Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 254
Filtrar
1.
Emerg Radiol ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38987490

RESUMEN

Infection of the scrotum and its contents is the most common cause of acute scrotum. Imaging plays an important role in evaluating disease extent, severity and its complications. Sonography is the modality of choice for imaging the acute scrotum. This pictorial review discusses the varied clinical and imaging features of scrotal infections and their complications, with correlative CT, when available.

2.
Indian J Clin Biochem ; 39(3): 429-437, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39005867

RESUMEN

Neuropsychiatric disorders are mainly concerned with the behavioural, emotional and cognition symptoms that may be due to disturbed cerebral functions or extracerebral disease. Klotho protein is an antiaging protein that is mostly associated with cognitive changes in these disorders and thus this meta-analysis is conducted in order to find Klotho proteins association with these disorders. We searched related topics in pubmed, by using the key word i.e. Klotho and related disorder from neuropsychiatry e.g. Klotho levels and schizophrenia, Klotho levels and parkinsonism etc. Total 82 studies were found till 9th February 2021 after extensive search and 10 studies were selected for further analysis. The meta-analysis of studies was performed using the Random effect model. The forest plot represented each study in the meta-analysis, so as to make the comparison of SMD value across studies. The meta-analysis outcome demonstrated that overall schizophrenia had higher klotho levels as compared with bipolar disorder, psychosocial stress, parkinsonism, multiple sclerosis, depression, Alzheimer's disease, and healthy controls, followed by MS. The meta-analysis also found that bipolar disorder and Alzheimer's disease were associated with low klotho levels as compared to schizophrenia. The results indicate a significant association of the klotho levels and schizophrenia. Further studies are needed to characterize the potential biological roles of klotho levels in psychiatric disorders.

3.
Microb Pathog ; 193: 106757, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38908454

RESUMEN

The PE and PPE family proteins of Mycobacterium tuberculosis (Mtb) is exclusively found in pathogenic Mycobacterium species, comprising approximately 8-10 % of the Mtb genome. These emerging virulent factors have been observed to play pivotal roles in Mtb pathogenesis and immune evasion through various strategies. These immunogenic proteins are known to modulate the host immune response and cell-death pathways by targeting the powerhouse of the cell, the mitochondria to support Mtb survival. In this article, we are focused on how PE/PPE family proteins target host mitochondria to induce mitochondrial perturbations, modulate the levels of cellular ROS (Reactive oxygen species) and control cell death pathways. We observed that the time of expression of these proteins at different stages of infection is crucial for elucidating their impact on the cell death pathways and eventually on the outcome of infection. This article focuses on understanding the contributions of the PE/PPE proteins by unravelling the triad of host mitochondria, oxidative stress and cell death pathways that facilitate the Mtb persistence. Understanding the role of these proteins in host cellular pathways and the intricate mechanisms paves the way for the development of novel therapeutic strategies to combat TB infections.

4.
PLoS One ; 19(5): e0294302, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38805446

RESUMEN

BACKGROUND: Low back pain stands as a prevalent contributor to pain-related disability on a global scale. In addressing chronic low back pain (CLBP), there is a growing emphasis on incorporating psychological strategies into the management process. Among these, pain education interventions strive to reshape pain beliefs and mitigate the perceived threat of pain. This randomized controlled trial sought to assess the effects of pain education on various aspects, including pain levels, disability, quality of life, self-efficacy, and prognostic characteristics in individuals grappling with CLBP. METHODS: The clinical trial, retrospectively registered with the Clinical Trials Registry of India (CTRI/2021/08/035963), employed a two-arm parallel randomized design. Ninety-two participants with CLBP were randomly assigned to either the standard physiotherapy care with a pain education program or the control group. Both groups underwent a 6-week intervention. Assessment of pain intensity (using NPRS), disability (using RMDQ), self-efficacy (using the general self-efficacy scale), and well-being (using WHO 5I) occurred both before and after the 6-week study intervention. FINDINGS: Post-intervention score comparisons between the groups revealed that the pain education intervention led to a significant reduction in disability compared to the usual standard care at 6 weeks (mean difference 8.2, p < 0.001, effect size Cohen d = 0.75), a decrease in pain intensity (mean difference 3.5, p < 0.001, effect size Cohen d = 0.82), and an improvement in the well-being index (mean difference 13.7, p < 0.001, effect size Cohen d = 0.58). CONCLUSION: The findings suggest that integrating a pain education program enhances the therapeutic benefits of standard physiotherapy care for individuals dealing with chronic LBP. In conclusion, the clinical benefits of pain education become apparent when delivered in conjunction with standard care physiotherapy during the management of chronic low back pain.


