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Cells Feb 2024Glycogen metabolism is a form of crucial metabolic reprogramming in cells. PYGB, the brain-type glycogen phosphorylase (GP), serves as the rate-limiting enzyme of... (Review)
Review
Glycogen metabolism is a form of crucial metabolic reprogramming in cells. PYGB, the brain-type glycogen phosphorylase (GP), serves as the rate-limiting enzyme of glycogen catabolism. Evidence is mounting for the association of PYGB with diverse human diseases. This review covers the advancements in PYGB research across a range of diseases, including cancer, cardiovascular diseases, metabolic diseases, nervous system diseases, and other diseases, providing a succinct overview of how PYGB functions as a critical factor in both physiological and pathological processes. We present the latest progress in PYGB in the diagnosis and treatment of various diseases and discuss the current limitations and future prospects of this novel and promising target.
Topics: Humans; Glycogen Phosphorylase; Glycogen; Brain
PubMed: 38334681
DOI: 10.3390/cells13030289 -
Pain Physician Feb 2024Chronic cancer-related pain remains underdiagnosed and undertreated, although it affects 40% of cancer survivors. Recent insights suggest that cytokine signaling between...
BACKGROUND
Chronic cancer-related pain remains underdiagnosed and undertreated, although it affects 40% of cancer survivors. Recent insights suggest that cytokine signaling between immune, neuro, and glial cells contributes to chronic pain.
OBJECTIVES
This study systematically reviewed cytokine levels and their relation to chronic cancer-related pain and, additionally, investigated differences in cytokine levels between cancer survivors with and without chronic pain.
STUDY DESIGN
Systematic review.
METHODS
This systematic review was conducted and reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines (PRISMA). The study conducted a systematic literature search in the databases PubMed, Web of Science, and Embase for articles examining cytokine levels and pain experience at a time point of a minimum of 3 months post-cancer diagnosis. Pain experience was categorized into a total pain score, pain intensity, and pain interference. The risk of bias was assessed using the Newcastle Ottawa Scale.
RESULTS
Eight articles were included, investigating 6 cancer types and 30 cytokines. Moderate evidence was found for pro-inflammatory cytokine IL-6 to be correlated with pain intensity, of which higher levels are observed in cancer survivors experiencing chronic pain compared to pain-free survivors. Moderate evidence was found for TNF-alpha to be not correlated with any pain experience, which is similar for anti-inflammatory cytokines IL-8 and IL-10 with pain intensity. For the remaining 26 cytokines and pain outcomes, only limited evidence was found for an association or alteration.
LIMITATIONS
The number of included studies was small. Overall, studies showed a moderate risk of bias, except one indicated a high risk of bias.
CONCLUSION
More standardized post-cancer treatment studies are warranted to confirm these results and explore associations and alterations of other cytokines. Nonetheless, moderate evidence suggests that elevated levels of IL-6, in contrast with TNF-alpha levels, are correlated with pain intensity in cancer survivors experiencing chronic pain compared to pain-free survivors.
Topics: Humans; Cytokines; Tumor Necrosis Factor-alpha; Chronic Pain; Interleukin-6; Cancer Survivors; Cancer Pain; Neoplasms
PubMed: 38324786
DOI: No ID Found -
The Oncologist May 2024The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer care, particularly in immune-inflamed tumors and tumors with a high mutational burden, like...
The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer care, particularly in immune-inflamed tumors and tumors with a high mutational burden, like microsatellite instable colorectal cancer (CRC). However, their effectiveness in microsatellite stable (MSS) CRC is limited. This systematic review aims to evaluate the efficacy of ICIs in MSS CRC and explore promising combination strategies. A comprehensive search from the Web of Science, Medline, and Embase databases, for studies published until 14 November 2022, identified 53 clinical trials included in the review. ICI monotherapy or ICI-ICI combinations demonstrated limited clinical activity for patients with MSS CRC, with overall response rates below (ORR) 10% in most studies. The ICI and tyrosine kinase inhibitor (TKI) garnered ORRs ranging from 10% to 40% and indicated a higher benefit for patients, particularly those without active liver metastases. The combination of ICIs with anti-VEGF agents showed modest ORRs, especially in the earlier treatment lines and in combination with chemotherapy. While these combinations could lead to modest improvements, well-defined biomarkers for long-term benefit are yet to be delineated. Combinations involving BRAF inhibitors with ICIs were studied, showing promising responses with combination approaches in molecularly defined subgroups. In conclusion, while ICI monotherapy has limited efficacy in MSS CRC, combination strategies hold promise to enhance survival outcomes. Further research is necessary to identify optimal combination approaches, predictive biomarkers for treatment response, as well as enrollment according to tumor molecular characteristics.
