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1.
RSC Adv ; 14(10): 6793-6804, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38405069

RESUMO

We report the extraction of keratin nanofibers from the medulla of a parent yarn after denaturing the cuticle and cortex microstructures of a merino wool yarn. Controlled alkaline hydrolysis, followed by high-speed blending in acetic acid, allowed for the extraction of keratin protein nanofibers with an average diameter of 25 nm and a length of less than 3 µm. SEM and AFM analyses showed the removal of cuticle cells from the yarn. FT-IR and DSC analyses confirmed the hydrolysis and denaturation of the sheet protein matrix of cuticle cells. XPS analysis provided strong evidence for the gradual removal of the epicuticle, cuticle cells, and cortex of the hierarchical wool structure with an increase in alkaline hydrolysis conditions. It was confirmed that the merino wool yarn subjected to hydrolysis under alkaline conditions exposed its internal fibrillar surface. In an acetic acid medium, these fibrillar surfaces obtained a surface charge, which further supported the defibrillation of the structure into its individual nanofibrils during high-speed blending. The extracted nanostructures constitute mainly α-helical proteins. The morphology of the nanofibers is composed of a uniform circular cross-section based on the images obtained using AFM, TEM, and SEM. The extracted nanofibers were successfully fabricated into transparent sheets that can be used in several applications.

2.
Eur J Hum Genet ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38253783

RESUMO

The inherited disease community in Sri Lanka has been widely neglected. This article aimed to present accumulated knowledge in establishing a pro bono cost-effective national, island-wide, free-of-charge molecular diagnostic service, suggesting a model for other developing countries. The project provided 637 molecular diagnostic tests and reports free of charge to a nation with limited resources. We pioneered the implementation of mobile clinics and home visits, where the research team acted as barefoot doctors with the concept of the doctor and the researcher at the patient's doorstep. Establishing pro bono, cost-effective molecular diagnostics is feasible in developing countries with limited resources and state funding through the effort of dedicated postgraduate students. This service could provide an accurate molecular diagnosis of Duchenne muscular dystrophy, Huntington's disease, Spinocerebellar ataxia, and Spinal muscular atrophy, a diagnostic yield of 54% (343/637), of which 43% (147/343) of the patients identified as amenable for available gene therapies. Initiated human resource development by double doctoral degree opportunities with international collaborations. Established a neurobiobank and a national registry in Sri Lanka, a rich and unique repository, wealth creation for translational collaborative research and sharing of information in neurological diseases, as well as a lodestar for aspiring initiatives from other developing countries.

3.
RSC Adv ; 14(5): 3379-3389, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38259984

RESUMO

The emergence of resistance in detrimental pathogenic bacteria towards well-recognized antibiotics has greatly impacted global medicine, consequently exploring potent antibacterial compounds is becoming a potential area of research. Although photocatalytic metal oxides have been extensively explored in this regard, their applicability is diminished due to the requirement of photon energy. Therefore, in our study, we explored the light-independent antibacterial effect of two unexplored titanium species, known as metatitanic acid (MTA) and potassium titanate, against Staphylococcus aureus, Escherichia coli, and Pseudomonas spp. using the disk diffusion method in Luria-Bertani agar medium, where the well-known antibiotic, gentamicin, was used as the positive control. These two titanium compounds were readily synthesized through a novel process which was originally developed for the extraction of TiO2 from ilmenite. The synthesized MTA was characterized using FT-IR, Raman spectroscopy, XRD, TGA, UV-visible spectroscopy, and SEM. According to our findings, both MTA and potassium titanate exhibited superior light-independent antibacterial properties, where for some concentrations, the effect was even greater than gentamicin. However, nano-TiO2 totally failed as an antibacterial compound against the tested three strains under dark conditions.

