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1.
IEEE Trans Vis Comput Graph ; 30(5): 2330-2336, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38437109

RESUMO

Researchers have used machine learning approaches to identify motion sickness in VR experience. These approaches would certainly benefit from an accurately labeled, real-world, diverse dataset that enables the development of generalizable ML models. We introduce 'VR.net', a dataset comprising 165-hour gameplay videos from 100 real-world games spanning ten diverse genres, evaluated by 500 participants. VR.net accurately assigns 24 motion sickness-related labels for each video frame, such as camera/object movement, depth of field, and motion flow. Building such a dataset is challenging since manual labeling would require an infeasible amount of time. Instead, we implement a tool to automatically and precisely extract ground truth data from 3D engines' rendering pipelines without accessing VR games' source code. We illustrate the utility of VR.net through several applications, such as risk factor detection and sickness level prediction. We believe that the scale, accuracy, and diversity of VR.net can offer unparalleled opportunities for VR motion sickness research and beyond.We also provide access to our data collection tool, enabling researchers to contribute to the expansion of VR.net.


Assuntos
Enjoo devido ao Movimento , Realidade Virtual , Humanos , Gráficos por Computador , Enjoo devido ao Movimento/diagnóstico , Software , Movimento
2.
Environ Sci Pollut Res Int ; 31(12): 18593-18613, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38349492

RESUMO

The adverse effects of arsenic-chelating drugs make it essential to replace invasive chelating therapy with non-invasive oral therapy for arsenic poisoning. The goal of the current investigation was to determine whether the uterine damage caused by arsenization could be repaired by the n-butanol fraction of Moringa oleifera seed (NB). The rats were orally administered with arsenic (10 mg/kg BW) for the initial 8 days, followed by NB (50 mg/kg) for the next 8 days without arsenic. The probable existence of different components in NB was evaluated by HPLC-MS. Pro and anti-inflammatory indicators were assessed by RT-PCR and western blot. ESR-α was detected via immunostaining. Arsenic-exposed rats had significantly increased lipid peroxidation and decreased antioxidant enzyme activity, which were markedly reduced after NB treatment. Weaker ESR-α expression and distorted uterine histomorphology following arsenication were retrieved significantly by NB. Meaningful restoration by NB was also achieved for altered mRNA and protein expression of various inflammatory and apoptotic indicators. Molecular interaction predicted that glucomoringin and methyl glucosinolate of moringa interact with the catalytic site of caspase-3 in a way that limits its activity. However, NB was successful in restoring the arsenic-mediated uterine hypofunction. The glucomoringin and methyl glucosinolate present in n-butanol fraction may play a critical role in limiting apoptotic event in the arsenicated uterus.


Assuntos
Arsênio , Moringa oleifera , Moringa , Feminino , Ratos , Animais , Arsênio/toxicidade , Estresse Oxidativo , 1-Butanol , Glucosinolatos/farmacologia , Antioxidantes/metabolismo , Moringa oleifera/metabolismo , Extratos Vegetais/farmacologia , Sementes/metabolismo
3.
Opt Lett ; 48(15): 4141-4144, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37527138

RESUMO

Plasmonic random lasers have drawn significant attention recently due to their versatility, low threshold, and the possibility of achieving tunable and coherent/incoherent outputs. However, in this Letter, the phenomenon of replica symmetry breaking is reported in intensity fluctuations of a rarely used colloidal plasmonic random laser (RL) illumination. Triangular nanosilver scatter particles produced incoherent RL action when used in a dimethylformamide (DMF) environment in a Rhodamine-6G gain medium. The use of gold-coated triangular nanosilver as the scatterer in place of triangular nanosilver offered a dual contribution of scattering and lower photo-reabsorption, which caused a reduction in the lasing threshold energy of 39% compared to that obtained with the latter. Further, due to its long-term photostability and chemical properties, a phase transition from the photonic paramagnetic to the glassy phase is observed experimentally in the RL system used. Interestingly, the transition occurs at approximately the lasing threshold value, which is a consequence of stronger correlation of modal behaviors at high input pump energies.

