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Chloride intracellular channels (CLICs) are a family of proteins that exist in soluble and transmembrane forms. The newest discovered member of the family CLIC6 is implicated in breast, ovarian, lung gastric, and pancreatic cancers and is also known to interact with dopamine-(D(2)-like) receptors. The soluble structure of the channel has been resolved, but the exact physiological role of CLIC6, biophysical characterization, and the membrane structure remain unknown. Here, we aimed to characterize the biophysical properties of this channel using a patch-clamp approach. To determine the biophysical properties of CLIC6, we expressed CLIC6 in HEK-293 cells. On ectopic expression, CLIC6 localizes to the plasma membrane of HEK-293 cells. We established the biophysical properties of CLIC6 by using electrophysiological approaches. Using various anions and potassium (K+) solutions, we determined that CLIC6 is more permeable to chloride-(Cl-) as compared to bromide-(Br-), fluoride-(F-), and K+ ions. In the whole-cell configuration, the CLIC6 currents were inhibited after the addition of 10 µM of IAA-94 (CLIC-specific blocker). CLIC6 was also found to be regulated by pH and redox potential. We demonstrate that the histidine residue at 648 (H648) in the C terminus and cysteine residue in the N terminus (C487) are directly involved in the pH-induced conformational change and redox regulation of CLIC6, respectively. Using qRT-PCR, we identified that CLIC6 is most abundant in the lung and brain, and we recorded the CLIC6 current in mouse lung epithelial cells. Overall, we have determined the biophysical properties of CLIC6 and established it as a Cl- channel.
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Canais de Cloreto , Cloretos , Animais , Humanos , Camundongos , Ânions/metabolismo , Canais de Cloreto/genética , Canais de Cloreto/metabolismo , Cloretos/metabolismo , Células Epiteliais/metabolismo , Células HEK293RESUMO
A series of new indole-oxadiazole derivatives was designed and synthesized to develop potential anti-breast cancer agents. The compounds exhibited significant inhibitory activity with IC50 values ranging from 1.78 to 19.74 µM against ER-positive human breast cancer (BC) cell lines T-47D and MCF-7. Among them, compounds (5a, 5c, 5e-5h, 5j-5o) displayed superior activity against ER-α dominant (ratio of ER-α/ER-ß is 9/1) T-47D cells compared to the standard drug bazedoxifene (IC50 = 12.78 ± 0.92 µM). Compounds 5c and 5o exhibited remarkable anti-proliferative activity with IC50 values of 3.24 ± 0.46 and 1.72 ± 1.67 µM against T-47D cells, respectively. Further, compound 5o manifested 1589-fold higher ER-α binding affinity (213.4 pM) relative to bazedoxifene (339.2 nM) in a competitive ER-α binding assay, while compound 5c showed a binding affinity of 446.6 nM. The Western blot analysis proved that both compounds influenced the ER-α protein's expression, impeding its subsequent transactivation and signalling pathway within T-47D cells. Additionally, a molecular docking study suggests that compounds 5c and 5o bind in such a fashion that induces conformational changes in the protein, culminating in their antagonistic effect. Also, pharmacokinetic profiles showed that all compounds have drug-like properties. Further, molecular dynamic (MD) simulations and density functional theory (DFT) analysis confirmed the stability, conformational behaviour, reactivity, and biological feasibility of compounds 5c and 5o. In conclusion, based on our findings, compounds 5c and 5o, which exhibit significant ER-α antagonistic activity, can act as potential lead compounds for developing anti-breast cancer agents.
