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1.
Dig Liver Dis ; 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38556409

RESUMO

BACKGROUND: Long-intergenic non-protein coding gene 01140 (LINC01140) a long non-coding RNA is highly expressed in various cancers. However, its biological functions in gastric cancer progression is still unknown. METHOD: To elucidate LINC01140 function, 70 GC tumor samples and 30 normal gastric tissues were collected. LINC01140 expression level were determined by qRT-PCR analysis and correlated with different clinico-pathological parameters. Then we tried to see the impact of LINC01140 on gastric cell line aggressiveness by knocking down the target gene and performing cell viability assay, migration assay and invasive capacity of the cell lines along with immunoblotting to check several protein levels. RESULT: LINC01140 RNA is found to be positively correlated with FGF9 and significantly up regulated in GC tissues. LINC01140 knockdown inhibited the viability, migratory capacity and invasive capacity of AGS cells. LINC01140 targets miR-140-5p, while miR-140-5p targeted FGF9 to form lncRNA-miRNA-mRNA axis. The affect of miR-140-5p inhibition on gastric cancer cell aggressiveness were opposite to those of LINC01140 or FGF9 knockdown. Additionally, inhibition partially reversed the effects of LINC01140 knockdown on FGF9 protein levels, gastric cancer cell phenotypes. CONCLUSION: LINC01140, miR-140-5p and FGF9 form a lncRNA-miRNA-mRNA axis that modulates the gastric cancer phenotypes and in turn affects gastric cancer cell aggressiveness.

2.
Cureus ; 16(1): e52891, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38406012

RESUMO

This analysis critically examines the profit-driven marketing of digestive enzymes as over-the-counter (OTC) supplements in the context of India, expressing ethical concerns regarding pharmaceutical companies prioritizing financial gain over genuine public health needs within the lucrative OTC supplement market. The review delves into various enzymes, their mechanisms of action, uses, adverse drug reactions, and provides evidence from various studies. The research method involves the exploration of profit-driven strategies employed by pharmaceutical companies, addressing regulatory challenges, investigating the gap between dietary supplements and pharmaceutical drugs, and emphasizing the impact of direct-to-consumer advertising on self-diagnosis and overuse. Additionally, the study reviews various e-pharmacy platforms in India, assessing formulations and pricing. Key findings highlight the diverse formulations on these platforms, exposing insights into cost variations and indicating a regulatory gap that necessitates a comprehensive re-evaluation by Indian and international authorities. The analysis emphasizes the influence of direct-to-consumer advertising on behavior and potential health risks, raising ethical concerns about oversimplified health claims that overlook the necessity for individualized treatment plans. In conclusion, the study underscores the ethical complexity of prioritizing profit over public health and advocates for regulatory re-evaluation, exploring broader implications such as cultural influences and alternative therapies. The evolving landscape, featuring plant-based and microbe-derived alternatives, is presented as transformative, particularly in conditions like celiac disease.

3.
Biomater Sci ; 12(6): 1502-1514, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38284150

RESUMO

Bacteria migration at catheter insertion sites presents a serious complication (bacteraemia) with high mortality rates. One strategy to mediate bacteraemia is a physical barrier at the skin-catheter interface. Herein a colorimetric biosensor adhesive (CathoGlu) is designed and evaluated for both colorimetric detection of bacterial infection and application as a bacteria barrier. The design intent combines viscous, hydrophobic bioadhesive with an organic pH indicator (bromothymol blue). Visual observation can then distinguish healthy skin at pH = ∼5 from an infected catheter insertion site at pH = ∼8. The liquid-to-biorubber transition of CathoGlu formulation occurs via a brief exposure to UVA penlight, providing an elastic barrier to the skin flora. Leachates from CathoGlu demonstrate no genotoxic and skin sensitization effect, assessed by OECD-recommended in vitro and in chemico assays. The CathoGlu formulation was found non-inferior against clinically approved 2-octyl-cyanoacrylate (Dermabond™), and adhesive tape (Micropore™) within an in vivo porcine model. CathoGlu skin adhesive provides new opportunities to prevent sepsis in challenging clinical situations.


