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1.
Lancet ; 404(10462): 1536-1546, 2024 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-39426836

RESUMO

BACKGROUND: Single-pill combinations (SPCs) of three low-dose antihypertensive drugs can improve hypertension control but are not widely available. A key issue for any combination product is the contribution of each component to efficacy and tolerability. This trial compared a new triple SPC called GMRx2, containing telmisartan, amlodipine, and indapamide, with dual combinations of components for efficacy and safety. METHODS: In this international, randomised, double-blind, active-controlled trial, we enrolled adults with hypertension receiving between zero and three antihypertensive drugs, with a screening systolic blood pressure (SBP) ranging from 140-179 mm Hg (on no drugs) to 110-150 mm Hg (on three drugs). Participants were recruited from Australia, the Czech Republic, New Zealand, Poland, Sri Lanka, the UK, and the USA. In a 4-week active run-in, existing medications were switched to GMRx2 half dose (telmisartan 20 mg, amlodipine 2·5 mg, and indapamide 1·25 mg). Participants were then randomly allocated (2:1:1:1) to continued GMRx2 half dose or to each possible dual combination of components at half doses (telmisartan 20 mg with amlodipine 2·5 mg, telmisartan 20 mg with indapamide 1·25 mg, or amlodipine 2·5 mg with indapamide 1·25 mg). At week 6, doses were doubled in all groups, unless there was a clinical contraindication. The primary efficacy outcome was mean change in home SBP from baseline to week 12, and the primary safety outcome was withdrawal of treatment due to an adverse event from baseline to week 12. Secondary efficacy outcomes included differences in clinic and home blood pressure levels and control rates. This study is registered with ClinicalTrials.gov, NCT04518293, and is completed. FINDINGS: The trial was conducted between July 9, 2021 and Sept 1, 2023. We randomly allocated 1385 participants to four groups: 551 to GMRx2, 276 to telmisartan-indapamide, 282 to telmisartan-amlodipine, and 276 to amlodipine-indapamide groups. The mean age was 59 years (SD 11), 712 (51%) participants self-reported as female and 673 (48·6%) male, and the mean clinic blood pressure at the screening visit was 142/85 mm Hg when taking an average of 1·6 blood pressure medications. Following the run-in on GMRx2 half dose, the mean clinic blood pressure level at randomisation was 133/81 mm Hg and the mean home blood pressure level was 129/78 mm Hg. At week 12, the mean home SBP was 126 mm Hg in the GMRx2 group, which was lower than for each of the dual combinations: -2·5 (95% CI -3·7 to -1·3, p<0·0001) versus telmisartan-indapamide, -5·4 (-6·8 to -4·1, p<0·0001) versus telmisartan-amlodipine, and -4·4 (-5·8 to -3·1, p<0·0001) versus amlodipine-indapamide. For the same comparisons, differences in clinic blood pressure at week 12 were 4·3/3·5 mm Hg, 5·6/3·7 mm Hg, and 6·3/4·5 mm Hg (all p<0·001). Clinic blood pressure control rate below 140/90 mm Hg at week 12 was superior with GMRx2 (74%) to with each dual combination (range 53-61%). Withdrawal of treatment due to adverse events occurred in 11 (2%) participants in the GMRx2 group, four (1%) in telmisartan-indapamide, three (1%) in telmisartan-amlodipine, and four (1%) in amlodipine-indapamide, with none of the differences being statistically significant. INTERPRETATION: A novel low-dose SPC product of telmisartan, amlodipine, and indapamide provided clinically meaningful improvements in blood pressure reduction compared with dual combinations and was well tolerated. This SPC provides a new therapeutic option for the management of hypertension and its use could result in a substantial improvement in blood pressure control in clinical practice. FUNDING: George Medicines.


Assuntos
Anlodipino , Anti-Hipertensivos , Hipertensão , Indapamida , Telmisartan , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anlodipino/administração & dosagem , Anlodipino/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Método Duplo-Cego , Combinação de Medicamentos , Hipertensão/tratamento farmacológico , Indapamida/administração & dosagem , Indapamida/efeitos adversos , Indapamida/uso terapêutico , Telmisartan/administração & dosagem , Resultado do Tratamento
2.
Am Heart J ; 277: 66-75, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39094841

