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European Journal of Pharmacology Aug 2024To provide a comprehensive framework of the current information on the potency and efficacy of interaction between phyto- and synthetic cannabinoids and their respective... (Review)
Review
To provide a comprehensive framework of the current information on the potency and efficacy of interaction between phyto- and synthetic cannabinoids and their respective receptors, an electronic search of the PubMed, Scopus, and EMBASE literature was performed. Experimental studies included reports of mechanistic data providing affinity, efficacy, and half-maximal effective concentration (EC). Among the 108 included studies, 174 structures, and 16 targets were extracted. The most frequent ligands belonged to the miscellaneous category with 40.2% followed by phytocannabinoid-similar, indole-similar, and pyrrole-similar structures with an abundance of 17.8%, 16.6%, and 12% respectively. 64.8% of structures acted as agonists, 17.1 % appeared as inverse agonists, 10.8% as antagonists, and 7.2% of structures were reported with antagonist/inverse agonist properties. Our outcomes identify the affinity, EC, and efficacy of the interactions between cannabinoids and their corresponding receptors and the subsequent response, evaluated in the available evidence. Considering structures' significance and very important effects of on the activities, the obtained results also provide clues to drug repurposing.
Topics: Cannabinoids; Humans; Animals; Structure-Activity Relationship; Receptors, Cannabinoid; Ligands; Cannabinoid Receptor Agonists
PubMed: 38821167
DOI: 10.1016/j.ejphar.2024.176679 -
Nutrition Reviews May 2024The relation of magnesium (Mg) intake with depression was previously investigated by meta-analyses. However, due to limited data, a dose-response analysis was not...
CONTEXT
The relation of magnesium (Mg) intake with depression was previously investigated by meta-analyses. However, due to limited data, a dose-response analysis was not performed.
OBJECTIVE
Considering the recently published articles, a systematic review and dose-response meta-analysis was conducted to summarize the relation of dietary Mg intake with depression in adults.
DATA SOURCES
Medline (PubMed), ISI Web of Science, Scopus, and Google Scholar were comprehensively searched up to August 2023.
DATA EXTRACTION
Observational studies that reported the relation of dietary Mg intake and depression in adults were included and their data were extracted.
DATA ANALYSIS
A total of 63 214 participants from 10 cross-sectional and 3 cohort studies were included in the current study. Pooling 15 effect sizes from 12 studies (including 50 275 participants) revealed that individuals with the highest Mg intake had a 34% lower risk of depression, compared with those with the lowest Mg intake (RR: 0.66; 95% CI: 0.57, 0.78). Moreover, the linear dose-response analysis revealed that each 100-mg/d increment in Mg intake was associated with a 7% reduced risk of depression (RR: 0.93; 95% CI: 0.90, 0.96). Additionally, based on nonlinear dose-response analysis, increasing Mg intake from 170 to 370 mg/d was associated with a reduced risk of depression. Analyses were also conducted on 9 studies (49 558 participants) with representative populations, and similar results were found in the meta-analysis (RR: 0.71; 95% CI: 0.61, 0.83) and linear (RR: 0.93; 95% CI: 0.90, 0.96) and nonlinear dose-response analysis.
CONCLUSION
The current study shows an inverse dose-dependent association between dietary Mg intakes and risk of depression in both a general and representative population of adults in a dose-response manner.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration no. CRD42024506570.
PubMed: 38812090
DOI: 10.1093/nutrit/nuae056 -
Seminars in Nuclear Medicine May 2024Neuroendocrine neoplasms (NENs), arising from various sites, present therapeutic challenges. Radioligand therapy (RLT) is effective for unresectable/metastatic NENs with... (Review)
Review
Neuroendocrine neoplasms (NENs), arising from various sites, present therapeutic challenges. Radioligand therapy (RLT) is effective for unresectable/metastatic NENs with increased somatostatin receptor uptake. While evidence supports RLT's efficacy in midgut NETs, its role in lung NETs remains underexplored. Clinical guidelines place RLT as a third or fourth-line option in this setting. However, in the last years several studies investigated mainly retrospectively effectiveness and safety of RLT in lung NET. The aim of this review is to assess the efficacy and safety of RLT in patients with lung NETs. Following PRISMA guidelines, a systematic review of MEDLINE and EMBASE databases retrieved English articles until March 31, 2023. Inclusion criteria encompassed studies involving RLT in lung NETs with efficacy and safety assessments. Twenty-seven studies met the criteria, totaling 786 patients. The pooled analysis revealed a 25.6% objective response rate and 75.6% disease control rate. Median progression-free survival averaged 20 months, while overall survival averaged 45 months. Factors affecting response included tumor burden, prior treatments, F-FDG PET scan uptake, and histological variants. RLT exhibited manageable grade 1/2 adverse effects, predominantly hematological, with Lu demonstrating a more favorable profile than Y. The findings support RLT's effectiveness in lung NETs, offering hope for advanced SSTR-positive patients. Although identifying predictive factors for response remains challenging, RLT retained efficacy even after prior therapies and typical carcinoids displayed a slightly better response than atypical ones. Prospective trials are imperative to establish RLT's definitive efficacy and its place in the therapeutic landscape for lung NETs.
