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Curcumin has anti-inflammatory properties but current evidence is limited to advocate its use in rheumatoid arthritis (RA). We explored whether curcumin could maintain remission in patients with RA while tapering conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARD). In this patient-and investigator-blinded trial, adults with RA in sustained remission for more than six months were randomized to oral curcumin (1 g) with piperine (5 mg) twice daily or matching placebo. Patients who had received biological DMARDs or curcumin supplements in the last 6 months were excluded. csDMARD were tapered and stopped sequentially as per a fixed protocol. The primary outcome was flare-free survival at 52 weeks. The secondary outcomes were flare rate, correlation of serum curcuminoid levels with flares and safety. 200 patients (100 per arm) entered the trial with comparable baseline characteristics. Per protocol analysis included 92 and 93 participants in the curcumin and the placebo group, respectively. Flare-free survival at week 52 was similar between both groups (60% versus 64%; p = 0.76). The median time to flare was similar [Curcumin: 219 days (IQR: 123) versus placebo: 214 days (95.8); p = 0.067]. Cox proportionate regression modelling showed that the flare-free survival was independent of serum curcuminoid levels [adjusted HR = 0.99 (95% CI: 0.97-1.0)]. The model showed that flare-free survival was not associated with age, gender, seropositivity, or csDMARD used at baseline. No serious adverse effects were noted. Curcumin did not impact the flare-free survival in patients with RA in remission during the tapering of csDMARDs despite achieving adequate serum levels.Trial registration: CTRI/2018/04/013279.
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Ginger is an important spice crop with medicinal values and gingerols are the most abundant pungent polyphenols present in ginger, responsible for most of its pharmacological properties. The present study focuses on the molecular mechanism of gingerol biosynthesis in ginger using transcriptome analysis. Suppression Subtractive Hybridization (SSH) was done in leaf and rhizome tissues using high gingerol-producing ginger somaclone B3 as the tester and parent cultivar Maran as the driver and generated high-quality leaf and rhizome Expressed Sequence Tags (ESTs). The Blast2GO annotations of the ESTs revealed the involvement of leaf ESTs in secondary metabolite production, identifying the peroxisomal KAT2 gene (Leaf EST 9) for the high gingerol production in ginger. Rhizome ESTs mostly coded for DNA metabolic processes and differential genes for high gingerol production were not observed in rhizomes. In the qRT-PCR analysis, somaclone B3 had shown high chalcone synthase (CHS: rate-limiting gene in gingerol biosynthetic pathway) activity (0.54 fold) in the leaves of rhizome sprouts. The presence of a high gingerol gene in leaf ESTs and high expression of CHS in leaves presumed that the site of synthesis of gingerols in ginger is the leaves. A modified pathway for gingerol/polyketide backbone formation has been constructed explaining the involvement of KAT gene isoforms KAT2 and KAT5 in gingerol/flavonoid biosynthesis, specifically the KAT2 gene which is otherwise thought to be involved mainly in ß-oxidation. The results of the present investigations have the potential of utilizing KAT/thiolase superfamily enzymes for protein/metabolic pathway engineering in ginger for large-scale production of gingerols. Supplementary Information: The online version contains supplementary material available at 10.1007/s13562-022-00825-x.