4.
Eur J Med Res ; 29(1): 37, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195599

RESUMO

BACKGROUND: The phenotype of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) patients is determined by the type of DMD gene variation, its location, effect on reading frame, and its size. The primary objective of this investigation was to determine the frequency and distribution of DMD gene variants (deletions/duplications) in Sri Lanka through the utilization of a combined approach involving multiplex polymerase chain reaction (mPCR) followed by Multiplex Ligation Dependent Probe Amplification (MLPA) and compare to the international literature. The current consensus is that MLPA is a labor efficient yet expensive technique for identifying deletions and duplications in the DMD gene. METHODOLOGY: Genetic analysis was performed in a cohort of 236 clinically suspected pediatric and adult myopathy patients in Sri Lanka, using mPCR and MLPA. A comparative analysis was conducted between our findings and literature data. RESULTS: In the entire patient cohort (n = 236), mPCR solely was able to identify deletions in the DMD gene in 131/236 patients (DMD-120, BMD-11). In the same cohort, MLPA confirmed deletions in 149/236 patients [DMD-138, BMD -11]. These findings suggest that mPCR has a detection rate of 95% (131/138) among all patients who received a diagnosis. The distal and proximal deletion hotspots for DMD were exons 45-55 and 6-15. Exon 45-60 identified as a novel in-frame variation hotspot. Exon 45-59 was a hotspot for BMD deletions. Comparisons with the international literature show significant variations observed in deletion and duplication frequencies in DMD gene across different populations. CONCLUSION: DMD gene deletions and duplications are concentrated in exons 45-55 and 2-20 respectively, which match global variation hotspots. Disparities in deletion and duplication frequencies were observed when comparing our data to other Asian and Western populations. Identified a 95% deletion detection rate for mPCR, making it a viable initial molecular diagnostic approach for low-resource countries where MLPA could be used to evaluate negative mPCR cases and cases with ambiguous mutation borders. Our findings may have important implications in the early identification of DMD with limited resources in Sri Lanka and to develop tailored molecular diagnostic algorithms that are regional and population specific and easily implemented in resource limited settings.


Assuntos
Patologia Molecular , Região de Recursos Limitados , Adulto , Humanos , Criança , Sri Lanka , Algoritmos , Fenótipo
5.
BMC Biotechnol ; 23(1): 52, 2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066557

RESUMO

BACKGROUND: In this study, we designed a novel genetic circuit sensitive to Cd2+, Zn2+ and Pb2+ by mimicking the CadA/CadR operon system mediated heavy metal homeostasis mechanism of Pseudomonas aeruginosa. The regular DNA motifs on natural operon were reconfigured and coupled with the enhanced Green Fluorescent Protein (eGFP) reporter to develop a novel basic NOT type logic gate CadA/CadR-eGFP to respond metal ions mentioned above. A Genetically Engineered Microbial (GEM)-based biosensor (E.coli-BL21:pJET1.2-CadA/CadR-eGFP) was developed by cloning the chemically synthesised CadA/CadR-eGFP gene circuit into pJET1.2-plasmid and transforming into Escherichia coli (E. coli)-BL21 bacterial cells. RESULTS: The GEM-based biosensor cells indicated the reporter gene expression in the presence of Cd2+, Zn2+ and Pb2+ either singly or in combination. Further, the same biosensor cells calibrated for fluorescent intensity against heavy metal concentration generated linear graphs for Cd2+, Zn2+ and Pb2+ with the R2 values of 0.9809, 0.9761 and 0.9758, respectively as compared to non-specific metals, Fe3+ (0.0373), AsO43- (0.3825) and Ni2+ (0.8498) making our biosensor suitable for the detection of low concentration of the former metal ions in the range of 1-6 ppb. Furthermore, the GEM based biosensor cells were growing naturally within the concentration range of heavy metals, at 37 °C and optimum pH = 7.0 in the medium, resembling the characteristics of wildtype E.coli. CONCLUSION: Finally, the novel GEM based biosensor cells developed in this study can be applied for detection of targeted heavy metals in low concentration ranges (1-6 ppb) at normal bacterial physiological conditions.