Assuntos
Bacteriemia , Cateterismo Periférico , Suínos , Animais , Cateteres de Demora , Pele
4.
NanoImpact ; 31: 100471, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37315844

RESUMO

Graphenic materials have excited the scientific community due to their exciting mechanical, thermal, and optoelectronic properties for a potential range of applications. Graphene and graphene derivatives have demonstrated application in areas stretching from composites to medicine; however, the environmental and health impacts of these materials have not been sufficiently characterized. Graphene oxide (GO) is one of the most widely used graphenic derivatives due to a relatively easy and scalable synthesis, and the ability to tailor the oxygen containing functional groups through further chemical modification. In this paper, ecological and health impacts of fresh and ultrasonically altered functional graphenic materials (FGMs) were investigated. Model organisms, specifically Escherichia coli, Bacillus subtilis, and Caenorhabditis elegans, were used to assess the consequences of environmental exposure to fresh and ultrasonically altered FGMs. FGMs were selected to evaluate the environmental effects of aggregation state, degree of oxidation, charge, and ultrasonication. The major findings indicate that bacterial cell viability, nematode fertility, and nematode movement were largely unaffected, suggesting that a wide variety of FGMs may not pose significant health and environmental risks.


Assuntos
Grafite , Animais , Grafite/toxicidade , Oxirredução , Caenorhabditis elegans , Exposição Ambiental , Escherichia coli
5.
Biomater Adv ; 144: 213174, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36428212

RESUMO

The wet environment in the oral cavity is challenging for topical disease management approaches. The compromised material properties leading to weak adhesion and short retention (<8 h) in such environment result in frequent reapplication of the therapeutics. Composites of bacterial cellulose (BC) and carbene-based bioadhesives attempt to address these shortcomings. Previous designs comprised of aqueous formulations. The current design, for the first time, presents dry, shelf-stable cellulose patches for convenient ready-to-use application. The dry patches simultaneously remove tissue surface hydration while retaining carbene-based photocuring and offers on-demand adhesion. The dry patch prototypes are optimized by controlling BC/adhesive mole ratios and dehydration technique. The adhesion strength is higher than commercial denture adhesives on soft mucosal tissues. The structural integrity is maintained for a minimum of 7 days in aqueous environment. The patches act as selective nanoporous barrier against bacteria while allowing permeation of proteins. The results support the application of BC-based adhesive patches as a flexible platform for wound dressings, drug depots, or combination thereof.


Assuntos
Adesivos , Celulose , Adesivos/química , Bactérias/química , Mucosa
6.
Med J Armed Forces India ; 78(Suppl 1): S55-S60, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36147418

RESUMO

Background: The dimensional accuracy of elastomeric impression materials has been evaluated by different methods but their reliability is still questionable. The aim of this study was to evaluate the dimensional accuracy of elastomeric impression material using 3D laser scanner. Method: In the present study, a metal die with its custom tray were designed. Using this die and tray, 10 impressions each were made from addition silicone (Aquasil LV; Dentsply), condensation silicone (Speedex coltene, Whaledent) and polyether (3M; ESPE). All the impressions were poured with Type IV die stone and total of 30 die replicas were obtained. These were scanned with a Picza 3D laser scanner (LPX 600, Roland,California) and the difference between the stone model was calculated by determining its volumetric changes using CAD-CAM pero version 2.0. One way analysis of variance (ANOVA) was used to compare the groups, whereas significance of mean difference between the groups was done by Tukey HSD. Results: All the three groups showed mean decrease indicating a dimensional shrinkage from the master die. Mean percentage dimensional change in condensation silicone was maximum (-319.02 ±15.50) followed by polyether (-122.59 ± 0.64) and least in addition silicone (-23.83 ± 0.43). All the results were statistically significant (p<0.001). Conclusion: Picza 3D laser scanner can precisely measure the volumetric changes in all the three elastomeric impression materials.

7.
RSC Adv ; 12(29): 18945-18972, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35873336

RESUMO

For the last couple of decades, azabenzene-based ligands have drawn much attention from inorganic chemists due to their ability to coordinate with different metal ions to form supramolecular clusters. These azabenzenes are weak σ donors and strong π acceptors and electron-deficient. Metallogrid complexes and non-grid oligomers are well-defined supramolecular clusters, formed by appropriate chelating ligands, and can show interesting optical, magnetic, and electronic properties. Self-assembly of [n × n] metallogrid complexes is dominated by the entropic factor while the formation of oligonuclear metal ion complexes is dominated by other effects like CFSE, electrostatic factors, ligand conformational characters, etc. Herein, the present article gives an overview of six-membered heterocyclic azine-based ligands and their potential for different metal ions to form polynuclear complexes. Moreover, their temperature-dependent magnetic properties and SCO phenomena are well described and tabulated.

