mode-dependent in terms of the A or B symmetry (in the C2 point group) and distance from the Co2+ core.

12.
Genomics Inform ; 19(4): e43, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35012287

RESUMO

Campylobacter jejuni is one of the most prevalent organisms associated with foodborne illness across the globe causing campylobacteriosis and gastritis. Many proteins of C. jejuni are still unidentified. The purpose of this study was to determine the structure and function of a non-annotated hypothetical protein (HP) from C. jejuni. A number of properties like physiochemical characteristics, 3D structure, and functional annotation of the HP (accession No. CAG2129885.1) were predicted using various bioinformatics tools followed by further validation and quality assessment. Moreover, the protein-protein interactions and active site were obtained from the STRING and CASTp server, respectively. The hypothesized protein possesses various characteristics including an acidic pH, thermal stability, water solubility, and cytoplasmic distribution. While alpha-helix and random coil structures are the most prominent structural components of this protein, most of it is formed of helices and coils. Along with expected quality, the 3D model has been found to be novel. This study has identified the potential role of the HP in 2-methylcitric acid cycle and propionate catabolism. Furthermore, protein-protein interactions revealed several significant functional partners. The in-silico characterization of this protein will assist to understand its molecular mechanism of action better. The methodology of this study would also serve as the basis for additional research into proteomic and genomic data for functional potential identification.

13.
Transbound Emerg Dis ; 68(4): 2514-2520, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33174386

RESUMO

Anthrax is a zoonotic disease caused by the bacterium Bacillus anthracis that is considered endemic in Bangladesh, where cases among animals and people have been reported almost annually since 2009. Contaminated by-products from animals are suspected to play a role in transmission to people, but minimal information is known on the supply chain of these potentially contaminated products. Between April 2013 and May 2016, we conducted a qualitative study in 17 villages located in five districts in Bangladesh, which had experienced suspected anthrax outbreaks. The study explored how by-products from suspected animal cases were collected, discarded, processed, distributed and used by people. We conducted open-ended interviews, group discussions and unstructured observations of people's exposure to animal by-products. The practice of slaughtering acutely ill domestic ruminants before they died was common. Respondents reported that moribund animals were typically butchered, and the waste products were discarded in nearby rivers, ditches, bamboo bushes, or on privately owned land. Regardless of health status before death, very few carcasses were buried, and none were incinerated or burned. The hides were reportedly used to make wallets, belts, shoes, balls and clothing. Discarded bones were often ground into granular and powder forms to produce bone meal and fertilizer. Therefore, given anthrax is endemic in the study region, livestock with acute onset of fatal disease or found dead with no known cause of death may be an anthrax case and subsequently pose a health risk to those involved in the collection and processing of the carcass, as well as the end-user of these products. Improved bio-security practices and safe carcass disposal measures could reduce the risk of human exposure, but resource and other constraints make implementation a challenge. Therefore, targeting at-risk animal populations for vaccination may be the most effective strategy to reduce anthrax outbreaks, protect the supply chain and reduce the risk of exposure to B. anthracis.


Assuntos
Antraz , Bacillus anthracis , Animais , Antraz/epidemiologia , Antraz/prevenção & controle , Antraz/veterinária , Bangladesh/epidemiologia , Surtos de Doenças , Humanos , Gado , Zoonoses/epidemiologia
14.
Biomaterials ; 266: 120431, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33099060

RESUMO

Synthetic mRNA represents an exciting cancer vaccine technology for the implementation of effective cancer immunotherapy. However, inefficient in vivo mRNA delivery along with a requirement for immune co-stimulation present major hurdles to achieving anti-tumor therapeutic efficacy. Here, we demonstrate a proof-of-concept adjuvant-pulsed mRNA vaccine nanoparticle (NP) that is composed of an ovalbumin-coded mRNA and a palmitic acid-modified TLR7/8 agonist R848 (C16-R848), coated with a lipid-polyethylene glycol (lipid-PEG) shell. This mRNA vaccine NP formulation retained the adjuvant activity of encapsulated C16-R848 and markedly improved the transfection efficacy of the mRNA (>95%) and subsequent MHC class I presentation of OVA mRNA derived antigen in antigen-presenting cells. The C16-R848 adjuvant-pulsed mRNA vaccine NP approach induced an effective adaptive immune response by significantly improving the expansion of OVA-specific CD8+ T cells and infiltration of these cells into the tumor bed in vivo, relative to the mRNA vaccine NP without adjuvant. The approach led to an effective anti-tumor immunity against OVA expressing syngeneic allograft mouse models of lymphoma and prostate cancer, resulting in a significant prevention of tumor growth when the vaccine was given before tumor engraftment (84% reduction vs. control) and suppression of tumor growth when given post engraftment (60% reduction vs. control). Our findings indicate that C16-R848 adjuvant pulsation to mRNA vaccine NP is a rational design strategy to increase the effectiveness of synthetic mRNA vaccines for cancer immunotherapy.