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Antineoplásicos , Proliferação de Células , Relação Dose-Resposta a Droga , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Receptor alfa de Estrogênio , Indóis , Oxidiazóis , Humanos , Receptor alfa de Estrogênio/metabolismo , Receptor alfa de Estrogênio/antagonistas & inibidores , Indóis/química , Indóis/farmacologia , Indóis/síntese química , Oxidiazóis/química , Oxidiazóis/farmacologia , Oxidiazóis/síntese química , Relação Estrutura-Atividade , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Simulação de Acoplamento Molecular , Linhagem Celular TumoralRESUMO
Grapevine Pinot gris virus (GPGV; genus Trichovirus in the family Betaflexiviridae) was detected in Australia in 2016, but its impact on the production of nursery material and fruit in Australia is still currently unknown. This study investigated the prevalence and genetic diversity of GPGV in Australia. GPGV was detected by reverse transcription-polymerase chain reaction (RT-PCR) in a range of rootstock, table and wine grape varieties from New South Wales, South Australia, and Victoria, with 473/2171 (21.8%) samples found to be infected. Genomes of 32 Australian GPGV isolates were sequenced and many of the isolates shared high nucleotide homology. Phylogenetic and haplotype analyses demonstrated that there were four distinct clades amongst the 32 Australian GPGV isolates and that there were likely to have been at least five separate introductions of the virus into Australia. Recombination and haplotype analysis indicate the emergence of new GPGV strains after introduction into Australia. When compared with 168 overseas GPGV isolates, the analyses suggest that the most likely origin of Australian GPGV isolates is from Europe. There was no correlation between specific GPGV genotypes and symptoms such as leaf mottling, leaf deformation, and shoot stunting, which were observed in some vineyards, and the virus was frequently found in symptomless grapevines.
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Flexiviridae , Austrália , Filogenia , Flexiviridae/genética , Europa (Continente) , FrutasRESUMO
PURPOSE: It is not known if the muscle matrix that becomes functional after gap arthroplasty (GA) in temporomandibular joint ankylosis (TMJA), induces growth of the mandible or the reconstructive arthroplasty with costochondral graft (CCG) is responsible for growth. The study aimed to evaluate the mandibular growth and functional outcome with the use of CCG/GA in the management of pediatric TMJA. METHODS: The investigators designed a cluster randomized controlled trial on pediatric (3 to 16 years) TMJA patients. Treatment applied (CCG and GA), was the primary predictor variable. Patients were divided into CCG and GA groups. The primary outcome variable was growth. Secondary outcome variables included etiology and duration of ankylosis, maximal incisal opening (MIO), reankylosis, occlusion, laterotrusion, chin deviation, facial asymmetry, occlusal tilt, and complications. The distance condylion (Co) to gnathion (Gn) was used to measure mandibular length. Ramal height was measured from Co- gonion (Go). Lower facial height was measured from the anterior nasal spine to Gn. Generalized estimating equations were used to calculate the regression coefficient adjusted for the cluster. The patient was considered as a cluster and the unit of analysis was joint. RESULTS: Fifty-six {n = 28 in each group, (n = 33 joint in the CCG group and n = 31 joints in GA group)} patients were analyzed. The median follow-up was 33-months (31.93 ± 15.24) in the CCG group and 32-months (32.85 ± 17.84) in the GA group. Intergroup comparison between the CCG and GA group showed a statistically significant difference in mandibular length (CCG = 77.51 ± 9.31 and GA = 66.66 ± 8.32 mm, P < .001), ramal height (CCG = 44.21 ± 7.3 and GA = 31.87 ± 8.4 mm, P < .001), and statistically insignificant difference in lower facial height (CCG = 52.53 ± 6.1 and GA = 50.19 ± 6.3 mm, P = 0.14) at follow-up. Statistically, significant improvement was seen in MIO in both groups (<.001). CONCLUSIONS: The results of the present study concluded that growth and jaw functions were better in reconstructive arthroplasty with CCG than GA in pediatric TMJA.
