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1.
J Mol Model ; 30(8): 250, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967840

RESUMO

CONTEXT: Carbon monoxide, also known as the "silent killer," is a colorless, odorless, tasteless, and non-irritable gas that, when inhaled, enters the bloodstream and lungs, binds with the hemoglobin, and blocks oxygen from reaching tissues and cells. In this work, the monolayer MoSe2-based CO gas sensors were designed using density functional theory calculation with several dopants including Al, Au, Pd, Ni, Cu, and P. Here, Cu and P were found to be the best dopants, with adsorption energies of -0.67 eV (Cu) and -0.54 eV (P) and recovery times of 1.66 s and 13.8 ms respectively. Cu conductivity for CO adsorption was found to be 2.74 times that of CO2 adsorption in the 1.0-2.26 eV range. P displayed the highest selectivity, followed by Pd and Ni. The dopants, Pd and Ni, were found suitable for building CO gas scavengers due to their high recovery times of 9.76 × 1020 s and 2.47 × 1011 s. Similarly, the adsorption of CO2 on doped monolayer MoSe2 was also investigated. In this study, it is found that monolayer MoSe2 could be employed to create high-performance CO sensors in a CO2-rich environment. METHOD: The electrical characteristics of all doped MoSe2 monolayers are obtained using a DFT calculation with the PBE-GGA method from the Quantum ESPRESSO package. The self-consistent field (SCF) computations were performed using a 7 × 7 × 1 k-point grid and a norm-conserving pseudo potential (NCPP) file. To determine electrical conductivity, the semi-classical version of Boltzmann transport theory, implemented in the Boltz Trap code, was used.

2.
Langmuir ; 40(23): 12226-12238, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38814099

RESUMO

We have red-shifted the light absorbance property of a Re(I)-tricarbonyl complex via distant conjugation of a ferrocene moiety and developed a novel complex ReFctp, [Re(Fctp)(CO)3Cl], where Fctp = 4'-ferrocenyl-2,2':6',2″-terpyridine. ReFctp showed green to red light absorption ability and blue emission, indicating its potential for photodynamic therapy (PDT) application. The conjugation of ferrocene introduced ferrocene-based transitions, which lie at a higher wavelength within the PDT therapeutic window. The time-dependent density functional theory and excited state calculations revealed an efficient intersystem crossing for ReFctp, which is helpful for PDT. ReFctp elicited both PDT type I and type II pathways for reactive oxygen species (ROS) generation and facilitated NADH (1,4-dihydro-nicotinamide adenine dinucleotide) oxidation upon exposure to visible light. Importantly, ReFctp showed effective penetration through the layers of clinically relevant 3D multicellular tumor spheroids and localized primarily in mitochondria (Pearson's correlation coefficient, PCC = 0.65) of A549 cancer cells. ReFctp produced more than 20 times higher phototoxicity (IC50 ∼1.5 µM) by inducing ROS generation and altering mitochondrial membrane potential in A549 cancer cells than the nonferrocene analogue Retp, [Re(CO)3(tp)Cl], where tp = 2,2':6',2″-terpyridine. ReFctp induced apoptotic mode of cell death with a notable photocytotoxicity index (PI, PI = IC50dark/IC50light) and selectivity index (SI, SI = normal cell's IC50dark/cancer cell's IC50light) in the range of 25-33.


Assuntos
Antineoplásicos , Compostos Ferrosos , Luz , Metalocenos , Compostos Ferrosos/química , Compostos Ferrosos/farmacologia , Humanos , Metalocenos/química , Metalocenos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/efeitos da radiação , Antineoplásicos/síntese química , Espécies Reativas de Oxigênio/metabolismo , Teoria da Densidade Funcional , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/efeitos da radiação , Complexos de Coordenação/síntese química , Linhagem Celular Tumoral , Ensaios de Seleção de Medicamentos Antitumorais , Luz Vermelha
3.
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 , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Catálise , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Luz Verde , Células HeLa , Estrutura Molecular , Processos Fotoquímicos , Piridinas/química , Piridinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Rutênio/química , Rutênio/farmacologia
4.
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
5.
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.

