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1.
Nature ; 630(8017): 654-659, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38839965

RESUMEN

Emissions reduction and greenhouse gas removal from the atmosphere are both necessary to achieve net-zero emissions and limit climate change1. There is thus a need for improved sorbents for the capture of carbon dioxide from the atmosphere, a process known as direct air capture. In particular, low-cost materials that can be regenerated at low temperatures would overcome the limitations of current technologies. In this work, we introduce a new class of designer sorbent materials known as 'charged-sorbents'. These materials are prepared through a battery-like charging process that accumulates ions in the pores of low-cost activated carbons, with the inserted ions then serving as sites for carbon dioxide adsorption. We use our charging process to accumulate reactive hydroxide ions in the pores of a carbon electrode, and find that the resulting sorbent material can rapidly capture carbon dioxide from ambient air by means of (bi)carbonate formation. Unlike traditional bulk carbonates, charged-sorbent regeneration can be achieved at low temperatures (90-100 °C) and the sorbent's conductive nature permits direct Joule heating regeneration2,3 using renewable electricity. Given their highly tailorable pore environments and low cost, we anticipate that charged-sorbents will find numerous potential applications in chemical separations, catalysis and beyond.


Asunto(s)
Dióxido de Carbono , Dióxido de Carbono/análisis , Dióxido de Carbono/química , Dióxido de Carbono/aislamiento & purificación , Adsorción , Electrodos , Hidróxidos/química , Atmósfera/química , Carbonatos/química , Aire , Temperatura , Carbón Orgánico/química , Porosidad , Carbono/química
2.
J Cell Physiol ; 239(9): e31388, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39034451

RESUMEN

Runt-related transcription factor 2 (Runx2) is a key regulator of osteoblast differentiation and bone formation. In Runx2-deficient embryos, skeletal development ceases at the cartilage anlage stage. These embryos die of respiratory failure upon birth and display a complete absence of bone and cartilage mineralization. Here, we identified Hakai, a type of E3 ubiquitin ligase as a potential Runx2 interacting partner through affinity pulldown-based proteomic approach. Subsequently, we observed that similar to Runx2, Hakai was downregulated in osteopenic ovariectomized rats, suggesting its involvement in bone formation. Consistent with this observation, Hakai overexpression significantly enhanced osteoblast differentiation in mesenchyme-like C3H10T1/2 as well as primary rat calvaria osteoblast (RCO) cells in vitro. Conversely, overexpression of a catalytically inactive Hakai mutant (C109A) exhibited minimal to no effect, whereas Hakai depletion markedly reduced endogenous Runx2 levels and impaired osteogenic differentiation in both C3H10T1/2 and RCOs. Mechanistically, Hakai physically interacts with Runx2 and enhances its protein turnover by rescuing it from Smad ubiquitination regulatory factor 2 (Smurf2)-mediated proteasome degradation. Wild-type Hakai but not Hakai-C109A inhibited Smurf2 protein levels through proteasome-mediated degradation. These findings underscore Hakai's functional role in bone formation, primarily through its positive modulation of Runx2 protein turnover by protecting it from Smurf2-mediated ubiquitin-proteasomal degradation. Collectively, our results demonstrate Hakai as a promising novel therapeutic target for osteoporosis.


Asunto(s)
Diferenciación Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Osteoblastos , Osteogénesis , Complejo de la Endopetidasa Proteasomal , Ubiquitina-Proteína Ligasas , Animales , Osteoblastos/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Osteogénesis/genética , Ratas , Femenino , Humanos , Ratones , Proteolisis , Ratas Sprague-Dawley , Ubiquitinación
3.
J Cell Physiol ; 239(5): e31217, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38327035