PubMed: 38811266
DOI: 10.1053/j.semnuclmed.2024.05.001 -
International Journal of Colorectal... May 2024Circulating tumour DNA (ctDNA) has emerged as a promising biomarker in various cancer types, including locally advanced rectal cancer (LARC), offering potential insights... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Circulating tumour DNA (ctDNA) has emerged as a promising biomarker in various cancer types, including locally advanced rectal cancer (LARC), offering potential insights into disease progression, treatment response and recurrence. This review aims to comprehensively evaluate the utility of ctDNA as a prognostic biomarker in LARC.
METHODS
PubMed, EMBASE and Web of Science were searched as part of our review. Studies investigating the utility of ctDNA in locally advanced rectal cancer (LARC) were assessed for eligibility. Quality assessment of included studies was performed using the Newcastle Ottawa Scale (NOS) risk of bias tool. Outcomes extracted included basic participant characteristics, ctDNA details and survival data. A meta-analysis was performed on eligible studies to determine pooled recurrence-free survival (RFS).
RESULTS
Twenty-two studies involving 1676 participants were included in our analysis. Methodological quality categorised by the Newcastle Ottawa Scale was generally satisfactory across included studies. ctDNA detected at various time intervals was generally associated with poor outcomes across included studies. Meta-analysis demonstrated a pooled hazard ratio of 8.87 (95% CI 4.91-16.03) and 15.15 (95% CI 8.21-27.95), indicating an increased risk of recurrence with ctDNA positivity in the post-neoadjuvant and post-operative periods respectively.
CONCLUSION
Our systematic review provides evidence supporting the prognostic utility of ctDNA in patients with LARC, particularly in identifying patients at higher risk of disease recurrence in the post-neoadjuvant and post-operative periods.
Topics: Humans; Biomarkers, Tumor; Circulating Tumor DNA; Disease-Free Survival; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Rectal Neoplasms
PubMed: 38809315
DOI: 10.1007/s00384-024-04656-1 -
Nutrition & Dietetics: the Journal of... May 2024Immune checkpoint inhibitor therapy used for lung cancer has significantly changed response and survival rates, however, the impact on patients' nutritional status... (Review)
Review
AIMS
Immune checkpoint inhibitor therapy used for lung cancer has significantly changed response and survival rates, however, the impact on patients' nutritional status remains largely unexplored. This review aims to identify common adverse events that increase nutrition risk induced in non-small cell lung cancer patients treated with immune checkpoint inhibitor therapy and assess impact on nutritional status.
METHODS
PubMed, Medline and CINAHL were systematically searched in September 2023 for randomised controlled trials comparing immune checkpoint inhibitor treatment of non-small cell lung cancer to a control group. Treatment-related adverse events that increased nutrition impact symptoms identified in the patient-generated subjective global assessment and clinical guidelines were extracted and qualitatively analysed. Risk of bias was assessed using Cochrane Risk of Bias tool 2.
RESULTS
Eleven eligible randomised controlled trial studies were identified and analysed. The data demonstrated immune checkpoint inhibitor treatment was associated with a lower percentage of reported nutrition impact symptoms, for example, decreased appetite, nausea, vomiting, compared to chemotherapy treatment. Conversely, immune checkpoint inhibitor treated patients recorded a greater percentage of immune-related adverse events that alter metabolism or nutrient absorption.
CONCLUSION
Non-small cell lung cancer patients treated with immune checkpoint inhibitors still experience nutrition impact symptoms but less frequently than patients treated with chemotherapy. This combined with unique nutrition-related consequences from colitis and thyroid disorders induced by immune checkpoint inhibitor therapy indicates patients should be screened, assessed and interventions implemented to improve nutrition.
