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1.
Pharmaceuticals (Basel) ; 17(6)2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38931416

RESUMEN

The treatment adherence of narcotics-addicted individuals with reduced incidences of relapse can be enhanced by a sustained drug release formulation of antinarcotics. So far, different drug formulations have been reported with sustained drug release periods of 28 and 35 days. To further enhance this duration, different formulations of injectable hydrogels (IHs) have been developed by combining low molecular weight (LMW) and high molecular weight (HMW) chitosan (CS) with guar gum (GG) and crosslinking them by sodium bi phosphate dibasic. The structural, morphological, and physicochemical properties of LMW-CS IH, and HMW-CS IH were evaluated using Fourier transform infrared spectroscopy (FT-IR), thermo-gravimetric analysis (TGA), scanning electron microscopy (SEM), and rheological, swelling, and biodegradation analysis. The HMW-CS IH showed high crosslinking, increased thermal stability, high mechanical strength, elevated swelling, and low biodegradation. The antinarcotic drugs naltrexone (NTX) and disulfiram (DSF) were loaded separately into the HMW-CS IH and LMW-CS IH. The release of NTX and DSF was investigated in phosphate buffer saline (PBS) and ethanol (0.3%, 0.4%, and 0.5%) over a 56-day period using an UV spectrophotometer. The drug release data were tested in zero-order, first-order, and Korsemeyer-Peppas mathematical models. In PBS, all prepared formulations followed non-Fickian drug release, while in ethanol, only NTX HMW-CS IH followed non-Fickian release in all three different concentrations of ethanol.

2.
Biomed Phys Eng Express ; 10(3)2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38224615

RESUMEN

Guided tissue/bone regeneration (GTR/GBR) is a widely used technique in dentistry to facilitate the regeneration of damaged bone and tissue, which involves guiding materials that eventually degrade, allowing newly created tissue to take its place. This comprehensive review the evolution of biomaterials for guided bone regeneration that showcases a progressive shift from non-resorbable to highly biocompatible and bioactive materials, allowing for more effective and predictable bone regeneration. The evolution of biomaterials for guided bone regeneration GTR/GBR has marked a significant progression in regenerative dentistry and maxillofacial surgery. Biomaterials used in GBR have evolved over time to enhance biocompatibility, bioactivity, and efficacy in promoting bone growth and integration. This review also probes into several promising fabrication techniques like electrospinning and latest 3D printing fabrication techniques, which have shown potential in enhancing tissue and bone regeneration processes. Further, the challenges and future direction of GTR/GBR are explored and discussed.


Asunto(s)
Regeneración Tisular Dirigida , Membranas Artificiales , Regeneración Tisular Dirigida/métodos , Materiales Biocompatibles , Huesos , Regeneración Ósea
3.
J Cell Biol ; 223(3)2024 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-38240799

RESUMEN

The highly conserved HEATR5 proteins are best known for their roles in membrane traffic mediated by the adaptor protein complex-1 (AP1). HEATR5 proteins rely on fast-evolving cofactors to bind to AP1. However, how HEATR5 proteins interact with these cofactors is unknown. Here, we report that the budding yeast HEATR5 protein, Laa1, functions in two biochemically distinct complexes. These complexes are defined by a pair of mutually exclusive Laa1-binding proteins, Laa2 and the previously uncharacterized Lft1/Yml037c. Despite limited sequence similarity, biochemical analysis and structure predictions indicate that Lft1 and Laa2 bind Laa1 via structurally similar mechanisms. Both Laa1 complexes function in intra-Golgi recycling. However, only the Laa2-Laa1 complex binds to AP1 and contributes to its localization. Finally, structure predictions indicate that human HEATR5 proteins bind to a pair of fast-evolving interacting partners via a mechanism similar to that observed in yeast. These results reveal mechanistic insight into how HEATR5 proteins bind their cofactors and indicate that Laa1 performs functions besides recruiting AP1.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Aparato de Golgi , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Humanos , Complejo 1 de Proteína Adaptadora/metabolismo , Proteínas Portadoras/metabolismo , Aparato de Golgi/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
4.
Clin Child Psychol Psychiatry ; 29(1): 274-286, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37864339

