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Frontiers in Oncology 2024Over the past years, there has been a growing interest in the role of immunotherapy in locally advanced (LA) and recurrent and metastatic head and neck squamous cell...
INTRODUCTION
Over the past years, there has been a growing interest in the role of immunotherapy in locally advanced (LA) and recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). High-quality data from prospective trials are lacking for the elderly subpopulation. This systematic review and meta-analysis aims to review the efficacy and safety of immunotherapy in older patients.
METHODS
A systematic literature search was conducted. Randomized clinical trials providing outcome data on a subgroup of elderly (>65 years old) were available for meta-analysis. Primary outcomes of interest were OS and PFS for efficacy analysis.
RESULTS
Seven studies were included in the systematic review and four in the efficacy analysis. The pooled analysis of OS and PFS showed a consistent benefit (HR 0.78 and 0.91, respectively).
CONCLUSIONS
Immunotherapy may be an effective and well-tolerated treatment option in the elderly population, but more prospective and randomized data are needed.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (CRD42022333891).
PubMed: 38800381
DOI: 10.3389/fonc.2024.1395838 -
Translational Psychiatry Apr 2024Deep brain stimulation (DBS) modulates local and widespread connectivity in dysfunctional networks. Positive results are observed in several patient populations;...
Deep brain stimulation (DBS) modulates local and widespread connectivity in dysfunctional networks. Positive results are observed in several patient populations; however, the precise mechanisms underlying treatment remain unknown. Translational DBS studies aim to answer these questions and provide knowledge for advancing the field. Here, we systematically review the literature on DBS studies involving models of neurological, developmental and neuropsychiatric disorders to provide a synthesis of the current scientific landscape surrounding this topic. A systematic analysis of the literature was performed following PRISMA guidelines. 407 original articles were included. Data extraction focused on study characteristics, including stimulation protocol, behavioural outcomes, and mechanisms of action. The number of articles published increased over the years, including 16 rat models and 13 mouse models of transgenic or healthy animals exposed to external factors to induce symptoms. Most studies targeted telencephalic structures with varying stimulation settings. Positive behavioural outcomes were reported in 85.8% of the included studies. In models of psychiatric and neurodevelopmental disorders, DBS-induced effects were associated with changes in monoamines and neuronal activity along the mesocorticolimbic circuit. For movement disorders, DBS improves symptoms via modulation of the striatal dopaminergic system. In dementia and epilepsy models, changes to cellular and molecular aspects of the hippocampus were shown to underlie symptom improvement. Despite limitations in translating findings from preclinical to clinical settings, rodent studies have contributed substantially to our current knowledge of the pathophysiology of disease and DBS mechanisms. Direct inhibition/excitation of neural activity, whereby DBS modulates pathological oscillatory activity within brain networks, is among the major theories of its mechanism. However, there remain fundamental questions on mechanisms, optimal targets and parameters that need to be better understood to improve this therapy and provide more individualized treatment according to the patient's predominant symptoms.
Topics: Mice; Humans; Rats; Animals; Deep Brain Stimulation; Rodentia; Brain; Epilepsy; Hippocampus
PubMed: 38605027
DOI: 10.1038/s41398-023-02727-5 -
Neurobiology of Disease Mar 2024Transgenic models of familial Alzheimer's disease (AD) serve as valuable tools for probing the molecular mechanisms associated with amyloid-beta (Aβ)-induced pathology.... (Meta-Analysis)
Meta-Analysis Review
Transgenic models of familial Alzheimer's disease (AD) serve as valuable tools for probing the molecular mechanisms associated with amyloid-beta (Aβ)-induced pathology. In this meta-analysis, we sought to evaluate levels of phosphorylated tau (p-tau) and explore potential age-related variations in tau hyperphosphorylation, within mouse models of AD. The PubMed and Scopus databases were searched for studies measuring soluble p-tau in 5xFAD, APP/PSEN1, J20 and APP23 mice. Data were extracted and analyzed using standardized procedures. For the 5xFAD model, the search yielded 36 studies eligible for meta-analysis. Levels of p-tau were higher in 5xFAD mice relative to control, a difference that was evident in both the carboxy-terminal (CT) and proline-rich (PR) domains of tau. Age negatively moderated the relationship between genotype and CT phosphorylated tau in studies using hybrid mice, female mice, and preparations from the neocortex. For the APP/PSEN1 model, the search yielded 27 studies. Analysis showed tau hyperphosphorylation in transgenic vs. control animals, evident in both the CT and PR regions of tau. Age positively moderated the relationship between genotype and PR domain phosphorylated tau in the neocortex of APP/PSEN1 mice. A meta-analysis was not performed for the J20 and APP23 models, due to the limited number of studies measuring p-tau levels in these mice (<10 studies). Although tau is hyperphosphorylated in both 5xFAD and APP/PSEN1 mice, the effects of ageing on p-tau are contingent upon the model being examined. These observations emphasize the importance of tailoring model selection to the appropriate disease stage when considering the relationship between Aβ and tau, and suggest that there are optimal intervention points for the administration of both anti-amyloid and anti-tau therapies.