Asunto(s)
Dolor Crónico , Dolor de la Región Lumbar , Calidad de Vida , Autoeficacia , Humanos , Dolor de la Región Lumbar/terapia , Dolor de la Región Lumbar/psicología , Masculino , Femenino , Adulto , Persona de Mediana Edad , Dolor Crónico/terapia , Dolor Crónico/psicología , Educación del Paciente como Asunto/métodos , Dimensión del Dolor , Modalidades de Fisioterapia , Personas con Discapacidad/psicología , Manejo del Dolor/métodos , Evaluación de la Discapacidad
5.
Neurochem Int ; 177: 105761, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38723902

RESUMEN

Alzheimer's disease (AD) remains one of the most formidable neurological disorders, affecting millions globally. This review provides a holistic overview of the therapeutic strategies, both conventional and novel, aimed at mitigating the impact of AD. Initially, we delve into the conventional approach, emphasizing the role of Acetylcholinesterase (AChE) inhibition, which has been a cornerstone in AD management. As our understanding of AD evolves, several novel potential approaches emerge. We discuss the promising roles of Butyrylcholinesterase (BChE) inhibition, Tau Protein inhibitors, COX-2 inhibition, PPAR-γ agonism, and FAHH inhibition, among others. The potential of the endocannabinoids (eCB) system, cholesterol-lowering drugs, metal chelators, and MMPs inhibitors are also explored, culminating in the exploration of the pivotal role of microRNA in AD progression. Parallel to these therapeutic insights, we shed light on the novel tools and methodologies revolutionizing AD research. From the quantitative analysis of gene expression by qRTPCR to the evaluation of mitochondrial function using induced pluripotent stem cells (iPSCs), the advances in diagnostic and research tools offer renewed hope. Moreover, we explore the current landscape of clinical trials, highlighting the leading drug interventions and their respective stages of development. This comprehensive review concludes with a look into the future perspectives, capturing the potential breakthroughs and innovations on the horizon. Through a synthesis of current knowledge and emerging research, this article aims to provide a consolidated resource for clinicians, researchers, and academicians in the realm of Alzheimer's disease.


Asunto(s)
Enfermedad de Alzheimer , Diagnóstico Precoz , Humanos , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/genética , Animales , Inhibidores de la Colinesterasa/uso terapéutico , Inhibidores de la Colinesterasa/farmacología
6.
Int Immunopharmacol ; 136: 112309, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-38810304

RESUMEN

Autoimmune uveitis, a severe inflammatory condition of the eye, poses significant challenges due to its complex pathophysiology and the critical balance between protective and detrimental immune responses. Central to this balance are microglia, the resident immune cells of the central nervous system, whose roles in autoimmune uveitis are multifaceted and dynamic. This review article delves into the dual nature of microglial functions, oscillating between neuroprotective and neurotoxic outcomes in the context of autoimmune uveitis. Initially, we explore the fundamental aspects of microglia, including their activation states and basic functions, setting the stage for a deeper understanding of their involvement in autoimmune uveitis. The review then navigates through the intricate mechanisms by which microglia contribute to disease onset and progression, highlighting both their protective actions in immune regulation and tissue repair, and their shift towards a pro-inflammatory, neurotoxic profile. Special emphasis is placed on the detailed pathways and cellular interactions underpinning these dual roles. Additionally, the review examines the potential of microglial markers as diagnostic and prognostic indicators, offering insights into their clinical relevance. The article culminates in discussing future research directions, and the ongoing challenges in translating these findings into effective clinical applications. By providing a comprehensive overview of microglial mechanisms in autoimmune uveitis, this review underscores the critical balance of microglial activities and its implications for disease management and therapy development.