RESUMEN

A few ubiquitin ligases have been shown to target Runx2, the key osteogenic transcription factor and thereby regulate bone formation. The regulation of Runx2 expression and function are controlled both at the transcriptional and posttranslational levels. Really interesting new gene (RING) finger ubiquitin ligases of which RNF138 is a member are important players in the ubiquitin-proteasome system, contributing to the regulation of protein turnover and cellular processes. Here, we demonstrated that RNF138 negatively correlated with Runx2 protein levels in osteopenic ovariectomized rats which implied its role in bone loss. Accordingly, RNF138 overexpression potently inhibited osteoblast differentiation of mesenchyme-like C3H10T1/2 as well primary rat calvarial osteoblast (RCO) cells in vitro, whereas overexpression of catalytically inactive mutant RNF138Δ18-58 (lacks RING finger domain) had mild to no effect. Contrarily, RNF138 depletion copiously enhanced endogenous Runx2 levels and augmented osteogenic differentiation of C3H10T1/2 as well as RCOs. Mechanistically, RNF138 physically associates within multiple regions of Runx2 and ubiquitinates it leading to its reduced protein stability in a proteasome-dependent manner. Moreover, catalytically active RNF138 destabilized Runx2 which resulted in inhibition of its transactivation potential and physiological function of promoting osteoblast differentiation leading to bone loss. These findings underscore the functional involvement of RNF138 in bone formation which is primarily achieved through its modulation of Runx2 by stimulating ubiquitin-mediated proteasomal degradation. Thus, our findings indicate that RNF138 could be a promising novel target for therapeutic intervention in postmenopausal osteoporosis.


Asunto(s)
Diferenciación Celular , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Osteoblastos , Osteogénesis , Ubiquitina-Proteína Ligasas , Ubiquitinación , Animales , Femenino , Humanos , Ratones , Ratas , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Células HEK293 , Osteoblastos/metabolismo , Ovariectomía , Complejo de la Endopetidasa Proteasomal/metabolismo , Estabilidad Proteica , Ratas Sprague-Dawley , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética
4.
J Am Chem Soc ; 146(33): 23171-23181, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39133641

RESUMEN

Conductive layered metal-organic frameworks (MOFs) have demonstrated promising electrochemical performances as supercapacitor electrode materials. The well-defined chemical structures of these crystalline porous electrodes facilitate structure-performance studies; however, there is a fundamental lack in the molecular-level understanding of charge storage mechanisms in conductive layered MOFs. To address this, we employ solid-state nuclear magnetic resonance (NMR) spectroscopy to study ion adsorption in nickel 2,3,6,7,10,11-hexaiminotriphenylene, Ni3(HITP)2. In this system, we find that separate resonances can be observed for the MOF's in-pore and ex-pore ions. The chemical shift of in-pore electrolyte is found to be dominated by specific chemical interactions with the MOF functional groups, with this result supported by quantum mechanics/molecular mechanics (QM/MM) and density functional theory (DFT) calculations. Quantification of the electrolyte environments by NMR was also found to provide a proxy for electrochemical performance, which could facilitate the rapid screening of synthesized MOF samples. Finally, the charge storage mechanism was explored using a combination of ex-situ NMR and operando electrochemical quartz crystal microbalance (EQCM) experiments. These measurements revealed that cations are the dominant contributors to charge storage in Ni3(HITP)2, with anions contributing only a minor contribution to the charge storage. Overall, this work establishes the methods for studying MOF-electrolyte interactions via NMR spectroscopy. Understanding how these interactions influence the charging storage mechanism will aid the design of MOF-electrolyte combinations to optimize the performance of supercapacitors, as well as other electrochemical devices including electrocatalysts and sensors.

5.
J Neurogenet ; 38(2): 27-34, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38975939

RESUMEN

Tropical ataxic neuropathy (TAN) is characterised by ataxic polyneuropathy, degeneration of the posterior columns and pyramidal tracts, optic atrophy, and sensorineural hearing loss. It has been attributed to nutritional/toxic etiologies, but evidence for the same has been equivocal. TAN shares common clinical features with inherited neuropathies and mitochondrial disorders, it may be hypothesised that genetic abnormalities may underlie the pathophysiology of TAN. This study aimed to establish evidence for mitochondrial dysfunction by adopting an integrated biochemical and multipronged genetic analysis. Patients (n = 65) with chronic progressive ataxic neuropathy with involvement of visual and/or auditory pathways underwent deep phenotyping, genetic studies including mitochondrial DNA (mtDNA) deletion analysis, mtDNA and clinical exome sequencing (CES), and respiratory chain complex (RCC) assay. The phenotypic characteristics included dysfunction of visual (n = 14), auditory (n = 12) and visual + auditory pathways (n = 29). Reduced RCC activity was present in 13 patients. Mitochondrial DNA deletions were noted in five patients. Sequencing of mtDNA (n = 45) identified a homoplasmic variant (MT-ND6) and a heteroplasmic variant (MT-COI) in one patient each. CES (n = 45) revealed 55 variants in nuclear genes that are associated with neuropathy (n = 27), deafness (n = 7), ataxia (n = 4), and mitochondrial phenotypes (n = 5) in 36 patients. This study provides preliminary evidence that TAN is associated with a spectrum of genetic abnormalities, including those associated with mitochondrial dysfunction, which is in contradistinction from the prevailing hypothesis that TAN is related to dietary toxins. Analysing the functional relevance of these genetic variants may improve the understanding of the pathogenesis of TAN.


