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1.
Anal Methods ; 16(19): 3007-3019, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38695537

RESUMO

We present a colorimetric probe based on polyvinylpyrrolidone-capped gold nanoparticles (PVP-AuNPs) that is sensitive and selective for cysteine (Cys). A microfluidic paper-based analytical device (µ-PAD) with embedded dried PVP-AuNPs at the polyethersulfone (PES) paper surface is used for Cys detection. When thiol molecules attach to PVP-AuNPs in the presence of Cys, they clump together, and this causes the solution's color to shift from red to blue within 5 minutes. The device is capable of detecting Cys levels between 1.0 µM and 50.0 µM with a limit of detection (LOD) of 0.2 µM under optimized conditions. The stability of the µ-PAD was tested for 100 days, demonstrating re-dispersibility to detect Cys levels in blood. Dried PVP-AuNP-µPADs were integrated with blood plasma separation modules for point-of-care (POC) Cys detection. Consequently, the device shows potential as a self-sustaining, quantification platform with a recovery percentage ranging from 98.44 to 111.9 in clinical samples.


Assuntos
Colorimetria , Cisteína , Ouro , Limite de Detecção , Nanopartículas Metálicas , Papel , Sistemas Automatizados de Assistência Junto ao Leito , Ouro/química , Cisteína/sangue , Cisteína/química , Nanopartículas Metálicas/química , Humanos , Colorimetria/métodos , Colorimetria/instrumentação , Povidona/química , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos
2.
Acta Neuropathol ; 147(1): 25, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38280071

RESUMO

We and others have shown that [18F]-Flortaucipir, the most validated tau PET tracer thus far, binds with strong affinity to tau aggregates in Alzheimer's (AD) but has relatively low affinity for tau aggregates in non-AD tauopathies and exhibits off-target binding to neuromelanin- and melanin-containing cells, and to hemorrhages. Several second-generation tau tracers have been subsequently developed. [18F]-MK-6240 and [18F]-PI-2620 are the two that have garnered most attention. Our recent data indicated that the binding pattern of [18F]-MK-6240 closely parallels that of [18F]-Flortaucipir. The present study aimed at the direct comparison of the autoradiographic binding properties and off-target profile of [18F]-Flortaucipir, [18F]-MK-6240 and [18F]-PI-2620 in human tissue specimens, and their potential binding to monoamine oxidases (MAO). Phosphor-screen and high resolution autoradiographic patterns of the three tracers were studied in the same postmortem tissue material from AD and non-AD tauopathies, cerebral amyloid angiopathy, synucleopathies, transactive response DNA-binding protein 43 (TDP-43)-frontotemporal lobe degeneration and controls. Our results show that the three tracers show nearly identical autoradiographic binding profiles. They all strongly bind to neurofibrillary tangles in AD but do not seem to bind to a significant extent to tau aggregates in non-AD tauopathies pointing to their limited utility for the in vivo detection of non-AD tau lesions. None of them binds to lesions containing ß-amyloid, α-synuclein or TDP-43 but they all show strong off-target binding to neuromelanin and melanin-containing cells, as well as weaker binding to areas of hemorrhage. The autoradiographic binding signals of the three tracers are only weakly displaced by competing concentrations of selective MAO-B inhibitor deprenyl but not by MAO-A inhibitor clorgyline suggesting that MAO enzymes do not appear to be a significant binding target of any of them. These findings provide relevant insights for the correct interpretation of the in vivo behavior of these three tau PET tracers.


Assuntos
Doença de Alzheimer , Carbolinas , Isoquinolinas , Doenças Neurodegenerativas , Piridinas , Tauopatias , Humanos , Doenças Neurodegenerativas/patologia , Melaninas/metabolismo , Encéfalo/patologia , Tauopatias/patologia , Monoaminoxidase/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas tau/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Doença de Alzheimer/patologia
3.
Life Sci ; 340: 122440, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38278350