RESUMO

BACKGROUND: Blood pressure (BP) control among treated patients in Africa is very suboptimal, with low levels of combination therapy use and therapeutic inertia being among the major barriers to effective control of hypertension. The VERONICA-Nigeria study aims to evaluate, among Black African adults with hypertension, the effectiveness and safety of a triple pill-based treatment protocol compared to Nigeria hypertension treatment protocol (standard care protocol) for the treatment of hypertension. METHODS: This study involves a randomized, parallel-group and open-label trial. Adults with uncontrolled hypertension (n = 300), untreated or receiving monotherapy, with no contraindication to study treatments will be randomly assigned 1:1 to treatment with a triple pill based-treatment protocol or standard care protocol. Follow-up is for 6 months, with interim follow up visits at month 1, 2, and 3. In a noncomparative extension treatment period, participants completing the 6 months randomized period and on ≤3 BP-lowering drugs will receive treatment with the triple pill-based treatment protocol for 12 months. The primary outcome is change in home mean SBP from baseline to month 6, and key secondary efficacy outcome is percentage of participants with clinic BP <140/90 mmHg at month 6. The primary safety outcome is discontinuation of trial treatment due to adverse events from randomization to month 6. Economic evaluation will be conducted to assess the cost-effectiveness of the triple pill-based treatment protocol, and process evaluation will be conducted to understand the context in which the trial was conducted, implementation of the trial and interventions and mechanisms of effect, and potential barriers and facilitators to implementing the intervention in clinical practice. CONCLUSION: The VERONICA-Nigeria trial will provide evidence of effectiveness and safety of the triple-based treatment protocol for the pharmacological management of hypertension, in Black African adults. TRIAL REGISTRATION: PACTR202107579572114.


Assuntos
Anti-Hipertensivos , Hipertensão , Humanos , Hipertensão/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Nigéria , Masculino , Pressão Sanguínea/efeitos dos fármacos , Feminino , Adulto , Quimioterapia Combinada , Pessoa de Meia-Idade , Combinação de Medicamentos
3.
Crit Rev Food Sci Nutr ; : 1-26, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39257284

RESUMO

Breast cancer remains a leading cause of cancer-related mortality among women worldwide. One of its defining features is resistance to apoptosis, driven by aberrant expression of apoptosis-related proteins, notably the overexpression of anti-apoptotic Bcl-2 proteins. These proteins enable breast cancer cells to evade apoptosis and develop resistance to chemotherapy, underscoring their critical role as therapeutic targets. Diet plays a significant role in breast cancer risk, potentially escalating or inhibiting cancer development. Recognizing the limitations of current treatments, extensive research is focused on exploring bioactive compounds derived from natural sources such as plants, fruits, vegetables, and spices. These compounds are valued for their ability to exert potent anticancer effects with minimal toxicity and side effects. While literature extensively covers the effects of various dietary compounds in inducing apoptosis in cancer cells, comprehensive information specifically on how dietary bioactive compounds modulate anti-apoptotic Bcl-2 protein expression in breast cancer is limited. This review aims to provide a comprehensive understanding of the interaction between Bcl-2 proteins and caspases in the regulation of apoptosis, as well as the impact of dietary bioactive compounds on the modulation of anti-apoptotic Bcl-2 in breast cancer. It further explores how these interactions influence breast cancer progression and treatment outcomes.

4.
J Fluoresc ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39042354

RESUMO

The fluorescence behavior of pyranine in anionic micellar system of sodium dodecyl sulphate was studied in the presence of selected amines. The amines included cyclopropylamine (CPA), ethylenediamine (EDA), benzylamine (BA), dibutylamine (DBA), cyclohexylamine (CHA), and polyethylenediamine (PEDA). All the studied amines quenched the intensity of pyranine. Study was performed in 0.05 M and 0.1 M SDS. The thermodynamic parameters were determined in order to understand the quenching of pyranine by the studied amines. Change in Gibbs free energy and quenching was found higher in 0.05 M SDS concentration and was found lower when SDS concentration was increased to 0.1 M SDS. Pyranine quenching by the amines studied were treated with an extended Stern-Volmer equation that produced the Stern-Volmer constant ([Formula: see text]). Binding constant (Kb), number of binding stoichiometry (n) and Gibbs free energy change (ΔGbinding) were found higher for lower surfactant concentration as compare to higher surfactant concentration. More negative (-ve) the Gibbs free energies more will be the quenching, higher will be the sensitivity and vice versa. The Gibbs free energies for all the studied amines were found in the order as cyclopropylamine > ethylenediamine > benzylamine > dibutylamine > cyclohexylamine > polyethylenediamine. Fluorescence quenching of pyranine by amines in aqueous SDS is reproducible and is useful for the determination of amines in environmental samples.