Asunto(s)
Ataxia , ADN Mitocondrial , Humanos , Masculino , Femenino , ADN Mitocondrial/genética , Adulto , Persona de Mediana Edad , Ataxia/genética , Adolescente , Enfermedades Mitocondriales/genética , Adulto Joven , Mitocondrias/genética , Niño , Anciano , Secuenciación del Exoma , Fenotipo
6.
Calcif Tissue Int ; 114(3): 295-309, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38102510

RESUMEN

Vascular dysfunction contributes to the development of osteopenia in hypertensive patients, as decreased blood supply to bones results in tissue damage and dysfunction. The effect of anti-hypertensive medicines on bone mass in hypertensive individuals is inconclusive because of the varied mechanism of their action, and suggests that reducing blood pressure (BP) alone is insufficient to enhance bone mass in hypertension. Pentoxifylline (PTX), a hemorheological drug, improves blood flow by reducing blood viscosity and angiogenesis, also has an osteogenic effect. We hypothesized that improving vascular function is critical to increasing bone mass in hypertension. To test this, we screened various anti-hypertensive drugs for their in vitro osteogenic effect, from which timolol and hydralazine were selected. In adult female spontaneously hypertensive rats (SHRs), timolol and hydralazine did not improve vascular function and bone mass, but PTX improved both. In female SHR animals, PTX restored bone mass, strength and mineralization, up to the level of normotensive control rats. In addition, we observed lower blood vasculature in the femur of adult SHR animals, and PTX restored them. PTX also restored the bone vascular and angiogenesis parameters that had been impaired in OVX SHR compared to sham SHR. This study demonstrates the importance of vascular function in addition to increased bone mass for improving bone health as achieved by PTX without affecting BP, and suggests a promising treatment option for osteoporosis in hypertensive patients, particularly at-risk postmenopausal women.


Asunto(s)
Hipertensión , Pentoxifilina , Humanos , Ratas , Femenino , Animales , Antihipertensivos/farmacología , Antihipertensivos/uso terapéutico , Densidad Ósea , Timolol/farmacología , Timolol/uso terapéutico , Hipertensión/tratamiento farmacológico , Ratas Endogámicas SHR , Pentoxifilina/farmacología , Hidralazina/farmacología , Hidralazina/uso terapéutico , Presión Sanguínea
7.
Int Microbiol ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740653

RESUMEN

The current study was aimed for the generation of Pleurotus extracellular extract-mediated selenium and zinc-oxide nanoparticles (NPs). The Pleurotus djamor (PD) and Pleurotus sajor-caju (PSC) extracts were incubated with different concentrations of sodium selenate and zinc acetate to yield BioSeNPs and BioZnONPs. The NPs formation led to visual color change (brick-red and white for Se and Zn nanosols, respectively). The synthesized NPs were spherical with size of 124 and 68 nm and 84 and 91 nm for PD and PSC BioSeNPs and BioZnONPs respectively. The UV absorbance peaks were recorded at 293.2 and 292.2 nm and 365.9 and 325.5 nm for BioSeNPs and BioZnONPs derived from PD and PSC respectively. FT-IR spectroscopy indicated specific functional group adoration on metal-based NPs. On supplementation in straw, these NPs improved the fruit body yield besides enhancing their protein and Se/ Zn contents. These biofortified mushrooms could be potential dietary supplement/ nutraceutical.

8.
Int Microbiol ; 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38506949

RESUMEN

Essential oils are highly complex volatile chemical compounds utilized for food preservation. The present study compares the antibacterial, and antibiofilm activities of essential oils (EOs) and their blends. Three EOs-basil, clove, and lemongrass-and their blends were evaluated against five food-borne bacterial pathogens. A concentration-dependent effect with maximum inhibition at minimum inhibitory concentration values was recorded while no synergistic activity was observed on blending of EOs. The mechanism of antibacterial action was identified as ROS burst, leakage of cytoplasmic content, and DNA degradation through fluorescence microscopy, electrical conductivity, and DNA cleavage studies. The role of EOs on biofilm growth was deciphered with lemongrass EO being most effective as it curbed biofilm formation on the surface of corn-starch packaging films. This work highlights the antibacterial action mechanism of EOs and their potential role in curtailing biofilm growth on food-grade packaging material.