RESUMEN

Behavior therapists play an important role in the life of children with an autism spectrum disorder (ASD). Literature reported that child's improvement depends on the quality of therapy they receive. Therefore, the current study aims to explore the psychosocial experiences of behavior therapist working with children having ASD, and suggest the coping strategies which they use to deal with those stressors. The study utilizes a qualitative research design with a phenomenological research approach to explore the psychosocial experiences. For this purpose, the researchers conduct semi-structured interviews of 6 behavior therapists, ages ranging from 25 to 35 years. They note the verbatim of the therapists and convert into codes to create themes and categories. Furthermore, the study utilizes Interpretative Phenomenological Analysis for the interpretation of the results. The results of this phenomenological research indicate six superordinate themes emerged from the transcripts. The results demonstrate professional and psychological experiences of behavior therapists along with the social and the health issues faced by the children with ASD, and the coping strategies used by the therapists that is emotion focused coping, problem focused coping and maladaptive copings. Gaining insight into therapists' psychosocial experiences can pave the way for developing approaches aimed at enhancing their overall welfare. These approaches may encompass initiatives to alleviate stress, mitigate burnout, and boost job satisfaction.


Asunto(s)
Trastorno del Espectro Autista , Niño , Humanos , Trastorno del Espectro Autista/terapia , Trastorno del Espectro Autista/psicología , Emociones , Habilidades de Afrontamiento , Investigación Cualitativa
5.
bioRxiv ; 2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-37662263

RESUMEN

The highly conserved HEATR5 proteins are best known for their roles in membrane traffic mediated by the adaptor protein complex-1 (AP1). HEATR5 proteins rely on fast-evolving co-factors to bind to AP1. However, how HEATR5 proteins interact with these co-factors is unknown. Here, we report that the budding yeast HEATR5 protein, Laa1, functions in two biochemically distinct complexes. These complexes are defined by a pair of mutually exclusive Laa1-binding proteins, Laa2 and the previously uncharacterized Lft1/Yml037c. Despite limited sequence similarity, biochemical analysis and structure predictions indicate that Lft1 and Laa2 bind Laa1 via structurally similar mechanisms. Both Laa1 complexes function in intra-Golgi recycling. However, only the Laa2-Laa1 complex binds to AP1 and contributes to its localization. Finally, structure predictions indicate that human HEATR5 proteins bind to a pair of fast-evolving interacting partners via a mechanism similar to that observed in yeast. These results reveal mechanistic insight into how HEATR5 proteins bind their co-factors and indicate that Laa1 performs functions besides recruiting AP1.

6.
J Neuroimmune Pharmacol ; 18(1-2): 183-194, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37261605

RESUMEN

Alzheimer's disease (AD) is globally recognized as a prominent cause of dementia for which efficient treatment is still lacking. New candidate compounds that are biologically potent are regularly tested. We, therefore, hypothesized to study the neuroprotective potential of Zinc Ortho Methyl Carbonodithioate (thereafter called ZOMEC) against Scopolamine (SCOP) induced Alzheimer's disease (AD) model using adult albino mice. We post-administered ZOMEC (30 mg/Kg) into two group of mice for three weeks on daily basis that received either 0.9% saline or SCOP (1 mg/Kg) for initial two weeks. The other two groups of mice received 0.9% saline and SCOP (1 mg/Kg) respectively. After memory related behavioral analysis the brain homogenates were evaluated for the antioxidant potential of ZOMEC and multiple protein markers were examined through western blotting. Our results provide enough evidences that ZOMEC decrease oxidative stress by increasing catalase (CAT) and glutathione S transferase (GST) and decreasing the lipid peroxidation (LPO). The SIRT1 and pre and post synaptic marker proteins, synaptophysin (SYP) as well as post synaptic density protein (PSD-95) expression were also enhanced upon ZOMEC treatment. Furthermore, memory impairment was rescued and ZOMEC appreciably abrogated the Aß accumulation, BACE1 expression C and the p-JNK pathway. The inflammatory protein markers, NF-kß and IL-1ß in ZOMEC treated mice were also comparable with control group. The predicted interaction of ZOMEC with SIRT1 was further confirmed by molecular docking. These findings thus provide initial reports on efficacy of ZOMEC in SCOP induced AD model.


