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1.
Pediatr Emerg Care ; 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39258980

RESUMEN

OBJECTIVES: Research highlights racial disparities among those experiencing intimate partner violence (IPV), yet little is known about disparities in addressing IPV in the emergency department (ED). This study was designed to examine variability in offering IPV universal education to adult caregivers across patient race within an urban pediatric ED and to explore provider attitudes regarding the role of race in this process. METHODS: We conducted a mixed-methods study using quantitative data on rates of offering adult caregivers IPV universal education and rates of missing documentation for when IPV universal education was not offered to adult caregivers from January 2016 to December 2020. Analyses compared both rates by patient race listed in the electronic health record. We also conducted semistructured interviews with ED providers, which were qualitatively analyzed for common themes. RESULTS: Caregivers of Black patients were both more likely to have received IPV universal education compared with caregivers of White patients (31.1% vs 27.3%, P < 0.05) and more likely to lack a documented reason for not offering than caregivers of White patients (70.4% vs 53.9%, P < 0.05). Our semistructured interviews with nurses, nurse practitioners, and physicians in the pediatric ED were able to ascertain specific racial biases that may influence these disparities. CONCLUSIONS: Our study showed that racial disparities exist in both offering IPV universal education and documentation deferral in our pediatric ED. Combined analysis of our quantitative and qualitative data shows the importance of identifying biases that cause health disparities and increasing diversity among healthcare providers. The results of this study can be used to inform new methodologies for healthcare providers to address their personal biases and ensure that all caregivers visiting the ED are offered IPV support resources.

2.
Planta ; 258(2): 29, 2023 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-37358736

RESUMEN

MAIN CONCLUSION: The main purpose of this review is to shed light on the role of millet models in imparting climate resilience and nutritional security and to give a concrete perspective on how NF-Y transcription factors can be harnessed for making cereals more stress tolerant. Agriculture faces significant challenges from climate change, bargaining, population, elevated food prices, and compromises with nutritional value. These factors have globally compelled scientists, breeders, and nutritionists to think of some options that can combat the food security crisis and malnutrition. To address these challenges, mainstreaming the climate-resilient and nutritionally unparalleled alternative crops like millet is a key strategy. The C4 photosynthetic pathway and adaptation to low-input marginal agricultural systems make millets a powerhouse of important gene and transcription factor families imparting tolerance to various kinds of biotic and abiotic stresses. Among these, the nuclear factor-Y (NF-Y) is one of the prominent transcription factor families that regulate diverse genes imparting stress tolerance. The primary purpose of this article is to shed light on the role of millet models in imparting climate resilience and nutritional security and to give a concrete perspective on how NF-Y transcription factors can be harnessed for making cereals more stress tolerant. Future cropping systems could be more resilient to climate change and nutritional quality if these practices were implemented.


Asunto(s)
Mijos , Factores de Transcripción , Factores de Transcripción/genética , Productos Agrícolas/genética , Grano Comestible/genética , Agricultura
3.
Skin Pharmacol Physiol ; 36(4): 195-204, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36927995

RESUMEN

INTRODUCTION: Along with climate changes, we see an increase in allergic symptoms and the number of pollen-allergic patients in many countries. Increased allergic symptoms are associated with an elevated ozone exposure which may be linked by impaired epithelial barrier function. This study aimed to quantify the clinical effect of ozone and pollen double exposure (DE). We tested whether ozone impairs barrier-related skin physiology and mucosal functions under DE with pollen in grass pollen-allergic patients versus healthy controls. METHODS: This case-control study included 8 grass pollen-allergic patients and 8 non-allergic healthy subjects exposed to grass pollen and ozone in the GA2LEN pollen chamber, comparing shorter and longer DE duration. Non-invasive skin physiological parameters were assessed, including stratum corneum hydration, skin redness, surface pH, and basal transepidermal water loss as a parameter for epidermal barrier function. The subjects' general well-being, bronchial, nasal, and ocular symptoms were documented. RESULTS: Skin physiology tests revealed that DE in allergic patients deteriorates the epidermal barrier function and increases the surface pH and skin redness. DE significantly induced nasal secretion in pollen-allergic versus healthy subjects, which was more pronounced with longer DE. The general well-being was significantly impaired under DE versus pollen or ozone alone, with a negative influence of DE duration. No relevant bronchial symptoms were recorded. CONCLUSION: Skin physiology and nasal mucosal symptoms are negatively affected by ozone and grass pollen DE in allergic patients. The negative effects showed, in some parameters, a dose (time)-response relationship. The pH can be regarded as a possible modulatory mechanism.