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Anquilose , Transtornos da Articulação Temporomandibular , Anquilose/cirurgia , Artroplastia , Criança , Humanos , Mandíbula/cirurgia , Articulação Temporomandibular/cirurgia , Transtornos da Articulação Temporomandibular/cirurgiaRESUMO
PURPOSE: In residual deformity cases, it is difficult to reposition the zygomaticomaxillary-complex (ZMC) intraoperatively, due to resorbed fracture edges, and lack of zygoma analysis to 3-dimensionally quantify the deformity. Instability after zygomatic osteotomy and miniplate fixation (ZOMF) due to the gap between osteotomized segments, scar tissue, muscle pull, and other factors is also unknown. The study aims to evaluate symmetry and stability after ZOMF. MATERIALS AND METHODS: In this prospective study, a ZMC analysis was designed and patients with unilateral post-traumatic residual deformity (>10 weeks) of ZMC were treated with ZOMF. Measurements were evaluated on affected and unaffected sides at preoperatively, immediately, and 6 months postoperatively using MIMICS software. The primary outcome variable was the symmetry and stability of ZMC. Secondary parameters were changes in orbital volume, diplopia, ocular motility, mouth opening, and patient satisfaction. P < .05 was considered statistically significant. The continuous variables were compared by paired t-test. The change within the continuous variable with time was assessed by repeated measure ANOVA, followed by multiple comparisons using the Bonferroni test. The changes within the categorical variable were assessed by the McNemar test. RESULTS: Ten patients were enrolled (mean age = 29.2 ± 9.97 years; male:female = 9:1; right:left = 4:6). The mean duration from trauma to surgery was 34.84 ± 31.35 weeks. There was an improvement in the symmetry in anteroposteriorly (P = .005), mediolaterally (P = .001), and at the arch (P = .011) postoperatively. All parameters remained stable at 6 months postoperatively (difference not significant, P > .05); with the median satisfaction score of 4 of 5. Significant improvement in mouth opening (P = .014) and orbital volume (P = .001) was noted. CONCLUSIONS: Virtual measurements as per the proposed protocol helped in communication and quantifying ZMC. Four-point fixation with miniplates provided enough stability over the 6-month follow-up period.
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Fraturas Maxilares , Fraturas Zigomáticas , Adulto , Feminino , Humanos , Masculino , Osteotomia , Estudos Prospectivos , Adulto Jovem , Zigoma/diagnóstico por imagem , Zigoma/cirurgia , Fraturas Zigomáticas/diagnóstico por imagem , Fraturas Zigomáticas/cirurgiaRESUMO
Cancer is a leading cause of death worldwide. Even after the availability of numerous drugs and treatments in the market, scientists and researchers are focusing on new therapies because of their resistance and toxicity issues. The newly synthesized drug candidates are able to demonstrate in vitro activity but are unable to reach clinical trials due to their rapid metabolism and low bioavailability. Therefore there is an imperative requisite to expand novel anticancer negotiators with tremendous activity as well as in vivo efficacy. Tetrazole is a promising pharmacophore which is metabolically more stable and acts as a bioisosteric analogue for many functional groups. Tetrazole fragment is often castoff with other pharmacophores in the expansion of novel anticancer drugs. This is the first systematic review that emphasizes on contemporary strategies used for the inclusion of tetrazole moiety, mechanistic targets along with comprehensive structural activity relationship studies to provide perspective into the rational design of high-efficiency tetrazole-based anticancer drug candidates.
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Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Tetrazóis/uso terapêutico , Animais , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Estrutura Molecular , Relação Estrutura-Atividade , Tetrazóis/síntese química , Tetrazóis/farmacologiaRESUMO