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BACKGROUND: People living in sub-Saharan Africa (SSA) are disproportionately exposed to trauma and may be at increased risk for posttraumatic stress disorder (PTSD). However, a dearth of population-level representative data from SSA is a barrier to assessing PTSD. This manuscript sought to calculate pooled PTSD prevalence estimates from nationally and regionally representative surveys in SSA. METHODS AND FINDINGS: The search was conducted in PubMed, Embase, PsycINFO, and PTSDpubs and was last run between October 18, 2019, and November 11, 2019. We included studies that were published in peer-reviewed journals; used probabilistic sampling methods and systematic PTSD assessments; and included ≥ 450 participants who were current residents of an SSA country, at least 50% of whom were aged between 15 and 65 years. The primary outcomes were point prevalence estimates of PTSD across all studies, and then within subgroups. The protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) (registration number CRD42016029441). Out of 2,825 unique articles reviewed, 25 studies including a total of 58,887 eligible participants (54% female) in 10 out of the 48 countries in SSA were identified. Most studies enrolled any adult aged 18 years or older. However, some studies only enrolled specific age brackets or persons as young as 15 years old. Six studies were national surveys, and 19 were regional. There were 4 key findings in the meta-analysis: (1) the overall pooled prevalence of probable PTSD was 22% (95% CI 13%-32%), while the current prevalence-defined as 1 week to 1 month-was 25% (95% CI 16%-36%); (2) prevalence estimates were highly variable, ranging from 0% (95% CI 0%-0%) to 74% (95% CI 72%-76%); (3) conflict-unexposed regions had a pooled prevalence of probable PTSD of 8% (95% CI 3%-15%), while conflict-exposed regions had a pooled prevalence of probable PTSD of 30% (95% CI 21%-40%; p < 0.001); and (4) there was no significant difference in the pooled prevalence of PTSD for men and women. The primary limitations of our methodology are our exclusion of the following study types: those published in languages other than English, French, and Portuguese; smaller studies; those that focused on key populations; those that reported only on continuous measures of PTSD symptoms; and unpublished or non-peer-reviewed studies. CONCLUSIONS: In this study, PTSD symptoms consistent with a probable diagnosis were found to be common in SSA, especially in regions exposed to armed conflict. However, these studies only represent data from 10 of the 48 SSA countries, and only 6 studies provided national-level data. Given the enormous heterogeneity expected across the continent, and also within countries and regions, this review cannot speak to rates of PTSD in any regions not included in this review. Thus, substantial gaps in our knowledge of PTSD prevalence in SSA remain. More research on population-level prevalence is needed to determine the burden of trauma symptoms and PTSD in SSA and to identify acceptable and feasible approaches to address this burden given limited mental healthcare resources.
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Terapia Cognitivo-Comportamental , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Transtornos de Estresse Pós-Traumáticos/terapia , África , África Subsaariana/epidemiologia , Feminino , Humanos , Masculino , Pacientes Desistentes do Tratamento/estatística & dados numéricos , PrevalênciaRESUMO
[This corrects the article DOI: 10.1371/journal.pmed.1003090.].
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Progesterone is a biphasic hormone whose confounding role in breast cancer cells involves an initial proliferative surge, followed by sustained growth arrest. Recently we reported that progesterone induces a time- and concentration-dependent release of reactive oxygen species and thus regulates the antiproliferative activity in the breast cancer cell line. Furthermore, the expression of p27, a crucial cell cycle control protein, was regulated by binding of progesterone on progesterone receptor B, thus leading to antiproliferative signaling via multiple signaling pathways including p53, PTEN, and antioxidant systems. Here, we performed an LC-MS/MS analysis of three different breast cancer cell lines. Bioinformatics data analysis and functional classification of proteins revealed a role of progesterone in calcium signaling in MCF-7 cells, and the major differentially expressed calcium regulators were S100A11, S100A10, calreticulin, VDAC1, SERCA3, and SERCA1. Later on we confirmed it by a cell-line-based system having a calcium cameleon sensor targeted at endoplasmic reticulum and found moderate calcium efflux from endoplasmic reticulum upon progesterone treatment. Real-time PCR, Western blot, and TMRM staining confirmed the role of calcium signaling regulators VDAC1 and SERCA3 in progesterone response. Taking together all of these results with our previous studies, we suggest that progesterone, by regulating important proteins involved in calcium signaling and transport, can modulate cell proliferation and cell death. Furthermore, our research may open new avenues for the hypothesis that surgery conducted during the luteal phase of the menstrual cycle might facilitate improved patient survival.