5.
Plant Cell Rep ; 43(3): 65, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341396

RESUMO

Microplastic pollution has emerged as a critical global environmental issue due to its widespread distribution, persistence, and potential adverse effects on ecosystems and human health. Although research on microplastic pollution in aquatic environments has gained significant attention. However, a limited literature has summarized the impacts of microplastic pollution the agricultural land and human health. Therefore, In the current review, we have discussed how microplastic(s) affect the microorganisms by ingesting the microplastic present in the soil, alternatively affecting the belowground biotic and abiotic components, which further elucidates the negative effects on the above-ground properties of the crops. In addition, the consumption of these crops in the food chain revealed a potential risk to human health throughout the food chain. Moreover, microplastic pollution has the potential to induce a negative impact on agricultural production and food security by altering the physiochemical properties of the soil, microbial population, nutrient cycling, and plant growth and development. Therefore, we discussed in detail the potential hazards caused by microplastic contamination in the soil and through the consumption of food and water by humans in daily intake. Furthermore, further study is urgently required to comprehend how microplastic pollution negatively affects terrestrial ecosystems, particularly agroecosystems which drastically reduces the productivity of the crops. Our review highlights the urgent need for greater awareness, policy interventions, and technological solutions to address the emerging threat of microplastic pollution in soil and plant systems and mitigation strategies to overcome its potential impacts on human health. Based on existing studies, we have pointed out the research gaps and proposed different directions for future research.


Assuntos
Metais Pesados , Microplásticos , Humanos , Microplásticos/toxicidade , Solo/química , Plásticos , Ecossistema , Metais Pesados/toxicidade , Produtos Agrícolas
6.
JAMA ; 332(13): 1070-1079, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39215620

RESUMO

Importance: With the high burden of hypertension in sub-Saharan Africa, there is a need for effective, safe and scalable treatment strategies. Objective: To compare, among Black African adults, the effectiveness and safety of a novel low-dose triple-pill protocol compared with a standard-care protocol for blood pressure lowering. Design and Setting: Randomized, parallel-group, open-label, multicenter trial conducted in public hospital-based family medicine clinics in Nigeria. Participants: Black African adults with uncontrolled hypertension (≥140/90 mm Hg) who were untreated or receiving a single blood pressure-lowering drug. Interventions: Participants were randomly allocated to low-dose triple-pill or standard-care protocols. The triple-pill protocol involved a novel combination of telmisartan, amlodipine, and indapamide in triple one-quarter, one-half, and standard doses (ie, 10/1.25/0.625 mg, 20/2.5/1.25 mg, and 40/5/2.5 mg), with accelerated up-titration. The standard-care protocol was the Nigeria hypertension treatment protocol starting with amlodipine (5 mg). Main Outcomes and Measures: The primary effectiveness outcome was the reduction in home mean systolic blood pressure, and the primary safety outcome was discontinuation of trial treatment due to adverse events, both from randomization to month 6. Results: The first participant was randomized on July 19, 2022, and the last follow-up visit was on July 18, 2024. Among 300 randomized participants (54% female; mean age, 52 years; baseline mean home blood pressure, 151/97 mm Hg; and clinic blood pressure, 156/97 mm Hg), 273 (91%) completed the trial. At month 6, mean home systolic blood pressure was on average 31 mm Hg (95% CI, 28 to 33 mm Hg) lower in the triple-pill protocol group and 26 mm Hg (95% CI, 22 to 28 mm Hg) lower in the standard-care protocol group (adjusted difference, -5.8 mm Hg [95% CI, -8.0 to -3.6]; P < .001]). At month 6, clinic blood pressure control (<140/90 mm Hg) was 82% vs 72% (risk difference, 10% [95% CI, -2% to 20%]) and home blood pressure control (<130/80 mm Hg) was 62% vs 28% (risk difference, 33% [95% CI, 22% to 44%]) in the triple-pill compared with the standard-care protocol group; these were 2 of 21 prespecified secondary effectiveness end points. No participants discontinued trial treatment due to adverse events. Conclusions and Relevance: Among Black African adults with uncontrolled hypertension, a low-dose triple-pill protocol achieved better blood pressure lowering and control with good tolerability compared with the standard-care protocol. Trial Registration: Pan African Clinical Trials Registry Identifier: PACTR202107579572114.