8.
J Biol Chem ; 298(8): 102208, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35772496

RESUMO

Antibiotic resistance via epigenetic methylation of ribosomal RNA is one of the most prevalent strategies adopted by multidrug resistant pathogens. The erythromycin-resistance methyltransferase (Erm) methylates rRNA at the conserved A2058 position and imparts resistance to macrolides such as erythromycin. However, the precise mechanism adopted by Erm methyltransferases for locating the target base within a complicated rRNA scaffold remains unclear. Here, we show that a conserved RNA architecture, including specific bulge sites, present more than 15 Å from the reaction center, is key to methylation at the pathogenic site. Using a set of RNA sequences site-specifically labeled by fluorescent nucleotide surrogates, we show that base flipping is a prerequisite for effective methylation and that distal bases assist in the recognition and flipping at the reaction center. The Erm-RNA complex model revealed that intrinsically flipped-out bases in the RNA serve as a putative anchor point for the Erm. Molecular dynamic simulation studies demonstrated the RNA undergoes a substantial change in conformation to facilitate an effective protein-rRNA handshake. This study highlights the importance of unique architectural features exploited by RNA to impart fidelity to RNA methyltransferases via enabling allosteric crosstalk. Moreover, the distal trigger sites identified here serve as attractive hotspots for the development of combination drug therapy aimed at reversing resistance.


Assuntos
Metiltransferases , RNA Ribossômico , Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Resistência Microbiana a Medicamentos/genética , Eritromicina/farmacologia , Metiltransferases/metabolismo , RNA , RNA Ribossômico/genética , RNA Ribossômico/metabolismo
9.
ACS Chem Biol ; 17(4): 829-839, 2022 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-35316014

RESUMO

Methylation of specific nucleotides is integral for ribosomal biogenesis and also serves as a common mechanism to confer antibiotic resistance by pathogenic bacteria. Here, by determining the high-resolution structure of the 30S-KsgA complex by cryo-electron microscopy, a state was captured, where KsgA juxtaposes between helices h44 and h45 of the 30S ribosome, separating them, thereby enabling remodeling of the surrounded rRNA and allowing the cognate site to enter the methylation pocket. With the structure as a guide, several mutant versions of the ribosomes, where interacting bases in the catalytic helix h45 and surrounding helices h44, h24, and h27, were mutated and evaluated for their methylation efficiency revealing factors that direct the enzyme to its cognate site with high fidelity. The biochemical studies show that the three-dimensional environment of the ribosome enables the interaction of select loop regions in KsgA with the ribosome helices paramount to maintain selectivity.


Assuntos
Metiltransferases , RNA , Microscopia Crioeletrônica , Escherichia coli/genética , Metiltransferases/química , RNA/análise , RNA Ribossômico , RNA Ribossômico 16S/química , Ribossomos/química
10.
J Mater Chem B ; 10(14): 2570-2583, 2022 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-34981107

RESUMO

Topical treatments for oral wounds and infections exhibit weak adhesion to wet surfaces which results in short retention duration (6-8 hours), frequent dosing requirement and patient incompatibility. To address these limitations, aqueous composites made of fibrillated bacterial cellulose and photoactive bioadhesives are designed for soft epithelial surfaces. The aqueous composites crosslink upon photocuring within a minute and exhibit a transition from viscous to elastic adhesive hydrogels. The light-cured composites have shear moduli mimicking oral mucosa and other soft tissues. The tunable adhesion strength ranges from 3 to 35 kPa on hydrated tissue-mimicking surfaces (collagen film). The results support the application of bacterial cellulose hydrogel systems for potential treatment of mucosal wounds.


