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1.
J Med Chem ; 67(8): 6537-6548, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38603561

RESUMO

Herein, we have compared the effectivity of light-based photoactivated cancer therapy and ultrasound-based sonodynamic therapy with Re(I)-tricarbonyl complexes (Re1-Re3) against cancer cells. The observed photophysical and TD-DFT calculations indicated the potential of Re1-Re3 to act as good anticancer agents under visible light/ultrasound exposure. Re1 did not display any dark- or light- or ultrasound-triggered anticancer activity. However, Re2 and Re3 displayed concentration-dependent anticancer activity upon light and ultrasound exposure. Interestingly, Re3 produced 1O2 and OH• on light/ultrasound exposure. Moreover, Re3 induced NADH photo-oxidation in PBS and produced H2O2. To the best of our knowledge, NADH photo-oxidation has been achieved here with the Re(I) complex for the first time in PBS. Additionally, Re3 released CO upon light/ultrasound exposure. The cell death mechanism revealed that Re3 produced an apoptotic cell death response in HeLa cells via ROS generation. Interestingly, Re3 showed slightly better anticancer activity under light exposure compared to ultrasound exposure.


Assuntos
Antineoplásicos , Fenantrolinas , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Ligantes , Células HeLa , Fenantrolinas/química , Fenantrolinas/farmacologia , Rênio/química , Rênio/farmacologia , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/efeitos da radiação , Apoptose/efeitos dos fármacos , Luz , Espécies Reativas de Oxigênio/metabolismo , Terapia por Ultrassom , Fotoquimioterapia , Ensaios de Seleção de Medicamentos Antitumorais , Neoplasias/tratamento farmacológico
2.
Inorg Chem ; 63(16): 7493-7503, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38578920

RESUMO

The relentless increase in drug resistance of platinum-based chemotherapeutics has opened the scope for other new cancer therapies with novel mechanisms of action (MoA). Recently, photocatalytic cancer therapy, an intrusive catalytic treatment, is receiving significant interest due to its multitargeting cell death mechanism with high selectivity. Here, we report the synthesis and characterization of three photoresponsive Ru(II) complexes, viz., [Ru(ph-tpy)(bpy)Cl]PF6 (Ru1), [Ru(ph-tpy)(phen)Cl]PF6 (Ru2), and [Ru(ph-tpy)(aip)Cl]PF6 (Ru3), where, ph-tpy = 4'-phenyl-2,2':6',2″-terpyridine, bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, and aip = 2-(anthracen-9-yl)-1H-imidazo[4,5-f][1,10] phenanthroline, showing photocatalytic anticancer activity. The X-ray crystal structures of Ru1 and Ru2 revealed a distorted octahedral geometry with a RuN5Cl core. The complexes showed an intense absorption band in the 440-600 nm range corresponding to the metal-to-ligand charge transfer (MLCT) that was further used to achieve the green light-induced photocatalytic anticancer effect. The mitochondria-targeting photostable complex Ru3 induced phototoxicity with IC50 and PI values of ca. 0.7 µM and 88, respectively, under white light irradiation and ca. 1.9 µM and 35 under green light irradiation against HeLa cells. The complexes (Ru1-Ru3) showed negligible dark cytotoxicity toward normal splenocytes (IC50s > 50 µM). The cell death mechanistic study revealed that Ru3 induced ROS-mediated apoptosis in HeLa cells via mitochondrial depolarization under white or green light exposure. Interestingly, Ru3 also acted as a highly potent catalyst for NADH photo-oxidation under green light. This NADH photo-oxidation process also contributed to the photocytotoxicity of the complexes. Overall, Ru3 presented multitargeting synergistic type I and type II photochemotherapeutic effects.


Assuntos
Antineoplásicos , Complexos de Coordenação , Luz , Piridinas , Rutênio , Humanos , Rutênio/química , Rutênio/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Piridinas/química , Piridinas/farmacologia , Catálise , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/efeitos da radiação , Ensaios de Seleção de Medicamentos Antitumorais , Processos Fotoquímicos , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Células HeLa , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Luz Verde
3.
Int J Low Extrem Wounds ; : 15347346241246339, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38659348

RESUMO

Chronic wounds have long been a significant public health concern, but the true impact of these wounds is unknown since research designs and measuring techniques vary, leading to inconsistent estimates. The definition of a wound is a loss of epithelial continuity caused by damage to the tissue. The following conditions can cause chronic wounds: panniculitis, pyoderma gangrenosum, traumatic, neurological, metabolic, hematologic, neoplastic, or infection-related. The growing global incidence of diabetes and the aging population necessitate greater attention to chronic wounds. Regrettably, it is sad that significant healthcare institutions have overlooked wound research. The study of health-related illnesses and occurrences in particular populations, including their distribution, frequency, and determinants, and the application of this research to control health problems.