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Neoplasias da Mama/metabolismo , Sinalização do Cálcio/efeitos dos fármacos , Progesterona/farmacologia , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/fisiologia , Canal de Ânion 1 Dependente de Voltagem/fisiologia , Neoplasias da Mama/patologia , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Células MCF-7 , Proteômica/métodosRESUMO
The reversal effect of troxerutin (TX) on obesity, insulin resistance, lipid accumulation, oxidative damage, and hypertension induced in the high-fat-high-fructose diet (HFFD)-fed mice model of metabolic syndrome was investigated. Adult male Mus musculus mice of body weight 25-30 g were fed either control diet or HFFD. Each group was divided into two and treated or untreated with TX (150 mg/kg bw, p.o.) from the 16th day. Assays were done in plasma and heart after 30 and 60 days of the experimental period. Significant increase in the levels of glucose and insulin, blood pressure (BP), and oxidative stress were observed after 30 days of HFFD feeding as compared to control. Animals fed HFFD for 60 days developed more severe changes in the above parameters compared to those fed for 30 days. Hearts of HFFD-fed mice registered downregulation of peroxisome proliferator-activated receptor-α and peroxisome proliferator-activated receptor gamma coactivator-1α, carnitine palmitoyl transferse-1b and AMP-activated protein kinase; and upregulation of cluster of differentiation 36, fatty acid-binding protein-1, and sterol regulatory element-binding protein-1c after 60 days. TX administration restricted obesity (as seen by Lee's index); improved whole body insulin sensitivity; reduced BP, lipid accumulation, and oxidative damage; upregulated fatty acid (FA) oxidation; and downregulated FA transport and lipogenesis. Histology of heart revealed that TX diminishes inflammatory cell infiltration and fatty degeneration in HFFD-fed mice. The antioxidant property of TX and its ability to influence lipid regulatory genes could be the underlying mechanisms for its beneficial effects.
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Antioxidantes/farmacologia , Dieta Hiperlipídica/efeitos adversos , Frutose/efeitos adversos , Hidroxietilrutosídeo/análogos & derivados , Miocárdio/metabolismo , Animais , Antioxidantes/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Proteínas de Transporte de Ácido Graxo/metabolismo , Expressão Gênica , Hidroxietilrutosídeo/farmacologia , Hidroxietilrutosídeo/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Síndrome Metabólica/tratamento farmacológico , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Camundongos , Miocárdio/patologia , Estresse Oxidativo , PPAR alfa/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismoRESUMO
BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most prevalent malignancy in the world with an alarming rate of mortality. Despite the advancement in treatment strategies and drug developments, the overall survival rate remains poor. Therefore, it is imperative to develop alternative or complimentary anti cancer drugs with minimum off target effects. Urolithin A, a microbial metabolite of ellagic acid and ellagitannins produced endogenously by human gut micro biome is considered to have anti-cancerous activity. However anti tumorigenic effect of urolithin A in OSCC is yet to be elucidated. In this study, we examined whether urolithin A inhibits cell growth and induces both apoptosis and autophagy dependent cell death in OSCC cell lines. PURPOSE: The present study aims to evaluate the potential of urolithin A to inhibit OSCC and its regulatory effect on OSCC proliferation and invasion in vitro and in vivo mouse models. METHODS: We evaluated whether urolithin A could induce cell death in OSCC in vitro and in vivo mouse models. RESULTS: Flow cytometric and immunoblot analysis on Urolithin A treated OSCC cell lines revealed that urolithin A markedly induced cell death of OSCC via the induction of endoplasmic reticulum stress and subsequent inhibition of AKT and mTOR signaling as evidenced by decreased levels of phosphorylated mTOR and 4EBP1. This further revealed a possible cross talk between apoptotic and autophagic signaling pathways. In vivo study demonstrated that urolithin A treatment reduced tumor size and showed a decrease in mTOR, ERK1/2 and Akt levels along with a decrease in proliferation marker, Ki67. Taken together, in vitro as well as our in vivo data indicates that urolithin A is a potential anticancer agent and the inhibition of AKT/mTOR/ERK signalling is crucial in Urolithin A induced growth suppression in oral cancer. CONCLUSION: Urolithin A exerts its anti tumorigenic activity through the induction of apoptotic and autophagy pathways in OSCC. Our findings suggest that urolithin A markedly induced cell death of oral squamous cell carcinoma via the induction of endoplasmic reticulum stress and subsequent inhibition of AKT and mTOR signaling as evidenced by decreased levels of phosphorylated mTOR and 4EBP1. Urolithin A remarkably suppressed tumor growth in both in vitro and in vivo mouse models signifying its potential as an anticancer agent in the prevention and treatment of OSCC. Henceforth, our findings provide a new insight into the therapeutic potential of urolithin A in the prevention and treatment of OSCC.