4.
J Trace Elem Med Biol ; 77: 127133, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36638706

RESUMO

BACKGROUND: Chronic fluoride toxicity induces oxidative strain and lipid peroxidation and imparts deleterious effects on human metabolic organs. AIM: The present study aimed to expose the defensive impact of ferulic acid against sodium fluoride (NaF) induced hepatorenal dysfunction at the biochemical and antioxidative systems. METHODS: In-vivo. Rats were arbitrarily separated into five groups as control, sodium fluoride-treated (200 ppm kg -1), vitamin C -as a positive control, and FA co-administered groups with 10 mg kg -1 and 20 mg kg -1 body weight for 56 days. In the present investigation, we measured antioxidant enzymes, superoxide dismutase, catalase, and lactate dehydrogenase by electrozymographic and spectrophotometric methods. Biochemical assessment of TBARS, conjugated diene, and different serum biomarkers was done for liver and kidney functionality tests. In-silico. An in-silico study was conducted through a molecular docking experiment to evaluate the binding potentiality of FA by employing AutoDock Vina [version 1.5.6] to overcome the abnormality in the activities of catalase, and superoxide dismutase in NaF promoted toxicity of hepatorenal system. In-vitro. An in vitro biochemical experiment was conducted to support the in-silico study. RESULTS: Superoxide dismutase and catalase were decreased in the intoxicated rat. Ferulic acid (FA) as an antioxidant remarkably defended the NaF-mediated deterioration of the antioxidative status in the hepatorenal system, lowering lipid peroxidation products, malondialdehyde, and conjugated diene. Serum biomarkers, ALT, AST, ALP, urea, and creatinine increased in the intoxicated group than in control. Ferulic acid significantly neutralized the ill effects of NaF on serum lipid profile. In-silico analysis hypothesized the strong interaction of FA with the active side of catalase and superoxide dismutase that prevented the binding of NaF at the active site of these mentioned enzymes and this was further validated by in-vitro assay. CONCLUSION: However, FA modulates free radical generation and protected these metabolic organs against sodium fluoride-induced injury.


Assuntos
Antioxidantes , Fluoretos , Humanos , Ratos , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Fluoretos/farmacologia , Fluoreto de Sódio/farmacologia , Simulação de Acoplamento Molecular , Glutationa/metabolismo , Ratos Wistar , Estresse Oxidativo , Fígado/metabolismo , Superóxido Dismutase/metabolismo , Biomarcadores/metabolismo , Peroxidação de Lipídeos
5.
Int J Pharm ; 630: 122439, 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36503846

RESUMO

Polymeric nanoparticles (NPs) are extremely promising for theranostic applications. However, their interest depends largely on their interactions with immune system, including the capacity to activate inflammation after their capture by macrophages. In the present study, we generated monodisperse poly(ethyl methacrylate) (PEMA) NPs loaded with hydrophobic photoluminescent gold nanoclusters (Au NCs) emitting in the NIR-II optical windows and studied their interaction in vitro with J774.1A macrophages. PEMA NPs showed an efficient time and dose dependent cellular uptake with up to 70 % of macrophages labelled in 24 h without detectable cell death. Interestingly, PEMA and Au-PEMA NPs induced an anti-inflammatory response and a strong down-regulation of nitric oxide level on lipopolysacharides (LPS) activated macrophages, but without influence on the levels of reactive oxygen species (ROS). These polymeric NPs may thus present a potential interest for the treatment of inflammatory diseases.


Assuntos
Nanopartículas Metálicas , Nanopartículas , Ouro/química , Nanopartículas/química , Polímeros , Espécies Reativas de Oxigênio/metabolismo , Nanopartículas Metálicas/química
6.
Clin Ophthalmol ; 16: 4215-4225, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36561374

RESUMO

Purpose: To assess real-world clinical outcomes and safety of the Clareon® intraocular lens (IOL) and AutonoMe® automated preloaded delivery system in an Indian population. Patients and methods: This was a prospective, single-arm, multicenter, 12-month clinical study in patients aged ≥20 years with unilateral or bilateral cataracts. Surgery was performed by phacoemulsification followed by implantation of the Clareon monofocal IOL (CNA0T0). Monocular best-corrected distance visual acuity (BCDVA) and uncorrected distance visual acuity (UCDVA) were assessed at 1 week and 1, 6, and 12 months after implantation. Posterior capsular opacification (PCO), surface haze, and glistenings were evaluated at all visits. Surgeons' satisfaction with automated injector system was also evaluated using a questionnaire. Safety was assessed by monitoring adverse events (AEs). Results: A total of 151 eyes received the CNA0T0 IOL. Mean ± SD monocular BCDVA improved from 0.53±0.44 logMAR preoperatively to 0.00±0.08 logMAR at week 1 and -0.03±0.08 logMAR at 12 months after implantation. At 12 months, 137/137 (100%) of eyes achieved BCDVA of 0.3 logMAR or better. Mean ± SD monocular UCDVA was 0.78±0.40 logMAR preoperatively, 0.11±0.15 logMAR at week 1, and 0.08±0.13 logMAR at 12 months after implantation. At 12 months, 132/137 (96%) eyes achieved UCDVA of 0.3 logMAR or better. Serious intraoperative AEs were posterior capsule rupture (n=1) and ciliary zonular dehiscence (n=1). Surgeons reported that the automated preloaded device was more intuitive compared with other push- or screw-style preloaded injector systems. None of the eyes in this study presented surface haze; all were graded as 0 glistenings at all visits. No clinically significant PCO or neodymium-doped yttrium aluminum garnet (Nd:YAG) capsulotomies were reported. Conclusion: The hydrophobic IOL preloaded in an automated injector system provided good visual and refractive outcomes, as well as no surface haze and grade 0 glistenings. None of the patients required Nd:YAG capsulotomy.