Assuntos
Técnicas Biossensoriais , Metais Pesados , Cádmio/metabolismo , Chumbo/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Calibragem , Metais Pesados/metabolismo , Zinco , Íons/metabolismo
6.
Sci Rep ; 13(1): 14737, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37679648

RESUMO

A procedure based on acid extraction using a mixture of conc. sulfuric and nitric acids (8:1) to recover graphite attached to rock pieces of the vein contact zones of graphite mines, is developed as a sustainable mining practice. When the extracted graphite is heated at 600 °C for 15 min, it is converted to a highly expanded form resembling worm-like structures. The unique properties of this graphite and expanded graphite are presented by characterizing using FT-IR, Raman, SEM-EDX and XRD. This expanded graphite has the oil absorption capacity of 120 g of oil per 1 g of expanded graphite, making it the material so far known to have the highest oil absorption capacity. For comparison purpose, properties of ball-milled graphite powder which was obtained from the middle of the vein is prepared and characterized. However, the ball-milled graphite does not expand upon heat-treatment at 600 °C for 15 min. The acid-extracted graphite (AEG) has lower purity than that of ball-milled graphite (BMG), but heat-treatment increases the purity of the AEG while BMG shows opposite results. The purity of AEG has increased considerably upon heat-treatment by lowering the O wt% (weight percentage) by 6.07% to half of its original value while increasing C wt% by 8.05%. On the contrary, the C wt% of BMG has decreased by 3.71% and O wt% increased by 3.84%. The increase of purity upon heat treatment of AEG is due to the removal of some carbon and sulfur impurities as their volatile oxides. The ball-milled graphite absorbs carbon dioxide from the atmosphere when heat-treated at 600 °C. As such, the ball-milled graphite powder can be used to extract carbon dioxide from the atmosphere. The crystallite size of AEG is 1.25 times larger than that of BMG and it has been increased by 8 and 2.9 times, respectively, upon heat-treatment at 600 °C for 15 min. This is a clear evidence to expanded nature of AEG compared to BMG.

7.
J Clin Med ; 12(17)2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37685704

RESUMO

Brain function and its effect on motor performance in Duchenne muscular dystrophy (DMD) is an emerging concept. The present study explored how cumulative dystrophin isoform loss, age, and a corticosteroid treatment affect DMD motor outcomes. A total of 133 genetically confirmed DMD patients from Sri Lanka were divided into two groups based on whether their shorter dystrophin isoforms (Dp140, Dp116, and Dp71) were affected: Group 1, containing patients with Dp140, Dp116, and Dp71 affected (n = 98), and Group 2, containing unaffected patients (n = 35). A subset of 52 patients (Group 1, n = 38; Group 2, n = 14) was followed for up to three follow-ups performed in an average of 28-month intervals. The effect of the cumulative loss of shorter dystrophin isoforms on the natural history of DMD was analyzed. A total of 74/133 (56%) patients encountered developmental delays, with 66/74 (89%) being in Group 1 and 8/74 (11%) being in Group 2 (p < 0.001). Motor developmental delays were predominant. The hip and knee muscular strength, according to the Medical Research Council (MRC) scale and the North Star Ambulatory Assessment (NSAA) activities, "standing on one leg R", "standing on one leg L", and "walk", declined rapidly in Group 1 (p < 0.001 In the follow-up analysis, Group 1 patients became wheelchair-bound at a younger age than those of Group 2 (p = 0.004). DMD motor dysfunction is linked to DMD mutations that affect shorter dystrophin isoforms. When stratifying individuals for clinical trials, considering the DMD mutation site and its impact on a shorter dystrophin isoform is crucial.