Asunto(s)
Hipersensibilidad , Ozono , Rinitis Alérgica Estacional , Humanos , Rinitis Alérgica Estacional/inducido químicamente , Rinitis Alérgica Estacional/diagnóstico , Estudios de Casos y Controles , Poaceae/efectos adversos , Polen , Hipersensibilidad/diagnóstico , Ozono/efectos adversos , Alérgenos
4.
Phytother Res ; 37(11): 5109-5158, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37536946

RESUMEN

Curcumin, a natural polyphenol, derived from Curcuma longa L. is extensively studied by various researchers across the globe and has established its immense potential in the management of several disorders at clinical level. The underlying mechanism of curcumin involves regulation of various molecular targets, namely, inflammatory cytokines, transcription factor, apoptotic genes, growth factors, oxidative stress biomarkers, and protein kinases. In clinical trials, curcumin as an adjuvant has significantly boost-up the efficacy of many proven drugs in the management of arthritis, neurodegenerative disorder, oral infection, and gastrointestinal disorders. Moreover, clinical studies have suggested curcumin as an appropriate candidate for the prevention and/or management of various cancers via regulation of signaling molecules including NF-kB, cytokines, C-reactive protein, prostaglandin E2, Nrf2, HO-1, ALT, AST, kinases, and blood profiles. This article highlights plethora of clinical trials that have been conducted on curcumin and its derivatives in the management of several ailments. Besides, it provides recent updates to the investigators for conducting future research to fulfill the current gaps to expedite the curcumin utility in clinical subjects bearing different pathological states.


Asunto(s)
Curcumina , Humanos , Curcumina/farmacología , Curcumina/uso terapéutico , Transducción de Señal , Estrés Oxidativo , FN-kappa B/metabolismo , Curcuma , Citocinas/metabolismo
5.
Phytother Res ; 37(12): 5435-5463, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37649266

RESUMEN

Cancer is the world's second leading cause of mortality and one of the major public health problems. Cancer incidence and mortality rates remain high despite the great advancements in existing therapeutic, diagnostic, and preventive approaches. Therefore, a quest for less toxic and more efficient anti-cancer strategies is still at the forefront of the current research. Traditionally important, curcumin commonly known as a wonder molecule has received considerable attention as an anti-cancer, anti-inflammatory, and antioxidant candidate. However, limited water solubility and low bioavailability restrict its extensive utility in different pathological states. The investigators are making consistent efforts to develop newer strategies to overcome its limitations by designing different analogues with better pharmacokinetic and pharmacodynamic properties. The present review highlights the recent updates on curcumin and its analogues with special emphasis on various mechanistic pathways involved in anti-cancer activity. In addition, the structure-activity relationship of curcumin analogues has also been precisely discussed. This article will also provide key information for the design and development of newer curcumin analogues with desired pharmacokinetic and pharmacodynamic profiles and will provide in depth understanding of molecular pathways involved in the anti-cancer activities.