Assuntos
Celulose , Metano , Humanos , Hidrogéis , Metano/análogos & derivados , Boca
11.
Carbohydr Polym ; 274: 118403, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34702445

RESUMO

Topical approaches to oral diseases require frequent dosing due to limited retention time. A mucoadhesive drug delivery platform with extended soft tissue adhesion capability of up to 7 days is proposed for on-site management of oral wound. Bacterial cellulose (BC) and photoactivated carbene-based bioadhesives (PDz) are combined to yield flexible film platform for interfacing soft tissues in dynamic, wet environments. Structure-activity relationships evaluate UV dose and hydration state with respect to adhesive strength on soft tissue mimics. The bioadhesive composite has an adhesion strength ranging from 7 to 17 kPa and duration exceeding 48 h in wet conditions under sustained shear forces, while other mucoadhesives based on hydrophilic macromolecules exhibit adhesion strength of 0.5-5 kPa and last only a few hours. The work highlights the first evaluation of BC composites for mucoadhesive treatments in the buccal cavity.


Assuntos
Adesivos/química , Celulose/química , Sistemas de Liberação de Medicamentos/métodos , Boca , Acetobacteraceae/metabolismo , Boca/química , Boca/microbiologia , Preparações Farmacêuticas Odontológicas/administração & dosagem
12.
ACS Appl Mater Interfaces ; 13(31): 36839-36848, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34342218

RESUMO

Carbene-based macromolecules are an emerging new stimuli-sensitive class of biomaterials that avoid the impediments of free radical polymerization but maintain a rapid liquid-to-biorubber transition. Activation of diazirine-grafted polycaprolactone polyol (CaproGlu) is limited to UVA wavelengths that have tissue exposure constraints and limited light intensities. For the first time, UVA is circumvented with visible light-emitting diodes at 445 nm (blue) to rapidly activate diazirine-to-carbene covalent cross-linking. Iridium photocatalysts serve to initiate diazirine, despite having little to no absorption at 445 nm. CaproGlu's liquid organic matrix dissolves the photocatalyst with no solvents required, creating a light transparent matrix. Considerable differences in cross-linking chemistry are observed in UVA vs visible/photocatalyst formulations. Empirical analysis and theoretical calculations reveal a more efficient conversion of diazirine directly to carbene with no diazoalkane intermediate detected. Photorheometry results demonstrate a correlation between shear moduli, joules light dose, and the lower limits of photocatalyst concentration required for the liquid-to-biorubber transition. Adhesion strength on ex vivo hydrated tissues exceeds that of cyanoacrylates, with a fixation strength of up to 20 kg·f·cm2. Preliminary toxicity assessment on leachates and materials directly in contact with mammalian fibroblast cells displays no signs of fibroblast cytotoxicity.


Assuntos
Adesivos/química , Materiais Biocompatíveis/química , Complexos de Coordenação/química , Diazometano/análogos & derivados , Animais , Catálise/efeitos da radiação , Colágeno/química , Complexos de Coordenação/efeitos da radiação , Complexos de Coordenação/toxicidade , Reagentes de Ligações Cruzadas/química , Irídio/química , Irídio/efeitos da radiação , Irídio/toxicidade , Luz , Camundongos , Células NIH 3T3 , Poliésteres/química , Suínos
13.
Mater Sci Eng C Mater Biol Appl ; 127: 112240, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34225880

RESUMO

Stimuli-sensitive biomaterials that are activated by light are in need of formulations that are stable under indoor lighting yet can be activated under direct sunlight. Carbene-based bioadhesives are a new generation of film-forming polymers that are stable under indoor lighting yet are rapidly activated with low-energy UVA light, but have never been evaluated under sunlight exposure. Previous investigations have evolved two flexible carbene-based platforms, where aryl-diazirine is grafted on to polyamidoamine dendrimers (PAMAM-NH2; generation-5) or hydrophobic liquid polycaprolactone tetrol to yield G5-Dzx and CaproGlu, respectively. For the first time the activation of G5-Dzx and CaproGlu is investigated by natural sunlight with intensities up to 10 mW·cm-2. Structure-property relationships of bioadhesion are investigated by: (1) joules dose of sunlight; (2) bioadhesive polymer structure; and (3) optical concentrators of magnifying glass and Fresnel lens. Using only natural sunlight, adhesion strength could be tuned from 20 to 150 kPa with crosslinking achieved in under 1 min. The results show that carbene-based polymers are a class of stimuli-sensitive biomaterials that are stable to indoor lighting, yet can be rapidly activated under direct sunlight, which may be useful for topical film forming polymers or as active ingredients in sunscreen formulations.