4.
Forensic Sci Med Pathol ; 20(1): 106-116, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37071347

RESUMO

Forensic age assessments are crucial in the evaluation of criminal responsibility and preventing false age claims. Of all the methods available, the Greulich and Pyle (GP) atlas is most commonly used for age estimation purposes. Therefore, the current study sought to analyze the reliability and applicability of the GP standard and, additionally, to determine any possible association between the socioeconomic status (SES), food habits, and estimated skeletal maturity in the North Indian population. The study included 627 (334 males and 293 females) healthy children up to 19 years of age with varying SES and food habits. The skeletal age (SA) was estimated by three different evaluators using the GP atlas. The chronological mean age (CA) and SA were compared in different age cohorts. A paired t-test and a Pearson chi-square test were applied to show the difference between CA and estimated SA and the association of skeletal maturity with SES and food habits. The estimated skeletal age in males was retarded by 0.142 years or 1.72 months (p ≤ 0.05), whereas in females, it was retarded by 0.259 years or 3.12 months (p ≤ 0.05). In males, the GP method has significantly underestimated SA in age cohorts 3-4, 4-5, 6-7, 7-8, 8-9, and 12-13, whereas it overestimated in 10-11 and 18-19 years. However, in females, the SA was significantly underestimated in age groups 10-11, 12-13, and 14-15, respectively. Estimated skeletal maturity had no significant association with SES and food habits. The current study concludes that the GP atlas may not be applicable to North India's population. The observed difference in assessed skeletal maturity may be due to geographical region, genetics, hormonal effects, etc., which require further investigation. Hence, population-specific standards are necessary to determine the bone age of Indian children accurately.


Assuntos
Determinação da Idade pelo Esqueleto , Povo Asiático , Criança , Masculino , Feminino , Humanos , Lactente , Reprodutibilidade dos Testes , Determinação da Idade pelo Esqueleto/métodos
5.
Chembiochem ; 25(2): e202300652, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-37921481

RESUMO

The increase in antibacterial drug resistance is threatening global health conditions. Recently, antibacterial photodynamic therapy (aPDT) has emerged as an effective antibacterial treatment with high cure gain. In this work, three Zn(II) complexes viz., [Zn(en)(acac)Cl] (1), [Zn(bpy)(acac)Cl] (2), [Zn(en)(cur)Cl] (3), where en=ethylenediamine (1 and 3), bpy=2,2'-bipyridine (2), acac=acetylacetonate (1 and 2), cur=curcumin monoanionic (3) were developed as aPDT agents. Complexes 1-3 were synthesized and fully characterized using NMR, HRMS, FTIR, UV-Vis. and fluorescence spectroscopy. The HOMO-LUMO energy gap (Eg), and adiabatic splittings (ΔS1-T1 and ΔS0-T1 ) obtained from DFT calculation indicated the photosensivity of the complexes. These complexes have not shown any potent antibacterial activity under dark conditions but the antibacterial activity of these complexes was significantly enhanced upon light exposure (MIC value up to 0.025 µg/mL) due to their light-mediated 1 O2 generation abilities. The molecular docking study suggested that complexes 1-3 interact efficiently with DNA gyrase B (PDB ID: 4uro). Importantly, 1-3 did not show any toxicity toward normal HEK-293 cells. Overall, in this work, we have demonstrated the promising potential of Zn(II) complexes as effective antibacterial agents under the influence of visible light.