Asunto(s)
Antineoplásicos , Curcumina , Neoplasias , Humanos , Curcumina/farmacología , Curcumina/uso terapéutico , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Relación Estructura-Actividad , Disponibilidad Biológica , Antiinflamatorios/farmacología
6.
Biochem Biophys Res Commun ; 597: 102-108, 2022 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-35134607

RESUMEN

Breast cancer stem cells (BCSCs) are slow cycling cells that escape the traditional chemo-radio-therapy, thereby contributing in resistance and recurrence. Although several markers have been identified, it is still challenging to develop strategies targeting them. In this study, we have isolated BCSCs from MCF-7 cell line using markers CD44+/CD24-/low, which showed higher percentage of mammospheres in CSC population. Moreover, in vivo tumorigenic potential of BCSCs showed as low as 10,000 cells had the ability to develop tumors when transplanted into NOD-SCID mice. We observed an increased level of EMT markers in CSC population. Overexpression of secretory phospholipase sPLA2-IIA was found in CSCs. Further, we have uncovered the upregulation of sPLA2-IIA mediated through JNK signaling in breast cancer cells whereas knockdown of sPLA2-IIA reduces JNK signaling, cell proliferation, EMT and in vivo tumorigenic potential in breast cancer cells. Our study reveals overexpression of sPLA2-IIA in two different breast cancer cells such as MCF7 (ER+,PR+) and a triple negative, MDA-MB-231 (ER-PR-HER2-). Further, the novel role of sPLA2-IIA was discerned by unraveling the molecular mechanism, which regulates the cell proliferation and metastasis in breast cancer cells.

7.
Mol Cell Biochem ; 477(10): 2359-2385, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35569080

RESUMEN

Curcumin, belongs to the curcuminoid family, is a natural phenolic compound, presenting low bioavailability and pleiotropic activity. Since ancient times, curcumin has been in use as food spices and folk remedy to treat cough, cold, cuts and wounds, and skin diseases. Preclinical and clinical studies have indicated that curcumin acts a promising therapeutic agent in the management of a wide array of health issues, viz., hyperlipidemia, metabolic syndrome, anxiety, arthritis, cancer and inflammatory diseases. Owing to its enormous potential, recent research has been focused on the synthesis of curcumin and its analogues for the management of metabolic disorders. In the current scenario, hypertension is considered as a key risk factor due to its involvement in various pathogeneses. Mechanistically, curcumin and its analogues like hexahydrocurcumin, tetrahydrocurcumin, etc. have been reported to elicit anti-hypertensive effect through diverse signalling pathways, viz., pathway mediated by Nrf2-ARE, NF-kB, NO/cGMP/PDE5/MMPs, RAAS/ACE, HAT/HDAC, G0/G1/apoptosis, CYP3A4, UCP2/PARP, VEGF/STAT/AXL/tyrosine kinase and TGF-ß/Smad-mediated pathways. Thus, the present review has been aimed to highlight different molecular pathways involved in the amelioration of hypertension and associated conditions.


Asunto(s)
Curcumina , Hipertensión , Antihipertensivos , Curcumina/farmacología , Curcumina/uso terapéutico , Citocromo P-450 CYP3A , Humanos , Hipertensión/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/metabolismo , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Proteínas Tirosina Quinasas , Factor de Crecimiento Transformador beta , Factor A de Crecimiento Endotelial Vascular
8.
Phytother Res ; 36(8): 3143-3180, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35790042

RESUMEN

Curcumin, isolated from turmeric (Curcuma longa L.) is one of the broadly studied phytomolecule owing to its strong antioxidant and anti-inflammatory potential and has been considered a promising therapeutic candidate in a wide range of disorders. Considering, its low bioavailability, different curcumin analogs have been developed to afford desired pharmacokinetic profile and therapeutic outcome in varied pathological states. Several preclinical and clinical studies have indicated that curcumin ameliorates mitochondrial dysfunction, inflammation, oxidative stress apoptosis-mediated neural cell degeneration and could effectively be utilized in the treatment of different neurodegenerative diseases. Hence, in this review, we have summarized key findings of experimental and clinical studies conducted on curcumin and its analogues with special emphasis on molecular pathways, viz. NF-kB, Nrf2-ARE, glial activation, apoptosis, angiogenesis, SOCS/JAK/STAT, PI3K/Akt, ERK1/2 /MyD88 /p38 MAPK, JNK, iNOS/NO, and MMP pathways involved in imparting ameliorative effects in the therapy of neurodegenerative disorders and associated conditions.