RESUMO

The connection between maternal microbiota and infant health has been greatly garnered interest for therapeutic purposes. The early resident microbiota perpetually exhibits much more flexibility as compared to that of the adults, and therefore, constant need of understanding the infant as well as maternal microbiota and their implications however has increased. In this review, we focus mainly on the diversity of overall maternal microbiota including the gut, vaginal, colostrum microbiota and how inflammatory markers fluctuate throughout the normal pregnancy as well in pregnancy with complications. The maternal body undergoes a cascade of physiological changes including hormonal, immunological and metabolic events to support the fetal development. These changes at the time of pregnancy have been correlated with alteration in the composition and diversity of maternal microbiota. Along with alteration in microbiome, the levels of circulatory cytokines fluctuate by complex network of inflammation, in order to prevent the fetal allograft throughout the pregnancy. The dynamic relationship of gut microbiota with the host and its immune system allows one to have greater insights of their role in pregnancy and newborn's health. Emerging evidence suggests that the vertical transmission of bacterial community from mother to newborn may begin in-utero which contributes in developing the immune system and infant gut microbiota.


Assuntos
Microbioma Gastrointestinal , Microbiota , Recém-Nascido , Lactente , Gravidez , Adulto , Feminino , Humanos , Vagina/microbiologia , Desenvolvimento Fetal , Fatores Imunológicos
4.
Bioinspir Biomim ; 18(5)2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37552773

RESUMO

Recent observations of wingless animals, including jumping nematodes, springtails, insects, and wingless vertebrates like geckos, snakes, and salamanders, have shown that their adaptations and body morphing are essential for rapid self-righting and controlled landing. These skills can reduce the risk of physical damage during collision, minimize recoil during landing, and allow for a quick escape response to minimize predation risk. The size, mass distribution, and speed of an animal determine its self-righting method, with larger animals depending on the conservation of angular momentum and smaller animals primarily using aerodynamic forces. Many animals falling through the air, from nematodes to salamanders, adopt a skydiving posture while descending. Similarly, plant seeds such as dandelions and samaras are able to turn upright in mid-air using aerodynamic forces and produce high decelerations. These aerial capabilities allow for a wide dispersal range, low-impact collisions, and effective landing and settling. Recently, small robots that can right themselves for controlled landings have been designed based on principles of aerial maneuvering in animals. Further research into the effects of unsteady flows on self-righting and landing in small arthropods, particularly those exhibiting explosive catapulting, could reveal how morphological features, flow dynamics, and physical mechanisms contribute to effective mid-air control. More broadly, studying apterygote (wingless insects) landing could also provide insight into the origin of insect flight. These research efforts have the potential to lead to the bio-inspired design of aerial micro-vehicles, sports projectiles, parachutes, and impulsive robots that can land upright in unsteady flow conditions.


Assuntos
Robótica , Animais , Voo Animal/fisiologia , Insetos , Gravitação , Sementes , Fenômenos Biomecânicos
5.
Genes Dis ; 10(4): 1318-1350, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37397537

RESUMO

Maintaining the balance between eliciting immune responses against foreign proteins and tolerating self-proteins is crucial for maintenance of homeostasis. The functions of programmed death protein 1 (PD-1) and its ligand programmed death ligand 1 (PD-L1) are to inhibit immune responses so that over-reacting immune cells does not cause any damage to its own body cells. However, cancer cells hijack this mechanism to attenuate immune cells functions and create an immunosuppressive environment that fuel their continuous growth and proliferation. Over the past few years' rapid development in cancer immunotherapy has opened a new avenue in cancer treatment. Blockade of PD-1 and PD-L1 has become a potential strategy that rescue the functions of immune cells to fight against cancer with high efficacy. Initially, immune checkpoint monotherapies were not very successful, making breast cancer less immunogenic. Although, recent reports support the presence of tumor infiltrating lymphocytes (TILs) in breast cancer that make it favorable for PD-1/PD-L1 mediated immunotherapy, which is effective in PD-L1 positive patients. Recently, anti-PD-1 (pembrolizumab) and anti-PD-L1 (atezolizumab) gets FDA approval for breast cancer treatment and make PD-1/PD-L1 immunotherapy is meaningful for further research. Likewise, this article gathered understanding of PD-1 and PD-L1 in recent years, their signaling networks, interaction with other molecules, regulations of their expressions and functions in both normal and tumor tissue microenvironments are crucial to find and design therapeutic agents that block this pathway and improve the treatment efficacy. Additionally, authors collected and highlighted most of the important clinical trial reports on monotherapy and combination therapy.