Topics: Mice; Female; Animals; Alzheimer Disease; Phosphorylation; Amyloid beta-Protein Precursor; Mice, Transgenic; tau Proteins; Amyloid beta-Peptides; Disease Models, Animal
PubMed: 38307366
DOI: 10.1016/j.nbd.2024.106427 -
Frontiers in Physiology 2023The pre-Bötzinger complex, situated in the ventrolateral medulla, serves as the central generator for the inspiratory phase of the respiratory rhythm. Evidence strongly...
The pre-Bötzinger complex, situated in the ventrolateral medulla, serves as the central generator for the inspiratory phase of the respiratory rhythm. Evidence strongly supports its pivotal role in generating, and, in conjunction with the post-inspiratory complex and the lateral parafacial nucleus, in shaping the respiratory rhythm. While there remains an ongoing debate concerning the mechanisms underlying these nuclei's ability to generate and modulate breathing, transgenic rodent models have significantly contributed to our understanding of these processes. However, there is a significant knowledge gap regarding the spectrum of transgenic rodent lines developed for studying respiratory rhythm, and the methodologies employed in these models. In this study, we conducted a scoping review to identify commonly used transgenic rodent lines and techniques for studying respiratory rhythm generation and modulation. Following PRISMA guidelines, we identified relevant papers in PubMed and EBSCO on 29 March 2023, and transgenic lines in Mouse Genome Informatics and the International Mouse Phenotyping Consortium. With strict inclusion and exclusion criteria, we identified 80 publications spanning 1997-2022 using 107 rodent lines. Our findings revealed 30 lines focusing on rhythm generation, 61 on modulation, and 16 on both. The primary method was whole-body plethysmography. The main method was hypoglossal/phrenic nerve recordings using the preparation. Additionally, we identified 119 transgenic lines with the potential for investigating the intricate mechanisms underlying respiratory rhythm. Through this review, we provide insights needed to design more effective experiments with transgenic animals to unravel the mechanisms governing respiratory rhythm. The identified transgenic rodent lines and methodological approaches compile current knowledge and guide future research towards filling knowledge gaps in respiratory rhythm generation and modulation.
PubMed: 38179140
DOI: 10.3389/fphys.2023.1295632 -
Clinical & Translational Oncology :... Feb 2024Glioblastoma (GBM) constitutes the most common primary brain tumor in adults. The challenges in GBM therapeutics have shed light on zebrafish used as a promising animal... (Review)
Review
Glioblastoma (GBM) constitutes the most common primary brain tumor in adults. The challenges in GBM therapeutics have shed light on zebrafish used as a promising animal model for preclinical GBM xenograft studies without a standardized methodology. This systematic review aims to summarize the advances in zebrafish GBM xenografting, compare research protocols to pinpoint advantages and underlying limitations, and designate the predominant xenografting parameters. Based on the PRISMA checklist, we systematically searched PubMed, Scopus, and ZFIN using the keywords "glioblastoma," "xenotransplantation," and "zebrafish" for papers published from 2005 to 2022, available in English. 46 articles meeting the review criteria were examined for the zebrafish strain, cancer cell line, cell labeling technique, injected cell number, time and site of injection, and maintenance temperature. Our review designated that AB wild-type zebrafish, Casper transparent mutants, transgenic Tg(fli1:EGFP), or crossbreeding of these predominate among the zebrafish strains. Orthotopic transplantation is more commonly employed. A number of 50-100 cells injected at 48 h post-fertilization in high density and low infusion volume is considered as an effective xenografting approach. U87 cells are used for GBM angiogenesis studies, U251 for GBM proliferation studies, and patient-derived xenograft (PDX) to achieve clinical relevance. Gradual acclimatization to 32-33 °C can partly address the temperature differential between the zebrafish and the GBM cells. Zebrafish xenograft models constitute valuable tools for preclinical studies with clinical relevance regarding PDX. The GBM xenografting research requires modification based on the objective of each research team. Automation and further optimization of the protocol parameters could scale up the anticancer drug trials.