Assuntos
Complexos de Coordenação , Curcumina , Fotoquimioterapia , Humanos , Curcumina/farmacologia , Simulação de Acoplamento Molecular , Complexos de Coordenação/química , Teoria da Densidade Funcional , Células HEK293 , Antibacterianos/farmacologia , Antibacterianos/química , Zinco/química
7.
Dalton Trans ; 52(46): 17562-17572, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-37965840

RESUMO

Herein, five novel polypyridyl-based Co(III) complexes of Schiff bases, viz., [Co(dpa)(L1)]Cl (1), [Co(dpa)(L2)]Cl (2), [Co(L3)(L2)]Cl (3), [Co(L3)(L1)]Cl (4), and [Co(L4)(L1)]Cl (5), where dpa (dipicolylamine) = bis(2-pyridylmethyl)amine; H2L1 = (E)-2-((2-hydroxybenzylidene)amino)phenol; H2L2 = (E)-5-(hydroxymethyl)-4-(((2-hydroxyphenyl)imino)methyl)-2-methylpyridin-3-ol; L3 = 4'-phenyl-2,2':6',2''-terpyridine (ph-tpy); and L4 = 4'-ferrocenyl-2,2':6',2''-terpyridine (Fc-tpy), were synthesized and characterized. Complexes 1, 3, and 4 were structurally characterized by single-crystal XRD, indicating an octahedral CoIIIN4O2 coordination core. The absorption bands of these complexes were observed in the visible range with a λmax at ∼430-485 nm. Complex 5 displayed an extra absorption band near 545 nm because of a ferrocene moiety. These absorptions in the visible region reflect the potential of the complexes to act as visible-light antimicrobial photodynamic therapy (aPDT) agents. All of these complexes showed reactive oxygen species (ROS)-mediated antibacterial effects against S. aureus (Gram-positive) and E. coli (Gram-negative bacteria) upon low-energy visible light (0.5 J cm-2, 400-700 nm) exposure. Additionally, 1-5 did not show any toxicity toward A549 (Human Lung adenocarcinoma) cells, reflecting their selective bacteria-killing abilities.


Assuntos
Complexos de Coordenação , Vitamina B 6 , Humanos , Piridinas/farmacologia , Piridinas/química , Bases de Schiff/farmacologia , Bases de Schiff/química , Staphylococcus aureus , Escherichia coli , Antibacterianos/farmacologia , Vitaminas , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química
8.
Indian J Public Health ; 67(3): 370-375, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37929377

RESUMO

Background: Thyroid dysfunction (TD) is considered a common cause of secondary hypertension (HT). Therefore, correcting TD may help in quicker and sustained achievement of desired blood pressure goals. However, there is a paucity of literature from India which estimates the relationship of HT with TD. Objectives: The objective of the study was to estimate the prevalence of TD with HT and to identify associated factors among Indian population. Materials and Methods: The survey data of the National Family Health Survey 4 (NFHS-4), conducted in India during 2015-2016, were analyzed using R statistical software for estimating the relationship between a history of HT and TD among women (N = 687246) aged 15-49 years and men (N = 108492) aged 15-54 years. Descriptive statistical tests and logistic regression were applied. Results: Among the persons suffering from the TD, the prevalence of HT was 32.8%, which was significantly higher than the prevalence of HT (21.9%) in euthyroid individuals. Further, the prevalence of TD was higher among hypertensive adults (2.5%) compared to nonhypertensive (1.5%). Conclusions: The study reported a higher prevalence of TD among the hypertensive persons and higher prevalence of HT among cases of TD. Therefore, screening for thyroid disorders should be routinely considered for better management of HT.


Assuntos
Hipertensão , Doenças da Glândula Tireoide , Masculino , Adulto , Humanos , Feminino , Prevalência , Índia/epidemiologia , Doenças da Glândula Tireoide/epidemiologia , Doenças da Glândula Tireoide/diagnóstico , Hipertensão/epidemiologia , Fatores de Risco , Inquéritos Epidemiológicos
9.
J Phys Chem B ; 127(48): 10266-10278, 2023 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-37988143

RESUMO

Photodynamic therapy (PDT) has evolved as a new therapeutic modality for cancer treatment with fewer side effects and drug resistance. Curcumin exhibits PDT activity, but its low bioavailability restricts its clinical application. Here, the bioavailability of curcumin was increased by its complex formation with the Zn(II) center. For a structure-activity relationship study, Zn(II)-based complexes (1-3) comprising N^N-based ligands (2,2'-bipyridine in 1 and 2 or 1,10-phenanthroline in 3) and O^O-based ligands (acetylacetone in 1, monoanionic curcumin in 2 and 3) were synthesized and thoroughly characterized. The X-ray structure of the control complex, 1, indicated a square pyramidal shape of the molecules. Photophysical and TD-DFT studies indicated the potential of 2 and 3 as good visible light type-II photosensitizers for PDT. Guided by the TD-DFT studies, the low-energy visible light-triggered singlet oxygen (1O2) generation efficacy of 2 and 3 was explored in solution and in cancer cells. As predicted by the TD-DFT calculations, these complexes produced 1O2 efficiently in the cytosol of MCF-7 cancer cells and ultimately displayed excellent apoptotic anticancer activity in the presence of light. Moreover, the molecular docking investigation showed that complexes 2 and 3 have very good binding affinities with caspase-9 and p-53 proteins and could activate them for cellular apoptosis. Further molecular dynamics simulations confirmed the stability of 3 in the caspase-9 protein binding site.