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Apoptose , Autofagia , Cumarínicos , Neoplasias Bucais , Proteínas Proto-Oncogênicas c-akt , Serina-Treonina Quinases TOR , Animais , Cumarínicos/farmacologia , Humanos , Apoptose/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Autofagia/efeitos dos fármacos , Neoplasias Bucais/tratamento farmacológico , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Camundongos , Camundongos Nus , Camundongos Endogâmicos BALB C , Proliferação de Células/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologiaRESUMO
Numerous studies shown that silicon (Si) enhanced plants' resistance to cadmium (Cd). Most studies primarily focused on investigating the impact of Si on Cd accumulation. However, there is a lack of how Si enhanced Cd resistance through regulation of water balance. The study demonstrated that Si had a greater impact on increasing fresh weight compared to dry weight under Cd stress. This effect was mainly attributed to Si enhanced plant relative water content (RWC). Plant water content depends on the dynamic balance of water loss and water uptake. Our findings revealed that Si increased transpiration rate and stomatal conductance, leading to higher water loss. This, in turn, negatively impacted water content. The increased water content caused by Si could ascribe to improve root water uptake. The Si treatment significantly increased root hydraulic conductance (Lpr) by 131 % under Cd stress. This enhancement was attributed to Si upregulation genes expression of NtPIP1;1, NtPIP1;2, NtPIP1;3, and NtPIP2;1. Through meticulously designed scientific experiments, this study showed that Si enhanced AQP activity, leading to increased water content that diluted Cd concentration and ultimately improved plant Cd resistance. These findings offered fresh insights into the role of Si in bolstering plant resistance to Cd.
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Aquaporinas , Cádmio , Nicotiana , Raízes de Plantas , Plântula , Silício , Água , Cádmio/toxicidade , Silício/farmacologia , Silício/química , Raízes de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Plântula/efeitos dos fármacos , Plântula/metabolismo , Nicotiana/efeitos dos fármacos , Nicotiana/metabolismo , Aquaporinas/metabolismo , Água/química , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Transpiração Vegetal/efeitos dos fármacosRESUMO
Tapentadol is a synthetic opioid analgesic with a low risk of abuse and diversion. The rising trend of abuse of tapentadol is largely attributable to its intrinsic pharmacological profile and easy availability due to poor regulatory control. We report a case of intravenous injection of crushed tapentadol tablets that presented with cutaneous adverse drug reactions. Cutaneous adverse reactions are common in injection drug abuse, and clinical examination is a must to inspect the injection sites. Stringent regulatory measures are required to restrict the increasing abuse of tapentadol in India.
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Analgésicos Opioides , Tapentadol , Humanos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Injeções Intravenosas , Comprimidos , Tapentadol/administração & dosagem , Tapentadol/efeitos adversosRESUMO
Hyponatremia is one of the most common electrolyte abnormality seen in oncology practice. The underlying pathogenetic mechanism for chemotherapy-induced hyponatremia is renal salt-wasting syndrome (RSWS) and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Fluid restriction is the treatment of choice in SIADH, whereas salt supplements is the mode of treatment in RSWS. Hence, differentiation between RSWS and SIADH is very important though difficult. Case reports of cisplatin (cis-dichloro-diammine-platinum-2)-induced RSWS and SIADH are rare in the literature. We report about a patient who developed hyponatremia, hypokalemia with excessive urinary excretion of sodium and potassium, renal glycosuria, and aminoaciduria on the third day of the first cycle of cisplatin-containing chemotherapy.