8.
Ceylon Med J ; 68(S1): 9-20, 2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37609911

RESUMO

Background: There is a co-existence of different forms of malnutrition leading to a Triple Burden of Malnutrition (TBM) in Sri Lanka. Accessing basic needs and services was a challenge during COVID-19 pandemic, which led to issues in food security with an effect on nutrition status of the population. Objectives: To estimate the prevalence of malnutrition and dietary intakes of the population aged 1 to 60 years. Methods: This study was conducted in 2021. A multistage cluster sample was drawn to represent households at national level using 75 clusters, and 24-hour dietary recalls were compared with estimated average requirements of different age groups. Height and weight of all selected participants were measured. Results: A total of 1776 households and 2991 individuals were studied. The prevalence of wasting, stunting and overweight of children aged 1-4 years (n=486) was 14%, 16.3% and 0.8% respectively. Thinness, stunting, overweight and obesity of children aged 5-9 years (n=388) was 21.4%, 8.5%, 5.2%, 5.1%; children aged 10-17 years (n=355) was 21.1%, 14.1%,11%, 8.2%; and adults aged 18-60 years (n=1762) was 9.9%, 5.4%, 32.6% and 11.5% respectively. Dietary intake gaps were minimal with energy and protein while it was wider with majority of vitamins, iron and calcium. Stunting of children aged 1-4 years was significantly associated with the low calcium and iron intakes. Conclusions: The presence of TBM amongst children and adults were observed with a dietary gap of essential micronutrients. This study highlights the need to re-orient the nutritional interventions to control TBM at population level.


Assuntos
COVID-19 , Ingestão de Alimentos , Desnutrição , Estado Nutricional , Sri Lanka/epidemiologia , Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , COVID-19/epidemiologia , Segurança Alimentar , Desnutrição/epidemiologia , Prevalência
9.
Heliyon ; 9(8): e18530, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37593636

RESUMO

Introduction: Documented Duchenne Muscular Dystrophy (DMD) biomarkers are confined to Caucasians and are poor indicators of cognitive difficulties and neuropsychological alterations. Materials and methods: This study correlates serum protein signatures with cognitive performance in DMD patients of South Asian origin. Study included 25 DMD patients aged 6-16 years. Cognitive profiles were assessed by Wechsler Intelligence Scale for Children. Serum proteome profiling of 1317 proteins was performed in eight DMD patients and eight age-matched healthy volunteers. Results: Among the several novel observations we report, better cognitive performance in DMD was associated with increased serum levels of MMP9 and FN1 but decreased Siglec-3, C4b, and C3b. Worse cognitive performance was associated with increased serum levels of LDH-H1 and PDGF-BB but reduced GDF-11, MMP12, TPSB2, and G1B. Secondly, better cognitive performance in Processing Speed (PSI) and Perceptual Reasoning (PRI) domains was associated with intact Dp116, Dp140, and Dp71 dystrophin isoforms while better performance in Verbal Comprehension (VCI) and Working Memory (WMI) domains was associated with intact Dp116 and Dp140 isoforms. Finally, functional pathways shared with Alzheimer's Disease (AD) point towards an astrocyte-centric model for DMD. Conclusion: Astrocytic dysfunction leading to synaptic dysfunction reported previously in AD may be a common pathogenic mechanism underlying both AD and DMD, linking protein alterations to cognitive impairment. This new insight may pave the path towards novel therapeutic approaches targeting reactive astrocytes.

10.
J Ayurveda Integr Med ; 14(4): 100751, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37506606

RESUMO

BACKGROUND: Since ancient times, the essential element sulphur has played an important role in different medical fields. It is one of the main materials used in herbo-mineral pharmaceutics in Ayurveda. However, for Ayurvedic pharmaceutical preparations, the purity of sulphur is crucial in avoiding any harmful reactions and to enhance the medicinal quality. Therefore, it is subjected to a process called 'gandhaka shodhana' using cow's milk, ghee or occasionally plant extracts. The plant, Eclipta alba (L.) Hassak, containing many bioactive compounds, is one of the extracts known to be used in the 'shodhana' process of sulphur. However, in comparison to the laboratory purification method of sulphur neither the effect of this 'shodhana' process in removing impurities from sulphur nor its effect on the structure and morphology of sulphur has been evaluated. OBJECTIVES: This study identifies physical, morphological, and structural changes that occur in sulphur when it is subjected to the 'shodhana' process compared to the changes that occur in sulphur obtained after simple laboratory purification. METHODOLOGY: Both samples were characterized using Scanning Electron Microscopy, Energy Dispersive X-ray Spectroscopy, X-ray Diffraction, Differential Scanning Calorimetry, Thermogravimetric Analysis, Fourier Transform Infrared spectroscopy, and Raman spectroscopy. Observed physical changes such as colour, allotropic form, odour, hardness, transparency, and lustre of the samples were also determined using recommended techniques. RESULTS: Although the laboratory purification method separates the sulphur from physical and chemical impurities, Ayurveda 'shodhana' process with E. alba converts the sulphur into a more pharmaceutically suitable form by making it more nebulous and introducing higher brittleness, FT-IR data shows removal of chemical impurities from sulphur during 'shodhana' process in contrast to laboratory purified sample.