Asunto(s)
Enfermedades Autoinmunes , Microglía , Neuroprotección , Uveítis , Microglía/inmunología , Humanos , Uveítis/inmunología , Animales , Enfermedades Autoinmunes/inmunología
7.
J Phys Condens Matter ; 36(28)2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38574668

RESUMEN

Flexible photodetectors (PDs) have exotic significance in recent years due to their enchanting potential in future optoelectronics. Moreover, paper-based fabricated PDs with outstanding flexibility unlock new avenues for future wearable electronics. Such PD has captured scientific interest for its efficient photoresponse properties due to the extraordinary assets like significant absorptive efficiency, surface morphology, material composition, affordability, bendability, and biodegradability. Quantum-confined materials harness the unique quantum-enhanced properties and hold immense promise for advancing both fundamental scientific understanding and practical implication. Two-dimensional (2D) materials as quantum materials have been one of the most extensively researched materials owing to their significant light absorption efficiency, increased carrier mobility, and tunable band gaps. In addition, 2D heterostructures can trap charge carriers at their interfaces, leading increase in photocurrent and photoconductivity. This review represents comprehensive discussion on recent developments in such PDs functionalized by 2D materials, highlighting charge transfer mechanism at their interface. This review thoroughly explains the mechanism behind the enhanced performance of quantum materials across a spectrum of figure of merits including external quantum efficiency, detectivity, spectral responsivity, optical gain, response time, and noise equivalent power. The present review studies the intricate mechanisms that reinforce these improvements, shedding light on the intricacies of quantum materials and their significant capabilities. Moreover, a detailed analysis of the technical applicability of paper-based PDs has been discussed with challenges and future trends, providing comprehensive insights into their practical usage in the field of future wearable and portable electronic technologies.

8.
Apoptosis ; 2024 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-38615303

RESUMEN

Mycobacterium tuberculosis (Mtb) genome possesses a unique family called Proline-Glutamate/Proline-Proline-Glutamate (PE/PPE) gene family, exclusive to pathogenic mycobacterium. Some of these proteins are known to play role in virulence and immune response modulation, but many are still uncharacterized. This study investigated the role of C-terminal region of Rv1039c (PPE15) in inducing mitochondrial perturbations and macrophage apoptosis. Our in-silico studies revealed the disordered, coiled, and hydrophobic C-terminal region in Rv1039c has similarity with C-terminal of mitochondria-targeting pro-apoptotic host proteins. Wild type Rv1039c and C-terminal deleted Rv1039c (Rv1039c-/-Cterm) recombinant proteins were purified and their M. smegmatis knock-in strains were constructed which were used for in-vitro experiments. Confocal microscopy showed localization of Rv1039c to mitochondria of PMA-differentiated THP1 macrophages; and reduced mitochondrial membrane depolarization and production of mitochondrial superoxides were observed in response to Rv1039c-/-Cterm in comparison to full-length Rv1039c. The C-terminal region of Rv1039c was found to activate caspases 3, 7 and 9 along with upregulated expression of pro-apoptotic genes like Bax and Bim. Rv1039c-/-Cterm also reduced the Cytochrome-C release from the mitochondria and the expression of AnnexinV/PI positive and TUNEL positive cells as compared to Rv1039c. Additionally, Rv1039c was observed to upregulate the TLR4-NF-κB-TNF-α signalling whereas the same was downregulated in response to Rv1039c-/-Cterm. These findings suggested that the C-terminal region of Rv1039c is a molecular mimic of pro-apoptotic host proteins which induce mitochondria-dependent macrophage apoptosis and evoke host immune response. These observations enhance our understanding about the role of PE/PPE proteins at host-pathogen interface.