Asunto(s)
Enfermedades del Sistema Nervioso Central , Curcumina , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Curcuma , Curcumina/farmacología , Curcumina/uso terapéutico , Humanos , Estrés Oxidativo , Fosfatidilinositol 3-Quinasas
9.
Physiol Plant ; 173(4): 1448-1462, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33934375

RESUMEN

The plants endomembrane system of the cellular compartments with its complex membrane trafficking network facilitates transport of macromolecules. The endomembrane dynamics are essential for maintaining basic and specific cellular functions including adaptation to the extracellular environment. The plant vacuole serves as a reservoir for nutrients and toxic metabolites and performs detoxification processes to maintain cellular homeostasis. The overexpression of AlRab7, a vesicle trafficking gene from Aeluropus lagopoides, improved germination and growth and reduced ionic and oxidative stress in transgenics. Moreover, the root and shoot of transgenic tobacco showed differential accumulation of phytohormone ABA and IAA with different ionic stresses. The improved growth (root and shoot length) can be co-related with higher IAA accumulation with NaCl stress. The low Na+ /K+ ratio with different NaCl stress treatments indicates better ion homeostasis in transgenics. Furthermore, the increased stomatal density and higher number of open stomata on both leaf surfaces in transgenics during NaCl stress suggest better gaseous exchange/functioning of guard cells. The maintained or increased superoxide dismutase, catalase, ascorbate peroxidase, guaiacol peroxidase, and glutathione reductase antioxidative enzyme activities suggest that an extensive reactive oxygen species (ROS) scavenging system was triggered to detoxify cellular ROS, which remained at low levels in transgenics during the different stress treatments. Our results suggest that the AlRab7 transgenic tobacco ameliorates ionic stress by facilitating differential and selective ion transport at vacuolar membrane regulating hormone signaling, ROS homeostasis, stomatal development, and movement.


Asunto(s)
Nicotiana , Poaceae , Homeostasis , Hormonas , Plantas Modificadas Genéticamente , Especies Reactivas de Oxígeno , Estrés Fisiológico , Nicotiana/genética
10.
Clin Nephrol ; 90(5): 305-312, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29956649

RESUMEN

BACKGROUND: Active vitamin D and cinacalcet, a treatment for secondary hyperparathyroidism and also with potential anti-inflammatory properties, have been associated with lower risk of death among dialysis patients. Vitamin D has also been described to decrease proteinuria in CKD patients. This study aims to assess the relationship of vitamin D and cinacalcet with survival and residual renal function preservation among peritoneal dialysis patients. MATERIALS AND METHODS: In a retrospective peritoneal dialysis cohort of 581 subjects, we assessed if vitamin D and cinacalcet therapy are associated with increased risk of death and residual renal function loss using Kaplan-Meier analysis and Cox proportional hazard analysis. RESULTS: Vitamin D treatment was associated with a 56% reduction in the risk of death (HR 0.44, 95% CI 0.28 - 0.67) and cinacalcet also with a 54% lower risk of death (HR 0.46, 95% CI 0.31 - 0.69) in multivariate models adjusting for each other. Hyperphosphatemia (> 6 mg/dL) was associated with an 85% increase in mortality (HR 1.85, 95% CI 1.30 - 2.65). Neither vitamin D (HR 1.04, 95% CI 0.45 - 2.39) nor cinacalcet (HR 0.74, 95% CI 0.45 - 1.20) were associated with a lower risk of anuria. CONCLUSION: Vitamin D and cinacalcet therapy was associated with a lower risk of death but not anuria, beyond other known risk factors among peritoneal dialysis patients.
.