11.
RSC Adv ; 13(27): 18605-18613, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37346959

RESUMO

A new approach was used to produce electrically conductive polyamide yarns, employing an electroless plating technique, which involved stabilizing silver nanoparticles on the surface of the yarn using Sn2+. First, the [Ag(NH3)2]+ complex was reduced using Sn2+ to produce silver nanoparticle seed layers on the fiber surface, followed by a formaldehyde reduction. The nucleation and growth of silver nanoparticles on the fiber surface were observed through SEM images, demonstrating varying degrees of silver deposition depending on the silver concentration. This deposition variation was confirmed through XRD patterns, TGA data and UV-vis spectra. Additionally, XPS characterization showed the evolution of the chemical state of silver and tin during the silver reduction process. Electrical resistance revealed that the resistance per unit length of the yarn ranged from 3 ± 0.3 Ω cm-1 to 70 ± 6 Ω cm-1, depending on the silver concentration. The resulting silver-plated yarn was incorporated into a stretchable device, demonstrating stable resistance over multiple cycles. This method of fabricating conductive yarn has the potential to open up new possibilities in the design and manufacture of stretchable conductive devices for flexible electronics.

12.
Artigo em Inglês | MEDLINE | ID: mdl-37089709

RESUMO

Neuroimmune diseases are a group of disorders that occur due to the dysregulation of both the nervous and immune systems, and these illnesses impact tens of millions of people worldwide. However, patients who suffer from these debilitating conditions have very few FDA-approved treatment options. Neuroimmune crosstalk is important for controlling the immune system both centrally and peripherally to maintain tissue homeostasis. This review aims to provide readers with information on how natural products modulate neuroimmune crosstalk and the therapeutic implications of natural products, including curcumin, epigallocatechin-3-gallate (EGCG), ginkgo special extract, ashwagandha, Centella asiatica, Bacopa monnieri, ginseng, and cannabis to mitigate the progression of neuroimmune diseases, such as Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson's disease, depression, and anxiety disorders. The majority of the natural products based clinical studies mentioned in this study have yielded positive results. To achieve the expected results from natural products based clinical studies, researchers should focus on enhancing bioavailability and determining the synergistic mechanisms of herbal compounds and extracts, which will lead to the discovery of more effective phytomedicines while averting the probable negative effects of natural product extracts. Therefore, future studies developing nutraceuticals to mitigate neuroimmune diseases that incorporate phytochemicals to produce synergistic effects must analyse efficacy, bioavailability, gut-brain axis function safety, chemical modifications, and encapsulation with nanoparticles.

13.
R Soc Open Sci ; 10(3): 221514, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36908995

RESUMO

Nano-zirconia (ZO) was synthesized using a microwave-assisted one-pot precipitation route. Two biopolymers, chitosan (CTS) and carboxymethyl cellulose were blended with ZO at different w/w ratios. The formulation with 30% w/w chitosan (ZO-CTS) was found to give enhanced uptake of F- and As(V). ZO and the most effective ZO-CTS system were characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. These confirmed the formation of a composite system containing nanoparticles of 50 nm in size, in which ZO was present in the amorphous form. It was observed that the combination of ZO with CTS improved the F- and As(V) adsorption capacity most notably at pH 5.5. Fluoride adsorption by ZO-CTS followed the Freundlich isotherm model, with an adsorption capacity of 120 mg g-1. Adsorption of As(V) by ZO-CTS could be fitted with both the Langmuir and Freundlich isotherm models and was found to have a capacity of 14.8 mg g-1. Gravity filtration studies conducted for groundwater levels indicated the effectiveness of ZO-CTS in adsorbing As(V) and F- at a pH of 5.5. The ability of the ZO-CTS in removing Cd(II) and Pb(II) was also investigated, and no such enhancement was observed, and found the neat ZO was the most potent sorbent here.