Assuntos
Anlodipino , Anti-Hipertensivos , Pressão Sanguínea , Hipertensão , Indapamida , Telmisartan , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anlodipino/administração & dosagem , Anlodipino/efeitos adversos , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , População Negra , Pressão Sanguínea/efeitos dos fármacos , Combinação de Medicamentos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Indapamida/administração & dosagem , Indapamida/efeitos adversos , Nigéria/epidemiologia , Telmisartan/administração & dosagem , Telmisartan/efeitos adversos
7.
Plant Cell Physiol ; 64(6): 686-699, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37036744

RESUMO

Reactive oxygen species (ROS) are highly reactive molecules, generated by nicotinamide adenine dinucleotide phosphate oxidases encoded by respiratory burst oxidase homologs. The functions of the OsRbohs gene family in rice are diverse and poorly understood. OsRbohI was recently identified as a newly evolved gene in the rice OsRbohs gene family. However, the function of OsRbohI in regulating rice growth is not yet reported. In this study, our results indicate that knockout (KO) OsRbohI mutants showed significantly shorter shoot and primary roots, along with lower ROS content than the control lines, whereas the overexpression (OE) lines displayed contrasting results. Further experiments showed that the abnormal length of the shoot and root is mainly caused by altered cell size. These results indicate that OsRbohI regulates rice shoot and root growth through the ROS signal. More importantly, RNA-seq analysis and jasmonic acid (JA) treatment demonstrated that OsRbohI regulates rice growth via the JA synthesis and signaling pathways. Compared with the control, the results showed that the KO mutants were more sensitive to JA, whereas the OE lines were less sensitive to JA. Collectively, our results reveal a novel pathway in which OsRbohI regulates rice growth and development by affecting their ROS homeostasis through JA synthesis and signaling pathway.


Assuntos
Oryza , Proteínas de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Oryza/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Raízes de Plantas/metabolismo , Oxilipinas/farmacologia , Oxilipinas/metabolismo , Ciclopentanos/farmacologia , Ciclopentanos/metabolismo , Transdução de Sinais , Crescimento e Desenvolvimento , Regulação da Expressão Gênica de Plantas
8.
Theor Appl Genet ; 136(5): 108, 2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37039968

RESUMO

KEY MESSAGE: Root hairs are required for water and nutrient acquisition in plants. Here, we report a novel mechanism that OsUGE1 is negatively controlled by OsGRF6 to regulate root hair elongation in rice. Root hairs are tubular outgrowths generated by the root epidermal cells. They effectively enlarge the soil-root contact area and play essential roles for nutrient and water absorption. Here, in this study, we demonstrated that the Oryza sativa UDP-glucose 4-epimerase 1-like (OsUGE1) negatively regulated root hair elongation and was directly targeted by Oryza sativa growth regulating factor 6 (OsGRF6). Knockout mutants of OsUGE1 using CRISPR-Cas9 technology showed longer root hairs than those of wild type. In contrast, overexpression lines of OsUGE1 displayed shorter root hair compared with those of wild type. GUS staining showed that it could specifically express in root hair. Subcellular localization analysis indicates that OsUGE1 is located in endoplasmic reticulum, nucleus and plasma membrane. More importantly, ChIP-qPCR, Yeast-one-hybrid and BiFC experiments revealed that OsGRF6 could bind to the promoter of OsUGE1. Furthermore, knockout mutants of OsGRF6 showed shorter root hair than those of wild type, and OsGRF6 dominantly expressed in root. In addition, the expression level of OsUGE1 is significantly downregulated in Osgrf6 mutant. Taken together, our study reveals a novel pathway that OsUGE1 is negatively controlled by OsGRF6 to regulate root hair elongation in rice.


Assuntos
Oryza , Oryza/genética , Proteínas de Plantas/genética , Membrana Celular/metabolismo , Regiões Promotoras Genéticas
9.
J Fluoresc ; 33(1): 261-265, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36401734

RESUMO

A group of selected phenols i.e., picric acid, p-Nitrophenol, m-Nitrophenol, o-Nitrophenol, and phenol interactions were studied with a fluorescent probe carbazole in a micellar system of CTAB. CTAB concentration was optimized for maximum quenching of carbazole for each studied phenol. Interaction was studied in 0.02 and 0.1 mol/dm3 CTAB. All the studied phenols resulted in the quenching of carbazole in both CTAB concentrations though lower CTAB concentration was found optimum for highest quenching of the probe carbazole. Carbazole fluorescence quenching with phenols were explained with the help of Stern-Volmer equation that produced the constants of Stern-Volmer ([Formula: see text]). [Formula: see text] shows the sensitiveness of the method for the studied phenol and were observed in the order picric acid > phenol > m-Nitrophenol > p-Nitrophenol > o-Nitrophenol. Detection threshold (DT) and quantification threshold (QT) were observed in the order 1.76 [Formula: see text] 10-7 - 6.30 [Formula: see text] 10-7 mol/dm3 and 5.898 [Formula: see text] 10-7 - 2.11 [Formula: see text] 10-6 mol/dm3 respectively. The method is reproducible and is effective for the determination of studied phenols in the samples.