9.
J Fluoresc ; 2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38411860

RESUMEN

Iron, an essential trace element exhibits detrimental effects on human health when present at higher or lower concentration than the required. Therefore, there is a pressing demand for sensitive and selective detection of Fe3+ in water, food etc. Unfortunately, in several instances, the traditional approaches suffer from a number of shortcomings like complicated procedures, limited sensitivity, poor selectivity and more expensive and time consuming. The scope of optical tuning and excellent photophysical properties of carbon- based nanomaterials like carbon dots (C-dots) and graphene dots (g-dots) have made them promising optical sensors of metal ions. Moreover, high surface area, superior stability of such materials contributes towards the fruitful development of sensors. The present review offered critical information on the fabrication and fluorimetric applications of these functional nanomaterials for sensitive and selective detection of Fe3+. An in-depth discussion on fluorescent C-dots made from naturally occurring materials and chemical techniques were presented. Effect of doping in C-dots was also highlighted in terms of improved fluorescence response and selectivity. In a similar approach g-dots were also discussed. Many of these sensors exhibited great selectivity, superior sensitivity, high quantum yield, robust chemical and photochemical stability and real-time applicability. Further improvement in these factors can be targeted to develop new sensors.

10.
Methods ; 217: 27-35, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37399850

RESUMEN

Schiff base probes (1 and 2) made from o-phenylenediamine and o-aminophenol were appeared as highly selective fluorimetric chemosensor of Cu2+ and Al3+ ions respectively. Strong fluorescence emission of probe 1 at 415 nm (excitation at 350 nm) was instantly turned off on addition of Cu2+. Very weak fluorescence of probe 2 at 506 nm (excitation at 400 nm) was immediately turned on specifically by Al3+. Job's plot and ESI-MS results suggested 1:1 molar stoichiometric ratio of metal ion and probe in their respective complexes. Probe 1 and 2 had demonstrated very low detection limit (9.9 and 2.5 nM respectively). Binding of Cu2+ with probe 1 was found chemically reversible on addition of EDTA, while complexation between Al3+ and probe 2 was not reversible. On the basis of density functional theory (DFT) and spectroscopic results, probable mode of sensing of the metal ions by the probes were proposed. Quenching of the fluorescence of probe 1 by Cu2+ was attributed to the extensive transfer of charge from the probe molecule to paramagnetic copper ion. Whereas, in the Al3+-complex of probe 2, photo-induced electron transfer (PET) process from the imine nitrogen to salicylaldehyde moiety was restricted and thereby the weak emission intensity of probe 2 was enhanced significantly. Effective pH range of sensing the metal ions by probe 1 and 2 were 4 to 8 and 6 to 10 respectively. Probe 1 was also applied in the design of a logic gate for Cu2+ detection. Moreover, probe 1 and 2 was also used in water sample analysis for quantitative estimation of Cu2+ and Al3+ respectively.


Asunto(s)
Cobre , Bases de Schiff , Cobre/química , Bases de Schiff/química , Metales , Iones , Espectrometría de Fluorescencia/métodos , Colorantes Fluorescentes/química
11.
Mol Biol Rep ; 51(1): 873, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39080117

RESUMEN

Macrofungi commonly referred to as Mushrooms are distributed worldwide and well known for their nutritional, medicinal, and organoleptic properties. Strain improvement in mushrooms is lagging due to paucity of efficient genome modification techniques. Thus, for advanced developments in research and commercial or economical viability and benefit, CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated nuclease 9) emerged as an efficient genome editing tool. The higher efficiency and precision of the desired genetic modification(s) are the most valuable attributes of this recent technology. The present review comprehensively summarizes various conventional methods utilized for strain improvement in mushrooms including hybridization, protoplast fusion, and di-mon mating. Furthermore, the problems associated with these techniques have been discussed besides providing the potential recluses. The significance of CRISPR/Cas9 strategies employed for improvement in various mushroom genera has been deliberated, as these strategies will paves the way forward for obtaining improved strain and effective cultivation methods for enhancing the yield and quality of the fruit bodies.