PURPOSE: The costochondral graft (CCG) is considered the reference standard for pediatric temporomandibular joint reconstruction. It has the disadvantages of unpredictable growth, donor site morbidity, and the need for intermaxillary fixation. It has been reported that transport disk distraction osteogenesis (TDDO) can result in the formation of a neocondyle and disc. We performed a randomized trial to measure and compare clinically relevant outcomes of ramus-condyle unit (RCU) reconstruction using CCG and TDDO for pediatric temporomandibular joint ankylosis (TMJA). MATERIALS AND METHODS: In the present randomized controlled trial (block randomization with a variable block size), pediatric patients with unilateral, nonrecurrent TMJA aged 3 to 16 years who had presented to our unit from December 2015 to June 2017 were enrolled. Instead of temporalis myofascial flap interposition, a buccal fat pad was used to fill the gap created by osteoarthrectomy. The primary outcome parameter was mouth opening. A mouth opening of at least 25 mm at the median follow-up point was considered success. The secondary outcome parameters were occlusion, laterotrusion, protrusion, reankylosis, neocondyle, chin deviation, facial asymmetry, midline shift, and neo-disc formation. Data were analyzed using the independent t test and rank sum test. RESULTS: A total of 24 patients were enrolled in the CCG and TDDO groups (n = 12 in each group). Trauma (40.9%) was the most common etiology with a slight male preponderance (59.09%). The mean age was 10.32 ± 2.85 years. The average distraction achieved in the TDDO group was 10.42 mm. The median follow-up duration was 31.5 months (range, 24 to 39 months). The mean preoperative maximal incisal opening had improved from 8.5 ± 4.1 and 9.5 ± 7.1 mm in the CCG and TDDO groups preoperatively to 35.7 ± 2.7 and 34.4 ± 8.9 mm, respectively, at the median follow-up point (P < .005). RCU reconstruction with both modalities resulted in improvement in all the parameters; however, the intergroup comparison showed statistically non-significant differences. No reankylosis or open bite was found. The 3-hour delayed gadolinium-enhanced magnetic resonance imaging scan showed successful neo-disc formation. CONCLUSIONS: Similar success can be achieved in RCU reconstruction using either CCG or TDDO for pediatric TMJA. Both techniques have some advantages and disadvantages. RCU reconstruction using CCG or TDDO results in formation of a neocondyle, maintenance of occlusion, and correction of facial asymmetry.
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Anquilose/cirurgia , Transplante Ósseo , Osteogênese por Distração , Transtornos da Articulação Temporomandibular/cirurgia , Adolescente , Artroplastia , Criança , Pré-Escolar , Humanos , Masculino , Côndilo Mandibular , Articulação Temporomandibular/cirurgiaAssuntos
Betametasona , Glucocorticoides , Mandíbula , Dente Serotino , Extração Dentária , Dente Impactado , Humanos , Dente Serotino/cirurgia , Dente Impactado/cirurgia , Betametasona/administração & dosagem , Betametasona/uso terapêutico , Mandíbula/cirurgia , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Resultado do Tratamento , Injeções , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/prevenção & controleRESUMO
BACKGROUND: Tolvaptan is an orally administered, nonpeptide, selective arginine vasopressin V(2) receptor antagonist that increases free water clearance, thereby correcting and increasing the low serum sodium levels in patients of cirrhosis, where hyponatremai is am major encountered problem. AIMS: Evaluate the efficacy and tolerabilty of tolvaptan in cirrhotics with symptomatic hyponatremia that resist correction with fluid restriction. Intellectual improvement assessed using Short Portable Mental Status Questionnaire (SPMSQ) pre and post therapy(on conclusion). Adverse drug reactions monitored to assess safety. METHDOLOGY: Study design: Prospective, pre and post drug efficacy and safety evaluating study with permission from ethical committe. Study Population: one hundred cirrhotic patients, irrespective of etiology, with hyponatremia, who fulfill the inclusion criteria. Protocol: All enrolled patients, treated with oral Tolvaptan at doses of 15 mg once daily in addition to the concurrent treatment regimen. Tolvaptan therapy was concluded as soon as the patient reached the normal sodium levels, which were monitored daily. RESULTS: Our study population had a majority of Hepatitis C patients (49%). Mean sodium levels at baseline were 125.79 + 3.49 which had a significant (130.25+3.28), and highly significant (133+ 3.19) change post 48 and 72 hours. In clinical parameters, urine output was altered significantly (pre drug mean 1530.76+619.02 to post drug mean of 1783+563.01. Body weight and Abdominal girth changes were not significant.