Assuntos
Adesivos , Luz Solar , Materiais Biocompatíveis , Diazometano , Polímeros
14.
Indian J Surg Oncol ; 12(Suppl 1): 85-92, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33994733

RESUMO

Gastric cancer (GC) is a serious fatal cancer on a global scale because of its presentation at advanced stage. The expressions of vascular endothelial growth factor (VEGF), E-cadherin, and matrix metalloproteinases (MMPs) in other cancers have been reported. However, its expression and underlying mechanisms are little known in gastric cancer in Indian context. In this study, we detected mRNA expression of VEGF, E-cadherin, and MMPs (MMP-1, MMP-2, and MMP-9) in 73 gastric cancer tissues and 27 normal controls by reverse-transcriptase polymerase chain reaction (RT-PCR). Receiver operator characteristics analysis was done for determining the diagnostic utility of VEGF, MMPs and E-cadherin with respect to the sensitivity and specificity. The association of VEGF, MMPs, and E-cadherin expression with the clinicopathological characteristics and the prognosis was subsequently analyzed. The mRNA expression results showed that E-cadherin was significantly downregulated in 47.9% of GC in comparison to control. There was no change in VEGF expression observed in 90.4% GC cases. MMP-1, MMP-2, and MMP-9 were overexpressed in 13.7%, 28.8%, and 11% of GC, respectively, with significant change in MMP-2 (p ≤ 0.0001) and MMP-9 (p = 0.027) in comparison to control. Our results strengthen the necessity of more studies to elucidate the prophetic role of these genes in the development of gastric cancer.

15.
Saudi J Gastroenterol ; 27(1): 54-59, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32801256

RESUMO

BACKGROUND: The aryl hydrocarbon receptor repressor (AHRR), a member of the growing superfamily, is a basic helix-loop-helix/PerAHR nuclear translocator (ARNT)-Sim (bHLH-PAS) protein. AHRR has been proposed to function as a putative new tumor suppressor gene based on studies in multiple types of human cancers. This current study aims to investigate AHHR expression and its prognostic significance in gallbladder cancer. METHODS: The study includes 48 gallbladder cancer and 34 chronic cholecystitis cases as controls. The expression level of AHRR was analyzed by using semi-quantitative PCR and immunohistochemical staining. The results were correlated with different clinical parameters. RESULTS: We demonstrate that the expression of AHRR is significantly down-regulated in gallbladder cancer tissue samples as compared to that in chronic cholecystitis tissue samples by reverse transcriptase PCR (RT-PCR) (P = 0.017) and immunohistochemistry analysis (P = 0.002). Interestingly, our RT-PCR data revealed that AHRR mRNA expression is frequently down-regulated (45.8%; 22/48) in cases as compared to 14.7% (5/34) in controls. Similarly, immunohistochemical analysis data show significant down-regulation of AHRR expression in 77.1% (37/48) of gallbladder cancer cases than 44.1% (15/34) in controls (P < 0.017). Reduced mRNA and protein expression is significantly associated with advanced T-stage (P = 0.001), histological differentiation (P = 0.001), and tumors with nodal metastasis (P = 0.001). Decreased expression of AHRR is significantly associated with poor prognosis in gallbladder cancer patients. CONCLUSION: In conclusion, the present study suggests that low AHRR expression may be critical in gallbladder cancer development. Our data suggests that AHRR may act as a tumor suppressor gene and its expression profile may be useful as a diagnostic marker in gallbladder cancer.


Assuntos
Neoplasias da Vesícula Biliar , Receptores de Hidrocarboneto Arílico , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Neoplasias da Vesícula Biliar/genética , Humanos , RNA Mensageiro , Receptores de Hidrocarboneto Arílico/genética , Proteínas Repressoras/genética
17.
Colloids Surf B Biointerfaces ; 185: 110611, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31704609