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BACKGROUND & OBJECTIVES: The mature fruits of Solanum nigrum contains steroidal glycosides. These are often used as vegetable and there are evidences on tribal use of these fruits as an oral contraceptive. The present study was carried out to evaluate the estrogenic potential of S. nigrum fruits by in vitro and in vivo assays. METHODS: Defatted methanol extract of dried S. nigrum fruits was column fractionated and the glycoside positive fractions pooled. Definite concentrations of the fraction were used for in vitro and in vivo assays. The effect on cell viability was analyzed in MCF-7 cell lines by MTT assay followed by in vitro evaluation of estrogenicity by hydroxy apatite (HAP) binding assay. The results were further evaluated in vivo by performing uterotrophic assay in ovariectomized mouse models. RESULTS: At low concentration (40 µg/ml), SNGF induced a dose-dependent increase in MCF-7 cell proliferation, while higher extract concentrations (80-320 µg/ml) caused progressive cell growth inhibition. The competitive binding assay using ³H-E2 suggests that this effect is mediated by estrogen receptor. Mouse uterotrophic assay revealed a classical uterotrophic response in ovariectomized mice in response to S. nigrum glycoside fraction (SNGF). SNGF at a dose of 100 mg/kg of body wt induced the maximum height of luminal epithelial cells which indicated an increase of 30.8 per cent over control (P<0.01) with a correlated increase in uterine wet wt (150% increase over control). Higher doses (250 and 500 mg/kg body wt) of SNGF did not induce any uterotrophic effect. INTERPRETATION & CONCLUSIONS: Our preliminary data demonstrate the hormone like activity of Solanum glycosides both in vitro and in vivo in mouse, which needs to be further explored to evaluate the possible mechanism and clinical implications.
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Estrogênios/farmacologia , Frutas/química , Glicosídeos/farmacologia , Extratos Vegetais/farmacologia , Solanum nigrum/química , Análise de Variância , Animais , Sobrevivência Celular/efeitos dos fármacos , Fracionamento Químico , Relação Dose-Resposta a Droga , Durapatita/metabolismo , Feminino , Técnicas Histológicas , Índia , Metanol , Camundongos , Microscopia de Fluorescência , Sais de Tetrazólio , Tiazóis , TrítioRESUMO
The development of clinically advanced multifaceted therapeutic materials for osteosarcoma is at the forefront of cancer research. Accordingly, this work presents the design of a multifunctional magnetic nanocomposite composed of maghemite, strontium doped hydroxyapatite and silica nanoparticles prospectively holding indispensable therapeutic features such as magnetic hyperthermia,in vitrobiomineralization, sustained drug release and intrinsic radiopacity for the treatment of osteosarcoma. The optimal composition has been identified by sequentially modulating the ratio of precursors of the magnetic nanocomposite synthesized by sol-gel technique. Structural and morphological characterization by x-ray diffraction, fourier transform infrared spectrum, Brunauer-Emmet-Teller and transmission electron microscopy analyses followed by VSM, hyperthermia and micro-CT analyses essentially assisted in the selective configuration of biofunctional properties. Results exemplify that MSHSr1 has a saturation magnetization of 47.4 emu g-1and attained hyperthermia temperature (42 °C) at a very low exposure time of 4 min. MSHSr1 is further unique with respect to its exceptional x-ray attenuation ability (contrast enhancement 154.5% in digital radiography; CT number 3100 HU), early biomimetic mineralization (in vitro) evident by the formation of spheroidal apatite layer (Ca/P ratio 1.33) harvested from FESEM-EDX analysis and controlled release of Doxorubicin, the clinically used chemotherapeutic drug: 87.7% at 120 h in tumour analogous pH (6.5) when compared to physiological pH (71.3% at 7.4). MTT assay complemented with cytoskeleton (F-actin) staining of human osteosarcoma (HOS) cells affirm biocompatibility of MSHSr1.In vitrobiomineralization authenticated by Alizarin red S and von Kossa staining has been further corroborated by semi-quantitative calcium estimation of HOS cells cultured with MSHSr1 for two weeks. The results therefore validate the multifunctionality of MSHSr1, and hence could be proposed as a combinatorial therapeutic nanocomposite for osteosarcoma treatment.