Asunto(s)
Agaricales , Sistemas CRISPR-Cas , Edición Génica , Genoma Fúngico , Edición Génica/métodos , Sistemas CRISPR-Cas/genética , Agaricales/genética
12.
Epilepsy Behav ; 153: 109703, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38452517

RESUMEN

BACKGROUND: Neuropsychological Rehabilitation (NR) helps manage cognitive deficits in epilepsy. As internationally developed programs have limited applicability to resource-limited countries, we developed a program to bridge this gap. This 6-week caregiver-assisted, culturally suitable program has components of (1) psychoeducation, (2) compensatory training, and, (3) cognitive retraining and is called EMPOWER (Indigenized Home Based Attention and Memory Rehabilitation Program for Adult Patients with Drug Refractory Epilepsy). Its efficacy needs to be determined. METHODS: We carried out an open-label parallel randomized controlled trial. Adults aged 18-45 years with Drug Refractory Epilepsy (DRE), fluency in Hindi and or English, with impaired attention or memory (n = 28) were randomized to Intervention Group (IG) and Control Group (CG). The primary outcomes were objective memory (Auditory Verbal Learning Test), patient and caregiver reported everyday memory difficulties (Everyday Memory Questionnaire-Revised), number of memory aids in use, depression (Hamilton Depression Rating Scale), anxiety (Hamilton Anxiety Rating Scale) and quality of life (Quality of Life in Epilepsy-31). Intention to treat was carried out for group analysis. In the absence of norms necessary for computing Reliable Change Indices (RCIs), a cut-off of +1.0 Standard Deviation (SD) was utilized to identify clinically meaningful changes in the individual analysis of objective memory. A cut-off of 11.8 points was used for quality of life. Feedback and program evaluation responses were noted. RESULTS: The majority of the sample comprised DRE patients with temporal lobe epilepsy who had undergone epilepsy surgery. Group analysis indicated improved learning (p = 0.013), immediate recall (p = 0.001), delayed recall (p < 0.001), long-term retention (p = 0.031), patient-reported everyday memory (p < 0.001), caregiver-reported everyday memory (p < 0.001), anxiety (p = 0.039) and total quality of life (p < 0.001). Individual analysis showed improvement in 50 %, 64 %, 71 %, 57 %, and 64 % of patients on learning, immediate recall, delayed recall, long-term retention, and total quality of life respectively. Despite improvements, themes indicative of a lack of awareness and understanding of cognitive deficits were identified. Overall, the program was rated favorably by patients and caregivers alike. CONCLUSION: NR shows promise for patients with DRE, however larger studies are warranted. The role of cognition in epilepsy needs to be introduced at the time of diagnosis to help lay the foundation for education and acceptance.


Asunto(s)
Epilepsia Refractaria , Epilepsia , Adulto , Humanos , Calidad de Vida/psicología , Pruebas Neuropsicológicas , Epilepsia/psicología , Memoria a Corto Plazo
13.
Small ; 19(26): e2300394, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36950767

RESUMEN

Hierarchical micro/nanostructures are constructed by micro-scaled objects with nanoarchitectures belonging to an interesting class of crystalline materials that has significant applications in diverse fields. Featured with a large surface-to-volume ratio, facile mass transportation, high stability against aggregation, structurally enhanced adsorption, and catalytical performances, three dimenisional (3D) hierarchical metal oxides have been considered as versatile functional materials for waste-water treatment. Due to the ineffectiveness of traditional water purification protocols for reclamation of water, lately, the use of hierarchical metal oxides has emerged as an appealing platform for the remediation of water pollution owing to their fascinating and tailorable physiochemical properties. The present review highlights various approaches to the tunable synthesis of hierarchical structures along with their surface modification strategies to enhance their efficiencies for the removal of different noxious substances. Besides, their applications for the eradication of organic and inorganic contaminants have been discussed comprehensively with their plausible mechanistic pathways. Finally, overlooked aspects in this field as well as the major roadblocks to the implementation of these metal oxide architectures for large-scale treatment of wastewater are provided here. Moreover, the potential ways to tackle these issues are also presented which may be useful for the transformation of current water treatment technologies.