Asunto(s)
Cinacalcet/uso terapéutico , Diálisis Peritoneal/mortalidad , Vitamina D/uso terapéutico , Cinacalcet/efectos adversos , Humanos , Hiperfosfatemia , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Vitamina D/efectos adversos
11.
Adv Exp Med Biol ; 870: 383-400, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26387110

RESUMEN

Although the proteins in all the current major classes considered to be druggable are folded in their native states, intrinsically disordered proteins (IDPs) are becoming attractive candidates for therapeutic intervention by small drug-like molecules. IDPs are challenging targets because they exist as ensembles of structures, thereby making them unsuitable for standard rational drug design approaches, which require the knowledge of the three-dimensional structure of the proteins to be drugged. As we review in this chapter, several different small molecule strategies are currently under investigation to target IDPs, including: (i) to stabilise IDPs in their natively disordered states, (ii) to inhibit interactions with ordered or disordered protein partners, and (iii) to induce allosteric inhibition. In this context, biophysical techniques, including in particular nuclear magnetic resonance (NMR) spectroscopy and small-angle X-ray scattering (SAXS) coupled with molecular dynamics simulations and chemoinformatics approaches, are increasingly used to characterize the structural ensembles of IDPs and the specific interactions that they make with their binding partners. By analysing the results of recent studies, we describe the main structural features that may render IDPs druggable, and describe techniques that can be used for drug discovery programs focused on IDPs.


Asunto(s)
Proteínas Intrínsecamente Desordenadas/química , Diseño de Fármacos , Proteínas Intrínsecamente Desordenadas/efectos de los fármacos , Resonancia Magnética Nuclear Biomolecular , Dispersión del Ángulo Pequeño , Difracción de Rayos X
12.
Cureus ; 16(8): e67062, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39286711

RESUMEN

Background Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis, predominantly affecting the lungs (pulmonary TB) and is a significant public health challenge in India. The study aims to analyze demographic, radiological, and clinical subgroups of pulmonary TB cases, examine the relationship between smear acid-fast bacillus (AFB examination) and cartridge-based nucleic acid amplification test (CBNAAT), evaluate CBNAAT sensitivity for Mycobacterium tuberculosis (MTB) in new and previously treated patients, and determine the proportion of rifampicin resistance. Methods This hospital-based prospective study was conducted among patients diagnosed with pulmonary TB at the Respiratory Medicine Department of a Government Hospital over 16 months (August 2019 to December 2020). The study included 150 diagnosed TB cases (new and previously treated). Data collection encompassed demographic details, clinical symptoms, comorbidities, radiological findings (chest X-ray), and microbiological results (smear AFB examination, CBNAAT). Sputum samples were subjected to Ziehl-Neelsen staining and CBNAAT for MTB detection and rifampicin resistance testing. Statistical analysis was performed using IBM SPSS Statistics version 21.0 (IBM Corp., Armonk, NY, USA). Results Of the 150 patients, 69.3% were male, and 48% were aged 21-40 years. The majority had a BMI of 18.5-24.9 kg/m² (50%) and resided in urban areas (63.3%). Common symptoms included cough (95.3%), fever (80%), and weight loss (74%). Cavitary lesions on chest X-ray were observed in 84% of patients. Smear microscopy detected MTB in 72.7% of cases, while CBNAAT detected MTB in 94% of cases. CBNAAT sensitivity for smear-positive and smear-negative samples was 93.97% and 94.12%, respectively. Rifampicin resistance was found in 3% of new cases and 6% of previously treated cases. The sensitivity of smear microscopy was 77.33%, and the sensitivity of CBNAAT was 94%. Conclusion The study underscores the high burden of pulmonary TB and the utility of CBNAAT in detecting MTB and rifampicin resistance, particularly in smear-negative samples. The findings highlight the necessity of universal drug susceptibility testing (DST) for effective TB management and the importance of addressing drug resistance to improve treatment outcomes.