Topics: Humans; Immune Checkpoint Inhibitors; Colorectal Neoplasms; Microsatellite Instability
PubMed: 38309719
DOI: 10.1093/oncolo/oyae013 -
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 Neurology 2023Over the past two decades, the field of radiation brain injury has attracted the attention of an increasing number of brain scientists, particularly in the areas of...
BACKGROUND
Over the past two decades, the field of radiation brain injury has attracted the attention of an increasing number of brain scientists, particularly in the areas of molecular pathology and therapeutic approaches. Characterizing global collaboration networks and mapping development trends over the past 20 years is essential.
OBJECTIVE
The aim of this paper is to examine significant issues and future directions while shedding light on collaboration and research status in the field of radiation brain injury.
METHODS
Bibliometric studies were performed using CiteSpaceR-bibliometrix and VOSviewer software on papers regarding radiation brain injury that were published before November 2023 in the Web of Science Core Collection.
RESULTS
In the final analysis, we found 4,913 records written in 1,219 publications by 21,529 authors from 5,007 institutions in 75 countries. There was a noticeable increase in publications in 2014 and 2021. The majority of records listed were produced by China, the United States, and other high-income countries. The largest nodes in each cluster of the collaboration network were Sun Yat-sen University, University of California-San Francisco, and the University of Toronto. Galldiks N, Barnett GH, Langen KJ and Kim JH are known to be core authors in the field. The top 3 keywords in that time frame are radiation, radiation necrosis, and radiation-therapy.
CONCLUSIONS
The objective and thorough bibliometric analysis also identifies current research hotspots and potential future paths, providing a retrospective perspective on RBI and offering useful advice to researchers choosing research topics. Future development directions include the integration of multi-omics methodologies and novel imaging techniques to improve RBI's diagnostic effectiveness and the search for new therapeutic targets.
PubMed: 38298563
DOI: 10.3389/fneur.2023.1275836 -
Journal of Cancer Research and Clinical... Jan 2024Human papilloma virus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) displays distinct epidemiological, clinical, and molecular characteristics compared to... (Review)
Review
PURPOSE
Human papilloma virus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) displays distinct epidemiological, clinical, and molecular characteristics compared to the negative counterpart. Alterations in autophagy play an important role in cancer, and emerging evidence indicates an interplay of autophagy in HNSCC carcinogenesis and tumor promotion. However, the influence of HPV infection on autophagy in HNSCC has received less attention and has not been previously reviewed. Therefore, we here aimed to systematically review the role of autophagy explicitly in HPV HNSCC.
METHODS
Studies accessible in PubMed, Embase, Scopus, and Web of Science investigating HNSCC, highlighting the molecular biological differences between HPV and HPV HNSCC and its influences on autophagy in HNSCC were analyzed according to the PRISMA statement. A total of 10 articles were identified, included, and summarized.
RESULTS
The HPV16 E7 oncoprotein was reported to be involved in the degradation of AMBRA1 and STING, and to enhance chemotherapy-induced cell death via lethal mitophagy in HNSCC cells. Autophagy-associated gene signatures correlated with HPV-subtype and overall survival. Additionally, immunohistochemical (IHC) analyses indicate that high LC3B expression correlates with poor overall survival in oropharyngeal HNSCC patients.
CONCLUSION
HPV may dampen general bulk autophagic flux via degradation of AMBRA1 but may promote selective autophagic degradation of STING and mitochondria. Interpretations of correlations between autophagy-associated gene expressions or IHC analyses of autophagy-related (ATG) proteins in paraffin embedded tissue with clinicopathological features without biological validation need to be taken with caution.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Papillomavirus Infections; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Autophagy; Adaptor Proteins, Signal Transducing
PubMed: 38291202
DOI: 10.1007/s00432-023-05514-3 -
Cureus Dec 2023Diabetic retinopathy (DR) is a leading cause of global visual impairment, necessitating a comprehensive understanding of its vascular and neural components for effective... (Review)
Review
A Systematic Review of the Neuroprotective Effects of Vascular Endothelial Growth Factor (VEGF) in Diabetic Retinopathy and Diabetic Macular Edema: Unraveling the Molecular Mechanisms and Clinical Implications.
Diabetic retinopathy (DR) is a leading cause of global visual impairment, necessitating a comprehensive understanding of its vascular and neural components for effective therapeutic interventions. While vascular pathology is well-established, recent evidence suggests a neurodegenerative role in DR. Vascular endothelial growth factor (VEGF), traditionally implicated in angiogenesis, has emerged as a key player with neuroprotective potential. This systematic review evaluates the literature to shed light on molecular mechanisms and clinical implications in this regard. The review adheres to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, encompassing a thorough search strategy across multiple databases. Three in vitro studies met the inclusion criteria, highlighting the limited research in this evolving field. Findings suggest VEGF's neuroprotective effects on retinal ganglion cells (RGCs) and retinal neurons, unveiling potential therapeutic avenues. However, concerns arise regarding anti-VEGF therapies' impact on RGC survival. The review discusses the need for further research to delineate specific isoforms and signaling pathways responsible for VEGF-mediated neuroprotection. The delicate balance between angiogenesis and neuroprotection poses challenges in therapeutic development, emphasizing the importance of targeted interventions. Despite limitations, this review provides valuable insights into the intricate relationship between VEGF and neuroprotection in DR, paving the way for future investigations and redefining therapeutic strategies.