10.
J Fluoresc ; 33(6): 2253-2256, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37010648

RESUMO

Phenanthrene fluorescence quenching in anionic micellar system of sodium dodecyl sulphate (SDS) was explored for the development of a sensitive and selective method for a group of selected aldehydes (2,6-dichlorobenzaldehyde, 4-(dimethylamino)benzaldehyde, 4-aminobenzaldehyde, 4-nitrobenzaldehyde, 2-chlorobenzaldehyde, benzaldehyde and 2-methoxybenzaldehyde). Experiments were performed in 0.02 mol L- 1 SDS. All the studied aldehydes quenched the fluorescence intensity of the probe (phenanthrene). Stern-Volmer equation was useful in explaining the phenanthrene quenching by the studied aldehydes. Stern-Volmer constants ([Formula: see text]) were obtained as a result of using the Stern-Volmer equation that gives the information in respect of sensitivity of the method for the studied aldehydes. Greater the [Formula: see text] higher will be the sensitivity and vice versa. [Formula: see text], detection limit (DL) and quantification limit (QL) were observed in the order 2,6-dichlorobenzaldehyde > 4-dimethylaminobenzaldehyde > 4-aminobenzaldehyde > 4-nitrobenzaldehyde > 2-chlorobenzaldehyde > benzaldehyde > 2-methoxybenzaldehyde. Phenanthrene fluorescence quenching by the studied aldehydes is useful for their determination in environmental samples.

11.
Cardiol Young ; 33(2): 309-312, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35725276

RESUMO

A 9 mm Occlutech septal occluder Flex II device was retrieved in a 4-year-old 22 kg child; A 6 Fr Cook® Flexor sheath (child) was inserted into a 9 Fr Occlutech® ASD Delivery Set (mother). Once the tip of the smaller sheath was close to the device, a 4 Fr right Judkins catheter was introduced with a snare. The right atrial hub was captured and withdrawn to the level of the 6 Fr sheath which was then withdrawn into the 9 Fr sheath before being removed completely. The "mother and child" technique offers a greater likelihood of slenderising and retrieving embolised devices.


Assuntos
Comunicação Interatrial , Dispositivo para Oclusão Septal , Feminino , Humanos , Pré-Escolar , Mães , Cateterismo Cardíaco/métodos , Aorta Torácica , Remoção de Dispositivo/métodos , Comunicação Interatrial/cirurgia , Desenho de Prótese , Resultado do Tratamento
12.
J Pak Med Assoc ; 73(2): 357-361, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36800725

RESUMO

Neck pain is the fourth leading cause of disability, and is the most common musculoskeletal disorder. High-heel shoes, one of the significant identities of females, cause pain in the neck as well as in feet and ankle regions. The current narrative review was planned to explore evidence to highlight the biomechanical factors of high-heel shoes as the source of neck pain, which mostly remains undiagnosed. PubMed and Google Scholar search engines were explored for full text of research articles published in English language from 2016 to 2021. Of the 82 studies initially found, 22(27%) were shortlisted for full-text assessment, and, of them, 6 (27.27%) were selected for detailed analysis. Despite other contributing factors, kinematics and kinetics should be considered primarily during neck pain management. Based on best available evidence, high heels increase the individual's height, but result in significant decrease in trunk flexion. Evidence also suggests that the type and width of heels do not affect as much as the height of the heels in the context of pain and functional issues in the cervical region.