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Meios de Contraste/química , Hipertermia Induzida , Nanopartículas de Magnetita/química , Nanocompostos/química , Osteossarcoma/metabolismo , Biomineralização/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , HumanosRESUMO
Contemporary demand calls for a high restorative index as an indispensable requirement for bone tissue engineering scaffolds, where therapeutic agents of natural origin function as a modulator for new bone formation become of utmost importance. The study presents a systematic investigation of the edible stem part of Cissus quadrangularis (CQ) as a natural resource of bioactive metabolites capable of invoking early biomineralization and osteogenesis in vitro. Phytochemical screening of CQ stem extracts (sequential solvent extraction: polarity hexaneAssuntos
Biomineralização/efeitos dos fármacos
, Cissus/química
, Osteogênese/efeitos dos fármacos
, Extratos Vegetais/farmacologia
, Caules de Planta/química
, Linhagem Celular Tumoral
, Sobrevivência Celular/efeitos dos fármacos
, Humanos
, Osteossarcoma
, Extratos Vegetais/química
, Engenharia Tecidual
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A bifronted cure system for osteosarcoma, a common aggressive bone tumor, is highly in demand to prevail the postsurgical adversities in connection with systemic chemotherapy and repair of critical-size bone defects. The hierarchically porous therapeutic scaffolds presented here are synthesized by free radical-initiated copolymerization of hydroxyethyl methacrylate and methyl methacrylate [HEMA/MMA 80:20 and 90:10 mM, H2O/NaCl porogen], which are further surface-phosphorylated [P-PHM] and transformed to bifunctional by impregnating doxorubicin (DOX) [DOXP-PHM]. The P-PHM scaffolds exhibited porous microarchitecture analogous to native cancellous bone (scanning electron microscopy analysis), while X-ray photoelectron spectroscopy analysis authenticated surface phosphorylation. Based on pore characteristics, swelling attributes and slow-pace degradation, P-PHM9163 and P-PHM8263 (HEMA/MMA 90:10 and 80:20 with H2O/NaCl: 60/3.0 weight %, respectively) were chosen from the series and evaluated for osteoinductive efficacy in vitro. Both P-PHM9163 and P-PHM8263 invoked calcium phosphate mineralization in simulated physiological conditions (day 14) with Ca/P ratios of 1.58 and 1.66 respectively, comparable to human bone (1.67). Early biomineralization (Alizarin Red S and von Kossa staining) was evidenced at day 7, while osteoblast differentiation was verified by time-dependent expression of the typical late marker, osteocalcin, at day 14 and 21 in rat bone marrow mesenchymal cells. DOX-loaded P-PHM9163 (DOXP-PHM9163) exhibited pH-responsive (tumor analogous pH; 6.5) sustained release of DOX for prolonged time (up to 45 days) and invoked cellular alterations by cortical stress fiber formation and DNA fragmentation in human osteosarcoma cells leading to early apoptosis (24 h), validated by annexin V/PI staining (FACS) and immunostaining (F-actin/DAPI). Subsequent to DOX release tenure, the scaffold induced the formation of well-organized, porous post-release Ca-P apatite coating (Ca/P is 1.3) in simulated body fluid (day 14) which further endorses the dual functionality of the system. Altogether, the results accentuate that DOXP-PHM9163 is a potential bifunctional therapeutic scaffold capable of extended localized chemotherapeutic delivery in-line with inherent osteogenesis for efficient bone cancer treatment.
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Neoplasias Ósseas , Osteossarcoma , Neoplasias Ósseas/tratamento farmacológico , Doxorrubicina , Humanos , Metacrilatos , Metilmetacrilatos , Osteossarcoma/tratamento farmacológico , Poli-Hidroxietil Metacrilato , Polimetil Metacrilato , PorosidadeRESUMO
Eight novel ERß selective daidzein analogues (NCE1-8) were synthesized and their anti-cancer activity was evaluated by in vitro and in vivo methods. Cytotoxicity study, Receptor binding studies, Luciferase assay, cMYC & Cyclin D1 expression and Caspase 3, 8 & 9 activities were measured to ascertain the anticancer activity and mechanism. Uterotropic, anti-androgenic and anti-tumour activities were performed in rodents. The results revealed that NCEs produced anti-prostate cancer activity in DU145, LNCaP and PC3 cell lines and 50% more active than genistein. NCEs was significantly down-regulated cMYC & Cyclin D1 genes and elevated caspase 3 & 9 levels and did not show any difference in uterotropic, anti-androgenic activities. The tumour weight was also reduced. The NCE 1 and 2 have shown ERß selectivity in receptor binding studies. Daidzein with methyl substitution at R or R1 position exhibited more ERß selectivity and could be considered as lead molecules for anti-prostate cancer activity.