6.
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
7.
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
8.
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.

9.
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.

10.
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
11.
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
12.
J Org Chem ; 88(1): 626-631, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36522290

RESUMO

Recently, interest has been given to developing photocatalytic anticancer drugs. This area of research is dominated by metal complexes. Here, we report the potential of lysosome/mitochondria targeting cyanine appended bipyridine compounds as the organic photocatalytic anticancer agents. The organocatalyst (bpyPCN) not only exhibits light-induced NADH oxidation but also generates intracellular ROS to demonstrate anticancer activity. This is the first example of organic compound induced catalytic NADH photo-oxidation in an aqueous solution and in cancer cells.


Assuntos
Antineoplásicos , Complexos de Coordenação , Neoplasias , 2,2'-Dipiridil/farmacologia , Oxirredução , NAD , Antineoplásicos/farmacologia
13.
Chembiochem ; 24(6): e202200597, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36385722

RESUMO

Sonodynamic therapy (SDT) for cancer treatment is gaining attention owing to its non-invasive property and ultrasound's (US) deep tissue penetration ability. In SDT, US activates the sonosensitizer at the target deep-seated tumors to generate reactive oxygen species (ROS), which ultimately damage tumors. However, drawbacks such as insufficient ROS production, aggregation of sonosensitizer, off-target side effects, etc., of the current organic/nanomaterial-based sonosensitizers limit the effectiveness of cancer SDT. Very recently, metal complexes with tunable physiochemical properties (such as sonostability, HOMO to LUMO energy gap, ROS generation ability, aqueous solubility, emission, etc.) have been devised as effective sonosensitizers, which could overcome the limitations of organic/nanomaterial-based sonosensitizers. This concept introduces all the reported metal-based sonosensitizers and delineates the prospects of metal complexes in cancer sonodynamic therapy. This new concept of metal-based sonosensitizer can deliver next-generation cancer drugs.


Assuntos
Antineoplásicos , Complexos de Coordenação , Neoplasias , Terapia por Ultrassom , Humanos , Espécies Reativas de Oxigênio , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral
14.
Am J Trop Med Hyg ; 107(4): 850-855, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-35940202

RESUMO

The current analysis is a part of an ongoing observational study that began in February 2021 in the Sir Sunder Lal Hospital (Varanasi, Uttar Pradesh) in northern India and is expected to continue until June 2022. This analysis aimed to delineate the clinical presentation and risk factors of occurrence and severity of COVID-19 in vaccinated individuals. The study enrolled health-care workers and the elderly receiving the COVID-19 vaccine at one of three centers linked to the study hospital. The participants received the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vaccine based on the chimpanzee adenovirus platform (manufactured in India by the Serum Institute of India). The adenovirus codes for the spike (S) protein of SARS-CoV-2. Participants were contacted by phone at pre-decided intervals and questioned about the occurrence of COVID-19, clinical presentation, severity, and persistence of symptoms. A logistic regression analysis was performed to predict the risk factors of occurrence and severity of COVID-19. Of the 1,500 participants included in the analysis, 418 developed COVID-19 (27.9%). Fever was the most common symptom (72%), followed by cough (34%) and rhinitis (26%). Cardiovascular involvement was seen in more than 2% of individuals, and 11% had post-COVID-19 complaints. Regression analysis showed 1.6 times greater odds of contracting the disease in females and in those younger than 40 years, 1.4 times greater odds in individuals who were overweight, and 2.9 times greater odds in those receiving only one dose, compared with respective comparators. Individuals receiving two doses at a gap of ≤ 30 days had 6.7 times greater odds of infection than those receiving at a > 60-day interval. There was no association between COVID-19 occurrence in the vaccinees and pre-vaccination history of SARS-CoV-2 infection. Males were at a 3.6 times greater risk, and persons with preexisting lung disease-mainly asthma-had a 5.9 times greater risk of experiencing moderate to severe COVID-19 than comparators. While an extended interval between the two vaccine doses seems to be a better strategy, gender differences and an association of asthma phenotypes with COVID-19 need to be explored.