Asunto(s)
Enfermedad de Alzheimer , Escopolamina , Ratones , Animales , Escopolamina/toxicidad , Escopolamina/metabolismo , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Secretasas de la Proteína Precursora del Amiloide/uso terapéutico , Sistema de Señalización de MAP Quinasas , Zinc/metabolismo , Zinc/uso terapéutico , Sirtuina 1/metabolismo , Simulación del Acoplamiento Molecular , Solución Salina/metabolismo , Solución Salina/uso terapéutico , Ácido Aspártico Endopeptidasas/metabolismo , Ácido Aspártico Endopeptidasas/uso terapéutico , Trastornos de la Memoria/inducido químicamente , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/metabolismo , Sinapsis
7.
Chemosphere ; 321: 138008, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36731664

RESUMEN

Alizarin red S (ARS) extraction from aqueous medium was carried out using hydrophobic ionic liquids (ILs) containing trioctylammonium cation paired with 4-tert-butylbenzoate ([TOA][Butbenz] (IL1), 4-phenylbutanoate ([TOA][PheBut] (IL2), 3-4-dimethylbenzoate ([TOA][DMbenz] (IL3), naphthoate, ([TOA][Naph]) (IL4), salicylate ([TOA][Sali]) (IL5) and nonanedioate ([TOA]2[Nona]) (IL6). The findings demonstrated that all of the tested ILs were efficient for extracting ARS, however, [TOA]2[Nona] was more effective than others. For the extraction of ARS from the aqueous phase, the effects of various parameters including the initial pH of the dye solution, contact time, ILs to dye volume ratio (VIL:VW), dye concentration, temperature, and salt effect were investigated. The spontaneity of the liquid-liquid extraction of ARS from the aqueous phase to the IL phase was confirmed by thermodynamic parameters. More than 90% of the ARS was extracted from the aqueous phase to the IL phase throughout all experiments. Interaction of selected IL with dyes were confirmed using FTIR analysis. The standard bacterial strains of Escherichia coli (E. coli) ATCC BAA-2471 (gram negative) and Methicillin-resistant Staphylococcus (MRSA) ATCC 43300 (gram positive) were used for evaluating antibacterial activity. The lower dose (250 ppm), the ILs1, 2, 3, 4, 5, and 6 inhibited 0.40, 1.50, 6.50, 1.50, 2.50, and 0.50 mm growth of E. coli, and 4.0, 2.0, 16.50, 0.40, 5.0, and 3.50 mm growth of MRSA, respectively. The experimental findings confirmed that the present ILs can be utilized as an effective solvent for ARS and other dyes extraction from aqueous media.


Asunto(s)
Compuestos de Amonio , Líquidos Iónicos , Staphylococcus aureus Resistente a Meticilina , Líquidos Iónicos/química , Escherichia coli , Agua/química , Antibacterianos , Colorantes , Textiles
8.
Int J Biol Macromol ; 232: 123476, 2023 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-36731696

RESUMEN

With the advancement in 3D bioprinting technology, cell culture methods can design 3D environments which are both, complex and physiologically relevant. The main component in 3D bioprinting, bioink, can be split into various categories depending on the criterion of categorization. Although the choice of bioink and bioprinting process will vary greatly depending on the application, general features such as material properties, biological interaction, gelation, and viscosity are always important to consider. The foundation of 3D bioprinting is the exact layer-by-layer implantation of biological elements, biochemicals, and living cells with the spatial control of the implantation of functional elements onto the biofabricated 3D structure. Three basic strategies underlie the 3D bioprinting process: autonomous self-assembly, micro tissue building blocks, and biomimicry or biomimetics. Tissue engineering can benefit from 3D bioprinting in many ways, but there are still numerous obstacles to overcome before functional tissues can be produced and used in clinical settings. A better comprehension of the physiological characteristics of bioink materials and a higher level of ability to reproduce the intricate biologically mimicked and physiologically relevant 3D structures would be a significant improvement for 3D bioprinting to overcome the limitations.


Asunto(s)
Bioimpresión , Andamios del Tejido , Andamios del Tejido/química , Impresión Tridimensional , Ingeniería de Tejidos , Tecnología
9.
Int J Biol Macromol ; 230: 123131, 2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36610570