7.
J Crohns Colitis ; 16(2): 286-300, 2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-34286840

RESUMO

BACKGROUND AND AIMS: Inflammatory bowel diseases are highly debilitating conditions that require constant monitoring and life-long medication. Current treatments are focused on systemic administration of immunomodulatory drugs, but they have a broad range of undesirable side-effects. RNA interference is a highly specific endogenous mechanism that regulates the expression of the gene at the transcript level, which can be repurposed using exogenous short interfering RNA [siRNA] to repress expression of the target gene. While siRNA therapeutics can offer an alternative to existing therapies, with a high specificity critical for chronically administrated drugs, evidence of their potency compared to chemical kinase inhibitors used in clinics is still lacking in alleviating an adverse inflammatory response. METHODS: We provide a framework to select highly specific siRNA, with a focus on two kinases strongly involved in pro-inflammatory diseases, namely JAK1 and JAK3. Using western-blot, real-time quantitative PCR and large-scale analysis, we assessed the specificity profile of these siRNA drugs and compared their efficacy to the most recent and promising kinase inhibitors for Janus kinases [Jakinibs], tofacitinib and filgotinib. RESULTS: siRNA drugs can reach higher efficiency and selectivity at lower doses [5 pM vs 1 µM] than Jakinibs. Moreover, JAK silencing lasted up to 11 days, even with 6 h pulse transfection. CONCLUSIONS: The siRNA-based drugs developed hold the potential to develop more potent therapeutics for chronic inflammatory diseases.


Assuntos
Doenças Inflamatórias Intestinais , Janus Quinases , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/genética , Janus Quinases/genética , Janus Quinases/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Transdução de Sinais
8.
Front Immunol ; 12: 722411, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34497612

RESUMO

Nonviral systems, such as lipid nanoparticles, have emerged as reliable methods to enable nucleic acid intracellular delivery. The use of cationic lipids in various formulations of lipid nanoparticles enables the formation of complexes with nucleic acid cargo and facilitates their uptake by target cells. However, due to their small size and highly charged nature, these nanocarrier systems can interact in vivo with antigen-presenting cells (APCs), such as dendritic cells (DCs) and macrophages. As this might prove to be a safety concern for developing therapies based on lipid nanocarriers, we sought to understand how they could affect the physiology of APCs. In the present study, we investigate the cellular and metabolic response of primary macrophages or DCs exposed to the neutral or cationic variant of the same lipid nanoparticle formulation. We demonstrate that macrophages are the cells affected most significantly and that the cationic nanocarrier has a substantial impact on their physiology, depending on the positive surface charge. Our study provides a first model explaining the impact of charged lipid materials on immune cells and demonstrates that the primary adverse effects observed can be prevented by fine-tuning the load of nucleic acid cargo. Finally, we bring rationale to calibrate the nucleic acid load of cationic lipid nanocarriers depending on whether immunostimulation is desirable with the intended therapeutic application, for instance, gene delivery or messenger RNA vaccines.


Assuntos
Cátions/química , Técnicas de Transferência de Genes , Lipídeos/química , Lipossomos/química , Nanopartículas/química , Ácidos Nucleicos/administração & dosagem , Animais , Células Apresentadoras de Antígenos/imunologia , Células Apresentadoras de Antígenos/metabolismo , Linhagem Celular , Sobrevivência Celular , Fenômenos Químicos , Citocinas/química , Portadores de Fármacos , Lipopolissacarídeos/química , Camundongos , Mitocôndrias/metabolismo , Espécies Reativas de Oxigênio
9.
Adv Sci (Weinh) ; 8(17): e2101433, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34197055