RESUMO

Nanocolloids are considered ideal carriers for hydrophobic drugs owing to their core-shell structure. Lapatinib is a potential anti-cancer agent, but its clinical use is limited because of its poor aqueous solubility, thus requiring larger oral doses with the associated toxicity. Thus, in the present study, we fabricated self-assembled nanocolloidal polymeric micelles (LP-PMs) of Soluplus® and Pluronic® F127 by the thin-film hydration method and assessed their delivery potential of the hydrophobic anti-cancer drug lapatinib (LP) and optimised these nanocolloidal polymeric micelles using Quality-by-Design approach. Amorphisation of the drug and no typical incompatibility other than hydrogen bonding in the LP-PMs was confirmed by solid-state characterisation. The LP-PMs exhibited a uniform size of 92.9 ± 4.07 nm, with a 5.06 mV zeta potential and approximately 87% drug encapsulation. The critical micellar concentration (CMC) of Soluplus® decreased from 6.63 × 10-3 to 4.4 × 10-3 mg/mL by incorporating Pluronic® F127. Further, the sustained release of LP from the LP-PMs was confirmed by in-vitro release studies showing 36% and 60% of LP released from the LP-PMs within 48 h in release media of pH 7.4 and pH 5.0, respectively. These results support their capability of preferential release at acidic tumor environment. Their hemocompatibility evidenced by hemolysis below accepted limits and no platelet aggregation with resistance to instant dilution illustrated their admirable blood compatibility and suitability for intravenous administration. The encapsulation of LP inside micelles enhanced the cytotoxicity of LP against SKBr3 breast cancer cells. Further, the LP-PMs were found to be stable over six months when stored at 2-8 °C. These findings indicate the improved potential of nanocolloidal polymeric micelles as promising carriers for the preferential and sustained delivery of hydrophobic anticancer drugs such as lapatinib to tumours.


Assuntos
Antineoplásicos/farmacologia , Coloides/química , Sistemas de Liberação de Medicamentos , Interações Hidrofóbicas e Hidrofílicas , Lapatinib/farmacologia , Nanopartículas/química , Polietilenoglicóis/farmacologia , Polivinil/farmacologia , Linhagem Celular Tumoral , Preparações de Ação Retardada/farmacologia , Liberação Controlada de Fármacos , Humanos , Micelas , Tamanho da Partícula , Agregação Plaquetária/efeitos dos fármacos , Polímeros/química , Espectroscopia de Infravermelho com Transformada de Fourier
18.
J Mol Neurosci ; 67(4): 564-573, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30649683

RESUMO

Oligodendrocyte progenitor cells (OPCs) originate from the sub-ventricular zone of the developing brain. They migrate and proliferate to occupy the white matter tracts of the central nervous system and transform into myelinating oligodendrocytes. Along their route of migration, OPCs are guided and controlled by several growth factors and chemokines. PDGF-A (platelet-derived growth factor), a growth factor, serves as a monogenic and mitogenic cue during the process and activates intracellular signaling pathways inside the cell. Activation of extracellular signal regulated kinase (ERK) signaling is one of the mechanisms by which PDGF-A induces the migration of OPCs. However, the mechanisms governing the PDGF-A-induced ERK-driven OPCs migration are still unclear. In the current study, we investigated further the role of PDGF-A-induced ERK signaling in OPC migration. First, we confirmed the role of PDGF-A-activated ERK signaling in OPC migration using the pharmacological inhibitor U0126, or siRNA-mediated suppression of ERK expression. Then, we demonstrated that PDGF-A-induced actin reorganization and interaction of focal adhesion kinase (FAK), Paxillin, and pERK signals are impaired in OPCs treated with the MEK inhibitor U0126. Thus, our findings demonstrated that PDGF-A induces OPC migration in an ERK-dependent mechanism via regulation of actin reorganization and FAK-Paxillin interaction.


Assuntos
Movimento Celular , Sistema de Sinalização das MAP Quinases , Células-Tronco Neurais/metabolismo , Oligodendroglia/metabolismo , Animais , Células Cultivadas , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Células-Tronco Neurais/fisiologia , Oligodendroglia/fisiologia , Paxilina/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Ratos
19.
Artif Cells Nanomed Biotechnol ; 47(1): 228-240, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30688107