RESUMEN

3-D Bioprinting is employed as a novel approach in biofabrication to promote skin regeneration following chronic-wounds and injury. A novel bioink composed of carbohydrazide crosslinked {polyethylene oxide-co- Chitosan-co- poly(methylmethacrylic-acid)} (PEO-CS-PMMA) laden with Nicotinamide and human dermal fibroblast was successfully synthesized via Free radical-copolymerization at 73 °C. The developed bioink was characterized in term of swelling, structural-confirmation by solid state 13C-Nuclear Magnetic Resonance (NMR), morphology, thermal, 3-D Bioprinting via extrusion, rheological and interaction with DNA respectively. The predominant rate of gelation was attributed to the electrostatic interactions between cationic CS and anionic PMMA pendant groups. The morphology of developed bioink presented a porous architecture satisfying the cell and growth-factor viability across the barrier. The thermal analysis revealed two-step degradation with 85 % weight loss in term of decomposition and molecular changes in the bioink moieties By applying low pressure in the range of 25-50 kPa, the optimum reproducibility and printability were determined at 37 °C in the viscosity range of 500-550 Pa. s. A higher survival rate of 92 % was observed for (PEO-CS-PMMA) in comparison to 67 % for pure chitosan built bioink. A binding constant of K ≈ 1.8 × 106 M-1 recognized a thermodynamically stable interaction of (PEO-CS-PMMA) with the Salmon-DNA. Further, the addition of PEO (5.0 %) was addressed with better self-healing and printability to produce skin-tissue constructs to replace the infected skin in human.


Asunto(s)
Bioimpresión , Quitosano , Humanos , Hidrogeles/química , Polimetil Metacrilato , Reproducibilidad de los Resultados , Impresión Tridimensional , Tecnología , Andamios del Tejido/química , Ingeniería de Tejidos
10.
Gels ; 9(1)2023 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-36661809

RESUMEN

Bilayer/multilayer tablets have been introduced to formulate incompatible components for compound preparations, but they are now more commonly used to tailor drug release. This research aimed to formulate a novel gastro-retentive tablet to deliver a combination of a fixed dose of two drugs to eliminate Helicobacter pylori (H. pylori) in the gastrointestinal tract. The bilayer tablets were prepared by means of the direct compression technique. The controlled-release bilayer tablets were prepared using various hydrophilic swellable polymers (sodium alginate, chitosan, and HPMC-K15M) alone and in combination to investigate the percent of swelling behavior and average drug release. The weight of the controlled-release floating layer was 500 mg, whereas the weight of the floating tablets of pantoprazole was 100 mg. To develop the most-effective formulation, the effects of the experimental components on the floating lag time, the total floating time, T 50%, and the amount of drug release were investigated. The drugs' and excipients' compatibilities were evaluated using ATR-FTIR and DSC. Pre-compression and post-compression testing were carried out for the prepared tablets, and they were subjected to in vitro characterization studies. The pantoprazole layer of the prepared tablet demonstrated drug release (95%) in 2 h, whereas clarithromycin demonstrated sustained drug release (83%) for up to 24 h (F7). The present study concluded that the combination of sodium alginate, chitosan, and HPMC polymers (1:1:1) resulted in a gastro-retentive and controlled-release drug delivery system of the drug combination. Thus, the formulation of the floating bilayer tablets successfully resulted in a biphasic drug release. Moreover, the formulation (F7) offered the combination of two drugs in a single-tablet formulation containing various polymers (sodium alginate, chitosan, and HPMC polymers) as the best treatment option for local infections such as gastric ulcers.

11.
Polymers (Basel) ; 14(23)2022 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-36501482

RESUMEN

Aromatic polyamides are well-known as high-performance materials due to their outstanding properties making them useful in a wide range of applications. However, their limited solubility in common organic solvents restricts their processability and becomes a hurdle in their applicability. This study is focused on the synthesis of processable ferrocene-based terpolyamides and their polydimethylsiloxane (PDMS)-containing block copolymers, using low-temperature solution polycondensation methodology. All the synthesized materials were structurally characterized using FTIR and 1H NMR spectroscopic techniques. The ferrocene-based terpolymers and block copolymers were soluble in common organic solvents, while the organic analogs were found only soluble in sulfuric acid. WXRD analysis showed the amorphous nature of the materials, while the SEM analysis exposed the modified surface of the ferrocene-based block copolymers. The structure-property relationship of the materials was further elucidated by their water absorption and thermal behavior. These materials showed low to no water absorption along with their high limiting oxygen index (LOI) values depicting their good flame-retardant behavior. DFT studies also supported the role of various monomers in the polycondensation reaction where the electron pair donation from HOMO of diamine monomer to the LUMO of acyl chloride was predicted, along with the calculation of various other parameters of the representative terpolymers and block copolymers.