Assuntos
Asma , COVID-19 , COVID-19/epidemiologia , Vacinas contra COVID-19 , ChAdOx1 nCoV-19 , Feminino , Humanos , Masculino , SARS-CoV-2 , Vacinação
15.
Chembiochem ; 23(15): e202200201, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35438233

RESUMO

Immunotherapy has made great progress in clinical cancer treatment in recent years, but its therapeutic efficacy is significantly limited by the lack of immunogenicity in the tumor microenvironment. Pyroptosis is a type of programmed cell death in which the dying cancer cells produce inflammatory cytokines to relieve the immuno-suppressive microenvironment and thus increase anti-tumor immunity. Reactive oxygen species (ROS) produced during photodynamic therapy (PDT) are one of the efficient activators that induce pyroptosis. Recently, a few photosensitizers have emerged with the ability to induce immunogenic cancer cell death via pyroptosis, opening a new field for PDT. This highlight introduces the latest research on antitumor strategies achieved by the combination of immunotherapy and photodynamic therapy through photo-pyroptosis.


Assuntos
Neoplasias , Fotoquimioterapia , Linhagem Celular Tumoral , Humanos , Imunoterapia , Neoplasias/tratamento farmacológico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Piroptose , Microambiente Tumoral
16.
Chem Commun (Camb) ; 58(31): 4825-4836, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35348152

RESUMO

The recent dramatic enhancement in cancer-related mortality and the drawbacks (side effects and resistance) of Pt-based first-generation chemotherapeutics have escalated the need for new cancer medicines with unique anticancer activities for better human life. To overcome the demerits of Pt-based cancer drugs, the concept of catalytic anticancer agents has recently been presented in the field of anticancer metallodrug development research. Many intracellular transformations in cancer cells are catalyzed by metal complexes, including pyruvate reduction to lactate, NAD(P)+ reduction to NAD(P)H and vice versa, and the conversion of 3O2 to reactive oxygen species (ROS). These artificial in-cell changes with non-toxic and catalytic dosages of metal complexes have been shown to disrupt several essential intracellular processes which ultimately cause cell death. This new approach could develop potent next-generation catalytic anticancer drugs. In this context, recently, several 16/18 electron Os(II)-based complexes have shown promising catalytic anticancer activities with unique anticancer mechanisms. Herein, we have delineated the catalytic anticancer activity of Os(II) complexes from a critical viewpoint. These catalysts are reported to induce the in-cell catalytic transfer hydrogenation of pyruvate and important quinones to create metabolic disorder and photocatalytic ROS generation for oxidative stress generation in cancer cells. Overall, these Os(II) catalysts have the potential to be novel catalytic cancer drugs with new anticancer mechanisms.


Assuntos
Antineoplásicos , Complexos de Coordenação , Antineoplásicos/farmacologia , Catálise , Complexos de Coordenação/farmacologia , Humanos , NAD , Ácido Pirúvico , Espécies Reativas de Oxigênio
17.
Chemosphere ; 293: 133459, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34995629

RESUMO

Citrus fruits are extensively cultivated, consumed and major processed horticulture crops around the globe. High processing and consumption generate huge quantities of solid organic wastes. Citrus waste represents approximately 40-50% of total fruit weight, which consists of rag (membranes and cores), pulp, seeds, and peel (albedo and flavedo), which are a potential source of value-added products including essential oils, carotenoids, pectin, dietary fibers, and polyphenols biofuel, etc. However, waste produced is discarded as waste in the environment, which causes a serious threat due to the presence of bioactive compounds. Recent research strategies on the integrated biorefinery approach explore various ways to utilize the waste obtained from the citrus wastes for their subsequent recovery of value-added products. Moreover, the citrus waste can be turned into various bio-products, viz., enzymes, biofuels, and biopolymers using the integrated biorefinery approach, which can optimize the development of green waste for sustainability and economic benefits. Given the sustainable solution for resource recovery and environmental management, the article reviews the latest advances in the novel valorization approach and valuation of the existing state-of-the-art green technologies for citrus waste utilization to bring a sustainable solution for increasing demand for food, fuel, and energy security. To achieve the zero-waste approach and industrial viability, more efforts should be given to scale-up green recovery techniques along with diverse product profiling.


Assuntos
Citrus , Gerenciamento de Resíduos , Biocombustíveis , Conservação dos Recursos Naturais , Frutas/química , Polifenóis/análise
18.
Int J Clin Pediatr Dent ; 15(2): 215-217, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37457208

RESUMO

Eruption cyst or eruption hematoma is a soft tissue cyst of odontogenic origin that occurs in mucosa, which forms shortly before the eruption of the primary or permanent tooth. It is usually found in children. In some cases, it has been seen that it disappears on its own. If there are complications like pain, bleeding or infection, surgical exposure and drainage are necessary. This case is associated with erupting permanent tooth, and its surgical crown exposure has been done by using a diode laser. How to cite this article: Bansal MB, Kumari A, Asrani KH, et al. Eruption Cyst Treated with Diode Laser: A Case Report. Int J Clin Pediatr Dent 2022;15(2):215-217.

19.
ChemMedChem ; 17(2): e202100615, 2022 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-34878223

RESUMO

In recent years, to overcome the problem of low tissue penetration power of light in photodynamic therapy (PDT), sonodynamic therapy (SDT) with ultrasound (US) as the drug stimulus has emerged as a potential alternative to PDT. The significantly higher tissue penetration capacity of US is reported to allow the treatment of deep-seated tumours. In general, organic molecules and nanomaterials dominate as the sonosensitizers in this area of research, and the potential of metal complexes in SDT is not yet well explored. In this highlight, we have summarized two recent literature reports in which researchers have explored the efficiency of metal complexes as sonosensitizers for the first time. These reports indicate the high potential of metal complexes in SDT.


Assuntos
Antineoplásicos/uso terapêutico , Complexos de Coordenação/uso terapêutico , Neoplasias/tratamento farmacológico , Terapia por Ultrassom , Antineoplásicos/química , Complexos de Coordenação/química , Humanos , Estrutura Molecular , Nanopartículas/química
20.
Nature ; 599(7886): 628-634, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34662886

RESUMO

A major goal in human genetics is to use natural variation to understand the phenotypic consequences of altering each protein-coding gene in the genome. Here we used exome sequencing1 to explore protein-altering variants and their consequences in 454,787 participants in the UK Biobank study2. We identified 12 million coding variants, including around 1 million loss-of-function and around 1.8 million deleterious missense variants. When these were tested for association with 3,994 health-related traits, we found 564 genes with trait associations at P ≤ 2.18 × 10-11. Rare variant associations were enriched in loci from genome-wide association studies (GWAS), but most (91%) were independent of common variant signals. We discovered several risk-increasing associations with traits related to liver disease, eye disease and cancer, among others, as well as risk-lowering associations for hypertension (SLC9A3R2), diabetes (MAP3K15, FAM234A) and asthma (SLC27A3). Six genes were associated with brain imaging phenotypes, including two involved in neural development (GBE1, PLD1). Of the signals available and powered for replication in an independent cohort, 81% were confirmed; furthermore, association signals were generally consistent across individuals of European, Asian and African ancestry. We illustrate the ability of exome sequencing to identify gene-trait associations, elucidate gene function and pinpoint effector genes that underlie GWAS signals at scale.


Assuntos
Bancos de Espécimes Biológicos , Bases de Dados Genéticas , Sequenciamento do Exoma , Exoma/genética , África/etnologia , Ásia/etnologia , Asma/genética , Diabetes Mellitus/genética , Europa (Continente)/etnologia , Oftalmopatias/genética , Feminino , Predisposição Genética para Doença/genética , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Hipertensão/genética , Hepatopatias/genética , Masculino , Mutação , Neoplasias/genética , Característica Quantitativa Herdável , Reino Unido
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