14.
Front Endocrinol (Lausanne) ; 14: 1028285, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36814577

RESUMO

Background: There is limited information about diabetes and thyroid related autoantibodies in children with type 1 diabetes (T1D) or their siblings in Sri Lanka. Objectives: To assess in T1D children and their unaffected siblings the prevalence of autoantibodies to (1) glutamic acid decarboxylase (GADA), insulinoma associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) using 3 Screen ICA™ (3-Screen) and individual ELISA assays; (2) insulin (IAA); and (3) thyroid peroxidase (TPOA), thyroglobulin (TgA) and the TSH receptor (TSHRA). Methods: We selected - (a) consecutive T1D children, and (b) their unaffected siblings of both sexes, from the T1D Registry at Lady Ridgeway Hospital, Colombo. Results: The median age (IQR) of 235 T1D children and 252 unaffected siblings was 11 (8.4, 13.2) and 9 (5.4, 14.9) years respectively, and the duration of T1D was 23 (7, 54) months. (1) T1D children (a) 79.1% were 3-Screen positive; (b) all 3-Screen positives were individual antibody positive (GADA in 74%; IA-2A 31.1%; ZnT8A 38.7%); (c) and were younger (p=0.01 vs 3-Screen negatives); (d) multiple autoantibodies were present in 45.1%; (e) IA-2A (p=0.002) and ZnT8A (p=0.006) prevalence decreased with T1D duration. (f) TPOA and TgA prevalence was higher in T1D children compared to unaffected siblings (28%, p=0.001 and 31%, p=0.004, respectively). (2) Unaffected siblings (a) 6.3% were 3-Screen positive (p=0.001 vs T1D), and 2.4% were positive for IAA; (b) four subjects had two diabetes related autoantibodies, one of whom developed dysglycaemia during follow-up. Conclusions: The 3-Screen assay, used for the first time in Sri Lankan T1D children and their siblings as a screening tool, shows a high prevalence of T1D related Abs with a high correlation with individual assays, and is also a helpful tool in screening unaffected siblings for future T1D risk. The higher prevalence of thyroid autoantibodies in T1D children is consistent with polyglandular autoimmunity.


Assuntos
Diabetes Mellitus Tipo 1 , Masculino , Feminino , Humanos , Criança , Sri Lanka , Irmãos , Glândula Tireoide , Prevalência , Autoanticorpos
15.
IBRO Neurosci Rep ; 14: 146-153, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36819775

RESUMO

Background: In this article, the authors discuss how they utilized the genetic mutation data in Sri Lankan Duchenne muscular dystrophy (DMD), Spinal muscular atrophy (SMA), Spinocerebellar ataxia (SCA) and Huntington's disease (HD) patients and compare the available literature from South Asian countries to identifying potential candidates for available gene therapy for DMD, SMA, SCA and HD patients. Methods: Rare disease patients (n = 623) with the characteristic clinical findings suspected of HD, SCA, SMA and Muscular Dystrophy were genetically confirmed using Multiplex Ligation Dependent Probe Amplification (MLPA), and single plex PCR. A survey was conducted in the "Wiley database on Gene Therapy Trials Worldwide" to identify DMD, SMA, SCA, and HD gene therapy clinical trials performed worldwide up to April 2021. In order to identify candidates for gene therapy in other neighboring countries we compared our findings with available literature from India and Pakistan which has utilized the same molecular diagnostic protocol to our study. Results: From the overall cohort of 623 rare disease patients with the characteristic clinical findings suspected of HD, SCA, SMA and Muscular Dystrophy, n = 343 (55%) [Muscular Dystrophy- 65%; (DMD-139, Becker Muscular Dystrophy -BMD-11), SCA type 1-3-53% (SCA1-61,SCA2- 23, SCA3- 39), HD- 52% (45) and SMA- 34% (22)] patients were positive for molecular diagnostics by MLPA and single plex PCR. A total of 147 patients in Sri Lanka amenable to available gene therapy; [DMD-83, SMA-15 and HD-49] were identified. A comparison of Sri Lankan finding with available literature from India and Pakistan identified a total of 1257 patients [DMD-1076, SMA- 57, and HD-124] from these three South Asian Countries as amenable for existing gene therapy trials. DMD, SMA, and HD gene therapy clinical trials (113 studies) performed worldwide up to April 2021 were concentrated mostly (99%) in High Income Countries (HIC) and Upper Middle-Income Countries (UMIC). However, studies on the potential use of anti-sense oligonucleotides (ASO) for treatment of SCAs have yet to reach clinical trials. Conclusion: Most genetic therapies for neurodegenerative and neuromuscular disorders have been evaluated for efficacy primarily in Western populations. No multicenter gene therapy clinical trial sites for DMD, SMA and HD in the South Asian region, leading to lack of knowledge on the safety and efficacy of such personalized therapies in other populations, including South Asians. By fostering collaboration between researchers, clinicians, patient advocacy groups, government and industry in gene therapy initiatives for the inherited-diseases community in the developing world would link the Global North and Global South and breathe life into the motto "Together we can make a difference".

16.
ACS Omega ; 7(42): 37264-37278, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36312427

RESUMO

This study reveals the state-of-the-art fabrication of a tripolymer-based electrospun nanofiber (NF) system to enhance the release, solubility, and transdermal penetration of curcumin (Cur) with the aid of in situ release of infused castor oil (Co). In this regard, Cur-loaded Co-infused polyethylene oxide (PEO), ethyl cellulose (EC), and polyvinyl pyrrolidone (PVP) tripolymer-based NF systems were developed to produce a hybridized transdermal skin patch. Weight percentages of 1-4% Cur and 3-10% of Co were blended with PEO-EC-PEO and PEO-EC-PVP polymer systems. The prepared NFs were characterized by SEM, TEM, FT-IR analysis, PXRD, differential scanning calorimetry (DSC), and XPS. Dialysis membranes and vertical Franz diffusion cells were used to study the in vitro drug release and transdermal penetration, respectively. The results indicated that maintaining a Cur concentration of 1-3 wt % with 3 wt % Co in both PEO-EC-Co-Cur@PEO and PEO-EC-Co-Cur@PVP gave rise to nanofibers with lowered diameters (144.83 ± 48.05-209.26 ± 41.80 nm and 190.20 ± 59.42-404.59 ± 45.31 nm). Lowered crystallinity observed from the PXRD patterns and the disappearance of exothermic peaks corresponding to the melting point of Cur suggested the formation of an amorphous NF structure. Furthermore, the XPS data revealed that the Cur loading will possibly take place at the inner interface of PEO-EC-Co-PEO and PEO-EC-Co-PVP NFs rather than on the surface. The beneficiary role of Co on the release and dermal penetration of Cur was further confirmed from the respective release data which indicated that PEO-EC-Co-Cur@PEO would lead to a rapid release (4-5 h), while PEO-EC-Co-Cur@PVP would lead to a sustained release over a period of 24 h in the presence of Co. Transdermal penetration of the released Cur was further evidenced with the development of color in the receiver compartment of the diffusion cell. DPPH results further corroborated that a sustained antioxidant activity is observed in the released Cur where the free-radical scavenging activity is intact even after subjecting to an electrospinning process and under extreme freeze-thaw conditions.

17.
ACS Omega ; 7(33): 29287-29296, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36033719

RESUMO

We report the synthesis of nitrogen-doped graphene oxide, with 5.7-7.0 wt % nitrogen doping, from different sizes of precursor graphite and study its effect on the oxygen evolution reaction (OER) activity of IrO2 in an acidic medium. The nitrogen-doped supports are expected to have pyridinic, pyrrolic, and graphitic functionalities at different ratios responsible for their improved performance. The N-doped supports and catalysts are synthesized via pyrolysis and the hydrothermal method using natural and synthetic graphite of three different flake sizes and evaluated for their structural and electrochemical characteristics. The average size of IrO2 nanoparticles deposited on the N-doped supports is independent of the flake size and doping amount of nitrogen. The catalysts show optimum current densities but improved stability with increasing flake sizes of 7, 20, and 125 µm. Our results demonstrate that the selection of the flake size of the doped support is necessary to achieve durable catalysts for the OER in an acidic medium.