14.
Microvasc Res ; 145: 104454, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36347299

RESUMEN

OBJECTIVE: Subclinical life style disease can cause endothelial dysfunction associated with perfusion abnormalities and reduced vascular compliance. Subclinical elevated beta type natriuretic peptide (BNP) has been associated with altered fluid shift from extra to intracellular space during acute hypoxia. Therefore we measured vascular response and BNP levels during acute hypoxia to study endothelial functions among healthy individuals. METHODS: Individuals were exposed to acute normobaric hypoxia of FiO2 = 0.15 for one hour in supine position and their pulmonary and systemic vascular response to hypoxia was compared. Individuals were divided into two groups based on either no response (Group 1) or rise in systolic pulmonary artery pressure to hypoxia (Group 2) and their BNP levels were compared. RESULTS: BNP was raised after hypoxia exposure in group 2 only from 18.52 ± 7 to 21.56 ± 10.82 picogram/ml, p < 0.05. Group 2 also showed an increase in mean arterial pressure and no fall in total body water in response to acute hypoxia indicating decreased endothelial function compared to Group 1. CONCLUSION: Rise in pulmonary artery pressure and BNP level in response to acute normobaric hypoxia indicates reduced endothelial function and can be used to screen subclinical lifestyle disease among healthy population.


Asunto(s)
Hipoxia , Péptido Natriurético Encefálico , Humanos , Hipoxia/diagnóstico , Pulmón/irrigación sanguínea , Vasodilatadores , Estilo de Vida , Arteria Pulmonar
15.
Histopathology ; 82(2): 296-304, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36208048

RESUMEN

Low-grade oncocytic tumour (LOT) of the kidney has recently emerged as a potential novel tumour type. Despite similarity to oncocytoma or eosinophilic chromophobe renal cell carcinoma, it shows diffuse keratin 7 immunohistochemistry (IHC) and negative KIT (CD117), which differs from both. We aimed to identify the molecular characteristics of these tumours. Seventeen tumours (one male, 16 female, nine previously published) fitting the original description of this entity (solid eosinophilic cell morphology, often with areas of tumour cells loosely stretched in oedematous stroma, and the above IHC features) were analysed with a next-generation sequencing panel of 324 cancer-associated genes from formalin-fixed, paraffin-embedded tissue. All tumours harboured at least one alteration in either TSC1 (n = 7, 41%), TSC2 (n = 2, 12%), MTOR (n = 5, 29%) or PIK3CA (n = 4, 24%). Four tumours harboured a second alteration, including two NF2, one each in conjunction with MTOR and TSC2 alterations, one PTEN with TSC1 alteration and one tumour with both MTOR and TSC1 alterations. No other renal cancer-related or recurring gene alterations were identified. In addition to the previously described IHC findings, 16 of 16 were positive for GATA3. Eleven patients with follow-up had no metastases or recurrent tumours. Recurrent tuberous sclerosis/MTOR pathway gene alterations in LOT support its consideration as a distinct morphological, immunohistochemical and genetic entity. PIK3CA is another pathway member that may be altered in these tumours. Further study will be necessary to determine whether tumour behaviour or syndromic associations differ from those of oncocytoma and chromophobe carcinoma, warranting different clinical consideration.


Asunto(s)
Adenoma Oxifílico , Carcinoma de Células Renales , Neoplasias Renales , Humanos , Masculino , Femenino , Recurrencia Local de Neoplasia , Carcinoma de Células Renales/genética , Neoplasias Renales/genética , Mutación , Adenoma Oxifílico/genética , Riñón , Serina-Treonina Quinasas TOR/genética , Factor de Transcripción GATA3/genética , Fosfatidilinositol 3-Quinasa Clase I/genética
16.
Nephrol Dial Transplant ; 38(2): 435-446, 2023 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-36130107

RESUMEN

BACKGROUND: Incremental haemodialysis initiation entails lower sessional duration and/or frequency than the standard 4 h thrice-weekly approach. Dialysis dose is increased as residual kidney function (RKF) declines. This systematic review evaluates its safety, efficacy and cost-effectiveness. METHODS: We searched MEDLINE, EMBASE, CINAHL and the Cochrane Library databases from inception to 27 February 2022. Eligible studies compared incremental haemodialysis (sessions either fewer than three times weekly or of duration <3.5 h) with standard treatment. The primary outcome was mortality. Secondary outcomes included treatment-emergent adverse events, loss of RKF, quality of life and cost effectiveness. The study protocol was prospectively registered. Risk of bias assessment used the Newcastle-Ottawa Scale and the revised Cochrane risk of bias tool, as appropriate. Meta-analyses were undertaken in Review Manager, Version 5.4. RESULTS: A total of 644 records were identified. Twenty-six met the inclusion criteria, including 22 cohort studies and two randomized controlled trials (RCTs). Sample size ranged from 48 to 50 596 participants (total 101 476). We found no mortality differences (hazard ratio = 0.99; 95% CI 0.80-1.24). Cohort studies suggested similar hospitalization rates though the two small RCTs suggested less hospitalization after incremental initiation (relative risk = 0.31; 95% CI 0.18-0.54). Data on other treatment-emergent adverse events and quality of life was limited. Observational studies suggested reduced loss of RKF in incremental haemodialysis. This was not supported by RCT data. Four studies reported reduced costs of incremental treatments. CONCLUSIONS: Incremental initiation of haemodialysis does not confer greater risk of mortality compared with standard treatment. Hospitalization may be reduced and costs are lower.