6.
Genes Dis ; 10(4): 1402-1428, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37334160

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes the complicated disease COVID-19. Clinicians are continuously facing huge problems in the treatment of patients, as COVID-19-specific drugs are not available, hence the principle of drug repurposing serves as a one-and-only hope. Globally, the repurposing of many drugs is underway; few of them are already approved by the regulatory bodies for their clinical use and most of them are in different phases of clinical trials. Here in this review, our main aim is to discuss in detail the up-to-date information on the target-based pharmacological classification of repurposed drugs, the potential mechanism of actions, and the current clinical trial status of various drugs which are under repurposing since early 2020. At last, we briefly proposed the probable pharmacological and therapeutic drug targets that may be preferred as a futuristic drug discovery approach in the development of effective medicines.

7.
Ann Med Surg (Lond) ; 85(4): 665-669, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37113856

RESUMO

Helicobacter pylori infection is seropositive in ~50% of people globally. Therefore, this study was conducted to evaluate its prevalence in dyspepsia patients. Methods: A cross-sectional study was conducted at Jinnah Postgraduate Medical Centre (JPMC) from January to June 2022 to find out the prevalence and risk factors of H. pylori in dyspepsia patients. A prevalidated questionnaire was used to collect the data from 180 patients. This study adheres to the principles outlined in the Helsinki Declaration. The χ 2-test was applied, and the odds ratio and 95% CI were calculated to find the association of H. pylori with the risk factors. Results: A total of 180 patients were enrolled in this study, of whom, 73 (40.6%) patients were male and 107 (59.4%) were female. In seropositive H. pylori patients, 80 (60.6%) patients had nausea or vomiting, 110 (83.3%) patients were found to have flatulence, 128 (97.7%) patients were experiencing frequent burping, and 114 (86.4%) patients were having epigastric pain. The household member greater than 4, smoking, rural area residence, NSAIDs consumption, BMI greater than 25, O+ blood group, and Rhesus positive status were significantly associated with H. pylori with a P value of less than 0.05. Conclusion: This study concludes that the prevalence of H. pylori in our population is high, and the risk factors identified are lower class, BMI greater than 25, smoking, O+ blood group, NSAID consumption, rural area residence, household member greater than 4, Rhesus positive status, and the symptoms of nausea or vomiting, frequent burping, epigastric pain, and flatulence. Patients with an increased number of risk factors should be taken into consideration for an appropriate checkup.

8.
Br J Clin Pharmacol ; 89(1): 114-149, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36184710

RESUMO

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced COVID-19 is a complicated disease. Clinicians are continuously facing difficulties to treat infected patients using the principle of repurposing of drugs as no specific drugs are available to treat COVID-19. To minimize the severity and mortality, global vaccination is the only hope as a potential preventive measure. After a year-long global research and clinical struggle, 165 vaccine candidates have been developed and some are currently still in the pipeline. A total of 28 candidate vaccines have been approved for use and the remainder are in different phases of clinical trials. In this comprehensive report, the authors aim to demonstrate, classify and provide up-to-date clinical trial status of all the vaccines discovered to date and specifically focus on the approved candidates. Finally, the authors specifically focused on the vaccination of different types of medically distinct populations.


Assuntos
COVID-19 , Vacinas Virais , Humanos , SARS-CoV-2 , Vacinas contra COVID-19 , Vacinas Virais/uso terapêutico , Desenvolvimento de Vacinas
9.
Cureus ; 15(12): e51066, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38269234

RESUMO

The relationship between insulin resistance and coronary artery disease (CAD) is a crucial study area in understanding the complex connection between metabolic dysregulation and cardiovascular morbidity. This scholarly investigation examines the intricate relationship between insulin resistance, a key characteristic of metabolic syndrome, and CAD development. The goal is to understand the detailed molecular and physiological connections that underlie the dangerous connection between the endocrine and cardiac systems. The recognition of insulin resistance as a key player in cardiovascular disease highlights the need to study the complex relationships between insulin signaling pathways and the development of atherosclerosis. This research analyzes the molecular processes by which insulin resistance leads to disruptions in lipid metabolism, inflammatory reactions, and malfunction of the blood vessel's inner lining. These processes create an environment that promotes the development and advancement of CAD. As we begin this scientific exploration, it becomes clear that insulin resistance acts as a metabolic indicator and a potent mediator of endothelial dysfunction, oxidative stress, and systemic inflammation. The complex interaction between insulin-sensitive tissues and the vascular endothelium plays a crucial role in defining the pathophysiological landscape of CAD. Furthermore, this discussion highlights the mutual interaction between the endocrine and cardiac systems, where CAD produced by myocardial ischemia worsens insulin resistance through complex molecular pathways. Discovering new therapeutic targets that disrupt the harmful cycle between insulin resistance and the development of CAD shows potential for creating specific therapies to reduce cardiovascular risk in people with insulin resistance. This study aims to clarify the complexities of the connection between the endocrine system and the heart, establishing the basis for a thorough comprehension of how insulin resistance contributes to the development and advancement of CAD.