12.
Polymers (Basel) ; 14(17)2022 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-36080621

RESUMEN

In this research work, polymer blends of poly-lactic acid (PLA)/ethylene vinyl acetate (EVA) were prepared as the drug carrier materials for a bi-layer drug-loaded coating film for coronary stents. Different optimum compositions of blends were prepared by using an intense mixer. Then, the blends were hot-pressed and later cold-pressed to prepare for films of different thickness. The changes in weight, surface analysis and biodegradability with increasing time were studied using Scanning electron microscopy (SEM), weight loss and biodegradability tests. The mechanical and thermal properties of drug-loaded films were studied through universal testing machine (UTM) and thermo-gravimetric analysis (TGA). The effects of PLA, EVA and drug contents on in-vitro drug contents were investigated through the Ultraviolet-Visible Spectroscopy (UV-VIS) chemical analysis technique. The results obtained clearly showed that the addition of PLA promoted the unleashing of the drug whereas the addition of EVA nearly did not have the same affect. The mechanical properties of these various films can be tuned by adjusting the contents of blend parts. The factors affecting the unleashing of the drug became a serious matter of concern in evaluating the performance of bio-resorbable drug eluting stents. As a result, today's chemical blends may be useful drug carrier materials for drug-loaded tube coatings capable delivering purgative drug in an incredibly tunable and regulated manner.

14.
Nat Cell Biol ; 24(7): 1019-1028, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35739317

RESUMEN

Neutrophils migrating towards chemoattractant gradients amplify their recruitment range by releasing the secondary chemoattractant leukotriene B4 (LTB4) refs. 1,2. We previously demonstrated that LTB4 and its synthesizing enzymes, 5-lipoxygenase (5-LO), 5-LO activating protein (FLAP) and leukotriene A4 hydrolase, are packaged and released in exosomes3. Here we report that the biogenesis of the LTB4-containing exosomes originates at the nuclear envelope (NE) of activated neutrophils. We show that the neutral sphingomyelinase 1 (nSMase1)-mediated generation of ceramide-enriched lipid-ordered microdomains initiates the clustering of the LTB4-synthesizing enzymes on the NE. We isolated and analysed exosomes from activated neutrophils and established that the FLAP/5-LO-positive exosome population is distinct from that of the CD63-positive exosome population. Furthermore, we observed a strong co-localization between ALIX and FLAP at the periphery of nuclei and within cytosolic vesicles. We propose that the initiation of NE curvature and bud formation is mediated by nSMase1-dependent ceramide generation, which leads to FLAP and ALIX recruitment. Together, these observations elucidate the mechanism for LTB4 secretion and identify a non-conventional pathway for exosome generation.


Asunto(s)
Exosomas , Proteínas Activadoras de la 5-Lipooxigenasa , Ceramidas/metabolismo , Factores Quimiotácticos/metabolismo , Exosomas/metabolismo , Leucotrieno B4/metabolismo , Neutrófilos/metabolismo , Membrana Nuclear/metabolismo
15.
HCA Healthc J Med ; 2(1): 51-55, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-37424885

RESUMEN

Description Trichobezoars are impactions of hair that accumulate in the gastrointestinal track and are most often located in the stomach. They are often associated with psychiatric illnesses like trichotillomania and trichophagia, which usually occurs in young and adolescent females. Gastric trichobezoars (GT) are the most common variety of bezoar found in the stomach. The most common complications that arise alongside GT include gastric erosion, ulceration or perforation of the small intestine. Gastric outlet obstruction, obstructive jaundice, pancreatitis and death have been reported, though these complications are rare. We report a 40-year-old female who presented to the hospital with dyspnea on exertion and ankle swellings. She also reported abdominal distension, a 40 pound weight loss, nausea and vomiting. Her examination was remarkable for sinus tachycardia, displaced apex beat and a split second sound. She was suspected of congestive heart failure. Upper endoscopy revealed a large trichobezoar in the antrum and the body of the stomach. She was found to be markedly anemic and in hypothyroid state. She underwent surgical removal of the GT subsequent to stabilization of heart failure. She later admitted to psychiatry a history of hair pulling and swallowing under stressful conditions.