RESUMO

The purpose of this study is to propose and validate a preclinical in vivo magnetic resonance imaging (MRI) tool to monitor neuroinflammation following ischemic stroke, based on injection of a novel multimodal nanoprobe, NanoGd, specifically designed for internalization by phagocytic cells. First, it is verified that NanoGd is efficiently internalized by microglia in vitro. In vivo MRI coupled with intravenous injection of NanoGd in a permanent middle cerebral artery occlusion mouse model results in hypointense signals in the ischemic lesion. In these mice, longitudinal two-photon intravital microscopy shows NanoGd internalization by activated CX3CR1-GFP/+ cells. Ex vivo analysis, including phase contrast imaging with synchrotron X-ray, histochemistry, and transmission electron microscopy corroborate NanoGd accumulation within the ischemic lesion and uptake by immune phagocytic cells. Taken together, these results confirm the potential of NanoGd-enhanced MRI as an imaging biomarker of neuroinflammation at the subacute stage of ischemic stroke. As far as it is known, this work is the first to decipher the working mechanism of MR signals induced by a nanoparticle passively targeted at phagocytic cells by performing intravital microscopy back-to-back with MRI. Furthermore, using a gadolinium-based rather than an iron-based contrast agent raises future perspectives for the development of molecular imaging with emerging computed tomography technologies.


Assuntos
Gadolínio , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Nanotecnologia/métodos , Doenças Neuroinflamatórias/diagnóstico por imagem , Acidente Vascular Cerebral/complicações , Animais , Encéfalo/diagnóstico por imagem , Modelos Animais de Doenças , Camundongos , Microscopia Eletrônica , Doenças Neuroinflamatórias/etiologia
10.
Environ Sci Pollut Res Int ; 28(30): 41095-41108, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33774797

RESUMO

The non-invasive treatment strategy is indispensable to overcome the side effects of conventional treatment with chelating agents against arsenic. Presence of catechins and flavonoids in Camellia sinensis have potential antioxidant properties and other beneficial effects. The aim of the study was to explore the curative potential role of Camellia sinensis against uterine damages produced by sodium arsenite in mature albino rats. A dose of 10 mg of Camellia sinensis ethyl acetate (CS-EA) fraction/100 gm body weight was provided to the sodium arsenite-treated rats (10 mg/Kg body weight). LC-MS analysis was used for the detection of active component in CS-EA fraction. Enzymatic antioxidants analysis carried out by reproducible native gel technique. Hormones and some pro and anti-inflammatory markers were detected by ELISA, PCR, and western blot techniques respectively. Immunostaining was performed for the detection of estradiol receptor alpha. LC-MS analysis of CS-EA fraction ensured the presence of active tea polyphenol and tea catechin of which highest peak of epigallocatechin-3 gallate (EGCG) was obtained in this study. Significant elevations of lipid peroxidation end products followed by the diminution of antioxidant enzymes activities were noted in arsenicated rats which were capably retrieved by the treatment of CS-EA fraction. Post-treatment with CS-EA fraction meaningfully improved gonadotrophins and estradiol signalling in association with a highly expressing estradiol receptor-α (ERα) in the ovary and uterus followed by the maintenance of normal utero-ovarian histoarchitecture in arsenic fed rats. CS-EA fractioned treated group overturned the sodium arsenite driven higher expression of pro-inflammatory cytokines and proapoptotic markers along with a low level of anti apoptotic Bcl-2 expression and comparatively lower NF-κB signalling in the uterus via regulating IKK ß kinase mostly by EGCG of CS-EA fraction. However, ethyl acetate fraction of Camellia sinensis played a critical role in minimizing arsenic-mediated uterine hypo-function.


Assuntos
Arsênio , Camellia sinensis , Acetatos , Animais , Antioxidantes , Arsênio/análise , Feminino , NF-kappa B/genética , Estresse Oxidativo , Ratos , Ratos Wistar , Chá , Útero , Proteína X Associada a bcl-2
11.
Clin Ophthalmol ; 15: 213-225, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33519183

RESUMO

PURPOSE: To evaluate the effectiveness and safety of a presbyopia-correcting trifocal intraocular lens (IOL), AcrySof® IQ PanOptix® (TFNT00), in an Indian population. PATIENTS AND METHODS: This prospective, multicenter, observational, single-arm, post-marketing study included 67 patients undergoing cataract surgery with bilateral implantation of TFNT00 across five Indian sites. Postoperative outcomes were assessed at 3 months after second eye surgery. Effectiveness outcomes included: mean binocular and monocular visual acuity (VA) at distance (4 m), intermediate (60 cm), and near (40 cm); binocular defocus curve; manifest refraction; and subjective symptom questionnaire evaluation. Safety outcomes included the rate of ocular adverse events and mesopic contrast sensitivity. RESULTS: Mean binocular and monocular distance-corrected and uncorrected VAs of 0.1 logMAR or better (approximately 20/25 Snellen) were achieved at distance, intermediate, and near. Overall, ≥70% of patients achieved binocular 0.1 logMAR vision or better across all distances. TFNT00 maintained a mean VA of 0.1 logMAR or better at the defocus range of +0.5 diopters (D) to -2.5 D (200 cm to 40 cm). The subjective symptom questionnaire-assessed frequency of halo visual disturbances was low at Month 3; halos were reported "none of the time" to "only some of the time" in 86.6% of patients. The large majority of patients (98.5%) were "satisfied" or "very satisfied" with their near, intermediate, and distance vision at Month 3, and ≥94.0% of patients reported spectacle independence for tasks at all distances. The adverse event rate was low; no patients discontinued due to an adverse event. CONCLUSION: TFNT00 provided a continuous range of vision of 20/25 or better for distance to near and performed effectively at an intermediate functional distance of 60 cm, resulting in high levels of spectacle independence and patient satisfaction. TFNT00 demonstrated a good safety profile and a low post-operative frequency of halo visual disturbances.