10.
Sci Rep ; 12(1): 16928, 2022 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-36209318

RESUMO

Climate change and its impact on agriculture productivity vary among crops and regions. The southeastern United States (SE-US) is agro-ecologically diversified, economically dependent on agriculture, and mostly overlooked by agroclimatic researchers. The objective of this study was to compute the effect of climatic variables; daily maximum temperature (Tmax), daily minimum temperature (Tmin), and rainfall on the yield of major cereal crops i.e., corn (Zea mays L.), rice (Oryza sativa L.), and wheat (Triticum aestivum L.) in SE-US. A fixed-effect model (panel data approach) was used by applying the production function on panel data from 1980 to 2020 from 11 SE-US states. An asymmetrical warming pattern was observed, where nocturnal warming was 105.90%, 106.30%, and 32.14%, higher than the diurnal warming during corn, rice, and wheat growing seasons, respectively. Additionally, a shift in rainfall was noticed ranging from 19.2 to 37.2 mm over different growing seasons. Rainfall significantly reduced wheat yield, while, it had no effect on corn and rice yields. The Tmax and Tmin had no significant effect on wheat yield. A 1 °C rise in Tmax significantly decreased corn (- 34%) and rice (- 8.30%) yield which was offset by a 1 °C increase in Tmin increasing corn (47%) and rice (22.40%) yield. Conclusively, overall temperature change of 1 °C in the SE-US significantly improved corn yield by 13%, rice yield by 14.10%, and had no effect on wheat yield.


Assuntos
Oryza , Triticum , Agricultura , Mudança Climática , Produtos Agrícolas , Temperatura , Zea mays
11.
Genes Dis ; 9(6): 1521-1555, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36157498

RESUMO

The carboxy-terminus of Hsp70-interacting protein (CHIP) is a ubiquitin ligase and co-chaperone belonging to Ubox family that plays a crucial role in the maintenance of cellular homeostasis by switching the equilibrium of the folding-refolding mechanism towards the proteasomal or lysosomal degradation pathway. It links molecular chaperones viz. HSC70, HSP70 and HSP90 with ubiquitin proteasome system (UPS), acting as a quality control system. CHIP contains charged domain in between N-terminal tetratricopeptide repeat (TPR) and C-terminal Ubox domain. TPR domain interacts with the aberrant client proteins via chaperones while Ubox domain facilitates the ubiquitin transfer to the client proteins for ubiquitination. Thus, CHIP is a classic molecule that executes ubiquitination for degradation of client proteins. Further, CHIP has been found to be indulged in cellular differentiation, proliferation, metastasis and tumorigenesis. Additionally, CHIP can play its dual role as a tumor suppressor as well as an oncogene in numerous malignancies, thus acting as a double agent. Here, in this review, we have reported almost all substrates of CHIP established till date and classified them according to the hallmarks of cancer. In addition, we discussed about its architectural alignment, tissue specific expression, sub-cellular localization, folding-refolding mechanisms of client proteins, E4 ligase activity, normal physiological roles, as well as involvement in various diseases and tumor biology. Further, we aim to discuss its importance in HSP90 inhibitors mediated cancer therapy. Thus, this report concludes that CHIP may be a promising and worthy drug target towards pharmaceutical industry for drug development.