Topics: Animals; Humans; Glioblastoma; Transplantation, Heterologous; Zebrafish; Heterografts; Brain Neoplasms; Cell Line, Tumor; Xenograft Model Antitumor Assays; Disease Models, Animal
PubMed: 37400666
DOI: 10.1007/s12094-023-03258-7 -
Nutrients Mar 2023In order to understand how omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplements affect breast cancer prevention and treatment, a systematic review of articles... (Review)
Review
In order to understand how omega-3 polyunsaturated fatty acid (ω-3 PUFA) supplements affect breast cancer prevention and treatment, a systematic review of articles published in the last 5 years in two databases was performed. Of the 679 articles identified, only 27 were included and examined based on five topics, taking into account: the induction type of the breast cancer used in animal models; the characteristics of the induction model by cell transplantation; the experimental design of the ω-3 supplementation-combined or not with a treatment antitumor drug; the fatty acids (FAs) composition used; the analysis of the studies' outcomes. There are diverse and well-established animal models of breast cancer in the literature, with very relevant histological and molecular similarities depending on the specific objective of the study, such as whether the method of tumor induction was transgenic, by cell transplantation, or by oncogenic drugs. The analyses of outcomes were mainly focused on monitoring tumor growth, body/tumor weight, and molecular, genetic, or histological analyses, and few studies evaluated latency, survival, or metastases. The best results occurred when supplementation with ω-3 PUFA was associated with antitumor drugs, especially in the analysis of metastases and volume/weight of tumors or when the supplementation was started early and maintained for a long time. However, the beneficial effect of ω-3 PUFA supplementation when not associated with an antitumor agent remains unclear.
Topics: Animals; Fatty Acids, Omega-3; Fatty Acids; Antineoplastic Agents; Dietary Supplements; Neoplasms
PubMed: 36986040
DOI: 10.3390/nu15061310 -
Frontiers in Pharmacology 2023Over the last decade, researchers have sought to develop novel medications against dementia. One potential agent under investigation is cannabinoids. This review...
Over the last decade, researchers have sought to develop novel medications against dementia. One potential agent under investigation is cannabinoids. This review systematically appraised and meta-analyzed published pre-clinical research on the mechanism of endocannabinoid system modulation in glial cells and their effects on cognitive function in animal models of Alzheimer's disease (AD). A systematic review complying with PRISMA guidelines was conducted. Six databases were searched: EBSCOHost, Scopus, PubMed, CINAHL, Cochrane, and Web of Science, using the keywords AD, cannabinoid, glial cells, and cognition. The methodological quality of each selected pre-clinical study was evaluated using the SYRCLE risk of bias tool. A random-effects model was applied to analyze the data and calculate the effect size, while I and -values were used to assess heterogeneity. The analysis included 26 original articles describing (1050 rodents) with AD-like symptoms. Rodents treated with cannabinoid agonists showed significant reductions in escape latency (standard mean difference [SMD] = -1.26; 95% confidence interval [CI]: -1.77 to -0.76, < 0.00001) and ability to discriminate novel objects (SMD = 1.40; 95% CI: 1.04 to 1.76, < 0.00001) compared to the control group. Furthermore, a significant decrease in Aβ plaques (SMD = -0.91; 95% CI: -1.55 to -0.27, = 0.006) was observed in the endocannabinoid-treated group compared to the control group. Trends were observed toward neuroprotection, as represented by decreased levels of glial cell markers including glial fibrillary acid protein (SMD = -1.47; 95% CI: -2.56 to -0.38, = 0.008) and Iba1 (SMD = -1.67; 95% CI: -2.56 to -0.79, = 0.0002). Studies on the wild-type mice demonstrated significantly decreased levels of pro-inflammatory markers TNF-α, IL-1, and IL-6 (SMD = -2.28; 95% CI: -3.15 to -1.41, = 0.00001). Despite the non-significant decrease in pro-inflammatory marker levels in transgenic mice (SMD = -0.47; 95% CI: -1.03 to 0.08, = 0.09), the result favored the endocannabinoid-treated group over the control group. The revised data suggested that endocannabinoid stimulation promotes cognitive function modulation of glial cells by decreasing pro-inflammatory markers in AD-like rodent models. Thus, cannabinoid agents may be required to modulate the downstream chain of effect to enhance cognitive stability against concurrent neuroinflammation in AD. Population-based studies and well-designed clinical trials are required to characterize the acceptability and real-world effectiveness of cannabinoid agents. [https://inplasy.com/inplasy-2022-8-0094/], identifier [Inplasy Protocol 3770].
