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1.
J Nanobiotechnology ; 21(1): 148, 2023 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-37149615

RESUMO

Nanobiotechnology, as a novel and more specialized branch of science, has provided a number of nanostructures such as nanoparticles, by utilizing the methods, techniques, and protocols of other branches of science. Due to the unique features and physiobiological characteristics, these nanostructures or nanocarriers have provided vast methods and therapeutic techniques, against microbial infections and cancers and for tissue regeneration, tissue engineering, and immunotherapies, and for gene therapies, through drug delivery systems. However, reduced carrying capacity, abrupt and non-targeted delivery, and solubility of therapeutic agents, can affect the therapeutic applications of these biotechnological products. In this article, we explored and discussed the prominent nanobiotechnological methods and products such as nanocarriers, highlighted the features and challenges associated with these products, and attempted to conclude if available nanostructures offer any scope of improvement or enhancement. We aimed to identify and emphasize the nanobiotechnological methods and products, with greater prospect and capacity for therapeutic improvements and enhancements. We found that novel nanocarriers and nanostructures, such as nanocomposites, micelles, hydrogels, microneedles, and artificial cells, can address the associated challenges and inherited drawbacks, with help of conjugations, sustained and stimuli-responsive release, ligand binding, and targeted delivery. We recommend that nanobiotechnology, despite having few challenges and drawbacks, offers immense opportunities that can be harnessed in delivering quality therapeutics with precision and prediction. We also recommend that, by exploring the branched domains more rigorously, bottlenecks and obstacles can also be addressed and resolved in return.


Assuntos
Nanocompostos , Nanopartículas , Nanoestruturas , Neoplasias , Humanos , Sistemas de Liberação de Medicamentos/métodos , Nanoestruturas/química , Micelas , Nanopartículas/química , Neoplasias/tratamento farmacológico , Portadores de Fármacos/química
2.
Hum Mol Genet ; 29(18): 3094-3106, 2020 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-32916703

RESUMO

High-altitude pulmonary edema (HAPE) is a noncardiogenic form of pulmonary edema, which is induced upon exposure to hypobaric hypoxia at high altitude (HA). Hypobaric hypoxia generates reactive oxygen species that may damage telomeres and disturb normal physiological processes. Telomere complex comprises of multiple proteins, of which, tankyrase (TNKS) is actively involved in DNA damage repairs. We hence investigated the association of TNKS and telomeres with HAPE to delineate their potential role at HA. The study was performed in three groups, High-altitude pulmonary edema patients (HAPE-p, n = 200), HAPE-resistant sojourners (HAPE-r, n = 200) and highland permanent healthy residents (HLs, n = 200). Variants of TNKS were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Plasma TNKS level was estimated using enzyme-linked immunosorbent assay, expression of TNKS and relative telomere length were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and telomerase activity was assessed by the telomere repeat amplification protocol assay. TNKS poly-ADP ribosylates the telomere-repeat factor (TRF), which is a negative regulator of telomere length. Consequently, TRF expression was also measured by RT-qPCR. The TNKS heterozygotes rs7015700GA were prevalent in HLs compared to the HAPE-p and HAPE-r. The plasma TNKS was significantly decreased in HAPE-p than HAPE-r (P = 0.006). TNKS was upregulated 9.27 folds in HAPE-p (P = 1.01E-06) and downregulated in HLs by 3.3 folds (P = 0.02). The telomere length was shorter in HAPE-p compared to HAPE-r (P = 0.03) and HLs (P = 4.25E-4). The telomerase activity was significantly higher in HAPE-p compared to both HAPE-r (P = 0.01) and HLs (P = 0.001). HAPE-p had the lowest TNKS levels (0.186 ± 0.031 ng/µl) and the highest telomerase activity (0.0268 amoles/µl). The findings of the study indicate the association of TNKS and telomeres with HA adaptation/maladaptation.


Assuntos
Doença da Altitude/genética , Predisposição Genética para Doença , Hipertensão Pulmonar/genética , Tanquirases/genética , Telomerase/genética , Homeostase do Telômero/genética , Adulto , Idoso , Alelos , Altitude , Doença da Altitude/fisiopatologia , Dano ao DNA/genética , Reparo do DNA/genética , Feminino , Estudos de Associação Genética , Genótipo , Voluntários Saudáveis , Humanos , Hipertensão Pulmonar/fisiopatologia , Hipóxia/genética , Hipóxia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição/genética , Telômero/genética
3.
Oral Dis ; 28(2): 284-306, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33063408

RESUMO

The aim was to provide a comprehensive qualitative and quantitative assessment of any potential differences in melatonin levels in periodontitis vs. the healthy state. The keyword combination "melatonin" AND "periodontitis" was searched in Web of Science, PubMed, and Scopus. Qualitative analysis and quantitative analysis were performed on articles satisfying the inclusion criteria. Only 14 studies were included in the systematic review, out of which only 10 had quantitative data compatible with a meta-analysis. Ten studies demonstrated low melatonin in periodontitis, three studies demonstrated an initial reduction in melatonin levels followed by elevation with worsening of periodontitis, and one study showed an elevation in melatonin levels in the transition from a healthy state to periodontitis. Grading of recommendations assessment, development, and evaluation revealed that all the included studies had low to very low overall evidence. The meta-analysis revealed a significant reduction (p < .0001) in salivary melatonin levels in chronic periodontitis (3.26 ± 3.44 pg/ml) compared with healthy controls (5.27 ± 5.39 pg/ml), with a mean difference of 2.65 ± 7.84 and a confidence interval of 1.94-3.36. The significantly lower salivary melatonin levels in periodontitis must be inferred with caution given the low quality of the included studies.


Assuntos
Periodontite Crônica , Melatonina , Procedimentos de Cirurgia Plástica , Bibliometria , Humanos
4.
Molecules ; 27(24)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36557823

RESUMO

Water gets polluted due to the dumping of untreated industrial waste into bodies of water, particularly those containing heavy metals and dyes. Industrial water contains both inorganic and organic wastes. Numerous adsorbents that are inexpensive and easily available can be used to address the issue of water deterioration. This review report is focused on polyacrylonitrile as an efficient constituent of adsorbents to extract toxic ions and dyes. It discusses the various formulations of polyacrylonitrile, such as ion exchange resins, chelating resins, fibers, membranes, and hydrogels, synthesized through different polymerization methods, such as suspension polymerization, electrospinning, grafting, redox, and emulsion polymerization. Moreover, regeneration of adsorbent and heavy metal ions makes the adsorption process more cost-effective and efficient. The literature reporting successful regeneration of the adsorbent is included. The factors affecting the performance and outcomes of the adsorption process are also discussed.


Assuntos
Metais Pesados , Poluentes Químicos da Água , Purificação da Água , Águas Residuárias , Poluentes Químicos da Água/análise , Metais Pesados/análise , Corantes , Purificação da Água/métodos , Adsorção , Íons , Água
5.
Molecules ; 27(4)2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35209118

RESUMO

The use of F. religiosa might be beneficial in inflammatory illnesses and can be used for a variety of health conditions. In this article, we studied the identification of antioxidants using (DPPH) 2,2-Diphenyl-1-picrylhydrazylradical scavenging activity in Ficus religiosa, as F. religiosa is an important herbal plant, and every part of it has various medicinal properties such as antibacterial properties that can be used by the researchers in the development and design of various new drugs. The 2,2-Diphenyl-1-picrylhydrazyl (DPPH) is a popular, quick, easy, and affordable approach for the measurement of antioxidant properties that includes the use of the free radicals used for assessing the potential of substances to serve as hydrogen providers or free-radical scavengers (FRS). The technique of DPPH testing is associated with the elimination of DPPH, which would be a stabilized free radical. The free-radical DPPH interacts with an odd electron to yield a strong absorbance at 517 nm, i.e., a purple hue. An FRS antioxidant, for example, reacts to DPPH to form DPPHH, which has a lower absorbance than DPPH because of the lower amount of hydrogen. It is radical in comparison to the DPPH-H form, because it causes decolorization, or a yellow hue, as the number of electrons absorbed increases. Decolorization affects the lowering capacity significantly. As soon as the DPPH solutions are combined with the hydrogen atom source, the lower state of diphenylpicrylhydrazine is formed, shedding its violet color. To explain the processes behind the DPPH tests, as well as their applicability to Ficus religiosa (F. religiosa) in the manufacture of metal oxide nanoparticles, in particular MgO, and their influence on antioxidants, a specimen from the test was chosen for further study. According to our findings, F. religiosa has antioxidant qualities and may be useful in the treatment of disorders caused by free radicals.


Assuntos
Compostos de Bifenilo/antagonistas & inibidores , Ficus/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Picratos/antagonistas & inibidores , Carboidratos/química , Fenóis/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Proteínas de Plantas/química , Açúcares/química
6.
J Oral Pathol Med ; 49(5): 375-385, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31975526

RESUMO

OBJECTIVE: To assess the efficacy of scaffold-mediated localized chemotherapy in cancer. METHODS: Databases including PubMed, Cochrane Library, and SCOPUS were searched for articles reporting the use of scaffold-mediated localized drug delivery in cancer. Essential data including scaffold fabrication material and methods, drug dosage and release duration and its effect on the cancer cells were extracted. RESULTS: 15 articles out of 60 screened, fulfilled the eligibility criteria. Among the 15 studies, 5 studies included only cell lines and 2 studies were on mouse models, while 8 studies involved a combination of cell lines and mouse models. Scaffold materials included both synthetic polymers such as poly-lactide, polycaprolactone and natural materials including d-periosteum and human micro-fragmented adipose tissueA wide number of other variables included the fabrication procedure, drugs used, and the methods used to assess the effects on cancer. As a result, it was not possible to make any direct comparison of the efficacy of the therapeutic strategy used in each of these studies. CONCLUSION: Irrespective of the many variables, a common consensus in all the included studies was that scaffold mediated localized drug delivery effectively reduced cancer cell viability by increasing drug bioavailability to the target tissue, while its localized effect reduced the risk of systemic toxicity.


Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Humanos , Polímeros
7.
Graefes Arch Clin Exp Ophthalmol ; 258(1): 167-173, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31713747

RESUMO

PURPOSE: To evaluate the long-term safety and efficacy of intrastromal bevacizumab for treatment of deep corneal neovascularization in candidates for high-risk cornea grafting. METHODS: A single-center retrospective study involving 14 eyes of 14 patients with chronic deep corneal neovascularization, treated with intrastromal bevacizumab by a single provider from 2011 to present. Intrastromal bevacizumab (0.05-0.1 mL of 2.5 mg/0.1 mL) was administered every 4-8 weeks. On average 1-3 intrastromal injections were performed prior to corneal grafting (penetrating keratoplasty or deep anterior lamellar keratoplasty). RESULTS: 64.2% patients had neurotrophic keratitis secondary to herpes zoster or simplex. Neovascularization was encroaching the visual axis in 50% and was paracentral in 42.8%. After intrastromal bevacizumab injection, 14.2% had complete regression of neovascularization, avoiding the need of future corneal transplant. Persistent neovascularization was noticed in 21.4%. Successful penetrating keratoplasty was performed in 57% of patients. Minimal adverse effects were noted; temporary epithelial defect was seen in two eyes and self-limited intrastromal hemorrhage in one. There was no evidence of recurrence of neovascularization or graft rejection in the transplant group (mean follow-up 3 years). CONCLUSION: Intrastromal bevacizumab appears to be a safe and effective modality in the treatment of chronic corneal neovascularization, producing durable regression of corneal neovascularization and allowing for durable success of subsequent corneal transplants in high-risk patients.


Assuntos
Bevacizumab/administração & dosagem , Neovascularização da Córnea/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Neovascularização da Córnea/diagnóstico , Substância Própria , Feminino , Seguimentos , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Estudos Retrospectivos , Resultado do Tratamento
8.
Clin Oral Investig ; 24(1): 13-23, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31707627

RESUMO

OBJECTIVE: To assess any potential association between Helicobacter pylori and oral squamous cell carcinoma/oral potentially malignant disorders. MATERIALS AND METHODS: Data mining was done using PubMed, Cochrane Library, and SCOPUS databases. The search included articles published up to May 2019. Newcastle-Ottawa scale was used to score the quality of the included articles. Data including the type of study, the sample population, the type of oral lesion, and the resulting statistical data were extracted. RESULTS: Out of 131 screened articles, only 15 articles fulfilled the eligibility criteria. Among the 15 studies, 9 focused on oral squamous cell carcinoma and 6 focused on oral potentially malignant disorders. Eight out of the 9 oral squamous cell carcinoma studies were included in the meta-analysis. Forest plot was generated using the odds ratio and confidence intervals calculated for each of the included studies. Due to the lack of sufficient studies, the meta-analysis was not performed for oral potentially malignant disorders. CONCLUSION: Due to the contradictory results of the included studies, it was not possible to make any conclusive statement on the potential association of H. pylori with oral squamous cell carcinoma. The variations in the methodology, especially the differences in the sensitivity/specificity of the diagnostic modalities could be the cause for differential results. CLINICAL RELEVANCE: Although the association of H. pylori with oral squamous cell carcinoma could not be confirmed, it is vital to reduce the excess oral microbial load, especially in patients exhibiting oral mucosal changes with no history of associated risk factors.


Assuntos
Carcinoma de Células Escamosas , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Bucais , Estudos Transversais , Humanos
9.
FASEB J ; 30(9): 3097-106, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27226520

RESUMO

HIV-infected individuals have activated monocytes with an IFNα phenotype and elevated levels of circulating LPS. These individuals also have a risk of premature cardiovascular disease. The effect of activated monocyte exosomes (Exos) on endothelial cells is unknown. To determine whether Exos from immune-activated monocytes could alter endothelial cell expression and contribute to monocyte/macrophage transmigration and adhesion, we isolated Exos from monocytes stimulated with IFNα, LPS, or both (I/L). We show that monocyte Exos contain different inflammatory microRNA cargo depending on stimulation. When LPS Exos or I/L Exos were added to HUVECs, we found a significant increase in adhesion molecule ICAM-1, chemokine ligand (CCL)-2, and cytokine IL-6 mRNAs and proteins compared with cells treated with IFNα Exos or Exos derived from unstimulated monocytes. Inhibition of transcription factor NF-κB, a common inflammatory cytokine pathway, prevented induction of CCL2, IL6, and ICAM1 Inhibition of TLR4 resulted in differential blockage of the targets. Our results demonstrate for the first time that primary human monocyte Exos enter endothelial cells and cause dysfunction via the TLR4 and NF-κB pathways, which may contribute to heart disease in HIV infection and other diseases involving chronic immune activation.-Tang, N., Sun, B., Gupta, A., Rempel, H., Pulliam, L. Monocyte exosomes induce adhesion molecules and cytokines via activation of NF-κB in endothelial cells.


Assuntos
Moléculas de Adesão Celular/fisiologia , Citocinas/metabolismo , Exossomos/fisiologia , Regulação da Expressão Gênica/fisiologia , Monócitos/fisiologia , NF-kappa B/metabolismo , Células Cultivadas , Citocinas/genética , Células Endoteliais/fisiologia , Humanos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
10.
Cutan Ocul Toxicol ; 36(3): 263-272, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28073339

RESUMO

CONTEXT: The prevalence of sensitive skin among the general population in industrialized countries is reported to be over 50%. Sensitive skin subjects often report significant reactions to contact with cosmetics, soaps and other consumer products. OBJECTIVE: This paper describes the overall skin compatibility and mildness program for a newly developed, lightly fragranced, colorant free laundry product (i.e. Arm & Hammer™ Sensitive Skin plus Skin-Friendly Fresh Scent), specially formulated for individuals with sensitive skin. The skin mildness of the product was compared to Arm & Hammer™ Free & Clear liquid laundry detergent with no fragrance or colorant, and an established history of safe use by sensitive skin consumers. MATERIALS AND METHODS: The test material was a liquid laundry product with a light scent formulated for sensitive skin consumers (Arm & Hammer™ Sensitive Skin plus Skin-Friendly Fresh Scent). The product was compared to commercially marketed products for sensitive skin with a history of skin safety in the marketplace, including: a very similar product formulation (Arm & Hammer™ Free & Clear with no fragrance), and several selected competitors' products. Studies were conducted among individuals with self-assessed sensitive skin (based on a questionnaire) using standard protocols for the Human Repeat Insult Patch Test (HRIPT), 10-Day Cumulative Irritation, the Wrist Band Wear test, and the Safety In-Use testing. Responses in all protocols were evaluated by visual scoring of potential dermatologic reactions, and recording any sensory effects at the time of the examination. In addition, sensory effects collected from panelists' daily diaries were also evaluated. RESULTS: The HRIPT confirmed that neither the fragrance alone, nor the product formulation with fragrance, induced contact sensitization in sensitive skin subjects. The 10-Day cumulative irritation study conducted using sensitive skin subjects showed highly favorable skin compatibility, and the test product was comparable to the control product (Arm & Hammer Free & Clear) and other nonirritant controls. In the Wrist Band Wear test, exposure to laundered fabrics under exaggerated conditions gave similar results for the test and control products, with no objective signs of skin irritation, and no self-reported persistent adverse sensory effects. Very mild, transient and isolated sensory effects were noted in daily diaries by a small proportion of subjects, and were similar for the test and control products. The Safety In-Use tests evaluated 4-week exposure to product and laundered fabrics under realistic use conditions. There were no clinically objective signs of skin irritation, and reports of transitory, mild sensory effects were minimal and similar for the test and controls. DISCUSSION AND CONCLUSION: A comprehensive skin safety program on a lightly scented sensitive skin laundry formulation (i.e. Arm & Hammer™ Sensitive Skin plus Skin-Friendly Fresh Scent) conducted among panels of self-assessed sensitive skin subjects demonstrated that the presence of a light fragrance did not adversely impact skin compatibility in any of the testing protocols when the product was compared to a similar product with no fragrance. The lightly fragranced product demonstrated overall skin compatibility and mildness when tested in a self-assessed sensitive skin population, and compared favorably to currently marketed sensitive skin products.


Assuntos
Detergentes/toxicidade , Perfumes/toxicidade , Pele/efeitos dos fármacos , Adolescente , Adulto , Idoso , Qualidade de Produtos para o Consumidor , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes do Emplastro , Adulto Jovem
11.
Methods ; 87: 31-45, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-25916618

RESUMO

Extracellular vesicles, including exosomes, are currently being investigated to better understand their biogenesis and biological functions. There is also a rapidly growing interest in utilizing exosomes present in patient biofluids for molecular diagnostics in the clinic. Exosomes are natural shuttles of RNA and protein cargo, making them attractive as potential therapeutic delivery vehicles. Here, we describe the methods for using the latest tools and technologies to study exosomes to better understand their roles in cell-to-cell communication, for discovery of clinical biomarkers and to engineer exosomes for therapeutic applications.


Assuntos
Biomarcadores Tumorais/isolamento & purificação , Exossomos/química , MicroRNAs/isolamento & purificação , Proteínas de Neoplasias/isolamento & purificação , Neoplasias/química , RNA Neoplásico/isolamento & purificação , Biomarcadores Tumorais/genética , Fracionamento Celular/instrumentação , Fracionamento Celular/métodos , Cromatografia em Gel , Floculação , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , MicroRNAs/genética , Microscopia Eletrônica , Proteínas de Neoplasias/genética , Neoplasias/diagnóstico , Neoplasias/genética , Neoplasias/patologia , Análise de Sequência com Séries de Oligonucleotídeos , RNA Neoplásico/genética , Kit de Reagentes para Diagnóstico , Ultracentrifugação , Ultrafiltração
12.
J Surg Res ; 193(2): 731-7, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25193578

RESUMO

BACKGROUND: There is concern about potential interference of iodinated contrast used in contrast-enhanced computerized tomography (CECT) with radioiodine therapy in differentiated thyroid carcinoma (DTC). The aim of this study was to determine the effect of iodinated contrast on urinary iodine concentration (UIC) in patients having thyroidectomy compared with control groups without CECT and without thyroidectomy. METHODS: This prospective control study consisted of 4 groups each comprising 32 patients. Group 1- DTC patients undergoing preoperative CECT, group 2- DTC patients not undergoing CECT, group 3- benign goiter patients undergoing preoperative CECT, and group 4- patients with non-thyroidal diseases undergoing preoperative CECT. Spot UIC before CECT, after surgery (5-7 d), and at follow-up (4-6 wk) were compared among the groups. RESULTS: The median basal UIC levels were not significantly different between the four groups (232.2 versus 263.9 versus 268.2 versus 178.2 µg/L, respectively, P = 0.443). In contrast, groups having preoperative CECT had significantly higher UIC levels at discharge (924 versus 329 versus 776 versus 661 µg/L, respectively, P = 0.001). These differences became insignificant at follow-up (225 versus 252 versus 310 versus 275 µg/L, respectively, P = 0.505). Patients having follow-up UIC values above the conventional cut-off of clinically relevant iodine excess (>200 µg/L) also had significantly higher basal values than those having lower follow-up values (283.0 versus 181.7 µg/L; P = 0.037). CONCLUSIONS: Irrespective of the fact whether a patient is thyroidectomized or not preoperative CECT using non-lipophilic contrast does not result in long-term iodine retention.


Assuntos
Carcinoma/radioterapia , Meios de Contraste , Radioisótopos do Iodo , Iodo/urina , Iohexol , Neoplasias da Glândula Tireoide/radioterapia , Adulto , Carcinoma/diagnóstico por imagem , Carcinoma/cirurgia , Contraindicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Tomografia Computadorizada por Raios X , Adulto Jovem
13.
BMC Genomics ; 15: 959, 2014 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-25373614

RESUMO

BACKGROUND: Over the course of its intraerythrocytic developmental cycle (IDC), the malaria parasite Plasmodium falciparum tightly orchestrates the rise and fall of transcript levels for hundreds of genes. Considerable debate has focused on the relative importance of transcriptional versus post-transcriptional processes in the regulation of transcript levels. Enzymatically active forms of RNAPII in other organisms have been associated with phosphorylation on the serines at positions 2 and 5 of the heptad repeats within the C-terminal domain (CTD) of RNAPII. We reasoned that insight into the contribution of transcriptional mechanisms to gene expression in P. falciparum could be obtained by comparing the presence of enzymatically active forms of RNAPII at multiple genes with the abundance of their associated transcripts. RESULTS: We exploited the phosphorylation state of the CTD to detect enzymatically active forms of RNAPII at most P. falciparum genes across the IDC. We raised highly specific monoclonal antibodies against three forms of the parasite CTD, namely unphosphorylated, Ser5-P and Ser2/5-P, and used these in ChIP-on-chip type experiments to map the genome-wide occupancy of RNAPII. Our data reveal that the IDC is divided into early and late phases of RNAPII occupancy evident from simple bi-phasic RNAPII binding profiles. By comparison to mRNA abundance, we identified sub-sets of genes with high occupancy by enzymatically active forms of RNAPII and relatively low transcript levels and vice versa. We further show that the presence of active and repressive histone modifications correlates with RNAPII occupancy over the IDC. CONCLUSIONS: The simple early/late occupancy by RNAPII cannot account for the complex dynamics of mRNA accumulation over the IDC, suggesting a major role for mechanisms acting downstream of RNAPII occupancy in the control of gene expression in this parasite.


Assuntos
Genoma de Protozoário , Malária Falciparum/parasitologia , Plasmodium falciparum/genética , Plasmodium falciparum/metabolismo , RNA Polimerase II/metabolismo , Anticorpos Monoclonais/farmacologia , Sítios de Ligação/genética , Imunoprecipitação da Cromatina , Análise por Conglomerados , Biologia Computacional , Eritrócitos/parasitologia , Dosagem de Genes , Estudo de Associação Genômica Ampla , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Anotação de Sequência Molecular , Fosforilação , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Subunidades Proteicas/antagonistas & inibidores , RNA Polimerase II/antagonistas & inibidores , RNA Polimerase II/química , RNA Mensageiro/genética , Transcrição Gênica , Ativação Transcricional
15.
J Neuroinflammation ; 11: 68, 2014 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-24694258

RESUMO

Exosomes are membrane-bound nanovesicles that are shed by cells of various lineages under normal as well as pathological conditions. Previously thought to be 'extracellular debris', exosomes have recently generated immense interest following their discovery as mediators of intercellular communication by delivering functional proteins, mRNA transcripts as well as miRNAs to recipient cells. Although suggested to primarily serve as signaling organelles which also remove unwanted cellular components in the brain, accumulating evidence suggests that exosomes can also significantly contribute to the development of several neuropathologies. Toxic forms of aggregated proteins such as α-synuclein, amyloid ß and prions, that are responsible for the development of Parkinson's disease, Alzheimer's disease and Creutzfeldt-Jacob disease (CJD) respectively, have been shown to get effectively packaged into exosomes and spread from one cell to another, initiating an inflammatory cascade. In addition, exosomes secreted by resident brain cells in response to pathogenic stimuli such as viral proteins can also influence bystander cells by the transfer of dysregulated miRNAs that suppress the expression of essential genes in the recipient cells. Given the relevance of exosomes in brain communication and neuropathogenesis, novel therapeutic strategies are now being developed that exploit the biology of these vesicles to deliver anti-inflammatory molecules to the CNS. Exosomes may alter the way we think about brain disorders and their treatments.


Assuntos
Exossomos/fisiologia , Inflamação/complicações , Inflamação/patologia , Doenças do Sistema Nervoso/complicações , Doenças do Sistema Nervoso/patologia , Comunicação Celular , Humanos
16.
PLoS Pathog ; 8(9): e1002937, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23028330

RESUMO

HIV-1 infection of macrophages plays a key role in viral pathogenesis and progression to AIDS. Polyinosine-polycytidylic acid (poly(I:C); a synthetic analog of dsRNA) and bacterial lipopolysaccharide (LPS), the ligands for Toll-like receptors (TLR) TLR3 and TLR4, respectively, are known to decrease HIV-1 infection in monocyte-derived macrophages (MDMs), but the mechanism(s) are incompletely understood. We found that poly(I:C)- and LPS-stimulation of MDMs abrogated infection by CCR5-using, macrophage-tropic HIV-1, and by vesicular stomatitis virus glycoprotein-pseudotyped HIV-1 virions, while TLR2, TLR7 or TLR9 agonists only partially reduced infection to varying extent. Suppression of infection, or lack thereof, did not correlate with differential effects on CD4 or CCR5 expression, type I interferon induction, or production of pro-inflammatory cytokines or ß-chemokines. Integrated pro-viruses were readily detected in unstimulated, TLR7- and TLR9-stimulated cells, but not in TLR3- or TLR4-stimulated MDMs, suggesting the alteration of post-entry, pre-integration event(s). Using microarray analysis and quantitative reverse transcription (RT)-PCR, we found increased microRNA (miR)-155 levels in MDMs upon TLR3/4- but not TLR7-stimulation, and a miR-155 specific inhibitor (but not a scrambled control) partially restored infectivity in poly(I:C)-stimulated MDMs. Ectopic miR-155 expression remarkably diminished HIV-1 infection in primary MDMs and cell lines. Furthermore, poly(I:C)-stimulation and ectopic miR-155 expression did not alter detection of early viral RT products, but both resulted in an accumulation of late RT products and in undetectable or extremely low levels of integrated pro-viruses and 2-LTR circles. Reduced mRNA and protein levels of several HIV-1 dependency factors involved in trafficking and/or nuclear import of pre-integration complexes (ADAM10, TNPO3, Nup153, LEDGF/p75) were found in poly(I:C)-stimulated and miR-155-transfected MDMs, and a reporter assay suggested they are authentic miR-155 targets. Our findings provide evidence that miR-155 exerts an anti-HIV-1 effect by targeting several HIV-1 dependency factors involved in post-entry, pre-integration events, leading to severely diminished HIV-1 infection.


Assuntos
HIV-1/fisiologia , Macrófagos/imunologia , Macrófagos/virologia , MicroRNAs/metabolismo , Receptor 3 Toll-Like/imunologia , Proteínas ADAM/genética , Proteínas ADAM/metabolismo , Proteína ADAM10 , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Antígenos CD4/biossíntese , Células Cultivadas , Quimiocinas CC/genética , Quimiocinas CC/imunologia , Quimiocinas CC/metabolismo , Citocinas/genética , Citocinas/imunologia , Citocinas/metabolismo , Células HEK293 , HIV-1/imunologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Interferon Tipo I/biossíntese , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Glicoproteínas de Membrana , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Poli I-C/metabolismo , Poli I-C/farmacologia , Interferência de RNA , RNA Interferente Pequeno , Receptores CCR5/biossíntese , Receptor 2 Toll-Like/imunologia , Receptor 4 Toll-Like/imunologia , Receptor 7 Toll-Like/imunologia , Receptor Toll-Like 9/imunologia , Proteínas do Envelope Viral
17.
Biopolymers ; 101(7): 795-813, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24415066

RESUMO

We have determined the geometric, vibrational, and electronic properties of N-acetylglycine oligomers by performing density functional theory quantum chemical calculations. The normal mode analysis was performed and the potential energy distribution was calculated among the internal coordinates. The optically active vibrational modes of PGI have been determined by selecting the modes from the calculated results of the pentamer and the observed vibrational spectra of PGI have been explained. The molecular electrostatic potential surface of N-acetylglycine pentamer reveals the sites of electrophilic attack and also provides clues for the role of electrostatic interactions involved in the reactivity. Natural bond orbital analysis has been performed to understand the charge transfer and various hyperconjugative interactions in the molecular system. The electronic properties of the oligomers have been discussed by calculating the transitions with the help of time dependent density functional theory method. The global reactivity descriptors such as hardness, chemical potential, and electrophilicity index have also been calculated.