9.
Food Chem Toxicol ; 188: 114667, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38653447

RESUMEN

Bisphenol A (BPA) is an endocrine-disrupting chemical (EDC), associated with obesity and insulin resistance. The FDA prohibited the use of BPA-based polycarbonate resins in infant formula packaging; thus, its analogs, viz. Bisphenol S (BPS) and Bisphenol F (BPF) were considered alternatives in epoxy resins, plastics, and food cans. As these analogs might evoke a similar response, we investigated the role of Bisphenols (BPA, BPF, and BPS), on insulin signaling in CHO-HIRc-myc-GLUT4eGFP cells at environmentally relevant concentrations of 2 nM and 200 nM. Insulin signaling demonstrated that Bisphenols reduced phosphorylation of IR and AKT2, GLUT4 translocation, and glucose uptake. This was accompanied by increased oxidative stress. Furthermore, SWATH-MS-based proteomics of 3T3-L1 cells demonstrated that Bisphenol-treated cells regulate proteins in insulin resistance, adipogenesis, and fatty acid metabolism pathways differently. All three Bisphenols induced differentially expressed proteins enriched similar pathways, although their abundance differed for each Bisphenol. This might be due to their varying toxicity level, structural differences, and estrogen-mimetic activity. This study has important implications in addressing health concerns related to EDCs. Given that the analogs of BPA are considered alternatives to BPA, the findings of this study suggest they are equally potent in altering fatty acid metabolism and inducing insulin resistance.


Asunto(s)
Compuestos de Bencidrilo , Cricetulus , Ácidos Grasos , Insulina , Fenoles , Transducción de Señal , Sulfonas , Compuestos de Bencidrilo/toxicidad , Fenoles/toxicidad , Animales , Ratones , Insulina/metabolismo , Transducción de Señal/efectos de los fármacos , Ácidos Grasos/metabolismo , Células CHO , Sulfonas/toxicidad , Células 3T3-L1 , Disruptores Endocrinos/toxicidad , Resistencia a la Insulina , Estrés Oxidativo/efectos de los fármacos , Fosforilación/efectos de los fármacos
10.
Neurosci Biobehav Rev ; 161: 105685, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38670299

RESUMEN

Alzheimer's Disease (AD) remains a formidable challenge due to its complex pathology, notably involving mitochondrial dysfunction and dysregulated microRNA (miRNA) signaling. This study delves into the underexplored realm of miRNAs' impact on mitochondrial dynamics and their interplay with amyloid-beta (Aß) aggregation and tau pathology in AD. Addressing identified gaps, our research utilizes advanced molecular techniques and AD models, alongside patient miRNA profiles, to uncover miRNAs pivotal in mitochondrial regulation. We illuminate novel miRNAs influencing mitochondrial dynamics, Aß, and tau, offering insights into their mechanistic roles in AD progression. Our findings not only enhance understanding of AD's molecular underpinnings but also spotlight miRNAs as promising therapeutic targets. By elucidating miRNAs' roles in mitochondrial dysfunction and their interactions with hallmark AD pathologies, our work proposes innovative strategies for AD therapy, aiming to mitigate disease progression through targeted miRNA modulation. This contribution marks a significant step toward novel AD treatments, emphasizing the potential of miRNAs in addressing this complex disease.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , MicroARNs , Microglía , Dinámicas Mitocondriales , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/genética , MicroARNs/metabolismo , MicroARNs/genética , Humanos , Péptidos beta-Amiloides/metabolismo , Dinámicas Mitocondriales/fisiología , Animales , Microglía/metabolismo , Transducción de Señal/fisiología
11.
Autops Case Rep ; 14: e2024470, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38476732