Assuntos
Calcanhar , Cervicalgia , Feminino , Humanos , Cervicalgia/etiologia , Cervicalgia/terapia , Sapatos , Pescoço ,
13.
Bioorg Chem ; 129: 106170, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36174443

RESUMO

P-glycoprotein (P-gp), a transmembrane glycoprotein, is mainly involved in lung cancer multidrug resistance. Several P-gp inhibitors have been developed to enhance the efficacy of chemotherapeutics and overcome drug resistance. However, most of them failed in the clinical stages due to undesirable side effects. Therefore, there is a requirement to develop P-gp inhibitors from natural sources. Dietary spice bioactives have been well-known for their anticancer activities. However, their role in modulating the P-gp activity has not been well investigated. Therefore, we have screened for the potential bioactives from various spice plants with P-gp modulatory activity using computational molecular docking analysis. The computational analysis revealed several key bioactives from curry leaves, specifically mahanimbine, exhibited a strong binding affinity with P-gp. Unfortunately, mahanimbine is available with few commercial sources at very high prices. Therefore, we prepared a curry leaves extract and isolated mahanimbine by a novel, yet simple, extraction method that requires less time and causes minimum environmental hazards. After purification, structure, and mass were confirmed for the isolated compound by IR spectrum and LC-MS/MS analysis, respectively. In the mechanistic study, hydrolysis of ATP and substrate efflux by P-gp are coupled. Hence, ATP binding at the ATPase-binding site is one of the fundamental steps for the P-gp efflux cycle. We found that mahanimbine demonstrated to stimulate P-gp ATPase activity. Concurrently, it enhanced the intracellular accumulation of P-gp substrates Rhodamine 123 and Hoechst stain, which indicates that mahanimbine modulates the function of P-gp. In addition, we have analyzed the complementary effect of mahanimbine with the chemotherapeutic drug gefitinib. We found that mahanimbine synergistically enhanced gefitinib efficiency by increasing its intracellular accumulation in lung cancer cells. Overall, mahanimbine has been shown to be a potent P-gp modulator. Therefore, mahanimbine can be further developed as a potential candidate to overcome chemoresistance in lung cancer.


Assuntos
Neoplasias Pulmonares , Murraya , Humanos , Murraya/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Resistencia a Medicamentos Antineoplásicos , Simulação de Acoplamento Molecular , Gefitinibe/farmacologia , Cromatografia Líquida , Espectrometria de Massas em Tandem , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Trifosfato de Adenosina , Adenosina Trifosfatases/metabolismo , Linhagem Celular Tumoral
14.
J Fluoresc ; 31(2): 595-598, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33502645

RESUMO

Pyrene interaction with a group of selected amines such as i.e. benzylamine, phenethylamine, trimethylamine, 1-phenylethylamine was studied in aqueous sodium dodecyl sulfate. All the four amines quenched the fluorescence intensity of pyrene in aqueous SDS. Pyrene acts as a sensitive and selective sensor for the detection of amines in environmental samples. Two different SDS concentrations (0.05 mol L- 1 and 0.1 mol L- 1) were used to get the optimum SDS concentration for maximum quenching and best detection and quantification limits. Lower SDS concentration (0.05 mol L- 1) was found the optimum for maximum quenching, lower detection and quantification limits. Fluorescence quenching of pyrene by the studied amines was treated with the Stern-Volmer equation that resulted in a Stern-Volmer constants (Ksv). Ksv reflects the sensitivity of pyrene for studied amines. Ksv varied between 1.962 × 104 - 0.020 × 103 mol L- 1. A sensitivity, detection limit (DL), quantification limit (QL) of pyrene for studied amines was found in the order Benzylamine > phenethylamie > trimethylamine > 1-phenylethylamine. DL varied from 4.53 × 10- 7 to 4.55 × 10- 4 mol L- 1 and QL varied from 1.51 × 10- 6 to 1.52 × 10- 3 mol L- 1. Method showed excellent reproducibility and is fruitful for the studied amines in environmental samples.


Assuntos
Aminas/química , Pirenos/química , Dodecilsulfato de Sódio/química , Estrutura Molecular , Espectrometria de Fluorescência , Água/química
15.
Ecotoxicol Environ Saf ; 226: 112844, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34619479