Assuntos
Antineoplásicos , Complexos de Coordenação , Curcumina , Fotoquimioterapia , Humanos , Curcumina/farmacologia , Teoria da Densidade Funcional , Zinco/química , Caspase 9/metabolismo , Simulação de Acoplamento Molecular , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Complexos de Coordenação/química , Antineoplásicos/química
10.
J Coll Physicians Surg Pak ; 33(10): 1204-1206, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37804032

RESUMO

COVID-19 ARDS (acute respiratory distress syndrome), caused by SARS-CoV-2, involves a decrease in the end expiratory lung volume (EELV), compliance, and hypoxemia. The authors retrospectively analysed the relationship between the EELV, Plateau pressure (Pplat), and compliance of the respiratory system in a group of 21 mechanically ventilated COVID ARDS patients with moderate to severe hypoxia who were subjected to a recruitment manoeuvre. Further, these parameters were studied after dividing them into two groups as Group 1 of clinically non-recruitable and Group 2 of clinically recruitable patients. There was relationship between EELV, compliance, and Pplat among those patients who were clinically recruited versus those who were not in a homogeneous group of COVID ARDS patients. In Group 1, the statistical value of EELV and compliance were r = 0.395, p>0.05, EELV and Pplat were r = 0.021, p>0.05, and compliance and Pplat were r = -0.848, p<0.001. In Group 2, the statistical values of EELV and compliance were (r = 0.605, p<0.001), EELV and Pplat were r = -0.391, p<0.05, compliance and Pplat were r = -0.848, p<0.001. The additional information gained after understanding this relationship can help to optimise ventilator settings. Key Words: COVID, ARDS, End expiratory lung volume, Plateau pressure, Compliance, Recruitment, Ventilation.


Assuntos
COVID-19 , Síndrome do Desconforto Respiratório , Humanos , Respiração com Pressão Positiva , Estudos Retrospectivos , SARS-CoV-2 , Pulmão , Síndrome do Desconforto Respiratório/terapia , Medidas de Volume Pulmonar , Respiração Artificial , Hipóxia
11.
Am J Trop Med Hyg ; 109(6): 1290-1297, 2023 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-37903443

RESUMO

Dengue experienced a rise in disease burden in 2021 in specific regions of India. We aimed to explore the risk factors of dengue occurrence and severity in the post-COVID-19 and post-COVID-19 vaccination era and performed an exploratory analysis involving participants from two prior observational studies conducted from February 2021 to April 2022 in a tertiary hospital in North India. Health care workers constituted the majority of the study participants. Individuals were stratified into five groups based on COVID-19 infection and timing of vaccination: COVID-No Vaccine, Vaccine-No COVID (VNC), COVID After Vaccine (CAV), Vaccine After COVID (VAC), and No Vaccine-No COVID (NVNC) groups. The occurrence of laboratory-confirmed dengue and severe forms of dengue were the main outcomes of interest. A total of 1,701 participants (1,520 vaccinated, 181 unvaccinated) were included. Of these, symptomatic dengue occurred in 133 (7.8%) and was "severe" in 42 (31.6%) cases. Individuals with a history of COVID-19 in 2020 had a 2-times-higher odds of developing symptomatic dengue (P = 0.002). The VAC group had 3.6 (P = 0.019)-, 2 (P = 0.002)-, and 1.9 (P = 0.01)-times-higher odds of developing symptomatic dengue than the NVNC, VNC, and CAV groups, respectively. The severity of dengue was not affected by COVID-19 vaccination but with marginal statistical significance, a 2-times-higher risk of severe dengue was observed with any COVID-19 of the past (P = 0.08). We conclude that COVID-19 may enhance the risk of developing symptomatic dengue. Future research should explore the predisposition of COVID-19-recovered patients toward other viral illnesses. Individuals receiving COVID-19 vaccines after recovering from COVID-19 particularly seem to be at greater risk of symptomatic dengue and need long-term watchfulness. Possible mechanisms, such as antibody-dependent enhancement or T-cell dysfunction, should be investigated in COVID-19-recovered and vaccinated individuals.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Dengue , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Vacinação , Dengue/epidemiologia , Índia/epidemiologia
12.
ChemMedChem ; 18(19): e202300326, 2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37436090