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Receptor beta de Estrogênio/efeitos dos fármacos , Isoflavonas/farmacologia , Neoplasias da Próstata/patologia , Animais , Caspases/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Ciclina D1/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Genisteína/farmacologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley , Receptores de Estrogênio/efeitos dos fármacos , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Silicon (Si) is an omnipresent and second most abundant element in the soil lithosphere after oxygen. Silicon being a beneficial element imparts several benefits to the plants and animals. In many plant species, including the cereals the uptake of Si from the soil even exceeds the uptake of essential nutrients. Cereals are the monocots which are known to accumulate a high amount of Si, and reaping maximum benefits associated with it. Cereals contribute a high amount of Si to the human diet compared to other food crops. In the present review, we have summarized distribution of the dietary Si in cereals and its role in the animal and human health. The Si derived benefits in cereals, specifically with respect to biotic and abiotic stress tolerance has been described. We have also discussed the molecular mechanism involved in the Si uptake in cereals, evolution of the Si transport mechanism and genetic variation in the Si concentration among different cultivars of the same species. Various genetic mutants deficient in the Si uptake have been developed and many QTLs governing the Si accumulation have been identified in cereals. The existing knowledge about the Si biology and available resources needs to be explored to understand and improve the Si accumulation in crop plants to achieve sustainability in agriculture.
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Grão Comestível , Silício , Animais , Transporte Biológico , Solo , Estresse FisiológicoRESUMO
Salt stress limits plant growth and productivity by severely impacting the fundamental physiological processes. Silicon (Si) supplementation is considered one of the promising methods to improve plant resilience under salt stress. Here, the role of Si in modulating physiological and biochemical processes that get adversely affected by high salinity, is discussed. Although numerous reports show the beneficial effects of Si under stress, the precise molecular mechanism underlying this is not well understood. Questions like whether all plants are equally benefitted with Si supplementation despite having varying Si uptake capability and salinity tolerance are still elusive. This review illustrates the Si uptake and accumulation mechanism to understand the direct or indirect participation of Si in different physiological processes. Evaluation of plant responses at transcriptomics and proteomics levels are promising in understanding the role of Si. Integration of physiological understanding with omics scale information highlighted Si supplementation affecting the phytohormonal and antioxidant responses under salinity as a key factor defining improved resilience. Similarly, the crosstalk of Si with lignin and phenolic content under salt stress also seems to be an important phenomenon helping plants to reduce the stress. The present review also addressed various crucial mechanisms by which Si application alleviates salt stress, such as a decrease in oxidative damage, decreased lipid peroxidation, improved photosynthetic ability, and ion homeostasis. Besides, the application and challenges of using Si-nanoparticles have also been addressed. Comprehensive information and discussion provided here will be helpful to better understand the role of Si under salt stress.
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Estresse Salino , Silício , Antioxidantes , Salinidade , Tolerância ao Sal , Silício/farmacologiaRESUMO
BACKGROUND & OBJECTIVES: Trigonella foenum graecum commonly known as fenugreek, has been widely cultivated in Asia, Africa and Mediterranean countries for the edible and medicinal values of its seeds. Earlier reports show that fenugreek seeds provide a mastogenic effect resulting in enhanced breast size. However, very little is known about its estrogenic effect. The present study investigated the effect of chloroform extracts of fenugreek seeds (FCE) in breast cancer cells for its estrogenic effect, and to assess its capacity as an alternative to hormone replacement therapy (HRT). METHODS: The effect of FCE on cell proliferation of estrogen receptor (ER) positive breast cancer cells, MCF-7 was studied by MTT assay at a concentration range of 20 to 320 microg/ml. The competitive ER binding assay (HAP assay) was done to find out the ER binding capacity of the extract. Transfection and reporter assay (DLR assay), and RT- PCR with an estrogen responsive gene pS2 were done to find out the transcriptional regulatory activity of FCE. RESULTS: FCE stimulated the proliferation of MCF-7 cells, showed binding to ER (IC(50) = 185.6 +/- 32.8 microg/ ml) and acted as an agonist for ER mediated transcription via ERE. It also induced the expression of estrogen responsive gene pS2 in MCF-7 cells. INTERPRETATION & CONCLUSION: Our study provided the evidence for estrogenic activities of fenugreek seeds. Further in vitro and in vivo studies could demonstrate its suitability as an alternative to HRT.