PubMed: 38288195
DOI: 10.7759/cureus.51351 -
Journal of the European Academy of... Jan 2024Mogamulizumab is a first-in-class IgG1k monoclonal antibody that selectively targets the chemokine receptor type 4. The drug has received Food and Drug administration... (Review)
Review
Mogamulizumab is a first-in-class IgG1k monoclonal antibody that selectively targets the chemokine receptor type 4. The drug has received Food and Drug administration authorisation for mycosis fungoides and Sézary syndrome following failure of at least one previous course of systemic therapy and now is available in Europe. One of the most common treatment-related side effects observed has been the mogamulizumab-associated rash (MAR), which affects up to a quarter of patients and is the most frequent adverse event leading to drug discontinuation. The aim of this study is to perform a systematic review of the literature on patients diagnosed with MAR and other mogamulizumab-related cutaneous events to describe the clinical and histological characteristics, the management in clinical practice and to assess whether these events have prognostic implications. In total, 2073 records were initially identified through a literature search, 843 of which were duplicates. After screening for eligibility and inclusion criteria, 49 articles reporting mogamulizumab-associated cutaneous events were included. Totally, 1516 patients were retrieved, with a slight male prevalence as for the available data (639 males and 570 females, i.e. 52.9% vs. 47.1%). Regarding the reported clinicopathological findings of the cutaneous reactions, the five most common patterns were spongiotic/psoriasiform dermatitis (22%), eruptions characterized by the presence of papules and/or plaques (16.1%), cutaneous granulomatosis (11.4%), morbilliform or erythrodermic dermatitis (9.4%) and photodermatitis (7.1%). Our results highlight how the majority of the reported cutaneous adverse events on mogamulizumab are of mild-to-moderate entity and generally manageable in clinical practice, though prompt recognition is essential and case-by-case assessment should be recommended. Future research will need to focus on the MAR prognostic implications and to identify genomic and molecular markers for a more rapid and accurate diagnosis.
PubMed: 38279614
DOI: 10.1111/jdv.19801 -
Cancers Jan 2024In 2019, the breakthrough of the coronavirus 2 disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represented one... (Review)
Review
BACKGROUND
In 2019, the breakthrough of the coronavirus 2 disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), represented one of the major issues of our recent history. Different drugs have been tested to rapidly find effective anti-viral treatments and, among these, antiandrogens have been suggested to play a role in mediating SARS-CoV-2 infection. Considering the high heterogeneity of studies on this topic, we decided to review the current literature.
METHODS
We performed a systematic review according to PRISMA guidelines. A search strategy was conducted on PUBMED and Medline. Only original articles published from March 2020 to 31 August 2023 investigating the possible protective role of antiandrogens were included. In vitro or preclinical studies and reports not in the English language were excluded. The main objective was to investigate how antiandrogens may interfere with COVID-19 outcomes.
RESULTS
Among 1755 records, we selected 31 studies, the majority of which consisted of retrospective clinical data collections and of randomized clinical trials during the first and second wave of the COVID-19 pandemic.
CONCLUSIONS
In conclusion, we can state that antiandrogens do not seem to protect individuals from SARS-CoV-2 infection and COVID-19 severity and, thus, their use should not be encouraged in this field.
PubMed: 38254788
DOI: 10.3390/cancers16020298 -
Military Medical Research Jan 2024Antimicrobial resistance is a global public health threat, and the World Health Organization (WHO) has announced a priority list of the most threatening pathogens... (Review)
Review
Antimicrobial resistance is a global public health threat, and the World Health Organization (WHO) has announced a priority list of the most threatening pathogens against which novel antibiotics need to be developed. The discovery and introduction of novel antibiotics are time-consuming and expensive. According to WHO's report of antibacterial agents in clinical development, only 18 novel antibiotics have been approved since 2014. Therefore, novel antibiotics are critically needed. Artificial intelligence (AI) has been rapidly applied to drug development since its recent technical breakthrough and has dramatically improved the efficiency of the discovery of novel antibiotics. Here, we first summarized recently marketed novel antibiotics, and antibiotic candidates in clinical development. In addition, we systematically reviewed the involvement of AI in antibacterial drug development and utilization, including small molecules, antimicrobial peptides, phage therapy, essential oils, as well as resistance mechanism prediction, and antibiotic stewardship.
Topics: Humans; Artificial Intelligence; Anti-Bacterial Agents; Drug Resistance, Bacterial; Public Health
PubMed: 38254241
DOI: 10.1186/s40779-024-00510-1