RESUMEN

Lymphangiomas are rare benign tumors that mainly involve the head and neck region in pediatric patients. Lymphangiomas of the small bowel mesentery in adults are rarer. We present two cases of mesenteric lymphangioma with acute abdominal pain on presentation. Case 1: A 38-year-old female presented with abdominal pain, vomiting, fever, and difficult evacuation. On abdominal examination, she had an ill-defined, tender lump, and radiological findings raised a possibility of perforation peritonitis. Thus, exploratory laparotomy was planned. Per-operatively, a mesenteric mass was found, which, on histopathological evaluation, was found to be a mesenteric lymphangioma involving the bowel. Case 2: A 27-year-old male presented with abdominal pain and difficult evacuation. Radiological evaluation revealed a multilobulated lesion involving the mesentery and with differential diagnoses of mesenteric fibromatoses and inflammatory pseudotumor. Histopathological assessment of the resected mass revealed a lymphangioma that was limited to the mesentery. Owing to their rarity and non-specific presentation, mesenteric lymphangiomas are often misdiagnosed on clinical examination and imaging. Thus, histopathological examination is the gold standard to reach a definitive diagnosis.

12.
Brain Res ; 1829: 148797, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38342422

RESUMEN

Alzheimer's Disease (AD) represents a complex interplay of neurological pathways and molecular mechanisms, with significant impacts on patients' lives. This review synthesizes the latest developments in AD research, focusing on both the scientific advancements and their clinical implications. We examine the role of microglia in AD, highlighting their contribution to the disease's inflammatory aspects. The cholinergic hypothesis, a cornerstone of AD research, is re-evaluated, including the role of Alpha-7 Nicotinic Acetylcholine Receptors in disease progression. This review places particular emphasis on the neurotransmission systems, exploring the therapeutic potential of GABAergic neurotransmitters and the role of NMDA inhibitors in the context of glutamatergic neurotransmission. By analyzing the interactions and implications of neurotransmitter pathways in AD, we aim to shed light on emerging therapeutic strategies. In addition to molecular insights, the review addresses the clinical and personal aspects of AD, underscoring the need for patient-centered approaches in treatment and care. The final section looks at the future directions of AD research and treatment, discussing the integration of scientific innovation with patient care. This review aims to provide a comprehensive update on AD, merging scientific insights with practical considerations, suitable for both specialists and those new to the field.


Asunto(s)
Enfermedad de Alzheimer , Receptores Nicotínicos , Humanos , Enfermedad de Alzheimer/metabolismo , Colinérgicos , Neurotransmisores , Transmisión Sináptica , Receptores Nicotínicos/metabolismo
13.
Biochim Biophys Acta Mol Cell Res ; 1871(4): 119702, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38408543

RESUMEN

Inhibition of Reactive Oxygen Species (ROS) is one of the strategies that Mycobacterium tuberculosis (Mtb) employs as its defence mechanism. In this study, the role of PPE15 (Rv1039c), a late-stage protein, has been investigated in modulating the cellular ROS. We discovered PPE15 to be a secretory protein that downregulates ROS generation in THP1 macrophages. Our in-silico analysis revealed the presence of a eukaryote-like SH3 (SH3e) domain in PPE15. The predicted SH3e-domain of PPE15 was found to interact with cytosolic components of NADPH Oxidase (NOX), p67phox and p47phox through molecular docking. In-vitro experiments using THP1 macrophages showed a diminished NADP/NADPH ratio, indicating reduced NOX activity. We also observed increased levels of p67phox and p47phox in the cytoplasmic fraction of PPE15 treated macrophages as compared to the plasma membrane fraction. To understand the role of the SH3e-domain in ROS modulation, this domain was deleted from the full-length PPE15 (PPE15-/-SH3). We observed an increase in cellular ROS and NADP/NADPH ratio in response to PPE15-/-SH3 protein. The interaction of PPE15-/-SH3 with p67phox or p47phox was also reduced in the cytoplasm, indicating migration of NOX subunits to the plasma membrane. Additionally, M. smegmatis expressing PPE15 was observed to be resistant to oxidative stress with significant intracellular survival in THP1 macrophages as compared to M. smegmatis expressing PPE15-/-SH3. These observations suggest that the SH3e-domain of PPE15 interferes with ROS generation by sequestering NOX components that inhibit NOX assembly at the cell membrane. Therefore, PPE15 acts like a molecular mimic of SH3-domain carrying eukaryotic proteins that can be employed by Mtb at late stages of infection for its survival. These findings give us new insights about the pathogen evading strategy of Mtb which may help in improving the therapeutics for TB treatment.