Assuntos
Proliferação de Células/efeitos dos fármacos , Fitoestrógenos/farmacologia , Extratos Vegetais/farmacologia , Sementes/química , Trigonella/química , Células Tumorais Cultivadas/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/fisiopatologia , Feminino , Humanos , Extratos Vegetais/uso terapêutico , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismoRESUMO
Natural pigment-based photosensitizers are an attractive pathway for realizing low cost and environmentally friendly solar cells. Here, broadband light-harvesting is achieved using two natural pigments, betanin and lawsone, absorbing in the green and blue region of the solar spectrum respectively. The use of bimodal size distribution of AgNPs tailored for each of the pigments to further increase their efficiency is the key feature of this work. This study demonstrates a significant enhancement in current-density, voltage, and efficiency by 20.1%, 5.5%, and 28.6% respectively, in a betanin-lawsone co-sensitized solar cell, via plasmonic enhancement using silver nanoparticles (AgNPs). The optimum sizes of the nanoparticles have been calculated by studying their optical response and electric field profiles using Finite Difference Time Domain (FDTD) simulations, aimed at matching their resonant wavelengths with the absorption bands of the dyes. Simulations show that AgNPs of diameters 20 nm and 60 nm are optimum for enhanced absorption by lawsone and betanin respectively. The FDTD simulations of the plasmonic photoelectrodes demonstrated 30% and 15% enhancement in the power absorption by betanin and lawsone at the LSPR peaks of the 60 nm and 20 nm AgNPs respectively. An optimum overall concentration of 2% (v/v) and a ratio of 4:1 (20 nm:60 nm) of the bimodal distribution of the AgNPs, was determined for incorporation in the photoanodes. An average efficiency of 1.02 ± 0.006% was achieved by the betanin-lawsone co-sensitized solar cell with the bimodal distribution of AgNPs, compared to 0.793 ± 0.006% achieved by the non-plasmonic solar cell of otherwise identical configuration. Electrochemical impedance spectroscopy confirmed that the incorporation of the bimodal distribution of AgNPs in the solar cells also enabled enhanced electron lifetime and reduced recombination compared to the non-plasmonic counterpart, thereby improving the charge transfer. The plasmonic enhancement methodology presented here can be applied to further improve the efficiency of other natural dye-sensitized solar cells.
RESUMO
Multifunctional scaffolds have recently attained superior significance in tissue regeneration due to combinational activity profile that is usually accomplished by separate sequential therapy. Here, we present a dual system comprised of surface-phosphorylated PET fibrous matrix coated with ciprofloxacin-impregnated biodegradable polymer poly (hydroxyethyl methacrylate) aiming at regeneration of bone tissue deprived of bacterial infections, particularly osteomyelitis. The ATR, XPS and FESEM/EDX results provided confirmative evidences for surface phosphorylation of PET and in situ coating of the polymer. Swelling and contact angle measurements demonstrated improved hydrophilicity which is further corroborated by in vitro degradation profile in PBS. Preliminary evaluation by MTT and actin staining proved its biocompatibility while enhanced in vitro mineralization in 1.5X SBF by FESEM/EDX clearly indicate the primary nucleation and secondary growth of beautiful apatite crystals with Ca/P ratio similar to human bone. Alizarin red S and von Kossa staining validated the biomineralization in MG-63 cells. The sequential expression of early and late biomarkers -alkaline phosphatase (ALP) and osteocalcin (OSN)- of osteoblast differentiation in rat bone marrow mesenchymal cells (BMC) has demonstrated osteoinductive nature of the system. The second functionality of the scaffold has been proven by step-wise ciprofloxacin-release profile (in vitro) with ~60% release within 120 h. In addition, antibacterial studies of ciprofloxacin- eluted from the scaffold have shown apparent zones of inhibition against Staphylococcus aureus (3.6 ± 0.3 cm) and Escherichia coli (3.0 ± 0.8 cm). Hence, the surface-transformed PET scaffold function as a dual system as localized antibiotic delivery vehicle against bone infections and undergo self-biomineralization leading to osteoinduction.