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Antagonistas dos Receptores de Hormônios Antidiuréticos/uso terapêutico , Hiponatremia/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Tolvaptan/uso terapêutico , Benzazepinas , Humanos , Estudos ProspectivosRESUMO
Thirty-two yeast isolates were retrieved from four soil samples collected from hydrocarbon-polluted locations of Hisar, Haryana, using enrichment culture technique with 1% (v/v) diesel as carbon source. Total nine isolates showing blood agar haemolysis were screened further for biosurfactant production. Yeast isolate, YK32, gave highest 8.4-cm oil displacement which was found to be significantly higher as compared to positive control, 0.2% (w/v) SDS (6.6 cm), followed by 6.2 and 6.0 cm by isolates YK20 and YK21, respectively. Maximum emulsification index was obtained in case of isolates YK20 and YK21 measuring 53.8%, after 6 days of incubation utilizing glucose as carbon source, whereas isolate YK32 was found to be reducing surface tension up to 93 dynes/cm and presented 99.6% degree of hydrophobicity. Olive oil has supported maximum surface tension reduction in isolates YK32 and YK21 equivalent to 53 and 48 dynes/cm and gave 88.3 and 88.5% degree of hydrophobicity, respectively. Diesel was not preferred as carbon source by most of the isolates except YK28 which generated 5.5-cm oil displacement, 25% emulsification index, reduced surface tension to the level of 38 dynes/cm and presented 89% degree of hydrophobicity. Conclusively, isolates YK20, YK21, YK22 and YK32 were marked as promising biosurfactant producers and were subjected to identification. Based on microscopic examination and biochemical peculiarities, isolates YK21 and YK22 might be identified as Candida spp., whereas, isolates YK20 and YK32 might be identified as Saccharomycopsis spp. and Brettanomyces spp., respectively. Interestingly it is the first report indicating Saccharomycopsis spp. and Brettanomyces spp. as a potential biosurfactant producer.
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Hidrocarbonetos/análise , Microbiologia do Solo , Tensoativos/metabolismo , Leveduras/metabolismo , Brettanomyces/isolamento & purificação , Brettanomyces/metabolismo , Candida/isolamento & purificação , Candida/metabolismo , Saccharomycopsis/isolamento & purificação , Saccharomycopsis/metabolismo , Solo/química , Poluentes do Solo , Leveduras/isolamento & purificaçãoRESUMO
The hexadentate ligands H2L1-L3 with mixed S, N, O donor sites and possessing substituents having either "no" or electron-releasing/withdrawing nature at terminal ends are synthesized. The ligands H2L1-L3 were tested for binding with library of metal ions, wherein maximum efficiency was observed with Ni(2+), and it motivated us to prepare the Ni(2+) complexes. The ligand H2L1 underwent deprotonation and formed binuclear complex when interacted with Ni(2+) as evident from its crystal structure. The H2L2 and H2L3 having electron-withdrawing/electron releasing groups, respectively, were also deprotonated; however, they afforded mononuclear complexes with Ni(2+) ion. This signifies the importance of steric parameters instead of electronic factors in these particular cases. Impressed by differential behavior of complexes of H2L1 and H2L2/H2L3 with Ni(2+) and their photophysical and electrochemical properties, all the metal complexes were studied for their chemosensing ability. Nowadays with increased use of organophosphate, there is alarming increase of these agents in the environment, and thus we require efficient technique to estimate the level of these agents with high sensitivity and selectivity in aqueous medium. The Ni(2+) complexes with hydrophobic nature were suspended into aqueous medium for testing them as sensor for organophosphate. The (L1)2.(Ni(2+))2 could sense phosmet with detection limit of 44 nM, whereas L2.Ni(2+) and L3.Ni(2+) exhibited the detection limits of 62 and 71 nM, respectively, for chlorpyrifos.
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Manual handling of municipal solid waste is of serious concern owing to emerging occupational risks. Considering this, health risks of municipal solid waste workers involved in street sweeping, waste collection, waste processing and rag picking were assessed in Chandigarh, India, using an interview schedule as a study tool. Result shows that the waste worker profession is mainly dominated by males, except in rag pickers, and with a lower literacy rate. Age distribution shows that 16% of waste collectors and 11% of rag pickers were below 18 years of age. Daily income of the waste workers ranges from â¹100 to â¹200. It was observed that 22.2% of waste collectors, 43.2% of street sweepers and 25.5% of rag pickers do not use any type of protective gears owing to their casual attitude, which results in various types of injuries. The major occupational health issues reported by various categories of waste workers were respiratory disorders, injuries and allergies having prevalence of 12.3%-17.6%, 4.9%-44.4% and 35.3%-48.9%, respectively. Waste workers are vulnerable to occupational health hazards and hence there is a need to safeguard them through formulation of new laws and policies.