Assuntos
Vacinas Anticâncer , Nanopartículas , Animais , Linfócitos T CD8-Positivos , Células Dendríticas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ovalbumina , RNA Mensageiro/genética
15.
Am J Trop Med Hyg ; 103(4): 1621-1629, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32783794

RESUMO

Infodemics, often including rumors, stigma, and conspiracy theories, have been common during the COVID-19 pandemic. Monitoring social media data has been identified as the best method for tracking rumors in real time and as a possible way to dispel misinformation and reduce stigma. However, the detection, assessment, and response to rumors, stigma, and conspiracy theories in real time are a challenge. Therefore, we followed and examined COVID-19-related rumors, stigma, and conspiracy theories circulating on online platforms, including fact-checking agency websites, Facebook, Twitter, and online newspapers, and their impacts on public health. Information was extracted between December 31, 2019 and April 5, 2020, and descriptively analyzed. We performed a content analysis of the news articles to compare and contrast data collected from other sources. We identified 2,311 reports of rumors, stigma, and conspiracy theories in 25 languages from 87 countries. Claims were related to illness, transmission and mortality (24%), control measures (21%), treatment and cure (19%), cause of disease including the origin (15%), violence (1%), and miscellaneous (20%). Of the 2,276 reports for which text ratings were available, 1,856 claims were false (82%). Misinformation fueled by rumors, stigma, and conspiracy theories can have potentially serious implications on the individual and community if prioritized over evidence-based guidelines. Health agencies must track misinformation associated with the COVID-19 in real time, and engage local communities and government stakeholders to debunk misinformation.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Saúde Pública , Mídias Sociais , COVID-19 , Análise de Dados , Coleta de Dados/métodos , Saúde Global , Humanos , Saúde Pública/tendências , Estudos Retrospectivos , SARS-CoV-2 , Discriminação Social/psicologia , Mídias Sociais/normas , Mídias Sociais/tendências , Estigma Social
16.
Artigo em Inglês | MEDLINE | ID: mdl-32850698

RESUMO

Adjuvant-pulsed peptide vaccines hold great promise for the prevention and treatment of different diseases including cancer. However, it has been difficult to maximize vaccine efficacy due to numerous obstacles including the unfavorable tolerability profile of adjuvants, instability of peptide antigens, limited cellular uptake, and fast diffusion from the injection site, as well as systemic adverse effects. Here we describe a robust lipidation approach for effective nanoparticle co-delivery of low-molecular weight immunomodulators (TLR7/8 agonists) and peptides (SIINFEKL) with a potent in vivo prophylactic effect. The lipidation approaches (C16-R848 and C16-SIINFEKL) increased their hydrophobicity that is intended not only to improve drug encapsulation efficiency but also to facilitate the membrane association, intracellular trafficking, and subcellular localization. The polymer-lipid hybrid nanoparticles (PLNs) are designed to sustain antigen/adjuvant levels with less systemic exposure. Our results demonstrated that a lipidated nanovaccine can induce effective immunity by enhancing the expansion and activation of antigen-specific CD8+ T cells. This adaptive immune response led to substantial tumor suppression with improved overall survival in a prophylactic setting. Our new methodology enhances the potential of nanovaccines for anti-tumor therapy.