13.
In Silico Pharmacol ; 12(2): 60, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38978708

RESUMEN

This study aimed to repurpose Drug Bank Compounds against P. falciparum Dihydroorotate dehydrogenase (Pf-DHODH)a potential molecular target for antimalarial drug development due to its vital role in P. falciparum survival. Initially, the MATGEN server was used to screen drugs against Pf-DHODH (PDB ID 6GJG), followed by revalidating the results through docking by Autodock Vina through PyRx. Based on the docking results, three drugs namely, Talnifumate, Sulfaphenazole, and (3S)-N-[(2S)-1-[2-(1H-indol-3-yl)ethylamino]-1-oxopropan-2-yl]-1-(4-methoxyphenyl)-5-oxopyrrolidine-3-carboxamide-were subjected to molecular dynamics simulation for 100 ns. Molecular dynamics simulation results indicate that (3S)-N-[(2S)-1-[2-(1H-indol-3-yl)ethylamino]-1-oxopropan-2-yl]-1-(4-methoxyphenyl)-5-oxopyrrolidine-3-carboxamide- and Sulfaphenazole may target Pf-DHODH by forming a stable protein-ligand complex as they showed better free binding energy -130.58 kJ/mol, and -79.84 kJ/mol, respectively as compared to the free binding energy 116.255 kJ/mol of the reference compound; 3,6-dimethyl- ~ {N}-[4-(trifluoromethyl)phenyl]-[1,2]oxazolo[5,4-d]pyrimidin-4-amine. Although the studied compounds are drugs, still we applied Lipinski's rules and ADMET analysis that reconfirmed that these drugs have favorable drug-like properties. In conclusion, the results of the study show that Talniflumate and Sulfaphenazole may be potential antimalarial drug candidates.The derivatives of these drugs could be designed and tested to develop better drugs against Plasmodium species.

14.
J Comp Psychol ; 138(3): 177-189, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38421739

RESUMEN

Animals navigate complex environments that present both hazards and essential resources. The prioritization of perceptual information that is relevant to their next actions, such as accessing or avoiding different resources, poses a potential challenge to animals, one that can impact survival. While animals' attentional biases toward negatively valanced and threatening stimuli have been explored, parallel biases toward differently valued resources remain understudied. Here, we assessed whether three primate species (chimpanzees [Pan troglodytes], gorillas [Gorilla gorilla gorilla], and Japanese macaques [Macaca fuscata]) prioritized their attention to positively valued resources-preferred foods compared to unpreferred foods. We employed a computerized dot probe attentional bias task in which we presented participants with paired images of their preferred and unpreferred foods in randomized locations (left or right). Latencies to touch the "probe" that replaced either image revealed that all three species responded faster to the probe when it replaced the preferred option (χ²(1) = 284.50, SE² = .03, p < .001). The uniformity of the primates' responses hints that a propensity to prioritize highly preferred items is rooted in these primates' evolutionary past, one that may serve as a mechanism to rapidly detect and locate resources such as highly valued foods. Future research will help disentangle the role that color plays in these biases. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Asunto(s)
Sesgo Atencional , Gorilla gorilla , Macaca fuscata , Pan troglodytes , Animales , Sesgo Atencional/fisiología , Masculino , Femenino , Gorilla gorilla/fisiología , Preferencias Alimentarias , Alimentos , Conducta Animal/fisiología , Conducta de Elección/fisiología , Adulto Joven
15.
J Ethnopharmacol ; 321: 117559, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38072294