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Doenças Profissionais/etiologia , Exposição Ocupacional/efeitos adversos , Eliminação de Resíduos/métodos , Adolescente , Adulto , Escolaridade , Feminino , Substâncias Perigosas , Humanos , Renda , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Roupa de Proteção/estatística & dados numéricos , Eliminação de Resíduos/economia , Fatores Socioeconômicos , Resíduos Sólidos , Adulto JovemRESUMO
OBJECTIVE: The objective of this prospective, non-interventional, 4-month observational study was to analyze and compare patient-reported quality of life (QOL) and their physical/psychosocial symptom burden during their respective chemotherapy sessions. MATERIALS AND METHODS: A prospective and descriptive study was carried out jointly by Pharmacology and Oncology Departments of a tertiary care center in Malwa region of Punjab. The data collection was performed by administering validated questionnaire/response after taking informed consent. RESULTS: A total of 131 cancer patients were recruited with the mean age of 49.05 ± 14.35 (SD (standard deviation)) years. As per the QOL scoring of Global Health Status (GHS) and four items of symptom scale, that is, insomnia, pain, appetite loss, and constipation, and financial difficulties attained a significance difference. GHS significantly improved in group three as compared to group one, indicating that the patient's overall health/QOL improved as the chemotherapy session progressed. CONCLUSION: Although QOL scoring system did not show significant improvement in all areas (except insomnia, pain, appetite loss, constipation, and financial difficulties) with reference to their respective chemotherapy cycles, but a judicious diagnosis with an appropriate treatment including chemotherapy may lessen the negative perception of cancer as a deadly and fatal disease in our rural population.
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A series of new indole-tetrazole derivatives were designed and synthesized to develop potential anti-breast cancer agents. The compounds exhibited in vitro anti-proliferative activity against ER-α positive T-47D (IC50 = 3.82-24.43 µM), MCF-7 (IC50 = 3.08-22.65 µM), and ER-α negative MDA-MB-231 (IC50 = 7.69-19.4 µM) human breast cancer cell lines. Compounds 5d and 5f displayed significant anti-proliferative activity compared to bazedoxifene (IC50 = 14.23 ± 0.68 µM), with IC50 values of 10.00 ± 0.59 and 3.83 ± 0.74 µM, respectively, against the ER-α dominant T-47D cell line. Also, both compounds showed non-significant cytotoxicity against normal cells HEK-293. Further, the ER-α binding affinity of 5d and 5f was assessed through a fluorescence polarization-based competitive binding assay, where 5d and 5f have shown significant binding with IC50 = 5.826 and 110.6 nM, respectively, as compared to the standard drug bazedoxifene (IC50 = 339.2 nM). Western blot analysis confirmed that compound 5d reduced ER-α protein expression in T-47D cells, hindering its transactivation and signalling pathways. Additionally, a molecular docking study suggests that compounds 5d and 5f bind in such a fashion that induces conformational changes in the protein, culminating in their antagonistic effect. Pharmacokinetic profiles showed that the compounds possessed drug-like properties. Furthermore, molecular dynamics simulation studies establish the dynamic stability and conformational behaviour of the ER-α protein and ligand complex of both compounds. Additionally, 5d and 5f ensure biological feasibility as per their DFT analysis through HOMO-LUMO energy gap analysis. In conclusion, compounds 5d and 5f, exhibiting significant ER-α antagonistic activity, can act as potential lead compounds for anti-breast cancer therapies.