12.
Nanoscale ; 13(6): 3767-3781, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33555278

RESUMO

Neuroinflammation is a process common to several brain pathologies. Despites its medical relevance, it still remains poorly understood; there is therefore a need to develop new in vivo preclinical imaging strategies to monitor inflammatory processes longitudinally. We here present the development of a hybrid imaging nanoprobe named NP3, that was specifically designed to get internalized by phagocytic cells and imaged in vivo with MRI and bi-photon microscopy. NP3 is composed of a 16 nm core of gadolinium fluoride (GdF3), coated with bisphosphonate polyethylene glycol (PEG) and functionalized with a Lemke-type fluorophore. It has a hydrodynamic diameter of 28 ± 8 nm and a zeta potential of -42 ± 6 mV. The MR relaxivity ratio at 7 T is r1/r2 = 20; therefore, NP3 is well suited as a T2/T2* contrast agent. In vitro cytotoxicity assessments performed on four human cell lines revealed no toxic effects of NP3. In addition, NP3 is internalized by macrophages in vitro without inducing inflammation or cytotoxicity. In vivo, uptake of NP3 has been observed in the spleen and the liver. NP3 has a prolonged vascular remanence, which is an advantage for macrophage uptake in vivo. The proof-of-concept that NP3 may be used as a contrast agent targeting phagocytic cells is provided in an animal model of ischemic stroke in transgenic CX3CR1-GFP/+ mice using three complementary imaging modalities: MRI, intravital two-photon microscopy and phase contrast imaging with synchrotron X-rays. In summary, NP3 is a promising preclinical tool for the multiscale and multimodal investigation of neuroinflammation.


Assuntos
Meios de Contraste , Gadolínio , Animais , Imageamento por Ressonância Magnética , Imagem Multimodal , Polietilenoglicóis
13.
Cells ; 10(1)2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33430453

RESUMO

Gold nanoparticles (AuNPs) have demonstrated outstanding performance in many biomedical applications. Their safety is recognised; however, their effects on the immune system remain ill defined. Antigen-presenting cells (APCs) are immune cells specialised in sensing external stimulus and in capturing exogenous materials then delivering signals for the immune responses. We used primary macrophages (Ms) and dendritic cells (DCs) of mice as an APC model. Whereas AuNPs did not alter significantly Ms and DCs functions, the exposure to AuNPs affected differently Ms and DCs in their responses to subsequent stimulations. The secretion of inflammatory molecules like cytokines (IL-6, TNF-α), chemokine (MCP-1), and reactive oxygen species (ROS) were altered differently in Ms and DCs. Furthermore, the metabolic activity of Ms was affected with the increase of mitochondrial respiration and glycolysis, while only a minor effect was seen on DCs. Antigen presentation to T cells increased when DCs were exposed to AuNPs leading to stronger Th1, Th2, and Th17 responses. In conclusion, our data provide new insights into the complexity of the effects of AuNPs on the immune system. Although AuNPs may be considered as devoid of significant effect, they may induce discrete modifications on some functions that can differ among the immune cells.


Assuntos
Células Dendríticas/metabolismo , Ouro/farmacologia , Macrófagos/metabolismo , Nanopartículas Metálicas/química , Animais , Células Apresentadoras de Antígenos/citologia , Células Apresentadoras de Antígenos/efeitos dos fármacos , Células Apresentadoras de Antígenos/metabolismo , Biomarcadores/metabolismo , Linhagem Celular , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Epitopos/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Ouro/toxicidade , Macrófagos/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Camundongos Endogâmicos C57BL , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fagocitose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo
14.
Nat Protoc ; 16(1): 327-351, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33277630