RESUMO

Nowadays, the applications of engineered nanoparticles (ENPs) have been significantly increased, thereby negatively affecting crop production and ultimately contaminating the food chain worldwide. Zinc oxide nanoparticles (ZnO NPs) induced oxidative stress has been clarified in previous studies. But until now, it has not been investigated that how ethylene mediates or participates in ZnO NPs-induced toxicity and related cellular ultrastructural changes in rice seedlings. Here, we reported that 500 mg/L of ZnO NPs reduced the fresh weight (54.75% and 55.64%) and dry weight (40.33% and 47.83%) in shoot and root respectively as compared to control. Furthermore, ZnO NPs (500 mg/L) reduced chlorophyll content (72% Chla, 70% Chlb), induced the stomatal closure and ultrastructural damages by causing oxidative stress in rice seedlings. These cellular damages were significantly increased by exogenous applications of ethylene biosynthesis precursor (ACC) in the presence of ZnO NPs. In contrary, ZnO NPs induced damages on the above-mentioned attributes were reversed through the exogenous supply of ethylene signaling and biosynthesis antagonists such as silver (Ag) and cobalt (Co) respectively. Interestingly, ZnO NPs accelerate ethylene biosynthesis by up-regulating the transcriptome of ethylene biosynthesis responsive genes. The antioxidant enzymes activities and related gene expressions were further increased in ethylene signaling and biosynthesis associated antagonists (Ag and Co) treated seedlings as compared to sole ZnO NPs treatments. In contrary, the above-reported attributes were further decreased by ACC together with ZnO NPs. In a nutshell, ethylene effectively contributes in ZnO NPs induced toxicity and causing ultrastructural and stomatal damage in rice seedlings. Such findings could have potential implications in producing genetic engineered crops, which will be able to tolerate nanoparticles toxicity in the environment.


Assuntos
Nanopartículas , Oryza , Óxido de Zinco , Etilenos , Nanopartículas/toxicidade , Oryza/genética , Estresse Oxidativo , Raízes de Plantas , Plântula , Óxido de Zinco/toxicidade
16.
Ecotoxicol Environ Saf ; 225: 112738, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34481352

RESUMO

Arsenic is a significant food safety and environmental concern due to its mutagenic and carcinogenic effect on living organism. Soybean (Glycine max [L.] Merrill) is a global staple crop grown intensively in arsenic-contaminated regions of the world (e.g., Southern Province of China). Therefore, the objective of this study was to investigate whether Se-NPs and/or ZnO-NPs could be used as an eco-friendly and efficient amendment to reduce arsenic uptake and toxicity in soybean. Ten-days-old seedling, grown in vermiculite, were transferred to hydroponic media and further grown till V2 growth stage appeared. AsV (25 µM Na2HAsO4) stressed plants were treated with ZnONP (25 µM ZnO) and SeNP (25 µM Se) separately and in combination, which were grown for another 10 d. The result demonstrated that arsenic-treated soybean plants displayed a reduction in photosynthetic efficiency, increased proline and glycine betaine accumulation in tissues, and altered antioxidant activity compared to an untreated control. The application of zinc oxide and selenium nanoparticles, both independently and in tandem, reduced arsenic stress in root and shoot tissues and rescued plant health. This was reflected through increased levels of reduced glutathione content, ascorbic acid, and various photosynthesis- and antioxidant-relevant enzymes. In addition, nanoparticle-treated soybean plants displayed higher expression of defense- and detoxification-related genes compared to controls. Cellular toxicants (i.e., oxidized glutathione, reactive oxygen species, and malondialdehyde) were reduced upon nanoparticle treatment. These data collectively suggest that selenium and zinc oxide nanoparticles may be a solution to ameliorate arsenic toxicity in agricultural soils and crop plants.


Assuntos
Nanopartículas , Óxido de Zinco , Antioxidantes , Nanopartículas/toxicidade , Fotossíntese , Raízes de Plantas , Plântula , Glycine max , Óxido de Zinco/toxicidade
17.
Cent Eur J Public Health ; 29(1): 45-55, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33831286

RESUMO

OBJECTIVES: The current study employed socio-demographic, health and lifestyle, and academic variables to assess the prevalence and independent predictors of daily smoking, attempts to quit smoking, and agreement with total smoking ban at university. METHODS: Students at the University of Turku (1,177) completed an online questionnaire that assessed socio-demographic, health and lifestyle, and academic characteristics, and three smoking variables (smoking, attempts to quit, agreement with total smoking ban at university). Bivariate relationships and multiple logistic regression assessed relationships between student characteristics and the three smoking variables before and after controlling for all other variables. RESULTS: Slightly < 80% of students never smoked, 16% were occasional, and about 6% were daily smokers, and about 40% had attempted to quit. Nearly half the sample agreed to total smoking ban at university. Physical activity, consuming alcohol, illicit drug/s use and daily smoking were significant independent predictors across > 1 of the three smoking variables. Age, health awareness, importance of achieving good grades, academic performance compared to peers, study burden, and mother's educational level were significant independent predictors of one of the three variables examined. CONCLUSION: Universities need to assess smoking, with specific focus on the modifiable independent predictors that were associated with > 1 the variables examined, to encourage physical activity and pay attention to reduce alcohol consumption and illicit drug/s and daily smoking, whilst targeting at-risk students. University strategies should be part of the wider country-wide effective tobacco control policies.