18.
Nano Lett ; 22(12): 4941-4948, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35687040

RESUMO

Angstrom-confined solvents in 2D laminates can travel through interlayer spacings, through gaps between adjacent sheets, and via in-plane pores. Among these, experimental access to investigate the mass transport through in-plane pores is lacking. Our experiments allow an understanding of this mass transport via the controlled variation of oxygen functionalities, size and density of in-plane pores in graphene oxide membranes. Contrary to expectations, our transport experiments show that higher in-plane pore densities may not necessarily lead to higher water permeability. We observed that membranes with a high in-plane pore density but a low amount of oxygen functionalities exhibit a complete blockage of water. However, when water-ethanol mixtures with a weaker hydrogen network are used, these membranes show an enhanced permeation. Our combined experimental and computational results suggest that the transport mechanism is governed by the attraction of the solvents toward the pores with functional groups and hindered by the strong hydrogen network of water formed under angstrom confinement.

19.
Growth Horm IGF Res ; 62: 101443, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34971854

RESUMO

OBJECTIVE: To identify and characterize a novel deletion at the LHX4 gene locus in a proband with growth hormone deficiency (GHD). METHODS: Long range polymerase chain reaction (PCR) amplification was used to confirm the suspected deletion and to identify the rough locations of the end points. Sanger sequencing was carried out to identify the exact end points of the deletion. RESULTS: Suspected deletion was confirmed via long range PCR amplification. Sanger sequencing identified the end points of the deletion within three nucleotide repeat sequences ("CTT"). The total length of the deleted segment was 12 127 base pairs and it includes complete exon 5 and exon 6 of the LHX4 gene. Therefore the homeodomain motif coded by exons 4 and 5, might be affected. CONCLUSION: We have identified a novel deletion that spans exon 5 and exon 6 of the LHX4 gene that could have occurred via microhomology mediated non-recurrent rearrangement. The deletion characterized does not appear to have been reported before. To our knowledge this novel deletion is the first identified LHX4 variant from Sri Lanka and it explains the phenotype of the proband characterized by growth hormone deficiency, hypoplastic anterior pituitary and subsequent deficiency of thyroid stimulating hormone and adrenocorticotropic hormone (ACTH).


Assuntos
Nanismo Hipofisário , Hipopituitarismo , Nanismo Hipofisário/genética , Deleção de Genes , Hormônio do Crescimento/genética , Humanos , Hipopituitarismo/genética , Proteínas com Homeodomínio LIM/genética , Fatores de Transcrição/genética
20.
Sci Rep ; 11(1): 22713, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34811409

RESUMO

A novel and simple flotation technique has been developed to prepare high-purity graphite from impure graphite. In this method, a suspension of pristine powdered graphite (PG) is dispersed and stirred in water without adding froth formers or supportive chemicals. This makes fine particles of graphite move upwards and float on water. X-ray diffraction (XRD) analysis reveals that the floated graphite (FG) has a lower c-axis parameter, indicating the removal of interlayer impurities. A notable increase in the intensity ratio of the D band to G band in the Raman spectra indicates that the FG has more edge defects due to their smaller crystallite sizes. Transmission electron microscopic (TEM) analysis shows the number of layers in FG has been reduced to 16 from 68 in PG. The absence of C=O vibration of Fourier Transformed Infrared (FT-IR) spectroscopy in treated and untreated samples suggests that their layers are not significantly oxidized. However, X-ray photoelectron spectroscopic (XPS) analysis shows the presence of C-O-C ether functionalities, possibly on edge planes. Further, the product has higher purity with increased carbon content. Therefore, the technique is helpful for the value enhancement of graphite, the reduction of the chemical cost of the conventional techniques, environmental friendliness, and improvement of its applications.

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