RESUMO

In antimalarial drug development research, overcoming drug resistance has been a major challenge for researchers. Nowadays, several drugs like chloroquine, mefloquine, sulfadoxine, and artemisinin are used to treat malaria. But increment in drug resistance has pushed researchers to find novel drugs to tackle drug resistance problems. The idea of using transition metal complexes with pharmacophores as ligands/ligand pendants to show enhanced antimalarial activity with a novel mechanism of action has gained significant attention recently. The advantages of metal complexes include tunable chemical/physical properties, redox activity, avoiding resistance factors, etc. Several recent reports have successfully demonstrated that the metal complexation of known organic antimalarial drugs can overcome drug resistance by showing enhanced activities than the parent drugs. This review has discussed the fruitful research works done in the past few years falling into this criterion. Based on transition metal series (3d, 4d, or 5d), the antimalarial metal complexes have been divided into three broad categories (3d, 4d, or 5d metal-based), and their activities have been compared with the similar control complexes as well as the parent drugs. Furthermore, we have also commented on the potential issues and their possible solution for translating these metal-based antimalarial complexes into the clinic.


Assuntos
Antimaláricos , Complexos de Coordenação , Malária Falciparum , Malária , Humanos , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Malária/tratamento farmacológico , Cloroquina/farmacologia , Mefloquina/uso terapêutico , Resistência a Medicamentos , Plasmodium falciparum , Malária Falciparum/tratamento farmacológico
13.
Heliyon ; 9(7): e17815, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37455949

RESUMO

Seaweed extracts have shown profoundly positive effects on crop growth, quality and reproduction in diverse agricultural and horticultural crops. Seaweed extracts can be used to promote the rooting and growth of cuttings in perennial fruit species like kiwifruit (Actinidia deliciosa). In this study, the cuttings were treated with 1, 5, 10 and 50% solutions of G Sap (Gracilaria edulis), K Sap (Kappaphycus alvarezii), AN (Ascophyllum nodosum), EM (Ecklonia maxima), HA (Humic acid) and control (water) for 6 h as base dipping. Subsequently, the treatments of G Sap, K Sap, AN, EM, HA and control were repeated every 15 days for a period of six months as application of 50 ml solutions in the potted cuttings. All the treatments exhibited significant effects on the rooting percent in all the kiwifruit cultivars, namely 'Monty', 'Abott', 'Hayward', 'Allison' and 'Bruno' (P ≤ 0.01) as compared to the control. Shoot and root growth parameters including leaf number per cutting, number of roots per cutting, number of branches, plant height, shoot diameter, root length, root diameter and root weight were all positively increased with the application of seaweed extracts (P ≤ 0.05). Cuttings treated with seaweed extract exhibited significantly higher levels of pigments (chlorophyll a, chlorophyll b and total carotenoids), metabolites (total carbohydrates and soluble phenols) and less electrolyte leakage as compared to the control cuttings. Significant positive and negative correlations were observed between biochemical parameters combined with plant nutrient concentration. Principal component analysis (PCA) revealed that PC1 and PC2 (first two principal components) accounted for 75% of the entire variation. While, PC1 accounted for 63% of the total variation, PC2 accounted for 11% of the total variation. The leaves and the roots of kiwifruit cultivar 'Hayward' treated with G Sap at 10%, K Sap at 10%, AN at 10%, EM at 10%, HA at 10% exhibited higher expression of all four root promoting candidate genes (GH3-3, LBD16, LBD29 and LRP1) compared to the control. Therefore, it can be concluded that, seaweed extract and humic acid can be used as a suitable alternative to synthetic hormones for promoting the rooting and growth of kiwifruit cuttings.