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BACKGROUND: Well-being is a multidimensional concept and has been extended to many areas. Student well-being has garnered attention over the last decade due to concerns that have been raised. Digital health interventions have the potential to enhance and improve student well-being. OBJECTIVE: The objective of the study is to design, develop, and pilot-test a digital health platform to enhance student well-being. METHODS: A sample size of 5000 participants will be recruited across Gujarat and Tamil Nadu, India. Students will be enrolled from Parul University in Vadodara, Gujarat, as well as Panimalar Medical College Hospital and Research Institute, Panimalar Engineering College, Panimalar Institute of Technology, and Panimalar College of Nursing in Chennai, Tamil Nadu. Current undergraduate and graduate students consenting to participate will be recruited using convenience sampling from these institutes. The study will collect baseline data to construct the student well-being index. Based on the risk profile, a random subset of the population will be provided access to the digital health intervention, which will deliver tailored interactive messages addressing the various dimensions of well-being among undergraduate and graduate students. The eligible study participants will be aged 18 years and older, enrolled in these institutes, and willing to give their consent to participate in the study. RESULTS: The proposed research is an unfunded study. The enrollment of the individuals in the study began in October 2022. Data gathered will be analyzed using SAS (version 9.3; SAS Institute) and results will be reported as 95% CIs and P values. CONCLUSIONS: The proposed study will help to determine the factors affecting well-being among college students and help in designing digital health interventions to improve the well-being of undergraduate and graduate students. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/39779.
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Estudantes , Humanos , Projetos Piloto , Índia , Estudantes/psicologia , Masculino , Feminino , Adulto Jovem , Adulto , Universidades , Adolescente , Projetos de PesquisaRESUMO
5H-Benzimidazo[1,2-c]quinazoline-6-thione (BI-QT), was synthesized as a benzimidazole-based probe to detect H2S. BI-QT exhibits a fluorescent "turn-on" response in DMSO/H2O (9:1, HEPES 10 mM, pH 7.4) upon the addition of H2S. The BI-QT probe can determine micromolar (0-600 µM) H2S concentrations in aqueous systems, with a detection limit of 1.12 µM. Interestingly, BI-QT exhibited an ultrafast response to H2S, with maximum intensity achieved almost instantly when exposed to H2S. BI-QT is largely unaffected by pH and responds reliably over the wide 4-11 pH range, which highlights its applicability to various physiological scenarios. UV-vis, fluorescence, and 1H NMR spectroscopic analyses investigated the sensing mechanism. The practicality of the probe was demonstrated using water samples and living cells.
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Pot experiments were carried out to study the effect of different dilutions of leachate generated from municipal solid waste (MSW) landfill on bread wheat (Triticum aestivum). Eight treatment groups with different concentrations (0-100%) of leachate were prepared and treatments were given to the plants till they reached complete vegetative phase (45 days). The growth performances of wheat plants were assessed in terms of various parameters such as shoot and root length, dry biomass and chlorophyll content. Plants treated with higher concentrations of leachate (75% and 100%) showed higher growth (2.5 and 6%) and 100% survival rate as compared to control. However, high shoot weight (0.028 and 0.030 gm) and high chlorophyll content (213 and 230%) was reported in 30 and 40% leachate treatment as compared to control. Some symptoms of stress (discoloration of leaf blade, wilting and yellowing of plants) were also observed in plants, which could be related to the presence of high concentration of salts in the leachate. The current study suggests that MSW landfill leachate is rich in nutrients and can be used as fertilizer but before its application, the salinity level and concentration of toxic metals present in leachate should be considered in accordance with the tolerance ability of any plant.
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Triticum/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Testes de Toxicidade , Triticum/crescimento & desenvolvimentoRESUMO
Cypermethrin, a synthetic pyrethroid, has broad spectrum use in domestic agriculture, and veterinary applications due to its high bioefficacy, enhanced stability and low mammalian toxicity. The present investigation was performed to investigate the sub acute effects of cypermethrin (25EC) in female rats. Cypermethrin (25EC) at a dose of 50 mg kg(-1) body weight (1/5th LD50) was orally given to female rats for 4 weeks. Control rats received similar amount of ground nut oil. Significant decrease in ovarian weight (15.4%) was observed after four weeks of cypermethrin administration while the uterine weight (68.2%) and thickness of myometrium increased at 2 and 4 weeks. Cypermethrin caused degenerative changes in ovary as evidenced by increased follicular atresia and decreased concentration of proteins (38%), lipids (20%), phospholipids (18%) and cholesterol (37%). Acid (49.2%) and alkaline phosphatase (41%) activities were increased while lactate dehydrogenase (37.9%) and 3beta-HSDH (31.3%) decreased in treated rat ovary.