Asunto(s)
Mycobacterium tuberculosis , Especies Reactivas de Oxígeno/metabolismo , NADP/metabolismo , Dominios Homologos src , Simulación del Acoplamiento Molecular , NADPH Oxidasas/genética , NADPH Oxidasas/metabolismo , Eucariontes
14.
Sci Rep ; 14(1): 2763, 2024 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-38307873

RESUMEN

The Beas River is one of the important rivers of the Indus River system located in Himachal Pradesh, India, that harbors a diverse range of freshwater fish species. The present study employed COI gene to investigate the ichthyofaunal diversity of river Beas. Through the sequencing of 203 specimens from Beas River, we identified 43 species, belonging to 31 genera, 16 families, and 10 orders. To analyze the genetic divergence and phylogeny of identified species, 485 sequences of Indian origin were retrieved from BOLD, resulting in a dataset of 688 sequences. Our findings consistently revealed a hierarchical increase in the mean K2P genetic divergence within species (0.80%), genus (9.06%), and families (15.35%). Automated Barcode Gap discovery, Neighbour Joining, and Bayesian inference consensus tree methodologies were employed to determine the putative species and their phylogeny, successfully delimiting most of the species with only a few exceptions. The results unveiled six species exhibiting high intra-species divergence (> 2%), suggesting the presence of sibling species and falsely identified sequences on online databases. The present study established the first DNA barcoding-based inventory of freshwater fish species in the Beas River providing comprehensive insights into economically exploited endangered and vulnerable species. In order to ensure the sustainable use of aquatic resources in the Beas River, we recommend the implementation of species measures to protect biodiversity and genetic resources.


Asunto(s)
Código de Barras del ADN Taxonómico , Ríos , Humanos , Animales , Código de Barras del ADN Taxonómico/métodos , Teorema de Bayes , Complejo IV de Transporte de Electrones/genética , Peces/genética , Agua Dulce , ADN , Filogenia , Biodiversidad
15.
PeerJ ; 12: e16799, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38288463

RESUMEN

Background: In 2020, 203 million people experienced neck pain, with a higher prevalence in women. By 2050, it is predicted that neck pain will affect 269 million people, representing a 32.5% increase. Physical rehabilitation is often employed for the treatment of chronic non-specific neck pain (CNSNP) and the associated functional loss. Taping is frequently used as an adjunct treatment alongside primary physical rehabilitation. Unlike kinesio tape (KT), the therapeutic benefits of dynamic tape (DT) have not been thoroughly explored and documented in non-athletic conditions. Therefore, the aim of this trial was to determine the effects of DT on pain, disability, and overall well-being in individuals experiencing CNSNP. Methods: A prospective parallel-group active controlled trial was conducted at a single center, involving 136 patients with CNSNP, randomly allocated in a 1:1 ratio. The sham taping group (STC) received standard physiotherapy care (n = 67) alongside DT without tension, while the dynamic taping group (DTC) (n = 69) underwent standard cervical offloading technique with appropriate tension in addition to standard physiotherapy care. Demographic information and three patient-reported outcome measures (PROMs), namely the Neck Disability Index (NDI), Visual Analogue Scale (VAS), and the World Health Organization-Five Well-Being Index (WHO-5), were collected for each participant at three time points (baseline, four weeks post-taping, and four weeks follow-up). Results: At baseline, no significant differences were observed between the STC and DTC for any outcome measure. Notably, all three PROMs exhibited a significant improvement from baseline to four weeks post-intervention, with moderate to small effect sizes (NDI ηp2 = 0.21, VAS ηp2 = 0.23, and WHO-55 ηp2 = 0.05). The WHO-5 scores for both groups demonstrated improvement from baseline through follow-up (p < 0.001). The NDI and VAS scores ameliorated from baseline to the four weeks post-taping period, with marginal improvements observed during the four weeks follow-up. Conclusion: The incorporation of DT as an adjunct to standard physiotherapy care yielded enhancements in pain levels, functional disability, and well-being among patients with CNSNP when compared to the sham group. However, the sustainability of these improvements beyond the taping period lacks statistical significance and warrants further validation.