16.
Int J Biol Macromol ; 147: 853-866, 2020 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-31739066

RESUMEN

Gums; composed of polysaccharides, carbohydrates, proteins, and minerals, are high molecular weight hydrophilic compounds with several biological applications. This study describes the nutritional and toxic elements content, chemical composition, synthesis of silver nanoparticles (G-AgNPs), and pharmacological and catalytic properties of Prunus armeniaca (apricot), Prunus domestica (plums), Prunus persica (peaches), Acacia modesta (phulai), Acacia arabica (kikar), and Salmalia malabarica (silk cotton tree) gums. The elemental contents were analyzed by inductively coupled plasma-optical emission spectroscopy (ICP-OES) and ICP-mass spectrometry (ICP-MS). NMR spectroscopy was used for the identification of class of compounds in the mixture, their functional groups were determined through FTIR techniques, and plasmon resonance and size of G-AgNPs through UV-Vis spectroscopic technique and transmission electron microscopy (TEM). From the results, nutritional elements were present at appreciable concentrations, whereas toxic elements showed content below the maximum permissible ranges. Using the elemental data, linear discriminant and principal component analyses classified the gums to 99.9% variability index. Furthermore, G-AgNPs exhibited significant antioxidant, antibacterial, and redox catalytic potential. Hence, the subject G-AgNPs could have promising nutritional, therapeutic and environmental remediation applications.


Asunto(s)
Antibacterianos , Antioxidantes , Nanopartículas del Metal/química , Gomas de Plantas/química , Plata/química , Antibacterianos/síntesis química , Antibacterianos/química , Antioxidantes/síntesis química , Antioxidantes/química , Catálisis
17.
Eur J Med Chem ; 181: 111544, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31374420

RESUMEN

There is a growing interest in the cancer cell growth inhibitory effects of organotin (IV) compounds and, accordingly, a new series of dimethyl-, di-(n-butyl)-, diphenyl- and chloro-phenyl tin(IV) complexes with a Schiff base core were prepared. Their binding to DNA was assessed by UV thermal denaturation showing no interaction and by UV-vis titration exhibiting moderate interaction by intercalation. Complexes having n-butyl substituents were more potent and cytotoxic against human leukemia, breast and cervical cancer cell lines than other organotin(IV) complexes tested. Unfortunately, some of these compounds showed similar cytotoxicity in a non-cancerous cell line. We may conclude that cytotoxic activity was dependent on the nature (lipophilicity and size, according to the structure-activity relationship studies) and substitution pattern on the different structures. These results may aid in the rational design of metallodrugs, expanding the scope of organotin complexes in formulating new metal based drugs with dibutyl moieties.


Asunto(s)
Antineoplásicos/farmacología , Compuestos Orgánicos de Estaño/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Células HL-60 , Células HeLa , Humanos , Células MCF-7 , Estructura Molecular , Compuestos Orgánicos de Estaño/síntesis química , Compuestos Orgánicos de Estaño/química , Relación Estructura-Actividad
18.
Medicina (Kaunas) ; 55(4)2019 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-30991760

RESUMEN

BACKGROUND AND OBJECTIVES: Cucumis melo, of family Cucurbitaceae, has traditionally been used to treat variety of kidney disorders. However to best of our knowledge there is no scientific study available that validates its renaoprotective uses. Therefore, this study aimed to evaluate nephroprotective effects of hydroalcoholic extract of Cucumis melo seeds (CMHE) and to identify its phytoconstituents. MATERIALS AND METHODS: HPLC was performed to identify key phytochemicals of CMHE. Gentamicin (100 mg/kg/day, i.p) was administered to induce nephrotoxicity in Swiss albino mice for 8 days. Gentamicin (100 mg/kg/day, i.p) and oral CMHE were co-administered to mice at doses of 250 and 500 mg/kg to evaluate protective effects of CMHE. Normal control group mice were administered normal saline. Changes in body weights, biochemical and histopathological studies were conducted to establish nephroprotective effects of CMHE. Results: HPLC analysis indicated presence of quercetin, m-coumaric acid, gallic acid, chlorogenic acid, and trans-4-hydroxy-3-methoxy cinnamic acid in CMHE. Mice treated with CMHE showed significant increase in body weight and decrease in kidney weight as compared with toxic control group. Dose-dependent significant decrease in total blood urea nitrogen, serum creatinine, serum urea, and uric acid levels were observed in CMHE-treated groups as compared with toxic control group. Histopathological analysis of CMHE-treated groups showed improvement in kidney structures as compared with toxic control group. Conclusions: Biochemical, histopathological, and phytochemical screening of hydroalcoholic extract of Cucumis melo seeds suggest that it has nephroprotective potential. Furthermore, standardization of extract against identified phytochemicals, as well as long-term toxicological studies are suggested before commencement of clinical trials.