PubMed: 36959856
DOI: 10.3389/fphar.2023.1053680 -
Viruses Dec 2022The baculovirus expression vector systems (BEVS) have been widely used for the recombinant production of proteins in insect cells and with high insert capacity. However,... (Review)
Review
The baculovirus expression vector systems (BEVS) have been widely used for the recombinant production of proteins in insect cells and with high insert capacity. However, baculovirus does not replicate in mammalian cells; thus, the BacMam system, a heterogenous expression system that can infect certain mammalian cells, was developed. Since then, the BacMam system has enabled transgene expression via mammalian-specific promoters in human cells, and later, the MultiBacMam system enabled multi-protein expression in mammalian cells. In this review, we will cover the continual development of the BEVS in combination with CRPISPR-Cas technologies to drive genome-editing in mammalian cells. Additionally, we highlight the use of CRISPR-Cas in glycoengineering to potentially produce a new class of glycoprotein medicines in insect cells. Moreover, we anticipate CRISPR-Cas9 to play a crucial role in the development of protein expression systems, gene therapy, and advancing genome engineering applications in the future.
Topics: Animals; Humans; Baculoviridae; CRISPR-Cas Systems; Genetic Vectors; Genetic Therapy; Mammals
PubMed: 36680093
DOI: 10.3390/v15010054 -
Frontiers in Plant Science 2022Fortification of food with mineral micronutrients and micronutrient supplementation occupied the center stage during the two-year-long Corona Pandemic, highlighting the...
Fortification of food with mineral micronutrients and micronutrient supplementation occupied the center stage during the two-year-long Corona Pandemic, highlighting the urgent need to focus on micronutrition. Focus has also been intensified on the biofortification (natural assimilation) of mineral micronutrients into food crops using various techniques like agronomic, genetic, or transgenic. Agronomic biofortification is a time-tested method and has been found useful in the fortification of several nutrients in several crops, yet the nutrient use and uptake efficiency of crops has been noted to vary due to different growing conditions like soil type, crop management, fertilizer type, etc. Agronomic biofortification can be an important tool in achieving nutritional security and its importance has recently increased because of climate change related issues, and pandemics such as COVID-19. The introduction of high specialty fertilizers like nano-fertilizers, chelated fertilizers, and water-soluble fertilizers that have high nutrient uptake efficiency and better nutrient translocation to the consumable parts of a crop plant has further improved the effectiveness of agronomic biofortification. Several new agronomic biofortification techniques like nutripriming, foliar application, soilless activation, and mechanized application techniques have further increased the relevance of agronomic biofortification. These new technological advances, along with an increased realization of mineral micronutrient nutrition have reinforced the relevance of agronomic biofortification for global food and nutritional security. The review highlights the advances made in the field of agronomic biofortification the improved new fertilizer forms, and the emerging techniques that achieve better micronutrient use efficiency of crop plants.
PubMed: 36570883
DOI: 10.3389/fpls.2022.1055278 -
Frontiers in Nutrition 2022Nutritious foods are essential for human health and development. However, malnutrition and hidden hunger continue to be a challenge globally. In most developing... (Review)
Review
Nutritious foods are essential for human health and development. However, malnutrition and hidden hunger continue to be a challenge globally. In most developing countries, access to adequate and nutritious food continues to be a challenge. Although hidden hunger is less prevalent in developed countries compared to developing countries where iron (Fe) and zinc (Zn) deficiencies are common. The United Nations (UN) 2nd Sustainable Development Goal was set to eradicate malnutrition and hidden hunger. Hidden hunger has led to numerous cases of infant and maternal mortalities, and has greatly impacted growth, development, cognitive ability, and physical working capacity. This has influenced several countries to develop interventions that could help combat malnutrition and hidden hunger. Interventions such as dietary diversification and food supplementation are being adopted. However, fortification but mainly biofortification has been projected to be the most sustainable solution to malnutrition and hidden hunger. Plant-based foods (PBFs) form a greater proportion of diets in certain populations; hence, fortification of PBFs is relevant in combating malnutrition and hidden hunger. Agronomic biofortification, plant breeding, and transgenic approaches are some currently used strategies in food crops. Crops such as cereals, legumes, oilseeds, vegetables, and fruits have been biofortified through all these three strategies. The transgenic approach is sustainable, efficient, and rapid, making it suitable for biofortification programs. Omics technology has also been introduced to improve the efficiency of the transgenic approach.
PubMed: 36570169
DOI: 10.3389/fnut.2022.1043655