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Tinospora cordifolia (T. cordifolia) (Willd.) Miers, a member of the Menispermaceae, family documented in the ancient textbooks of the Ayurveda System of Medicine, has been used in the management of sciatica pain and diabetic neuropathy. AIM: The study has been designed to evaluate the antinociceptive potential of various extracts of T. cordifolia stem in Paclitaxel (PT)-generated neuropathic pain model in albino rats and explore its possible mechanism employing molecular docking studies. METHODS: Stems of T. cordifolia were shade dried, grinded in fine powder, and extracted separately with different solvents viz. ethanol, water & hydro-alcoholic and characterized using LCMS/MS. The antinociceptive property of T. cordifolia stem (200 and 400 mg/kg) was examined in albino rats using a PT-induced neuropathic pain model. Further, the effect of these extracts was also observed using different behavioral assays viz. cold allodynia, mechanical hyperalgesia (pin-prick test), locomotor activity test, walking track test, and Sciatic Functional Index (SFI) in rats. Tissue lysate of the sciatic nerve was used to determine various biochemical markers such as GSH, SOD, TBARS, tissue protein, and nitrite. Further to explore the possible mechanism of action, the most abundant and therapeutically active compounds available in aqueous extract were analyzed for binding affinity towards soluble epoxide hydrolase (sEH) enzyme (PDB ID: 3wk4) employing molecular docking studies. RESULTS: The results of the LCMS/MS study of different extracts of T. cordifolia indicated presence of alkaloids, glycosides, terpenoids, sterols and sugars such as amritoside A, tinocordin, magnoflorine, N-methylcoclaurine, coridine, 20ß-hydroxyecdysone and menaquinone-7 palmatin, cordifolioside A and tinosporine etc. Among all the three extracts, the hydroalcoholic extract (400 mg/kg) showed the highest response followed by aqueous and ethanolic extracts as evident in in vivo behavioral and biochemical evaluations. Furthermore, docking studies also exposed that these compounds viz. N-methylcoclaurine tinosporin, palmatine, tinocordin, 20ß-hydroxyecdysone, and coridine exhibited well to excellent affinity towards target sEH protein. CONCLUSION: T. cordifolia stem could alleviate neuropathic pain via soluble epoxide hydrolase inhibitory activity.


Asunto(s)
Neuralgia , Tinospora , Ratas , Animales , Paclitaxel , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/química , Tinospora/química , Epóxido Hidrolasas , Simulación del Acoplamiento Molecular , Neuralgia/inducido químicamente , Neuralgia/tratamiento farmacológico , Analgésicos/farmacología , Analgésicos/uso terapéutico
16.
Photochem Photobiol ; 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39049138

RESUMEN

Curcumin serves as a photosensitizer (PS) in the context of microbial inactivation when subjected to light exposure, to produce reactive oxygen species, which exhibit efficacy in eradicating microorganisms. This remarkable property underscores the growing potential of antimicrobial photodynamic therapy (aPDT) in the ongoing fight against bacterial infections. Considering this, we investigate the efficacy of various in vitro curcumin formulations within a PDT protocol designed to target Staphylococcus aureus. Specifically, we conduct a comparative analysis involving synthetic curcumin (Cur-Syn) and curcumin derivatives modified with chlorine (Cl), selenium (Se), and iodine (I) (Cur-Cl, Cur-Se, Cur-I). To assess the impact of aPDT, we subject S. aureus to incubation with curcumin, followed by irradiation at 450 nm with energy doses of 3.75, 7.5, and 15 J/cm2. Our investigation encompasses an evaluation of PS uptake and photobleaching across the various curcumin variants. Notably, all three modifications (Cur-Cl, Cur-Se, Cur-I) induce a significant reduction in bacterial viability, approximately achieving a 3-log reduction. Interestingly, the uptake kinetics of Cur-Syn and Cur-Se exhibit similarities, reaching saturation after 20 min. Our findings suggest that modifications to curcumin have a discernible impact on the photodynamic properties of the PS molecule.

17.
Eur J Neurosci ; 37(10): 1564-72, 2013 May.
Artículo en Inglés | MEDLINE | ID: mdl-23489835

RESUMEN

Mouse models with prenatal alterations in dopaminergic functioning can provide new opportunities to identify fetal behavioral abnormalities and the underlying neural substrates dependent on dopamine. In this study, we tested the hypothesis that prenatal loss of nigrostriatal function is associated with fetal akinesia, or difficulty initiating movement. Specific behaviors were analysed in fetal offspring derived from pregnant Pitx3(ak) /2J and C57BL/6J dams on the last 4 days before birth (E15-18 of a 19-day gestation). Using digital videography, we analysed: (i) behavioral state, by quantification of high- and low-amplitude movements, (ii) interlimb movement synchrony, a measure of the temporal relationship between spontaneous movements of limb pairs, (iii) facial wiping, a characteristic response to perioral tactile stimulation similar to the defensive response in human infants, and (iv) oral grasp of a non-nutritive nipple, a component of suckling in the human infant. Pitx3 mutants showed a selective decrease in interlimb movement synchrony rates at the shortest (0.1 s) temporal interval coupled with significantly increased latencies to exhibit facial wiping and oral grasp. Collectively, our findings provide evidence that the primary fetal neurobehavioral deficit of the Pitx3 mutation is akinesia related to nigrostriatal damage. Other findings of particular interest were the differences in neurobehavioral functioning between C57BL/6J and Pitx3 heterozygous subjects, suggesting the two groups are not equivalent controls. These results further suggest that fetal neurobehavioral assessments are sensitive indicators of emerging neural dysfunction, and may have utility for prenatal diagnosis.