12.
Cureus ; 14(6): e25937, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35844318

RESUMO

INTRODUCTION:  Persistent and prolonged symptoms, termed as long COVID (coronavirus disease), have been reported in several patients who recovered from the acute phase at different intervals. However, there has been largely unclear data regarding the full range of long-term sequelae of coronavirus disease 2019 (COVID-19) patients. This study aims to evaluate the prevalence of long COVID syndrome. METHODS: A long-term research was conducted in the COVID-19 unit of a tertiary care hospital in Pakistan from July 2020 to December 2021 in which 2,000 patients who had recovered from COVID-19 and had been discharged were included in the study. Symptoms were noted at the time of discharge and at follow-up after 12 months. Data were analyzed using Statistical Package for the Social Sciences (SPSS) v. 22.0 (IBM Corporation, Armonk, New York, United States). RESULTS: The mean age of the participants was 43 ± 10 years, 801 (53.8%) males and 688 (46.2%) females. At the time of discharge, the most common symptom was fatigue (26.93%), followed by dyspnea (20.34%) and muscle pain (8.86%). The most common symptom on follow-up was fatigue (6.78%). CONCLUSION: We strongly emphasize discussing and exploring further knowledge on the post-infection syndrome, with an aim to bring healthcare professionals' attention to the importance of handling COVID patients, their counseling, warning for alarming signs, and a long-term follow-up with necessary investigations and treatment.

13.
Indian J Crit Care Med ; 25(10): 1137-1146, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34916746

RESUMO

In acute respiratory failure due to severe coronavirus disease 2019 (COVID-19) pneumonia, mechanical ventilation remains challenging and may result in high mortality. The use of noninvasive ventilation (NIV) may delay required invasive ventilation, increase adverse outcomes, and have a potential aerosol risk to caregivers. Data of 30 patients were collected from patient files and analyzed. Twenty-one (70%) patients were weaned successfully after helmet-NIV support (NIV success group), and invasive mechanical ventilation was required in 9 (30%) patients (NIV failure group) of which 8 (26.7%) patients died. In NIV success vs failure patients, the mean baseline PaO2/FiO2 ratio (PFR) (147.2 ± 57.9 vs 156.8 ± 59.0 mm Hg; p = 0.683) and PFR before initiation of helmet (132.3 ± 46.9 vs 121.6 ± 32.7 mm Hg; p = 0.541) were comparable. The NIV success group demonstrated a progressive improvement in PFR in comparison with the failure group at 2 hours (158.8 ± 56.1 vs 118.7 ± 40.7 mm Hg; p = 0.063) and 24 hours (PFR-24) (204.4 ± 94.3 vs 121.3 ± 32.6; p = 0.016). As predictor variables, PFR-24 and change (delta) in PFR at 24 hours from baseline or helmet initiation (dPFR-24) were significantly associated with NIV success in univariate analysis but similar significance could not be reflected in multivariate analysis perhaps due to a small sample size of the study. The PFR-24 cutoff of 161 mm Hg and dPFR-24 cutoff of -1.44 mm Hg discriminate NIV success and failure groups with the area under curve (confidence interval) of 0.78 (0.62-0.95); p = 0.015 and 0.74 (0.55-0.93); p = 0.039, respectively. Helmet interface NIV may be a safe and effective tool for the management of patients with severe COVID-19 pneumonia with acute respiratory failure. More studies are needed to further evaluate the role of helmet NIV especially in patients with initial PFR <150 mm Hg to define PFR/dPFR cutoff at the earliest time point for prediction of helmet-NIV success. How to cite this article Jha OK, Kumar S, Mehra S, Sircar M, Gupta R. Helmet NIV in Acute Hypoxemic Respiratory Failure due to COVID-19: Change in PaO2/FiO2 Ratio a Predictor of Success. Indian J Crit Care Med 2021;25(10):1137-1146.