RESUMO

Using siRNAs to genetically manipulate immune cells is important to both basic immunological studies and therapeutic applications. However, siRNA delivery is challenging because primary immune cells are often sensitive to the delivery materials and generate immune responses. We have recently developed an amphiphilic dendrimer that is able to deliver siRNA to a variety of cells, including primary immune cells. We provide here a protocol for the synthesis of this dendrimer, as well as siRNA delivery to immune cells such as primary T and B cells, natural killer cells, macrophages, and primary microglia. The dendrimer synthesis entails straightforward click coupling followed by an amidation reaction, and the siRNA delivery protocol requires simple mixing of the siRNA and dendrimer in buffer, with subsequent application to the primary immune cells to achieve effective and functional siRNA delivery. This dendrimer-mediated siRNA delivery largely outperforms the standard electroporation technique, opening a new avenue for functional and therapeutic studies of the immune system. The whole protocol encompasses the dendrimer synthesis, which takes 10 days; the primary immune cell preparation, which takes 3-10 d, depending on the tissue source and cell type; the dendrimer-mediated siRNA delivery; and subsequent functional assays, which take an additional 3-6 d.


Assuntos
Linfócitos B/metabolismo , Dendrímeros/química , Interferência de RNA , RNA Interferente Pequeno/administração & dosagem , Linfócitos T/metabolismo , Animais , Linhagem Celular , Células Cultivadas , Química Click , Dendrímeros/síntese química , Humanos , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/genética
15.
Chronobiol Int ; 38(1): 140-148, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33043698

RESUMO

COVID-19 is a highly contagious disease caused by Severe Acute Respiratory Syndrome coronavirus-2, capable of high human transmission. To protect against the COVID-19 pandemic, the World Health Organization proposed intervening guidance that included movement restrictions, isolation, restriction of national and international travel or movement, and full or partial closure of organizations and institutions. Police personnel play a vital role in safeguarding the spread of COVID-19; thus, potentially causing severe stress due to increased consignment and direct exposure to infection during duty. The study aimed to determine the effect of the added stress of the COVID-19 pandemic and population lockdown on the sleep/wake 24 h rhythm of traffic police. A concise online questionnaire survey was conducted among the traffic police personnel of India. Collected data were analyzed statistically. Disorientation of working schedule, fear of being vulnerable to disease, pressure of maintaining law, and orders during lockdown increased stress level. The survey identified discontinuation of sleep, shift of mid-sleep time, increase in depression, plus stress and anxiety among traffic police personnel that affected their chronobiological milieu. Proper awareness of adequate health and safety measures, use of personnel protection equipment, regular conversation with family members, and meditation can help reduce stress during this pandemic situation.


Assuntos
COVID-19/prevenção & controle , COVID-19/psicologia , Controle de Doenças Transmissíveis/métodos , SARS-CoV-2 , Transtornos do Sono do Ritmo Circadiano , Estresse Psicológico , Ritmo Circadiano , Coleta de Dados , Feminino , Humanos , Índia , Masculino , Polícia , Inquéritos e Questionários
16.
Ecotoxicol Environ Saf ; 199: 110675, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32402895

RESUMO

An oral painless dietary therapy is also indispensable in the management of arsenic toxicity despite of its conventional painful therapeutic management. The present study focused on the management of arsenic mediated female reproductive dysfunctions by dietary therapy of N-acetyl cysteine (NAC). Here, sodium arsenite was given at the dose of 10 mg/kg body weight orally for the first 8 day. Day 9 onwards up to day 16 these arsenicated rats were provided with NAC (250 mg/kg body weight) enriched basal diet once daily. Arsenic intoxicated group exhibited a comparable inactivation of antioxidant enzymes superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) due to oxidative stress in reproductive organs along with a simultaneous elevation of lipid peroxidation state and decline in non-protein soluble thiols (NPSH) level in female reproductive organs. Arsenic intoxication also accomplished with the up-regulation of inflammatory markers tumour necrosis factor (TNF α) and nuclear factor κB (NF κB). Pro-apoptotic Bax gene and p53 gene expressions were also raised due to arsenic intoxication while anti-apoptotic Bcl-2 gene expression was suppressed. In fact, arsenication decreased the circulating level of vitamin B12 and folic acid. Dietary NAC supplementation significantly reversed back the activity of antioxidant enzymes in arsenite fed rats towards normalcy and also sustained the normal reproductive cyclicity, utero-ovarian histo-morphology and estradiol receptor α (ER-α) expression in these reproductive organs. Dietary NAC exerted its positive action against arsenic intoxication by up-regulation of Bcl-2 gene expression along with the suppression of pro-apoptotic Bax gene and p53 gene. Thus, dietary NAC also plays anti-apoptotic, anti-inflammatory, and anti-oxidative role against arsenic toxicity. NAC also regulates the components (vitamin B12 and folic acid) of S-adenosylmethionine pool in the way of probable removal of arsenic from the system.