Asunto(s)
Dolor Crónico , Dolor de Cuello , Humanos , Femenino , Dolor de Cuello/terapia , Calidad de Vida , Estudios Prospectivos , Dolor Crónico/terapia , Cuello
16.
Mol Cancer Ther ; 23(1): 24-34, 2024 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-37723046

RESUMEN

Therapeutic resistance remains a major obstacle to successful clinical management of diffuse intrinsic pontine glioma (DIPG), a high-grade pediatric tumor of the brain stem. In nearly all patients, available therapies fail to prevent progression. Innovative combinatorial therapies that penetrate the blood-brain barrier and lead to long-term control of tumor growth are desperately needed. We identified mechanisms of resistance to radiotherapy, the standard of care for DIPG. On the basis of these findings, we rationally designed a brain-penetrant small molecule, MTX-241F, that is a highly selective inhibitor of EGFR and PI3 kinase family members, including the DNA repair protein DNA-PK. Preliminary studies demonstrated that micromolar levels of this inhibitor can be achieved in murine brain tissue and that MTX-241F exhibits promising single-agent efficacy and radiosensitizing activity in patient-derived DIPG neurospheres. Its physiochemical properties include high exposure in the brain, indicating excellent brain penetrance. Because radiotherapy results in double-strand breaks that are repaired by homologous recombination (HR) and non-homologous DNA end joining (NHEJ), we have tested the combination of MTX-241F with an inhibitor of Ataxia Telangiectasia Mutated to achieve blockade of HR and NHEJ, respectively, with or without radiotherapy. When HR blockers were combined with MTX-241F and radiotherapy, synthetic lethality was observed, providing impetus to explore this combination in clinically relevant models of DIPG. Our data provide proof-of-concept evidence to support advanced development of MTX-241F for the treatment of DIPG. Future studies will be designed to inform rapid clinical translation to ultimately impact patients diagnosed with this devastating disease.


Asunto(s)
Neoplasias del Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Humanos , Niño , Ratones , Animales , Glioma Pontino Intrínseco Difuso/tratamiento farmacológico , Glioma Pontino Intrínseco Difuso/genética , Glioma Pontino Intrínseco Difuso/metabolismo , Recurrencia Local de Neoplasia , Reparación del ADN , Transducción de Señal , ADN/uso terapéutico , Neoplasias del Tronco Encefálico/tratamiento farmacológico , Neoplasias del Tronco Encefálico/genética , Neoplasias del Tronco Encefálico/patología
17.
Autops. Case Rep ; 14: e2024470, 2024. graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1533854

RESUMEN

ABSTRACT Lymphangiomas are rare benign tumors that mainly involve the head and neck region in pediatric patients. Lymphangiomas of the small bowel mesentery in adults are rarer. We present two cases of mesenteric lymphangioma with acute abdominal pain on presentation. Case 1: A 38-year-old female presented with abdominal pain, vomiting, fever, and difficult evacuation. On abdominal examination, she had an ill-defined, tender lump, and radiological findings raised a possibility of perforation peritonitis. Thus, exploratory laparotomy was planned. Per-operatively, a mesenteric mass was found, which, on histopathological evaluation, was found to be a mesenteric lymphangioma involving the bowel. Case 2: A 27-year-old male presented with abdominal pain and difficult evacuation. Radiological evaluation revealed a multilobulated lesion involving the mesentery and with differential diagnoses of mesenteric fibromatoses and inflammatory pseudotumor. Histopathological assessment of the resected mass revealed a lymphangioma that was limited to the mesentery. Owing to their rarity and non-specific presentation, mesenteric lymphangiomas are often misdiagnosed on clinical examination and imaging. Thus, histopathological examination is the gold standard to reach a definitive diagnosis.