15.
Mol Neurodegener ; 16(1): 1, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413517

RESUMO

BACKGROUND: TDP-43 proteinopathy is a pathological hallmark of many neurodegenerative diseases including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). So far, there is no therapy available for these neurodegenerative diseases. In addition, the impact of TDP-43 proteinopathy on neuronal translational profile also remains unknown. METHODS: Biochemical, immunohistology and assay-based studies were done with cell cultures and transgenic mice models. We also used Ribotag with microarray and proteomic analysis to determine the neuronal translational profile in the mice model of ALS/FTD. RESULTS: Here, we report that oral administration of a novel analog (IMS-088) of withaferin-A, an antagonist of nuclear factor kappa-B (NF-ĸB) essential modulator (NEMO), induced autophagy and reduced TDP-43 proteinopathy in the brain and spinal cord of transgenic mice expressing human TDP-43 mutants, models of ALS/FTD. Treatment with IMS-088 ameliorated cognitive impairment, reduced gliosis in the brain of ALS/FTD mouse models. With the Ribotrap method, we investigated the impact of TDP-43 proteinopathy and IMS-088 treatment on the translation profile of neurons of one-year old hTDP-43A315T mice. TDP-43 proteinopathy caused translational dysregulation of specific mRNAs including translational suppression of neurofilament mRNAs resulting in 3 to 4-fold decrease in levels type IV neurofilament proteins. Oral administration of IMS-088 rescued the translational defects associated with TDP-43 proteinopathy and restored the synthesis of neurofilament proteins, which are essential for axon integrity and synaptic function. CONCLUSIONS: Our study revealed that induction of autophagy reduces TDP-43 pathology and ameliorates the translational defect seen in mice models of ALS/FTD. Based on these results, we suggest IMS-088 and perhaps other inducers of autophagy should be considered as potential therapeutics for neurodegenerative disorders with TDP-43 proteinopathies.


Assuntos
Esclerose Lateral Amiotrófica/metabolismo , Autofagia/fisiologia , Demência Frontotemporal/metabolismo , RNA Mensageiro/metabolismo , Proteinopatias TDP-43/metabolismo , Esclerose Lateral Amiotrófica/patologia , Animais , Encéfalo/metabolismo , Modelos Animais de Doenças , Demência Frontotemporal/patologia , Humanos , Filamentos Intermediários/metabolismo , Filamentos Intermediários/patologia , Camundongos , Neurônios/metabolismo , Medula Espinal/metabolismo
16.
Neurotherapeutics ; 18(1): 286-296, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33078279

RESUMO

Withaferin-A, an active withanolide derived from the medicinal herbal plant Withania somnifera induces autophagy, reduces TDP-43 proteinopathy, and improves cognitive function in transgenic mice expressing mutant TDP-43 modelling FTLD. TDP-43 is a nuclear DNA/RNA-binding protein with cellular functions in RNA transcription and splicing. Abnormal cytoplasmic aggregates of TDP-43 occur in several neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration (FTLD), and limbic-predominant age-related TDP-43 encephalopathy (LATE). To date, no effective treatment is available for TDP-43 proteinopathies. Here, we tested the effects of withaferin-A (WFA), an active withanolide extracted from the medicinal herbal plant Withania somnifera, in a transgenic mouse model of FTLD expressing a genomic fragment encoding mutant TDP-43G348C. WFA treatment ameliorated the cognitive performance of the TDP-43G348C mice, and it reduced NF-κB activity and neuroinflammation in the brain. WFA alleviated TDP-43 pathology while it boosted the levels of the autophagic marker LC3BII in the brain. These data suggest that WFA and perhaps other autophagy inducers should be considered as potential therapy for neurodegenerative diseases with TDP-43 pathology.


Assuntos
Cognição/efeitos dos fármacos , Proteínas de Ligação a DNA/antagonistas & inibidores , Degeneração Lobar Frontotemporal/tratamento farmacológico , Vitanolídeos/uso terapêutico , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Western Blotting , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Células Cultivadas , Proteínas de Ligação a DNA/genética , Modelos Animais de Doenças , Feminino , Imunofluorescência , Masculino , Camundongos , Camundongos Transgênicos , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
Carbohydr Polym ; 250: 116991, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33049903

RESUMO

Kithul starch was treated by EN (energetic neutral nitrogen) atoms at 6 W,12 W and 18 W for 15 min and incorporated lauric acid for the development of starch-lauric acid inclusion complexes. EN atoms treatment significantly (p ≤ 0.05) increased the complex index (CI). Severe morphological alterations on the kithul starch granules by EN atoms treatment enhanced starch-lauric acid complex formation. Relative crystallinity of EN atoms treated lauric acid incorporated kithul starch samples increased with plasma power. Moreover, lower pasting property, storage modulus (G'), loss modulus (G''), hardness and higher Tanδ indicated decrease in gelation and retrogradation property. ENL-18 W showed the lowest complex viscosity (È *). Lauric acid incorporation in EN atoms treated kithul starch reduced in vitro digestibility and significantly (p ≤ 0.05) increased RS (resistant starch). Hence, EN atoms treatment on the kithul starch granules prior to fatty acid incorporation is an effective technique for the development of starch-fatty acid complexes.