Asunto(s)
Calidad de Vida , Diálisis Renal , Humanos , Diálisis Renal/métodos , Estudios de Cohortes , Riesgo
17.
Nephrol Dial Transplant ; 38(10): 2330-2339, 2023 09 29.
Artículo en Inglés | MEDLINE | ID: mdl-36805738

RESUMEN

BACKGROUND: There is great potential to improve outcomes of arteriovenous fistulas (AVFs) by focusing more on the preoperative period of AVF creation. We aim to systematically review the evidence on safety and efficacy of various preoperative interventions that have been tried to improve AVF maturation and success rate. METHODS: We searched five databases: PubMed, Embase, CINAHL, Cochrane Library and King's Fund Library. Experimental studies that investigated the effect of various preoperative interventions to improve AVF outcomes among advanced chronic kidney disease (CKD) patients were searched. The effect size for primary outcome was calculated as the weighted mean difference in the final vessel calibre, rate of AVF maturation or primary failure between the intervention and control arm. We also assessed adverse effects and dropout rates. This review was preregistered in the International Prospective Register of Systematic Reviews (CRD42020193257). RESULTS: Eight eligible studies were identified involving three types of intervention: hand exercise (n = 6), cholecalciferol supplementation (n = 1) and pneumatic compression of the arm using a Fist Assist device (n = 1). The overall effect size of hand exercise on distal cephalic vein calibre was 0.24 mm [95% confidence interval (CI) 0.03-0.45] on meta-analysis of hand exercise studies. On restricting analysis to two randomized controlled trials (RCTs) that had independent control groups, the effect size was higher, at 0.29 mm (95% CI 0.11-0.47). Hand exercise was a well-tolerated intervention, especially when confined to the first 4 weeks. DISCUSSION: Hand exercise is the predominant intervention tried in the preoperative period of AVF creation, although there is methodological heterogeneity. Intermittent pneumatic compression using a Fist Assist device is a novel intervention that has shown some promise. Well-designed prospective RCTs are needed on preoperative interventions among advanced CKD patients, aimed at improving AVF outcomes.


Asunto(s)
Fístula Arteriovenosa , Derivación Arteriovenosa Quirúrgica , Insuficiencia Renal Crónica , Humanos , Derivación Arteriovenosa Quirúrgica/efectos adversos , Diálisis Renal , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/cirugía , Terapia por Ejercicio , Fístula Arteriovenosa/etiología
18.
BMC Nephrol ; 24(1): 356, 2023 12 04.
Artículo en Inglés | MEDLINE | ID: mdl-38049710

RESUMEN

BACKGROUND: Services for patients with kidney disease underwent radical adaptations in response to the COVID-19 pandemic. We undertook an online national survey of UK kidney centres to understand the nature, range, and degree of variation in these changes and to explore factors contributing to differing practice. METHODS: The survey was designed by a multidisciplinary team of kidney professionals, service users and researchers. It enquired about centre services and staffing, including psychosocial provision, and changes to these in response to the COVID-19 pandemic. Links to the survey were sent to all 68 UK kidney centres and remained active from December 2021 to April 2022, and a revised version to nurses in late 2022 for additional data. Quantitative data were analysed descriptively. Content analysis on free-text responses identified common themes. RESULTS: Analysable responses were received from 41 out of the 68 UK centres (60%), with partial data from an additional 7 (11%). Adaptations were system-wide and affected all aspects of service provision. Some changes were almost universal such as virtual consultations for outpatient appointments, with significant variation in others. Outpatient activity varied from fully maintained to suspended. Many centres reduced peritoneal dialysis access provision but in some this was increased. Centres considered that changes to transplant surgical services and for patients with advanced CKD approaching end-stage kidney disease had the greatest impact on patients. Few centres implemented adjustments aimed at vulnerable and underrepresented groups, including the frail elderly, people with language and communication needs, and those with mental health needs. Communication issues were attributed to rapid evolution of the pandemic, changing planning guidance and lack of resources. Staffing shortages, involving all staff groups particularly nurses, mainly due to COVID-19 infection and redeployment, were compounded by deficiencies in staffing establishments and high vacancy levels. Centres cited three main lessons influencing future service delivery, the need for service redesign, improvements in communication, and better support for staff. CONCLUSION: Kidney centre responses to the pandemic involved adaptations across the whole service. Though some changes were almost universal, there was wide variation in other areas. Exploring the role of centre characteristics may help planning for potential future severe service disruptions.