Assuntos
Acetilcisteína/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Apoptose/efeitos dos fármacos , Arsenitos/toxicidade , Expressão Gênica/efeitos dos fármacos , Ovário/efeitos dos fármacos , Útero/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Apoptose/genética , Suplementos Nutricionais , Feminino , Masculino , Ovário/metabolismo , Ovário/patologia , Ovário/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Útero/metabolismo , Útero/patologia , Útero/fisiopatologia
17.
Drug Chem Toxicol ; 43(1): 1-12, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30208742

RESUMO

The painful invasive chelation therapy makes it challenging to continue the prolonged treatment against arsenic toxicity. Hence, the significance of the present preliminary investigation was to explore a noninvasive treatment strategy against sodium arsenite (As3+) by the use of a hydroethanolic extract of Moringa oleifera (MO) seed. Arsenic treatment (10 mg/kg body-weight) in animals showed significant level of oxidative stress as evidenced by increased serum levels of malondialdehyde (MDA), conjugated dienes (CD) and reduced level of non-protein thiol (NPSH). A significant diminution in the activities of enzymatic antioxidants was noted in As3+-treated rats. As3+ treatment showed a lengthy phase of metestrous in animals followed by significantly diminished ovarian steroidogenesis, increased ovarian follicular degeneration and distortion of uterine tissue histomorphology. In addition, there was a significant depletion of Vitamin-B9 (folate) and B12 following As3+ ingestion. The levels of circulating TNF-α, homocysteine (Hcy), uterine-IL-6, and liver metallothionein (MT-1) were significantly elevated in arsenic treated rats. MO at a dose of 100 mg/kg body-weight could successfully mitigate the uterine ROS generation by maintaining the uterine antioxidant status in As3+- treated rats. This seed extract prevented the deterioration of As3+-mediated ovarian-steroidogenesis and ovarian and uterine histoarchitecture significantly. B9 and B12 levels were also improved following the ingestion of the MO extract in arsenicated animals. Elevation of Hcy, TNF-α and IL-6 was also prevented by this MO seed extract in As3+-treated rats. A further increase of MT-1 level was achieved after MO ingestion in As3+-treated rats. Here, the alleviation of arsenic toxicity might involve via the regulation of the components of S-adenosine methionine (SAM) pool and MT-1.


Assuntos
Arsenitos/toxicidade , Moringa oleifera/química , Extratos Vegetais/farmacologia , Compostos de Sódio/toxicidade , Útero/efeitos dos fármacos , Administração Oral , Animais , Antioxidantes/metabolismo , Feminino , Homocisteína/metabolismo , Metalotioneína/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar , Sementes , Útero/patologia , Complexo Vitamínico B/metabolismo
18.
Asia Pac J Ophthalmol (Phila) ; 8(4): 335-349, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31403494

RESUMO

AcrySof IQ PanOptix Model TFNT00 (Alcon Laboratories, Fort Worth, TX) is a 1-piece aspheric hydrophobic presbyopia-correcting intraocular lens (IOL) launched in 2015. Unlike traditional trifocal IOLs that usually have an intermediate focal point of 80 cm, the PanOptix IOL is designed to have an intermediate focal point of 60 cm (arms-length), a more natural and comfortable working distance to perform functional tasks on computers, laptops, mobiles, among others. The non-apodized PanOptix IOL uses the ENhanced LIGHT ENergy (ENLIGHTEN; Alcon Laboratories, Fort Worth, TX) optical technology that provides high (88%) utilization of light energy, low dependence on pupil size in all lighting conditions, and a more comfortable near-to-intermediate range of vision than traditional trifocal IOLs. This review provides an overview of the clinical performance of the PanOptix IOL and discusses it in the context of other commercially available trifocal IOLs, FineVision Micro F (PhysIOL, Liege, Belgium), the AT LISA tri 839MP (Carl Zeiss Meditec AG, Jena, Germany) and the extended depth of focus IOL, TECNIS Symfony (Abbott Medical Optics, Santa Ana, CA). A literature search was performed in the PubMed database to identify studies that have assessed the visual and other clinical outcomes with the PanOptix IOL. In total, 12 studies were included in this review article. Overall, the clinical evidence suggests that in general good visual outcomes, along with a high degree of spectacle independence, are achieved in patients implanted with the PanOptix, FineVision, AT LISA and Symfony IOLs. However, every MIOL has its benefits and limitations, which along with patient's needs and clinical conditions are important factors to consider while selecting an IOL to achieve best possible post-operative outcomes.