Assuntos
Política Antifumo , Finlândia/epidemiologia , Humanos , Prevalência , Fumar/epidemiologia , Inquéritos e Questionários , Universidades
18.
Cent Eur J Public Health ; 29(3): 201-208, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34623120

RESUMO

OBJECTIVES: Virtually no previous research assessed physical activity (PA) of university students in Finland, and their associations with depressive symptoms, whilst simultaneously controlling for potential confounders. METHODS: Students at the University of Turku (1,177) completed an online health and wellbeing questionnaire that assessed depressive symptoms (22 items), as well as their achievement of the guidelines of four forms of low, moderate, vigorous, and muscle strengthening PA (LPA, MPA, VPA, MSPA, respectively). We explored the associations of depressive symptoms with these PA forms, accounting for socio-demographic and health confounders (age, gender, year of study, marital status, accommodation during semesters, self-rated health). RESULTS: Achievement of PA guidelines was generally low for these young adult Finnish undergraduates. Bivariate relationships (no controlling for confounders) between depressive symptoms and four forms of PA guidelines achievement showed that in males, good/very good/excellent self-rated health, and achievement of the MSPA guidelines were significantly negatively associated with depressive symptoms. Conversely, low PA was significantly positively associated with depressive symptoms. Multiple regression (controlling for confounders) showed that achievement of the MSPA guidelines was independently significantly negatively associated with depressive symptoms; and whilst achievement of the MPA and VPA guidelines was negatively associated with depressive symptoms, the relationships did not reach statistical significance. Likewise, low PA was positively associated with depressive symptoms, but the relationships were again not statistically significant. CONCLUSION: Universities would benefit from multipronged strategies and approaches employing effective interventions aimed at improving students' general awareness of their health and promoting more physically active lifestyles among students.


Assuntos
Depressão , Saúde Mental , Depressão/epidemiologia , Exercício Físico , Finlândia/epidemiologia , Humanos , Masculino , Estudantes , Adulto Jovem
19.
J Pak Med Assoc ; 71(3): 977-981, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34057957

RESUMO

Musculoskeletal disorders are common conditions involving joints, muscles, nerves, ligaments and tendons. These disorders affect normal activities and cause discomfort. These discomforts are managed by different types of interventions, including exercise, acupuncture, soft tissue release and manual therapy, as conservative modes of management. Soft tissue release, including active release technique, fascial abrasion, and myo-fascial release are considered effective for musculoskeletal function improvement. Advanced technology-improved and instrument-assisted techniques are being used nowadays. These instruments are sensitive in the localisation, specification and facilitation of the target area with the help of mechanical pressure applied on tissue with movement of specific muscle. Prognosis varies with good outcomes using fewer sessions than the others. But it needs proper localisation of the muscle involved and special training. The advantage considered is that musculoskeletal disorders can also be prevented in practitioners as well.


Assuntos
Terapia por Acupuntura , Doenças Musculoesqueléticas , Exercício Físico , Humanos , Massagem , Doenças Musculoesqueléticas/terapia
20.
J Phys Chem A ; 124(8): 1508-1514, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32040313

RESUMO

Electrons and •OH-radicals have been generated by using low-energy laser pulses of 6 ns duration (1064 nm wavelength) to create plasma in a suspension of plasmid DNA (pUC19) in water. Upon thermalization, these particles induce single and double strand breakages in DNA along with possible base oxidation/base degradation. The time-evolution of the ensuing structural modifications has been measured; damage to DNA is seen to occur within 30 s of laser irradiation. The time-evolution is also measured upon addition of physiologically relevant concentrations of salts containing monovalent, divalent, or trivalent alkali ions. It is shown that some alkali ions can significantly inhibit strand breakages while some do not. The inhibition is due to electrostatic shielding of DNA, but significantly, the extent of such shielding is seen to depend on how each alkali ion binds to DNA. Results of experiments on strand breakages induced by thermalized particles produced upon plasma-induced photolysis of water, and their inhibition, suggest implications beyond studies of DNA; they open new vistas for utilizing simple nanosecond lasers to explore the effect of ultralow energy radiation on living matter under physiologically relevant conditions.


Assuntos
Quebras de DNA de Cadeia Dupla , DNA/química , Elétrons , Radical Hidroxila/química , Plasmídeos , Termodinâmica , Água/química
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