Asunto(s)
Antioxidantes/análisis , Antioxidantes/uso terapéutico , Cucumis melo/química , Enfermedades Renales/tratamiento farmacológico , Fitoterapia/efectos adversos , Extractos Vegetales/análisis , Extractos Vegetales/uso terapéutico , Semillas/química , Análisis de Varianza , Animales , Antioxidantes/administración & dosificación , Peso Corporal , Cromatografía Líquida de Alta Presión , Creatinina/sangre , Gentamicinas , Enfermedades Renales/inducido químicamente , Enfermedades Renales/patología , Ratones , Pakistán , Extractos Vegetales/administración & dosificación , Resultado del Tratamiento , Urea/sangre , Ácido Úrico/análisis
19.
J Biol Chem ; 294(4): 1410-1419, 2019 01 25.
Artículo en Inglés | MEDLINE | ID: mdl-30523155

RESUMEN

Cellular membrane trafficking mediated by the clathrin adaptor protein complex-1 (AP-1) is important for the proper composition and function of organelles of the endolysosomal system. Normal AP-1 function requires proteins of the HEAT repeat-containing 5 (HEATR5) family. Although HEATR5 proteins were first identified based on their ability to interact with AP-1, the functional significance of this interaction was unknown. We used bioinformatics-based phenotypic profiling and information from genome-wide fluorescence microscopy studies in the budding yeast Saccharomyces cerevisiae to identify a protein, Laa2, that mediates the interaction between AP-1 and the yeast HEATR5 protein Laa1. Further characterization of Laa2 revealed that it binds to both Laa1 and AP-1. Laa2 contains a motif similar to the characterized γ-ear-binding sites found in other AP-1-binding proteins. This motif in Laa2 is essential for the Laa1-AP-1 interaction. Moreover, mutation of this motif disrupted AP-1 localization and function and caused effects similar to mutations that remove the γ-ear of AP-1. These results indicate that Laa2 mediates the interaction between Laa1 and AP-1 and reveal that this interaction promotes the stable association of AP-1 with membranes in yeast.


Asunto(s)
Complejo 1 de Proteína Adaptadora/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Complejo 1 de Proteína Adaptadora/química , Proteínas Adaptadoras Transductoras de Señales/química , Biología Computacional , Proteínas de Unión al ADN/química , Microscopía Fluorescente , Fenotipo , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/crecimiento & desarrollo , Proteínas de Saccharomyces cerevisiae/química
20.
Sci Rep ; 8(1): 11919, 2018 08 09.
Artículo en Inglés | MEDLINE | ID: mdl-30093662

RESUMEN

Chemical sensitivity, growth inhibition in response to a chemical, is a powerful phenotype that can reveal insight into diverse cellular processes. Chemical sensitivity assays are used in nearly every model system, however the yeast Saccharomyces cerevisiae provides a particularly powerful platform for discovery and mechanistic insight from chemical sensitivity assays. Here we describe a simple and inexpensive approach to determine chemical sensitivity quantitatively in yeast in the form of half maximal inhibitory concentration (IC50) using common laboratory equipment. We demonstrate the utility of this method using chemicals commonly used to monitor changes in membrane traffic. When compared to traditional agar-based plating methods, this method is more sensitive and can detect defects not apparent using other protocols. Additionally, this method reduces the experimental protocol from five days to 18 hours for the toxic amino acid canavanine. Furthermore, this method provides reliable results using lower amounts of chemicals. Finally, this method is easily adapted to additional chemicals as demonstrated with an engineered system that activates the spindle assembly checkpoint in response to rapamycin with differing efficiencies. This approach provides researchers with a cost-effective method to perform chemical genetic profiling without specialized equipment.


Asunto(s)
Bioensayo/métodos , Endosomas/metabolismo , Saccharomyces cerevisiae/metabolismo , Red trans-Golgi/metabolismo , Bencenosulfonatos/farmacología , Bioensayo/economía , Membrana Celular/metabolismo , Análisis Costo-Beneficio , Endosomas/efectos de los fármacos , Concentración 50 Inhibidora , Transporte de Proteínas/efectos de los fármacos , Reproducibilidad de los Resultados , Saccharomyces cerevisiae/efectos de los fármacos , Proteínas de Saccharomyces cerevisiae/metabolismo , Factores de Tiempo , Red trans-Golgi/efectos de los fármacos
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