Asunto(s)
Dopamina/metabolismo , Movimiento Fetal/genética , Proteínas de Homeodominio/genética , Fenotipo , Factores de Transcripción/genética , Animales , Heterocigoto , Ratones , Ratones Endogámicos C57BL , Sustancia Negra/embriología , Sustancia Negra/fisiología
18.
Psychol Sci ; 24(4): 432-8, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23404083

RESUMEN

Decision makers generally feel disconnected from their future selves, an experience that leads them to prefer smaller immediate gains to larger future gains. This pervasive tendency is known as temporal discounting, and researchers across disciplines are interested in understanding how to overcome it. Following recent advances in the power literature, we suggest that the experience of power enhances one's connection with the future self, which in turn results in reduced temporal discounting. In Study 1, we found that participants assigned to high-power roles were less likely than participants assigned to low-power roles to display temporal discounting. In Studies 2 and 3, priming power reduced temporal discounting in monetary and nonmonetary tasks, and, further, connection with the future self mediated the relation between power and reduced discounting. In Study 4, experiencing a general sense of power in the workplace predicted actual lifetime savings. These results have important implications for future research.


Asunto(s)
Toma de Decisiones , Poder Psicológico , Recompensa , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Adulto Joven
19.
J Food Sci Technol ; 50(4): 723-30, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24425974

RESUMEN

Fresh dried and old (6-12 months) dried kachri (Cucumis callosus) were treated with 0, 2.5, 5 and 7 kGy of gamma radiation in a cobalt 60 gamma cell (GC-1200). The irradiated samples of kachri were stored at room temperature (28 ± 2 °C). Total bacterial count and nutrient composition were evaluated immediately after irradiation and at regular intervals of 1 month during 3 months of storage. Results indicated that gamma radiation reduced the total bacterial counts of dried samples of both fresh and old dried kachri. Dose of 5.0 kGy was sufficient to eliminate total bacterial count and there was no microbial growth in 5.0 kGy irradiated samples during the storage period. No significant differences were observed in the proximate composition of both types of kachri at all irradiation doses. It was concluded that irradiation treatments of kachri improves keeping quality of both freshly dried and old dried Kachri.

20.
World J Stem Cells ; 15(5): 438-452, 2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37342225

RESUMEN

Head and neck squamous cell carcinoma is the seventh most common cancer worldwide with high mortality rates. Amongst oral cavity cancers, tongue carcinoma is a very common and aggressive oral cavity carcinoma. Despite the implementation of a multimodality treatment regime including surgical intervention, chemo-radiation as well as targeted therapy, tongue carcinoma shows a poor overall 5-year survival pattern, which is attributed to therapy resistance and recurrence of the disease. The presence of a rare population, i.e., cancer stem cells (CSCs) within the tumor, are involved in therapy resistance, recurrence, and distant metastasis that results in poor survival patterns. Therapeutic agents targeting CSCs have been in clinical trials, although they are unable to reach into therapy stage which is due to their failure in trials. A more detailed understanding of the CSCs is essential for identifying efficient targets. Molecular signaling pathways, which are differentially regulated in the CSCs, are one of the promising targets to manipulate the CSCs that would provide an improved outcome. In this review, we summarize the current understanding of molecular signaling associated with the maintenance and regulation of CSCs in tongue squamous cell carcinoma in order to emphasize the need of the hour to get a deeper understanding to unravel novel targets.

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