14.
J. bras. nefrol ; 45(2): 199-209, June 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1506573

RESUMO

ABSTRACT Introduction: Idiopathic steroid resistant nephrotic syndrome (SRNS) has variable outcomes in children. The primary objective of the present study was to assess the cumulative remission rate and the secondary objectives were to assess factors affecting the remission status, kidney function survival, and adverse effects of medications. Methods: One hundred fourteen patients with SRNS were included. Calcineurin inhibitor-based treatment protocol along with prednisolone and angiotensin-converting enzyme inhibitor were used, and patients were followed over 5 years. Results: Median age was 4.5 years; 53.5% of cases were between 1 to 5 years of age. Sixty-two patients (54.4%) were at initial stage and 52 (45.6%) were at a late SRNS stage. Median eGFRcr was 83.5 mL/min/1.73m2 at presentation. Of the 110 patients, 63 (57.3%) achieved remission [complete remission 30 (27.3%), partial remission 33 (30%)], and 47 (42.7%) had no remission. Kidney function survival was 87.3% and 14 cases (12.7%) had progression to CKD (G3-8, G4-3, G5-1, and G5D-2). Median duration of follow up was 36 months (IQR 24, 60). Age of onset, cyclosporine/tacrolimus, eGFRcr, and histopathology (MCD/FSGS) did not affect remission. Similarly, remission status in addition to age of onset, drug protocol, and histopathology did not significantly affect kidney function during a period of 5 years. Hypertension, cushingoid facies, short stature, cataract, and obesity were observed in 37.7, 29.8, 25.5, 17.5, and 0.7% of cases, respectively. Conclusion: About half of the cases achieved remission. Age of onset of disease, cyclosporine/tacrolimus use, and histopathological lesion neither affected remission status nor short-term kidney function survival in SRNS.


RESUMO Introdução: A síndrome nefrótica idiopática córtico-resistente (SNICR) apresenta desfechos variáveis em crianças. O objetivo principal deste estudo foi avaliar a taxa de remissão cumulativa. Os objetivos secundários foram avaliar fatores que afetam status de remissão, sobrevida da função renal e efeitos adversos de medicamentos. Métodos: Foram incluídos 114 pacientes com SNCR. Utilizou-se protocolo de tratamento baseado em inibidores de calcineurina juntamente com prednisolona e inibidor da enzima conversora de angiotensina. Os pacientes foram acompanhados durante 5 anos. Resultados: A idade mediana foi 4,5 anos; 53,5% dos casos tinham entre 1 e 5 anos. 62 pacientes (54,4%) estavam em estágio inicial; 52 (45,6%) em estágio tardio da SNCR. A TFGecr mediana foi 83,5 mL/min/1,73 m2 na apresentação. Dos 110 pacientes, 63 (57,3%) alcançaram remissão [remissão completa 30 (27,3%), remissão parcial 33 (30%)], e 47 (42,7%) não apresentaram remissão. A sobrevida da função renal foi 87,3%; 14 casos (12,7%) progrediram para DRC (G3-8, G4-3, G5-1, G5D-2). A duração mediana do acompanhamento foi 36 meses (IIQ 24, 60). Idade no início, ciclosporina/tacrolimus, TFGecr e histopatologia (DLM/GESF) não afetaram a remissão. Igualmente, status de remissão, além da idade no início, protocolo de medicamentos e histopatologia não afetaram significativamente a função renal por 5 anos. Observou-se hipertensão, fácies cushingoide, baixa estatura, catarata e obesidade em 37,7; 29,8; 25,5; 17,5; e 0,7% dos casos, respectivamente. Conclusão: Aproximadamente metade dos casos alcançou remissão. Idade no início, uso de ciclosporina/tacrolimus e lesão histopatológica não afetaram o status de remissão nem a sobrevida da função renal a curto prazo na SNICR.

15.
J Clin Endocrinol Metab ; 108(9): e861-e870, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37246587

RESUMO

CONTEXT: Events during gestation greatly influence the risk of cardiometabolic diseases including diabetes in offspring during later life. OBJECTIVE: This study aimed to investigate relationships between serial ultrasound-derived fetal growth trajectories and markers of insulin resistance in young adults in the Raine Study, an Australian pregnancy cohort. METHODS: Linear mixed modeling examined the relationship between fetal growth trajectory groups, constructed using serial ultrasound-based abdominal circumference (AC), femur length (FL), and head circumference (HC) from 1333 mother-fetal pairs, and offspring Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), as a marker of diabetes risk, at 20 (n = 414), 22 (n = 385), and 27 (n = 431) years. Analyses were adjusted for age, sex, ethnicity, socioeconomic status, adult lifestyle factors, and maternal factors during pregnancy. RESULTS: The study identified 7 AC, 5 FL, and 5 HC growth trajectory groups. Compared to the average-stable (reference) group, a low-falling AC growth trajectory (26%; P = .005) and 2 low HC growth trajectories (20%; P = .006% and 8%; P = .021) were associated with higher adult HOMA-IR. Trajectories representing a high-stable FL and a rising HC were associated with 12% (P = .002) and 9% (P = .021) lower adult HOMA-IR, respectively, compared to the reference group. CONCLUSION: Restricted fetal HC and AC from early pregnancy are associated with higher relative insulin resistance in the offspring during adulthood. These data strengthen our understanding of the importance of the intrauterine environment and its effect on the risk of predisposition to adult diabetes and related metabolic disorders.


Assuntos
Resistência à Insulina , Gravidez , Feminino , Humanos , Adulto Jovem , Adulto , Estudos Prospectivos , Austrália/epidemiologia , Desenvolvimento Fetal , Ultrassonografia Pré-Natal
16.
Drug Saf ; 46(6): 553-563, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37133805

RESUMO

INTRODUCTION: Various vaccines for protection against COVID-19 were provided emergency approval in late 2020 to early 2021. There is a scarcity of long-term safety data for many of these. OBJECTIVE: The main aim of this study is to provide the one-year safety results of the ChAdOx1-nCoV-19/AZD1222 vaccine and determine the risk factors of adverse events of special interest (AESIs) and persistent AESIs. METHODS: This was a prospective observational study conducted from February 2021 to April 2022 in a tertiary hospital in North India and its two associated centers. Health care workers, other frontline workers, and the elderly vaccinated with the ChAdOx1-nCoV-19 vaccine constituted the study population. Individuals were contacted telephonically at pre-decided intervals for one year and health issues of significant concern were recorded. Atypical adverse events developing after a booster dose of the COVID-19 vaccine were assessed. Regression analysis was conducted to determine risk factors of AESI occurrence and determinants of AESIs persisting for at least one month at the time of final telephonic contact. RESULTS: Of 1650 individuals enrolled, 1520 could be assessed at one-year post-vaccination. COVID-19 occurred in 44.1% of participants. Dengue occurred in 8% of participants. The majority of the AESIs belonged to the MedDRA® SOC of musculoskeletal disorders (3.7% of 1520). Arthropathy (knee joint involvement) was the most common individual AESI (1.7%). Endocrinal disorders such as thyroid abnormalities and metabolic disorders such as newly diagnosed diabetes developed in 0.4% and 0.3% of individuals, respectively. Regression analysis showed females, individuals with a pre-vaccination history of COVID-19, diabetes, hypothyroidism, and arthropathy had 1.78-, 1.55-, 1.82-, 2.47- and 3.9-times higher odds of AESI development. Females and individuals with hypothyroidism were at 1.66- and 2.23-times higher risk of persistent AESIs. Individuals receiving the vaccine after COVID-19 were at 2.85- and 1.94 times higher risk of persistent AESIs compared, respectively, to individuals with no history of COVID-19 and individuals developing COVID-19 after the vaccine. Among participants receiving a booster dose of the COVID-19 vaccine (n = 185), 9.7% developed atypical adverse events of which urticaria and new-onset arthropathy were common. CONCLUSION: Nearly half of the ChAdOx1-nCoV-19 vaccine recipients developed COVID-19 over one year. Vigilance is warranted for AESIs such as musculoskeletal disorders. Females, individuals with hypothyroidism, diabetes, and pre-vaccination history of COVID-19 are at higher risk of adverse events. Vaccines received after natural SARS-CoV-2 infection may increase the risk of persistence of adverse events. Sex and endocrinal differences and timing of the COVID-19 vaccine with respect to natural infection should be explored as determinants of AESIs in the future. Pathogenetic mechanisms of vaccine-related adverse events should be investigated along with comparisons with an unvaccinated arm to delineate the overall safety profile of COVID-19 vaccines.


Assuntos
COVID-19 , Hipotireoidismo , Doenças Musculoesqueléticas , Idoso , Feminino , Humanos , ChAdOx1 nCoV-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Índia/epidemiologia , SARS-CoV-2 , Vacinação/efeitos adversos
18.
Nanoscale ; 15(10): 4682-4693, 2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36779637

RESUMO

Silicon photonics is rapidly evolving as an advanced chip framework for implementing quantum technologies. With the help of silicon photonics, general-purpose programmable networks with hundreds of discrete components have been developed. These networks can compute quantum states generated on-chip as well as more extraordinary functions like quantum transmission and random number generation. In particular, the interfacing of silicon photonics with complementary metal oxide semiconductor (CMOS) microelectronics enables us to build miniaturized quantum devices for next-generation sensing, communication, and generating randomness for assembling quantum computers. In this review, we assess the significance of silicon photonics and its interfacing with microelectronics for achieving the technology milestones in the next generation of quantum computers and quantum communication. To this end, especially, we have provided an overview of the mechanism of a homodyne detector and the latest state-of-the-art of measuring squeezed light along with its integration on a photonic chip. Finally, we present an outlook on future studies that are considered beneficial for the wide implementation of silicon photonics for distinct data-driven applications with maximum throughput.

19.
Chembiochem ; 24(10): e202300033, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-36763497

RESUMO

Four new CoII complexes, [Co(bpy)2 (acac)]Cl (1), [Co(phen)2 (acac)]Cl (2), [Co(bpy)2 (cur)]Cl (3), [Co(phen)2 (cur)]Cl (4), where bpy=2,2'-bipyridine (1 and 3), phen=1,10-phenanthroline (2 and 4), acac=acetylacetonate (1 and 2), cur=curcumin monoanion (3 and 4) have been designed, synthesized and fully characterized. The X-ray crystal structures of 1 and 2 indicated that the CoN4 O2 core has a distorted octahedral geometry. The photoactivity of these complexes was tuned by varying the π conjugation in the ligands. Curcumin complexes 3 and 4 had an intense absorption band near 435 nm, which made them useful as visible-light photodynamic therapy agents; they also showed fluorescence with λem ≈565 nm. This fluorescence was useful for studying their intracellular uptake and localization in MCF-7 breast cancer cells. The acetylacetonate complexes (1 and 2) were used as control complexes to understand the role of curcumin. The white-light-triggered anticancer profiles of the cytosol targeting complexes 3 and 4 were investigated in detail. These non-dark toxic complexes displayed significant apoptotic photo-cytotoxicity (under visible light) against MCF-7 cells through ROS generation. The control complexes 1 and 2 did not induce significant cell death in the light or dark. Interestingly, 1-4 produced a remarkable antibacterial response upon light exposure. Overall, the reported results here can increase the boundary of the CoII -based anticancer and antibacterial drug development.


Assuntos
Antineoplásicos , Complexos de Coordenação , Curcumina , Fotoquimioterapia , Humanos , Curcumina/farmacologia , Curcumina/química , Hidroxibutiratos , Pentanonas , Antineoplásicos/farmacologia , Antineoplásicos/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Antibacterianos/farmacologia
20.
J Mater Chem B ; 11(9): 1958-1970, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36751878

RESUMO

The aim of the present study was to design a unique bioelectrode for the quantitative analysis of a potential cancer biomarker, platelet-derived growth factor-BB (PDGF-BB), which can be used for the early detection of cancer. We report the fabrication of succinic acid-capped selenomolybdate polyoxometalate nanodots, POM (SA), decorated antimonene hybrid film on glassy carbon as a suitable bioelectrode. Antimonene nanosheets, synthesized by the chemical exfoliation of antimony provided a large surface area for the symmetric dispersal of POM (SA) nanodots, resulting in site-specific covalent immobilization of the aptamer, PDGF-BB. A comprehensive electrochemical immunosensing investigation was performed on the electrode for sensing of a target antigen, Ag-PDGF-BB. The sensitivity, selectivity, and reproducibility of the bioelectrode were investigated using a best-fit equivalent circuit model that fitted the impedance response. The bioelectrode showed a linear impedimetric response in a broad range for Ag-PDGF-BB (10 pM to 100 nM in pH 7.4 PB) with a limit of detection of 3.5 pM and sensitivity of 80 Ω cm2 per decade. The response sensitivity of the POM(SA)/antimonene hybrid based bioelectrode toward PDGF-BB was approximately ∼1.8-fold higher than that of the POM(SA) only modified bioelectrode. The dissociation constant of immunoreaction between the aptamer-functionalized bioelectrode and target Ag-PDGF-BB was 76 nM, indicating a high binding affinity between the aptamer PDGF-BB and target Ag-PDGF-BB on the electrode surface.


Assuntos
Aptâmeros de Nucleotídeos , Becaplermina , Proteínas Proto-Oncogênicas c-sis/análise , Reprodutibilidade dos Testes , Impedância Elétrica
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