17.
Sci Transl Med ; 12(553)2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32718990

RESUMO

Atherosclerotic lesional macrophages express molecules that promote plaque progression, but lack of mechanisms to therapeutically target these molecules represents a major gap in translational cardiovascular research. Here, we tested the efficacy of a small interfering RNA (siRNA) nanoparticle (NP) platform targeting a plaque-destabilizing macrophage molecule-Ca2+/calmodulin-dependent protein kinase γ (CaMKIIγ). CaMKIIγ becomes activated in advanced human and mouse plaque macrophages and drives plaque necrosis by suppressing the expression of the efferocytosis receptor MerTK. When macrophage-targeted siCamk2g NPs were administered to Western diet-fed Ldlr -/- mice, the atherosclerotic lesions showed decreased CaMKIIγ and increased MerTK expression in macrophages, improved phagocytosis of apoptotic cells (efferocytosis), decreased necrotic core area, and increased fibrous cap thickness-all signs of increased plaque stability-compared with mice treated with control siRNA NPs. These findings demonstrate that atherosclerosis-promoting genes in plaque macrophages can be targeted with siRNA NPs in a preclinical model of advanced atherosclerosis.


Assuntos
Nanopartículas , Placa Aterosclerótica , Animais , Apoptose , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Macrófagos , Camundongos , Camundongos Knockout , RNA Interferente Pequeno
18.
Pharmaceutics ; 12(1)2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31906277

RESUMO

DNA vaccines offer a flexible and versatile platform to treat innumerable diseases due to the ease of manipulating vaccine targets simply by altering the gene sequences encoded in the plasmid DNA delivered. The DNA vaccines elicit potent humoral and cell-mediated responses and provide a promising method for treating rapidly mutating and evasive diseases such as cancer and human immunodeficiency viruses. Although this vaccine technology has been available for decades, there is no DNA vaccine that has been used in bed-side application to date. The main challenge that hinders the progress of DNA vaccines and limits their clinical application is the delivery hurdles to targeted immune cells, which obstructs the stimulation of robust antigen-specific immune responses in humans. In this updated review, we discuss various nanodelivery systems that improve DNA vaccine technologies to enhance the immunological response against target diseases. We also provide possible perspectives on how we can bring this exciting vaccine technology to bedside applications.

19.
Int J Phytoremediation ; 21(12): 1234-1240, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31148460

RESUMO

High content of chromium in plants hampers plants' metabolism, disrupts plant growth and development. Therefore, improving plants' tolerance to Cr toxicity is very essential. In our present study, we investigated the role of citric acid (CA) on chromium detoxification in terms of stress tolerance in rice. Application of CA under Cr stress restore the growth parameters, total protein content and membrane stability confirming that CA plays important role in Cr detoxification in rice. However, supplementation of CA under Cr stress caused no significant change in root Cr content but increased shoot Cr concentration (97 µg/g) compare with Cr stressed plant (24 µg/gm), suggesting that CA alleviates Cr toxicity by its chelating properties. Moreover, Fe content showed no significant changes due to CA supplementation under Cr stress, implying that Fe regulation is not involved with CA-mediated mitigation of Cr toxicity in rice. Furthermore, increased CAT, POD, and GR activity along with raised metabolites (glutathione and proline) indicates active participation in ROS scavenging and palliate the Cr toxicity in rice.


Assuntos
Oryza , Biodegradação Ambiental , Cromo , Ácido Cítrico , Inativação Metabólica , Raízes de Plantas
20.
Biomaterials ; 192: 75-94, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30439573

RESUMO

Vaccines are one of the greatest medical interventions of all time and have been successful in controlling and eliminating a myriad of diseases over the past two centuries. Among several vaccination strategies, mucosal vaccines have wide clinical applications and attract considerable interest in research, showing potential as innovative and novel therapeutics. In mucosal vaccination, targeting (microfold) M cells is a frontline prerequisite for inducing effective antigen-specific immunostimulatory effects. In this review, we primarily focus on materials engineered for use as vaccine delivery platforms to target M cells. We also describe potential M cell targeting areas, methods to overcome current challenges and limitations of the field. Furthermore, we present the potential of biomaterials engineering as well as various natural and synthetic delivery technologies to overcome the challenges of M cell targeting, all of which are absent in current literature. Finally, we briefly discuss manufacturing and regulatory processes to bring a robust perspective on the feasibility and potential of this next-generation vaccine technology.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Mucosa Intestinal/metabolismo , Nódulos Linfáticos Agregados/metabolismo , Vacinação/métodos , Vacinas/administração & dosagem , Animais , Materiais Biocompatíveis/química , Portadores de Fármacos/química , Humanos , Vacinas/farmacocinética
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