Asunto(s)
COVID-19 , Insuficiencia Renal Crónica , Humanos , Anciano , COVID-19/epidemiología , Pandemias , Diálisis Renal , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia , Riñón , Reino Unido/epidemiología
19.
J Sci Food Agric ; 103(5): 2681-2689, 2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-36350071

RESUMEN

BACKGROUND: Hemp seeds are highly nutritious and a sustainable source of protein and omega-fatty acids. The outer shell of the seeds restricts its utilization in the food industry. Dehulling of the seeds leads to a lot of processing losses due to high oil content and hard shell of the seed. Therefore, in the present study, hydrothermal treatment of the hemp seeds (Cannabis sativa L.) before dehulling was proposed to reduce the endosperm breakage and improve dehulling yield of seeds. RESULT: The hemp seeds were subjected to four types of treatments, namely moisture addition (at 14%) with tempering for 10 min and 60 min followed by drying (28-30 °C) and steaming at atmospheric pressure for 5 min and 10 min. Results from the study showed that the hydrothermal treatments impacted the hardness of the endosperm and therefore improved the dehulling yield by 1.3 to 1.5 folds. Also, the dehulling losses significantly reduced from 26.80% to 9.52% after the steaming treatments. Though steaming to some extent affected the colour of the dehulled seeds compared to other treatments, it showed an increment in protein digestibility from 86.53% to 88.73%. CONCLUSION: Among all the hydrothermal treatments, steaming showed significant improvement in the yield of dehulled hemp seeds. It reduced endosperm breakage without affecting the seeds' fatty acid profile and nutritional quality. It can be concluded that steaming as a pretreatment can be used for improved dehulling of hemp seeds, aiding the better valourization of hemp seeds in the food industry. © 2022 Society of Chemical Industry.


Asunto(s)
Cannabis , Ácidos Grasos , Ácidos Grasos/análisis , Cannabis/química , Semillas/química , Endospermo
20.
Microbiology (Reading) ; 168(8)2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35917161

RESUMEN

Era GTPase is universally present in microbes including Mycobacterium tuberculosis (Mtb) complex bacteria. While Era is known to regulate ribosomal assembly in Escherichia coli and predicted to be essential for in vitro growth, its function in mycobacteria remains obscured. Herein, we show that Era ortholog in the attenuated Mtb H37Ra strain, MRA_2388 (annotated as EraMT) is a cell envelope localized protein harbouring critical GTP-binding domains, which interacts with several envelope proteins of Mtb. The purified Era from M. smegmatis (annotated as EraMS) exhibiting ~90 % sequence similarity with EraMT, exists in monomeric conformation. While it is co-purified with RNA upon overexpression in E. coli, the presence of RNA does not modulate the GTPase activity of the EraMS as against its counterpart from other organisms. CRISPRi silencing of eraMT does not show any substantial effect on the in vitro growth of Mtb H37Ra, which suggests a redundant function of Era in mycobacteria. Notably, no effect on ribosome assembly, protein synthesis or bacterial susceptibility to protein synthesis inhibitors was observed upon depletion of EraMT in Mtb H37Ra, further indicating a divergent role of Era GTPase in mycobacteria.


Asunto(s)
Proteínas de Escherichia coli , Mycobacterium tuberculosis , Proteínas ras/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , GTP Fosfohidrolasas/genética , GTP Fosfohidrolasas/metabolismo , Proteínas de Unión al GTP/química , Proteínas de Unión al GTP/genética , Proteínas de Unión al GTP/metabolismo , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/metabolismo , ARN , Ribosomas/genética , Ribosomas/metabolismo
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