18.
J Mech Behav Biomed Mater ; 147: 106145, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37797557

RESUMEN

The review paper starts with the introduction to hydrogels along with broad literature survey covering different modes of synthesis including high energy radiation methods. After that, paper covered broad classification of the hydrogels depending upon the basis of their source of origin, method of synthesis, type of cross-linking present and ionic charges on bound groups. Another advanced category response triggered hydrogels, which includes pH, temperature, electro, and light and substrate responsive hydrogels was also studied. Presented paper summarises chemical structure, properties, and synthesis of different kinds of hydrogels. Main focus was given to the preparation super absorbents such as: Semi-interpenetrating networks (semi-IPNs), Interpenetrating networks (IPNs) and cross-linked binary graft copolymers (BGCPs). The weak mechanical properties and easy degradation limit the uses of bio-based -hydrogels in biomedical field. Their properties can be improved through different chemical and physical methods. These methods were also discussed in the current research paper. Also, it includes development of hydrogels as controlled drug delivery devices, as implants and biomaterials to replace malfunctioned body parts along with their use in several other applications listed in the literature. Literature survey on the application of hydrogels in different fields like biomedical, nano-biotechnology, tissue engineering, drug delivery and agriculture was also carried out.


Asunto(s)
Materiales Biocompatibles , Hidrogeles , Hidrogeles/química , Materiales Biocompatibles/química , Sistemas de Liberación de Medicamentos , Temperatura , Polímeros/química
19.
J Biomol Struct Dyn ; : 1-11, 2023 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-37811549

RESUMEN

2,4-Dibromophenol (DBP) has several industrial applications, including as a wood preservative and flame retardant. This study investigated the interaction between DBP and human hemoglobin (Hb) using spectroscopic, molecular docking and molecular dynamic techniques. The UV-visible spectra showed ground-state complex formation between DBP and Hb. Fluorescence studies revealed that DBP binding caused significant quenching of Hb fluorescence by the static quenching mechanism. The binding of DBP to Hb is a spontaneous process that involves van der Waals forces and hydrogen bonds. There is one DBP binding site on each Hb molecule that is located at the α1ß2 interface of Hb. DBP binding did not alter the microenvironment of tyrosine and tryptophan residues in Hb. Circular dichroism studies revealed that DBP increased the α-helical content of Hb. The intrinsic esterase activity of Hb was inhibited by DBP in a concentration-dependent manner. Molecular docking showed that DBP binds to Hb via hydrogen bonds, hydrophobic, van der Waals and π-π interactions. Molecular dynamics simulation confirmed that the Hb-DBP complex is stable. Overall, the results of this study clearly show that DBP induces structural changes and interferes with the function of Hb. This can have important implications for human health.Communicated by Ramaswamy H. Sarma.

20.
Neoplasia ; 44: 100931, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37647805

RESUMEN

Therapeutic resistance remains a major obstacle to preventing progression of H3K27M-altered Diffuse Midline Glioma (DMG). Resistance is driven in part by ALDH-positive cancer stem cells (CSC), with high ALDH1A3 expression observed in H3K27M-mutant DMG biopsies. We hypothesized that ALDH-mediated stemness and resistance may in part be driven by the oncohistone itself. Upon deletion of H3K27M, ALDH1A3 expression decreased dramatically and was accompanied by a gain in astrocytic marker expression and a loss of neurosphere forming potential, indicative of differentiation. Here we show that the oncohistone regulates histone acetylation through ALDH1A3 in a Wnt-dependent manner and that loss of H3K27M expression results in sensitization of DMGs to radiotherapy. The observed elevated Wnt signaling in H3K27M-altered DMG likely stems from a dramatic suppression of mRNA and protein expression of the Wnt inhibitor EYA4 driven by the oncohistone. Thus, our findings identify EYA4 as a bona fide tumor suppressor in DMG that upon suppression, results in aberrant Wnt signaling to orchestrate stemness and differentiation. Future studies will explore whether overexpression of EYA4 in DMG can impede growth and invasion. In summary, we have gained mechanistic insight into H3K27M-mediated regulation of cancer stemness and differentiation, which provides rationale for exploring new therapeutic targets for DMG.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA