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1.
Chin Med J Pulm Crit Care Med ; 2(2): 63-71, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39169931

RESUMEN

Cell-cell interactions are essential components of coordinated cell function in lung homeostasis. Lung diseases involve altered cell-cell interactions and communication between different cell types, as well as between subsets of cells of the same type. The identification and understanding of intercellular signaling in lung fibrosis offer insights into the molecular mechanisms underlying these interactions and their implications in the development and progression of lung fibrosis. A comprehensive cell atlas of the human lung, established with the facilitation of single-cell RNA transcriptomic analysis, has enabled the inference of intercellular communications using ligand-receptor databases. In this review, we provide a comprehensive overview of the modified cell-cell communications in lung fibrosis. We highlight the intricate interactions among the major cell types within the lung and their contributions to fibrogenesis. The insights presented in this review will contribute to a better understanding of the molecular mechanisms underlying lung fibrosis and may guide future research efforts in developing targeted therapies for this debilitating disease.

2.
Mol Ther Nucleic Acids ; 35(3): 102268, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39171140

RESUMEN

Acute myeloid leukemia (AML) cells resist differentiation stimuli despite high expression of innate immune receptors, such as Toll-like receptor 9 (TLR9). We previously demonstrated that targeting Signal Transducer and Activator of Transcription 3 (STAT3) using TLR9-targeted decoy oligodeoxynucleotide (CpG-STAT3d) increases immunogenicity of human and mouse AML cells. Here, we elucidated molecular mechanisms of inv(16) AML reprogramming driven by STAT3-inhibition/TLR9-activation in vivo. At the transcriptional levels, AML cells isolated from mice after intravenous administration of CpG-STAT3d or leukemia-targeted Stat3 silencing and TLR9 co-stimulation, displayed similar upregulation of myeloid cell differentiation (Irf8, Cebpa, Itgam) and antigen-presentation (Ciita, Il12a, B2m)-related genes with concomitant reduction of leukemia-promoting Runx1. Single-cell transcriptomics revealed that CpG-STAT3d induced multilineage differentiation of AML cells into monocytes/macrophages, erythroblastic and B cell subsets. As shown by an inducible Irf8 silencing in vivo, IRF8 upregulation was critical for monocyte-macrophage differentiation of leukemic cells. TLR9-driven AML cell reprogramming was likely enabled by downregulation of STAT3-controlled methylation regulators, such as DNMT1 and DNMT3. In fact, the combination of DNA methyl transferase (DNMT) inhibition using azacitidine with CpG oligonucleotides alone mimicked CpG-STAT3d effects, resulting in AML cell differentiation, T cell activation, and systemic leukemia regression. These findings highlight immunotherapeutic potential of bi-functional oligonucleotides to unleash TLR9-driven differentiation of leukemic cells by concurrent STAT3 and/or DNMT inhibition.

3.
Afr J Thorac Crit Care Med ; 30(2): e1352, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39171151

RESUMEN

Abstract: Pulmonary hypertension (PH) is a haemodynamic disorder in which elevated blood pressure in the pulmonary circulation is caused by abnormal vascular tone. Despite advances in treatment, PH mortality remains high, and drug repurposing has been proposed as a mitigating approach. This article reviews the studies that have investigated drug repurposing as a viable option for PH. We provide an overview of PH and highlight pharmaceutical drugs with repurposing potential, based on limited evidence of their mechanisms of action. Moreover, studies have demonstrated the benefits of medicinal plants in PH, most of which are of Indian or Asian origin. Africa is a rich source of many medicinal plants that have been scientifically proven to counteract myriad pathologies. When perusing these studies, one will notice that some African medicinal plants can counteract the molecular pathways (e.g. proliferation, vasoconstriction, inflammation, oxidative stress and mitochondrial dysfunction) that are also involved in the pathogenesis of PH. We review the actions of these plants with actions applicable to PH and highlight that they could be repurposed as adjunct PH therapies. However, these plants have either never been tested in PH, or there is little evidence of their actions against PH. We therefore encourage caution, as more research is needed to study these plants further in experimental models of PH while acknowledging that the outcomes of such proof of-concept studies may not always yield promising findings. Regardless, this article aims to stimulate future research that could make timely contributions to the field. Study synopsis: What the study adds. Pulmonary hypertension (PH) remains a fatal disease, and 80% of the patients live in developing countries where resources are scarce and specialised therapies are often unavailable. Drug repurposing is a viable option to try to improve treatment outcomes.Implications of the findings. We propose that another form of 'drug' repurposing is the use of medicinal plants, many of which have demonstrated benefits against pathological processes that are also key in PH, e.g. apoptosis, tumour-like growth of cells, proliferation, oxidative stress and mitochondrial dysfunction.

4.
Artif Intell Med ; 156: 102951, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39173421

RESUMEN

Anticancer peptides (ACPs) are a class of molecules that have gained significant attention in the field of cancer research and therapy. ACPs are short chains of amino acids, the building blocks of proteins, and they possess the ability to selectively target and kill cancer cells. One of the key advantages of ACPs is their ability to selectively target cancer cells while sparing healthy cells to a greater extent. This selectivity is often attributed to differences in the surface properties of cancer cells compared to normal cells. That is why ACPs are being investigated as potential candidates for cancer therapy. ACPs may be used alone or in combination with other treatment modalities like chemotherapy and radiation therapy. While ACPs hold promise as a novel approach to cancer treatment, there are challenges to overcome, including optimizing their stability, improving selectivity, and enhancing their delivery to cancer cells, continuous increasing in number of peptide sequences, developing a reliable and precise prediction model. In this work, we propose an efficient transformer-based framework to identify ACPs for by performing accurate a reliable and precise prediction model. For this purpose, four different transformer models, namely ESM, ProtBERT, BioBERT, and SciBERT are employed to detect ACPs from amino acid sequences. To demonstrate the contribution of the proposed framework, extensive experiments are carried on widely-used datasets in the literature, two versions of AntiCp2, cACP-DeepGram, ACP-740. Experiment results show the usage of proposed model enhances classification accuracy when compared to the literature studies. The proposed framework, ESM, exhibits 96.45% of accuracy for AntiCp2 dataset, 97.66% of accuracy for cACP-DeepGram dataset, and 88.51% of accuracy for ACP-740 dataset, thence determining new state-of-the-art. The code of proposed framework is publicly available at github (https://github.com/mstf-yalcin/acp-esm).

5.
Front Pharmacol ; 15: 1430236, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39144618

RESUMEN

Atherosclerosis (AS) is the primary pathology behind various cardiovascular diseases and the leading cause of death and disability globally. Recent evidence suggests that AS is a chronic vascular inflammatory disease caused by multiple factors. In this context, the NLRP3 inflammasome, acting as a signal transducer of the immune system, plays a critical role in the onset and progression of AS. The NLRP3 inflammasome is involved in endothelial injury, foam cell formation, and pyroptosis in AS. Therefore, targeting the NLRP3 inflammasome offers a new treatment strategy for AS. This review highlights the latest insights into AS pathogenesis and the pharmacological therapies targeting the NLRP3 inflammasome, focusing on optimal targets for small molecule inhibitors. These insights are valuable for rational drug design and the pharmacological assessment of new targeted NLRP3 inflammasome inhibitors in treating AS.

6.
Transl Cancer Res ; 13(7): 3898-3903, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39145080

RESUMEN

The skin is a complex organ that serves as a critical barrier against external pathogens and environmental impact. Recent advances in immunometabolism have highlighted the intricate link between cellular metabolism and immune function, particularly in the context of skin cancers. This review aims to provide a comprehensive overview of the key metabolic pathways and adaptations that occur in immune cells during homeostasis and activation, and explore how metabolic reprogramming contributes to the pathogenesis of specific skin cancers. We discuss the complex interplay between tumor cells and infiltrating immune cells, which shapes the tumor microenvironment and influences disease outcomes. The review delves into the role of various metabolic pathways, such as glycolysis, oxidative phosphorylation, and lipid metabolism, in the regulation of immune cell function and their impact on the development and progression of skin cancers. Furthermore, we examine the potential of targeting metabolic pathways as a therapeutic strategy in skin cancers and discuss the challenges and future perspectives in this rapidly evolving field. By understanding the metabolic basis of skin immune responses, we can develop novel, personalized therapies for the treatment of skin cancers, ultimately improving patient outcomes and quality of life. The insights gained from this review will contribute to the growing body of knowledge in immunometabolism and its application in the management of skin cancers, paving the way for more effective and targeted interventions in the future.

7.
Pain Manag Nurs ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39147681

RESUMEN

OBJECTIVES: This paper describes phantom limb pain (PLP), its impact on patients, and the various treatment options, including pharmacologic and complementary therapies. It investigates the efficacy of incorporating complementary and alternative therapies, both invasive and noninvasive, for amputees who have not achieved satisfactory results with pharmacologic treatments and suffer from adverse drug events. Furthermore, with the predicted increase in limb amputations, it is crucial for nurses, as frontline providers, to understand PLP, be prepared to manage persistent pain and associated psychological and functional issues and educate patients and families about alternative treatment options. APPROACH: The review includes recent studies on pharmacologic interventions for PLP, case reports, and randomized clinical trials on non-pharmacologic complementary therapies, covering both invasive and noninvasive modalities. Studies from 2013 to 2022 were identified using the PubMed search engine with terms such as "Amputation," "phantom limb pain," "invasive therapies," and "non-invasive therapies." RESULTS AND CONCLUSION: The pathogenesis of PLP remains unclear, complicating the identification of causes and the selection of targeted therapies for each patient. Uncontrolled PLP can severely impact the quality of life, causing psychological distress and loss of productivity. Traditional pharmacologic therapy often requires supplementation with other options due to PLP's refractory nature. A comprehensive, multimodal treatment plan, including non-pharmacologic therapies, can enhance rehabilitation and reduce complications. Incorporating these therapies can decrease reliance on medications, particularly opioids, and mitigate side effects. Although many potential PLP treatments exist, further clinical studies are needed to determine their effectiveness and establish protocols for optimizing patient outcomes.

8.
Zool Res ; 45(5): 1001-1012, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39147715

RESUMEN

Thrombosis and inflammation are primary contributors to the onset and progression of ischemic stroke. The contact-kinin pathway, initiated by plasma kallikrein (PK) and activated factor XII (FXIIa), functions bidirectionally with the coagulation and inflammation cascades, providing a novel target for therapeutic drug development in ischemic stroke. In this study, we identified a bat-derived oligopeptide from Myotis myotis (Borkhausen, 1797), designated LE6 (Leu-Ser-Glu-Glu-Pro-Glu, 702 Da), with considerable potential in stroke therapy due to its effects on the contact kinin pathway. Notably, LE6 demonstrated significant inhibitory effects on PK and FXIIa, with inhibition constants of 43.97 µmol/L and 6.37 µmol/L, respectively. In vitro analyses revealed that LE6 prolonged plasma recalcification time and activated partial thromboplastin time. In murine models, LE6 effectively inhibited carrageenan-induced mouse tail thrombosis, FeCl 3-induced carotid artery thrombosis, and photochemically induced intracerebral thrombosis. Furthermore, LE6 significantly decreased inflammation and stroke injury in transient middle cerebral artery occlusion models. Notably, the low toxicity, hemolytic activity, and bleeding risk of LE6, along with its synthetic simplicity, underscore its clinical applicability. In conclusion, as an inhibitor of FXIIa and PK, LE6 offers potential therapeutic benefits in stroke treatment by mitigating inflammation and preventing thrombus formation.


Asunto(s)
Oligopéptidos , Accidente Cerebrovascular , Animales , Ratones , Oligopéptidos/farmacología , Accidente Cerebrovascular/tratamiento farmacológico , Quirópteros , Trombosis , Inflamación , Masculino , Antiinflamatorios/farmacología
9.
Support Care Cancer ; 32(9): 610, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39174797

RESUMEN

BACKGROUND: MEK inhibitors cause a wide spectrum of mucocutaneous toxicities which can delay or interrupt life-saving therapy. PURPOSE: To summarize the morphology, incidence, and clinical presentation of mucocutaneous toxicities from MEK inhibitors via a scoping review of the literature. METHODS: We conducted a scoping review of the published literature, including clinical trials, retrospective and prospective studies, reviews, and case reports and series. All included literature was analyzed by a panel of pediatric and adult oncodermatologists. RESULTS: Of 1626 initial citations, 227 articles met final inclusion criteria. Our review identified follicular reactions, ocular toxicities, xerosis, eczematous dermatitis, edema, and paronychia as the most common mucocutaneous side effects from MEK inhibitor therapy. Grade 1 and 2 reactions were the most prevalent and were typically managed while continuing treatment; however, grade 3 toxicities requiring dose reductions or treatment interruptions were also reported. CONCLUSION: Mucocutaneous toxicities to MEK inhibitor therapy are common and most often mild in severity. Early recognition and treatment can mitigate disruptions in oncologic therapy.


Asunto(s)
Inhibidores de Proteínas Quinasas , Humanos , Inhibidores de Proteínas Quinasas/efectos adversos , Antineoplásicos/efectos adversos , Neoplasias/tratamiento farmacológico , Índice de Severidad de la Enfermedad , Erupciones por Medicamentos/etiología
10.
BMC Sports Sci Med Rehabil ; 16(1): 176, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39175073

RESUMEN

BACKGROUND: This study aimed to compare the effects of two 12-week training intervention experimental ball games combined with standard behavioral rehabilitation against a control group solely utilizing standard behavioral rehabilitation on social communication impairments (SCI) in preschool children with Autism Spectrum Disorder (ASD). METHODS: A multi-arm controlled study design was implemented, involving 41 children diagnosed with ASD (mean age: 4.99 ± 0.76 years). 41 participants were randomized assigned to two experimental groups and a control group, The experimental group carried out ball combination training program group (BCTP) and mini-basketball training program group (MBTP) on the basis of routine behavioral rehabilitation, which underwent 12-week training interventions 5 times a week. The control group (n = 14) received only standard behavioral rehabilitation. Evaluations were conducted before and after interventions using the Social Responsiveness Scale, Second Edition (SRS-2). RESULTS: The results suggest that both 12-week interventions, BCTP, and MBTP, led to significant improvements in social communication impairment among children with ASD (p < 0.05). Despite enhancing the overall scores on the SRS-2, these interventions displayed varying impacts across different sub-dimensions. BCTP primarily exhibited significant enhancements in social awareness and behavior pattern (p < 0.05), whereas MBTP significantly improved social cognition and social communication (p < 0.05). Both interventions showed slight improvements in social motivation. CONCLUSIONS: The utilization of recreational ball games has showed to be effective in decreasing the impairment levels of children with ASD, while the control group experienced a worsening of outcomes. This suggests that irrespective of the specific ball game strategy employed, both can be employed on a weekly basis to complement standard behavioral rehabilitation and enhance the ability to improve the quality of life for children diagnosed with ASD. TRIAL REGISTRATION: The trial is retrospectively registered on the Chinese Clinical Trial Registry (ChiCTR1900024973;August 5, 2019).

11.
Int J Soc Psychiatry ; : 207640241270800, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39175172

RESUMEN

BACKGROUND: Women are disproportionately impacted by depression and anxiety disorders and in particular, women from minoritised ethnic communities experience inequalities in access to outcomes of psychological treatment for these disorders. Better understanding from the views of service users about the factors that impact their access to, and experiences of care could help to optimise treatment for these groups. METHOD: This study explored experiences of treatment and gathered suggestions about treatment improvement, from the perspectives of women currently using psychological therapy services. Semi-structured interviews were conducted with 12 female NHS Talking Therapies for anxiety and depression (NHSTTad) service users from minoritised ethnic communities. Data were analysed using thematic analysis. RESULTS: Four high-order themes were identified: (1) cultural identity and experiences of mental health and treatment, (2) challenges associated with treatment, (3) facilitators of good treatment experiences and outcomes and (4) improvements for women from minoritised ethnic communities. CONCLUSIONS: Findings showed that cultural sensitivity and awareness are important to minoritised ethnic women receiving therapy. Challenges included access difficulties and limitations of treatment options offered, alongside personal challenges of engaging in therapy. Facilitators of good treatment experiences and outcomes included flexibility on the part of the service, as well as therapist-related factors such as identity characteristics (age, gender and culture of therapist), a good therapeutic relationship and the therapist's ability to deliver person-centred care. Improvements included ensuring care is culturally sensitive, reducing waiting times or providing better support for people on waiting lists, providing a flexible service that takes individual needs into account, increasing workforce diversity and reaching out to underserved communities. Many of the suggested improvements are generalisable to underserved minoritised ethnic groups, regardless of gender and could be applied to other psychological therapies services other than NHSTTad.

12.
Zh Nevrol Psikhiatr Im S S Korsakova ; 124(7. Vyp. 2): 26-32, 2024.
Artículo en Ruso | MEDLINE | ID: mdl-39175236

RESUMEN

Adherence to therapy largely determines the success of treatment interventions: low levels of adherence are associated with reduced treatment effectiveness. For many chronic diseases, the level of adherence to treatment is about 50% or less, which confirms the relevance of this topic and requires its research. The high costs of treatment, the need for long-term continuous use of drugs and the special socio-economic significance of a disease such as multiple sclerosis (MS) determine the importance of maintaining a high level of adherence to its treatment. An analysis of literature data on the concept of treatment adherence, methods of its definition and influencing factors was carried out, the values of the level of adherence in the treatment of MS, as well as measures to maintain it during the COVID-19 pandemic were considered. Increasing awareness of healthcare professionals about the problem of treatment adherence and ways to improve it helps to improve the efficiency of managing patients with MS. The paper considers the primary stage of the strategy to improve treatment adherence among patients with MS, namely the formation of expanded knowledge of the problem by specialists of a multidisciplinary team involved in the diagnosis and treatment of patients with MS.


Asunto(s)
COVID-19 , Cumplimiento de la Medicación , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/tratamiento farmacológico , COVID-19/epidemiología , SARS-CoV-2
13.
Front Oncol ; 14: 1455464, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39175472

RESUMEN

Although multiple myeloma is an incurable disease, the past decade has witnessed significant improvement in patient outcomes. This was brought about by the development of T-cell redirection therapies such as chimeric antigen receptor (CAR) T-cells, which can leverage the natural ability of the immune system to fight myeloma cells. The approval of the B-cell maturation antigen (BCMA)-directed CAR T, idecabtagene vicleucel (ide-cel), and ciltacabtagene autoleucel (cilta-cel) has resulted in a paradigm shift in the treatment of relapsed/refractory multiple myeloma. Overall response rates ranging from 73 to 97% are currently achievable. However, the limitations of KarMMa-1 and CARTITUDE-1 studies spurred the generation of real-world data to provide some insights into the effectiveness of ide-cel and cilta-cel among patients who were excluded from clinical trials, particularly those who received prior BCMA-targeted or other T-cell redirection therapies. Despite their unprecedented clinical efficacy in heavily pretreated patients, responses to CAR T remain non-durable. Although the underlying mechanisms of resistance to these agents haven't been fully elucidated, studies have suggested that resistance patterns could be multifaceted, implicating T-cell exhaustion and tumor intrinsic mechanisms such as BCMA target loss, upregulation of gamma-secretase, and others. Herein, we provide a succinct overview of the development of CAR T-cells, manufacturing process, and associated toxicities/complications. In this review, we also recapitulate the existing literature pertaining MM CAR-T as well as emerging data from some of the ongoing clinical trials designed to mitigate the shortcomings of these agents, and improve the clinical efficacy of CAR T, especially in the relapsed/refractory setting.

14.
Glob Med Genet ; 11(4): 251-262, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39176108

RESUMEN

Although gastrointestinal stromal tumors (GISTs) has been reported in patients of all ages, its diagnosis is more common in elders. The two most common types of mutation, receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor a (PDGFRA) mutations, hold about 75 and 15% of GISTs cases, respectively. Tumors without KIT or PDGFRA mutations are known as wild type (WT)-GISTs, which takes up for 15% of all cases. WT-GISTs have other genetic alterations, including mutations of the succinate dehydrogenase and serine-threonine protein kinase BRAF and neurofibromatosis type 1. Other GISTs without any of the above genetic mutations are named "quadruple WT" GISTs. More types of rare mutations are being reported. These mutations or gene fusions were initially thought to be mutually exclusive in primary GISTs, but recently it has been reported that some of these rare mutations coexist with KIT or PDGFRA mutations. The treatment and management differ according to molecular subtypes of GISTs. Especially for patients with late-stage tumors, developing a personalized chemotherapy regimen based on mutation status is of great help to improve patient survival and quality of life. At present, imatinib mesylate is an effective first-line drug for the treatment of unresectable or metastatic recurrent GISTs, but how to overcome drug resistance is still an important clinical problem. The effectiveness of other drugs is being further evaluated. The progress in the study of relevant mechanisms also provides the possibility to develop new targets or new drugs.

15.
Mol Ther Nucleic Acids ; 35(3): 102271, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39176177

RESUMEN

Amyotrophic lateral sclerosis (ALS), a progressive neurodegenerative disease, presents considerable challenges in both diagnosis and treatment. It is categorized into sporadic and familial amyotrophic lateral sclerosis (fALS); the latter accounts for approximately 10% of cases and is primarily inherited in an autosomal dominant manner. This review summarizes the molecular genetics of fALS, highlighting key mutations that contribute to its pathogenesis, such as mutations in SOD1, FUS, and C9orf72. Central to this discourse is exploring antisense oligonucleotides (ASOs) that target these genetic aberrations, providing a promising therapeutic strategy. This review provides a detailed overview of the molecular mechanisms underlying fALS and the potential therapeutic value of ASOs, offering new insights into treating neurodegenerative diseases.

16.
J Cosmet Dermatol ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39176982

RESUMEN

BACKGROUND: Androgenetic alopecia is the most common cause of hair loss that affects over 50% of the world population. It is a condition that is multifactorial in origin, with no specific causative factor, making treatment an enervating experience for the patient as well as the doctor. In recent times, a number of modalities have been introduced for the treatment of alopecia. However, the evidence supporting them is unstructured and sparse. Therefore, this article aims to explore the current trends in minimally invasive treatments for the management of androgenetic alopecia. METHODS: An in-depth literature search on injectables used in the treatment of alopecia in PubMed/MEDLINE, Embase, PsycINFO, TRIP Cochrane Library, and Cochrane Skin databases between January 2000 and May 2023 was performed. The studies included were randomized controlled trials, non-randomized trials, quasi trials, single arm interventions, and cohort studies. RESULTS: Sixteen of the 1071 studies that were found during the original search were accepted in accordance with the inclusion criteria. Twelve studies assessed the effectiveness of the injectable group by comparing it to a control group consisting of saline, distilled water, and topical minoxidil. In the treatment of alopecia, dutasteride and injectable growth factor formulations achieved clinically significant results. CONCLUSION: The usage of injectables and topical medicines to treat hair loss has increased in the recent years. Overall results from clinical investigations, pilot studies, and trials looking at the efficacy and safety of these growth factors in the AGA show satisfactory efficacy.

17.
Handb Exp Pharmacol ; 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39177748

RESUMEN

The outcome for children with cancer has improved significantly over the past 60 years, with more than 80% of patients today becoming 5-year survivors. Despite this progress, cancer remains the leading cause of death from disease in children in the United States and Europe, with significant short- and long-term toxicity of treatment continuing to impact most children. While the past 15 years have witnessed dramatic scientific innovation for certain cancers in adult patients, pediatric cancer treatment innovation lags increasingly behind. To help bridge the adult-pediatric therapeutic development gap, collaborative efforts are essential among stakeholders within and outside the pediatric oncology community. Prioritizing collaboration in areas such as cancer characterization, target identification and validation, drug discovery, and approaches to currently "undruggable" targets is imperative to improving the outcomes for children with cancer.

18.
Kidney Int Rep ; 9(8): 2337-2352, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39156157

RESUMEN

Immune-mediated renal diseases are a diverse group of disorders caused by antibody, complement, or cell-mediated autosensitization. Although these diseases predispose to infection on their own, a growing array of traditional and newer, more targeted immunosuppressant medications are used to treat these diseases. By understanding their mechanisms of action and the infections associated with suppression of each arm of the immune system, nephrologists can better anticipate these risks and effectively prevent and recognize opportunistic infections. Focusing specifically on nonkidney transplant recipients, this review discusses the infections that can be associated with each of the commonly used immunosuppressants by nephrologists and suggest interventions to prevent infectious complications in patients with immune-mediated renal disease.

19.
Front Cell Dev Biol ; 12: 1408852, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39156971

RESUMEN

Significant advancements in our understanding and clinical treatment of cholangiocarcinoma (CCA) have been achieved over the past 5 years. Groundbreaking studies have illuminated the immune landscape and pathological characteristics of the tumor microenvironment in CCA. The development of immune- and metabolism-based classification systems has enabled a nuanced exploration of the tumor microenvironment and the origins of CCA, facilitating a detailed understanding of tumor progression modulation. Despite these insights, targeted therapies have not yet yielded satisfactory clinical results, highlighting the urgent need for innovative therapeutic strategies. This review delineates the complexity and heterogeneity of CCA, examines the current landscape of therapeutic strategies and clinical trials, and delves into the resistance mechanisms underlying targeted therapies. Finally, from a single-cell and spatial transcriptomic perspective, we address the challenge of therapy resistance, discussing emerging mechanisms and potential strategies to overcome this barrier and enhance treatment efficacy.

20.
J Reprod Infertil ; 25(1): 60-65, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39157286

RESUMEN

Background: Sperm DNA fragmentation (SDF) can affect fertilization rate and embryo development, making it a useful measure for assessing male fertility. Available evidence supports the association between high sperm DNA fragmentation and poor outcomes, with regard to natural conception. Several treatment options are being adopted with varying degrees of success. Some of the commonly used treatment options are the intake of oral antioxidants, varicocele repair, and techniques like micro-manipulation-based sperm selection and use of testicular sperm for intracytoplasmic sperm injection. Case Presentation: Studies have shown that around 29% of couples depend on complementary and alternative medicine (CAM) modality for the treatment of infertility. However, there is a lack of substantial evidence regarding its efficacy in treating various aspects of infertility in couples. The current case report is about a 44 year-old male patient with infertility, who has a known diagnosis of sex chromosome abnormalities. Meanwhile, the SDF study reports indicated the presence of chromosomal abnormalities. This patient was treated exclusively with Ayurveda therapy aimed towards qualitative improvement in reproductive tissues (Shukra Dhatu as per Ayurveda). Patient was assessed periodically for changes in chromosomal abnormality. After four months of treatment, the evaluations demonstrated the presence of completely normal chromosomes. Conclusion: This case study indicates the potential of Ayurveda therapy in treating cases of male infertility caused by DNA fragmentation. Furthermore, observations and systematically designed clinical trials are warranted to establish a stronger level of evidence before making further clinical recommendations.

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