RESUMO

Microbial infection and oxidative damage of the fibroblast often results in prolonged and incomplete wound healing. Therefore, there is an increasing demand for a scaffold being effective to prevent any possible infection and neutralize excessively released free radicals. Herein, we designed a PCL-based nanofiber loaded with ciprofloxacin hydrochloride (CHL) and quercetin. Developed nanofiber showed the formation of smooth and continuous nanofiber with 101.59 ± 29.18 nm average diameter and entrapping the drugs in amorphous form without any possible physico-chemical interaction between drugs and excipient. High entrapment efficiency (CHL: 92.04% and Que: 94.32%) and prolonged in-vitro release (for 7 days) demonstrated the capability of scaffold to suppress any probable infection and oxidative damage, which was further confirmed by in-vitro antibacterial and antioxidant activity. The biocompatibility of scaffold for direct application to wound site was evaluated through hemocompatibility and cytocompatibility assay. The wound healing efficacies of nanofiber were assessed using full thickness wound model in rats, which displayed accelerated wound healing with complete re-epithelialization and improved collagen deposition within 16 days. In-vivo wound healing finding was further corroborated by SOD, catalase, and hydroxyproline assay. The current study validates the application of ciprofloxacin HCl and quercetin functionalized nanofiber as a potential wound dressing material.


Assuntos
Ciprofloxacina/química , Ciprofloxacina/farmacologia , Membranas Artificiais , Nanofibras/química , Quercetina/química , Quercetina/farmacologia , Cicatrização/efeitos dos fármacos , Antibacterianos/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Colágeno/biossíntese , Liberação Controlada de Fármacos , Eletricidade , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Hidroxiprolina/metabolismo , Teste de Materiais , Estresse Oxidativo/efeitos dos fármacos
20.
J Prosthodont ; 28(2): e843-e848, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28834052

RESUMO

PURPOSE: To estimate the incidence of obstructive sleep apnea (OSA) in elderly edentulous patients (aged 60-65 years) and investigate a correlation of serum serotonin levels with the apnea-hypopnea index (AHI), respiratory effort-related arousal (RERA), and respiratory disturbance index (RDI). MATERIALS AND METHODS: 381 elderly completely edentulous patients (307 male, 74 female) aged 60 to 65 years with a history of edentulism of 12 to 15 months, seeking oral rehabilitation at the prosthodontic clinic at Saraswati Dental College & Hospital, Lucknow, India, between January 2014 and January 2016 were enrolled for the present study. After application of the inclusion and exclusion criteria of this study, 183 patients (162 male, 21 female) who were found susceptible, were subjected to the BERLIN questionnaire and Epworth Sleepiness Scale (ESS) to assess sleep disordered breathing (SDB) and then put through all-night polysomnography (PSG). On the basis of AHI, RERA, and RDI scores, 156 patients (143 male, 13 female) who tested positive for OSA were classified according to its intensity. All 156 patients underwent body-mass index (BMI) estimation, cephalometry, and intraoral examination for skeletal and soft tissue profile record. Serum serotonin was estimated from whole blood samples for the 156 OSA and the 27 normal patients. The 156 (147 nonobese, 9 obese) OSA-positive patients were provided with complete dentures and were trained to use the same as a modified mandibular advancement device (MAD) during sleep at night. These patients were kept on a quarterly follow-up for 9 months. Data collected was subjected to statistical analysis, and inferences drawn. RESULTS: The incidence of OSA in elderly edentulous subjects was found to be 32.03% in males and 8.91% in females. A mere 9 out of 156 (5.76%) elderly edentulous OSA patients were found to be obese (Class I) on the basis of BMI estimation. Cephalometry of the patients showed that they had a skeletal class I maxillomandibular relationship. AHI scores of nonobese patients revealed that most of the patients had moderate OSA, followed by mild OSA and severe OSA. Serum serotonin levels ranged from 53 to 83 ng/dL. AHI score of the 9 obese patients were in the moderate to severe range, and their serum serotonin levels were 60 to 70 ng/dL. A correlation between severity of OSA and serum serotonin level was validated in this study. CONCLUSION: OSA was found to be prevalent in edentulous subjects due to pharyngeal collapse and decreased neuromuscular control. An inverse relationship of serum serotonin levels and AHI scores was established.


Assuntos
Boca Edêntula/complicações , Serotonina/sangue , Apneia Obstrutiva do Sono/epidemiologia , Idoso , Índice de Massa Corporal , Cefalometria , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Polissonografia , Índice de Gravidade de Doença , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/etiologia
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