Assuntos
Arecaceae/crescimento & desenvolvimento , Ácidos Láuricos/metabolismo , Nitrogênio/metabolismo , Reologia , Amido/metabolismo , Arecaceae/metabolismo , Géis , Ácidos Láuricos/química , Nitrogênio/química , Amido/química , Temperatura
18.
3 Biotech ; 10(8): 355, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32766096

RESUMO

One of the characteristic features of obesity is increased body weight and accumulation of adipose tissue. It is associated with low grade inflammation and gut dysbiosis. Probiotics and its products could be an ideal strategy to prevent or treat diabetes. In the present study, animals were induced obesity by providing them with high fat diet. Three purified bacteriocins i.e., DT24, PJ4 and TSU4, previously isolated and purified from various probiotic strains, were given as treatment strategies, following the induction of obesity. Upon the completion of the study, animals were sacrificed and were checked for their tissue expression of inflammatory mediators and adipokines. Serum hormone and cytokines analysis were performed to check their inflammatory state. Treatment with purified bacteriocin DT24 did not show any therapeutic effect in any of the parameter studied. Bacteriocin TSU4 on the other hand showed better reversal compared to DT24. Bacteriocin PJ4 showed the most promising results by reversing all the altered parameters significantly. It significantly reversed all the biochemical, immunological in terms of serum cytokines as well as altered morphological characteristics. PJ4 can be further explored to determine its mode of action. The anti-microbial proteins or to be more specific, bacteriocins, which shows broad spectrum efficacy, could be a better alternative in modulating gut microflora for the treatment of obesity and diabetes characteristics. The efficacy of bacteriocin PJ4 may also be due to the source of the host of Lactobacillus.

19.
J Food Sci Technol ; 57(8): 2916-2925, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32624597

RESUMO

Effect of hydrothermal modifications (autoclaving, annealing and heat moisture treatment) on physico-chemical, rheological properties and in vitro digestibility of kithul starch was studied. Annealing and heat moisture treatment decreased swelling index, solubility and increased crystalline properties as compared with autoclaving. Autoclaving, annealing and heat moisture treatment caused significant morphological damages such as large holes and fissures on the kithul starch, in addition, granules changed from oval to donut shape. Heat moisture treatment formed higher number of agglomerated starch granules. Light transmittance decreased after hydrothermal modifications. Autoclaving and annealing increased the pasting viscosities (except break down viscosity) of kithul starch. A significant increase (p ≤ 0.05) in peak temperature, conclusion temperature and enthalpy was found in annealed and heat moisture treated kithul starches. The digestibility of kithul starch decreased with increasing resistant starch after annealing and heat moisture treatment. Autoclaved, annealed and heat moisture treated kithul starches exhibited higher value of storage modulus (G') and loss modulus (G″) than native kithul starch. It entail to higher firmness of modified starch gel. The current study showed that the remarkable changes formed by hydrothermal modifications increased the industrial acceptance of kithul starch.

20.
J Food Sci Technol ; 57(8): 2941-2948, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32624599

RESUMO

Native buckwheat starch was extracted and modified by heat-moisture treatment (HMT) with different treatment time (15, 30 and 45 min) to investigate its effect on physicochemical, morphological, functional properties, starch profile (rapidly digestible starch, RDS; slowly digestible starch, SDS and resistant starch, RS fractions) and expected glycemic index (eGI). Results revealed that with increasing time duration of HMT from 15 to 45 min, amylose content, pasting temperature and thermostability increased substantially whereas swelling power, solubility and viscosity parameters decreased. The SEM micrographs showed that HMT caused fissures in the granule and surface indentation. HMT-45 (starch treated for 45 min) had the lowest RDS content (29.33%) and the highest SDS (51.30%) and RS (8.21%) levels. The decreased hydrolysis rate, high amylose and RS content of HMT-45 resulted in a significant decrease in estimated glycemic index (eGI) values from 51.49% (Native) to 44.16% (HMT-45) thus indicating its role in prevention of non-insulin- dependent diabetes.

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