Assuntos
Algoritmos , Glicina/análogos & derivados , Oligopeptídeos/química , Peptídeos/química , Biologia Computacional/métodos , Cristalografia por Raios X , Elétrons , Glicina/química , Modelos Moleculares , Estrutura Molecular , Conformação Proteica , Teoria Quântica , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Análise Espectral Raman/métodos , Eletricidade Estática , Termodinâmica , Vibração
18.
Public Health Rev ; 45: 1606803, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455869

RESUMO

Objectives: Community Health Workers (CHWs) are important healthcare professionals and key members of team. The purpose of this research is to identify the roles and responsibilities of CHWs in developed and developing countries who provide healthcare assistance to pregnant and lactating women. Methods: For this particular study, a comparison was conducted between CHWs role in seven developed countries, seven South Asian developing countries, and India, with special emphasis on improving maternal health status. Results: CHW programs are essential in communities, institutional health programs, and outreach delivery systems. Without active community involvement, CHWs cannot reach their full potential. Developed countries have frameworks for CHWs, such as the Swasthya Shebika Program, Village Health Worker Cadret, Lady Health Worker Programme, and Accredited Social Health Activist program. CHWs are well-paid in developed nations and work with marginalized groups to spread health messages. However, up to 60% of community health workers in low- and lower-middle-income countries do not receive remuneration. Conclusion: Health systems must support CHWs in choosing technical interventions and providing necessary training, supervision, and logistical support.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38279725

RESUMO

AIMS: Leishmaniasis is a deadly tropical disease that is neglected in many countries. World Health Organization, along with a few other countries, has been working together to protect against these parasites. Many novel drugs from the past few years have been discovered and subjected against leishmaniasis, which have been effective but they are quite expensive for lower-class people. Some drugs showed no effect on the patients, and the longer use of these medicines has made resistance against these deadly parasites. Researchers have been working for better medication by using natural products from medicinal plants (oils, secondary metabolites, plant extracts) and other alternatives to find active compounds as an alternative to the current synthetic drugs. MATERIALS AND METHODS: To find more potential natural products to treat Leishmania spp, a study has been conducted and reported many plant metabolites and other natural alternatives from plants and their extracts. Selected research papers with few term words such as natural products, plant metabolites, Leishmaniasis, in vivo, in vitro, and treatment against leishmaniasis; in the Google Scholar, PubMed, and Science Direct databases with selected research papers published between 2015 and 2021 have been chosen for further analysis has been included in this report which has examined either in vivo or in vitro analysis. RESULTS: This paper reported more than 20 novel natural compounds in 20 research papers that have been identified which report a leishmanicidal activity and shows an action against promastigote, axenic, and intracellular amastigote forms. CONCLUSION: Medicinal plants, along with a few plant parts and extracts, have been reported as a possible novel anti-leishmanial medication. These medicinal plants are considered nontoxic to Host cells. Leishmaniasis treatments will draw on the isolated compounds as a source further and these compounds compete with those already offered in clinics.


Assuntos
Antiprotozoários , Produtos Biológicos , Leishmania , Leishmaniose , Plantas Medicinais , Humanos , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico , Leishmaniose/tratamento farmacológico , Animais , Plantas Medicinais/química , Leishmania/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico
20.
Cureus ; 16(3): e56443, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38638772

RESUMO

Introduction Pancreatic fluid collection (PFC) is one of the most frequent complications associated with acute pancreatitis. The route of drainage is guided by the size and site of collection. The present study aims to assess the clinical and technical success of transgastric percutaneous drainage (PCD) for managing retrogastric walled-off pancreatic necrosis (WOPN). Materials and methods A total of 44 patients with acute pancreatitis diagnosed with WOPN who underwent transgastric PCD with ultrasound or CT guidance as part of standard clinical management were included in the study. Patients were observed for improvement in clinical parameters, and treatment outcomes were noted in terms of technical success, clinical success, adverse events, need for additional procedures, hospital stay, and duration of placement of all drains. Data for the internalization of transgastric PCD was also observed in the study. Results Technical success during the drain placement was observed in 93% (n=41) of patients.Internalization of the transgastric drain was attempted in 12 patients and successful in 11 (91%). The median duration of hospital stay from the time of placement of the first PCD until discharge and the median duration of all PCDs placed were higher in patients where the transgastric drain was not internalized as compared to patients where the transgastric drain was internalized. Conclusion In WOPN, transgastric drain placement and successful internalization in any form help in the early resolution of peripancreatic and abdominal collections. It also reduces the time to percutaneous catheter removal, which in turn reduces the morbidity and decreases the need for additional interventions or surgery.

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