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Inseticidas/toxicidade , Ovário/efeitos dos fármacos , Piretrinas/toxicidade , Útero/efeitos dos fármacos , Animais , Feminino , Inseticidas/administração & dosagem , Piretrinas/administração & dosagem , RatosRESUMO
BACKGROUND: Breast cancer is considered to be 2nd most common cancer subtype investigated worldwide. It is mainly prevalent in postmenopausal women. Estrogen Receptor (ER) is a primary transcription factor for the survival and growth of tumors. Around 80% BCs of all classes are ER-positive (ER+). Powerful evidence for estrogen proved to be involved in BC pathogenesis both exogenously and endogenously. It brings the concept of ER inhibitors to treat BC with distinct mechanisms into focus and ER PROTACs (Proteolysis-Targeting Chimeras), AIs (Aromatase inhibitors), SERMs (Selective estrogen receptor modulators), and SERDs (Selective estrogen receptor degrader) were developed. For over 30 years, Tamoxifen, a triphenylethylene SERM, was the drug of choice solely to treat ER+BC patients. Although several SERMs got approval by US FDA after tamoxifen, complicacies remain because of dangerous adverse effects like endometrial carcinoma, hot flashes, and VTE (Venous thromboembolism). In addition to that, drug-resistant tumors put a surging need for novel, potent candidates with no or low adverse effects for ER+ BC prevention. OBJECTIVES: This article explores the possibilities of SERMs as effective BC agents. METHODS: A detailed literature survey of the history and recent advancements of SERMs has been carried out, taking BC as the primary target. This review provides information about ER structure, signaling, pharmacological action, chemical classification with SAR analysis, and benefits and adverse effects of SERMs as potential BC agents. RESULTS: Exhaustive literature studies suggested that SERMs having an agonistic, antagonistic or mixed activity to ER could efficiently inhibit BC cell proliferation. CONCLUSION: Each chemical class of SERMs comprises some salient features and potentials, which may be further investigated to obtain novel effective SERMs in BC therapy.
Assuntos
Neoplasias da Mama , Moduladores Seletivos de Receptor Estrogênico , Feminino , Humanos , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Moduladores Seletivos de Receptor Estrogênico/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Receptores de Estrogênio , Tamoxifeno/farmacologia , Tamoxifeno/uso terapêutico , EstrogêniosRESUMO
BACKGROUND: Neurodegenerative diseases are among the diseases that cause the foremost burden on the health system of the world. The diseases are multifaceted and difficult to treat because of their complex pathophysiology, which includes protein aggregation, neurotransmitter breakdown, metal dysregulation, oxidative stress, neuroinflammation, excitotoxicity, etc. None of the currently available therapies has been found to be significant in producing desired responses without any major side effects; besides, they only give symptomatic relief otherwise indicated off-episode relief. Targeting various pathways, namely choline esterase, monoamine oxidase B, cannabinoid system, metal chelation, ï¢-secretase, oxidative stress, etc., may lead to neurodegeneration. By substituting various functional moieties over the coumarin nucleus, researchers are trying to produce safer and more effective neuroprotective agents. OBJECTIVES: This study aimed to review the current literature to produce compounds with lower side effects using coumarin as a pharmacophore. METHODS: In this review, we have attempted to compile various synthetic strategies that have been used to produce coumarin and various substitutional strategies used to produce neuroprotective agents from the coumarin pharmacophore. Moreover, structure-activity relationships of substituting coumarin scaffold at various positions, which could be instrumental in designing new compounds, were also discussed. RESULTS: The literature review suggested that coumarins and their derivatives can act as neuroprotective agents following various mechanisms. CONCLUSION: Various studies have demonstrated the neuroprotective activity of coumarin due to an oxaheterocyclic loop, which allows binding with a broad array of proteins, thus motivating researchers to explore its potential as a lead against various neurodegenerative diseases.