Assuntos
Lentes Intraoculares , Satisfação do Paciente , Pseudofacia/cirurgia , Refração Ocular/fisiologia , Visão Binocular/fisiologia , Acuidade Visual/fisiologia , Humanos , Facoemulsificação , Desenho de Prótese , Pseudofacia/fisiopatologia
19.
Food Chem Toxicol ; 131: 110545, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31163222

RESUMO

This investigation explored a dietary therapy of pectic polysaccharide (CCPS) (2 mg/ Kg BW) against female repro-toxicity and infertility triggered by sodium arsenite (As3+) (10 mg/ Kg BW) in Wistar rats. The isolated CCPS consists of D-galactose and D-methyl galacturonate with a molar ratio of 1: 4. FTIR spectral analysis of CCPS and CCPS- sodium arsenite (As3+) complex indicated a possible chelating property of CCPS in presence of binding sites (OH-/COOH) for As3+. Series of negatively charged galacturonate residues in CCPS provide better potential for cation chelation. CCPS significantly mitigated As3+ induced ovarian, uterine lipid peroxidation, and reactive oxygen species (ROS) generation by the restoration of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) activities. CCPS post-treatment enhanced ovarian steroidogenesis along with a restoration of normal tissue histoarchitecture in As3+ fed rats by regulating the estradiol receptor alpha (ER-α). CCPS suppressed anti-inflammatory properties effectively found since a down-regulation of NF-kappa B (NF-қB), pro-inflammatory tumor necrosis-α (TNF-α) and interleukin-6 (IL-6) were observed in arsenicated rats with CCPS. This study confirmed the up-regulation of uterine pro-apoptotic/ apoptotic proteins caspase-3, poly ADP ribose polymerase (PARP), proliferating cell nuclear antigen (PCNA), phospho p53 and Bax, followed by down-regulation of Bcl-2 and protein Kinase B (AKT) signaling pathway along with uterine tissue regeneration in As3+ exposed rats. Oral CCPS attenuated the above apoptotic expressional changes significantly and dietary CCPS ensured successful fertility with the birth of healthy pups in lieu of infertile condition in As3+ fed rats. Moreover, this study also supports that CCPS treatment attenuated the As3+ toxicity by modulating the S-adenosine methionine (SAM) pool components, B12, folate and homocysteine.


Assuntos
Anti-Inflamatórios/uso terapêutico , Apoptose/efeitos dos fármacos , Infertilidade Feminina/tratamento farmacológico , Momordica charantia/química , Pectinas/uso terapêutico , Animais , Anti-Inflamatórios/isolamento & purificação , Arsenitos , Catalase/metabolismo , Feminino , Expressão Gênica/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Infertilidade Feminina/induzido quimicamente , Masculino , Ovário/patologia , Estresse Oxidativo/efeitos dos fármacos , Pectinas/isolamento & purificação , Gravidez , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Compostos de Sódio , Superóxido Dismutase/metabolismo , Útero/patologia
20.
Probiotics Antimicrob Proteins ; 11(1): 30-42, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-28994024

RESUMO

Managing arsenic intoxication with conventional metal chelators is a global challenge. The present study demonstrated the therapeutic role of probiotics against arsenic-induced oxidative stress and female reproductive dysfunction. Sodium arsenite-treated (1.0 mg/100 g body weight) Wistar female rats were followed up by a post-treatment of commercially available probiotic mixture in powder form (0.25 mg/100 g body weight) orally. Rats that experienced arsenic ingestion showed a significant lessening in the activities of uterine superoxide dismutase (SOD), catalase activities, and the level of non-protein soluble thiol (NPSH) with a concomitant increase in malondialdehyde (MDA) and conjugated dienes (CD). Exposure to arsenic significantly lowered the levels of vitamin B12 and estradiol. Exposure to arsenic highly expressed the inflammatory marker and transcription factor NF-κB. Arsenic-mediated instability of these above parameters was controlled by the probiotics with a rebuilding of better function of anti-oxidant components. Besides its function in regulating endogenous anti-oxidant system, probiotics were able to augment the protection against mutagenic uterine DNA-breakage, necrosis, and ovarian-uterine tissue damages in arsenicated rats.


Assuntos
Arsenitos/farmacologia , L-Lactato Desidrogenase/sangue , NF-kappa B/fisiologia , Probióticos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Compostos de Sódio/farmacologia , Útero/metabolismo , Vitamina B 12/sangue , Animais , Dano ao DNA , Estradiol/sangue , Feminino , Peroxidação de Lipídeos , Ratos , Superóxido Dismutase/metabolismo
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