PubMed: 38804022
DOI: 10.1111/1747-0080.12879 -
Neurological Sciences : Official... May 2024Myophosphorylase deficiency, also known as McArdle disease or Glycogen Storage Disease type V (GSD-V), is an autosomal recessive metabolic myopathy that results in... (Review)
Review
INTRODUCTION AND METHODS
Myophosphorylase deficiency, also known as McArdle disease or Glycogen Storage Disease type V (GSD-V), is an autosomal recessive metabolic myopathy that results in impaired glycogen breakdown in skeletal muscle. Despite being labelled as a "pure myopathy," cardiac involvement has been reported in some cases, including various cardiac abnormalities such as electrocardiographic changes, coronary artery disease, and cardiomyopathy. Here, we present a unique case of a 72-year-old man with GSD-V and both mitral valvulopathy and coronary artery disease, prompting a systematic review to explore the existing literature on cardiac comorbidities in McArdle disease.
RESULTS
Our systematic literature revision identified 7 case reports and 1 retrospective cohort study. The case reports described 7 GSD-V patients, averaging 54.3 years in age, mostly male (85.7%). Coronary artery disease was noted in 57.1% of cases, hypertrophic cardiomyopathy in 28.5%, severe aortic stenosis in 14.3%, and genetic dilated cardiomyopathy in one. In the retrospective cohort study, five out of 14 subjects (36%) had coronary artery disease.
DISCUSSION AND CONCLUSION
Despite McArdle disease primarily affecting skeletal muscle, cardiac involvement has been observed, especially coronary artery disease, the frequency of which was moreover found to be higher in McArdle patients than in the background population in a previous study from a European registry. Exaggerated cardiovascular responses during exercise and impaired glycolytic metabolism have been speculated as potential contributors. A comprehensive cardiological screening might be recommended for McArdle disease patients to detect and manage cardiac comorbidities. A multidisciplinary approach is crucial to effectively manage both neurological and cardiac aspects of the disease and improve patient outcomes. Further research is required to establish clearer pathophysiological links between McArdle disease and cardiac manifestations in order to clarify the existing findings.
PubMed: 38802689
DOI: 10.1007/s10072-024-07600-x -
The British Journal of Surgery May 2024Systemic inflammatory response markers have been found to have a prognostic role in several cancers, but their value in predicting the response to neoadjuvant... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Systemic inflammatory response markers have been found to have a prognostic role in several cancers, but their value in predicting the response to neoadjuvant chemotherapy in breast cancer is uncertain. A systematic review and meta-analysis of the literature was carried out to investigate this.
METHODS
A systematic search of electronic databases was conducted to identify studies that explored the predictive value of circulating systemic inflammatory response markers in patients with breast cancer before commencing neoadjuvant therapy. A meta-analysis was undertaken for each inflammatory marker where three or more studies reported pCR rates in relation to the inflammatory marker. Outcome data are reported as ORs and 95% confidence intervals.
RESULTS
A total of 49 studies were included, of which 42 were suitable for meta-analysis. A lower pretreatment neutrophil-to-lymphocyte ratio was associated with an increased pCR rate (pooled OR 1.66 (95% c.i. 1.32 to 2.09); P < 0.001). A lower white cell count (OR 1.96 (95% c.i. 1.29 to 2.97); P = 0.002) and a lower monocyte count (OR 3.20 (95% c.i. 1.71 to 5.97); P < 0.001) were also associated with a pCR. A higher lymphocyte count was associated with an increased pCR rate (OR 0.44 (95% c.i. 0.30 to 0.64); P < 0.001).
CONCLUSION
The present study found the pretreatment neutrophil-to-lymphocyte ratio, white cell count, lymphocyte count, and monocyte count of value in the prediction of a pCR in the neoadjuvant treatment of breast cancer. Further research is required to determine their value in specific breast cancer subtypes and to establish optimal cut-off values, before their adoption in clinical practice.
Topics: Female; Humans; Biomarkers, Tumor; Breast Neoplasms; Chemotherapy, Adjuvant; Leukocyte Count; Lymphocyte Count; Neoadjuvant Therapy; Neutrophils; Predictive Value of Tests; Prognosis
PubMed: 38801441
DOI: 10.1093/bjs/znae132 -
Frontiers in Immunology 2024Currently, therapies such as chimeric antigen receptor-T Cell (CAR-T) and immune checkpoint inhibitors like programmed cell death protein-1 (PD-1) blockers are showing...
Currently, therapies such as chimeric antigen receptor-T Cell (CAR-T) and immune checkpoint inhibitors like programmed cell death protein-1 (PD-1) blockers are showing promising results for numerous cancer patients. However, significant advancements are required before CAR-T therapies become readily available as off-the-shelf treatments, particularly for solid tumors and lymphomas. In this review, we have systematically analyzed the combination therapy involving engineered CAR-T cells and anti PD-1 agents. This approach aims at overcoming the limitations of current treatments and offers potential advantages such as enhanced tumor inhibition, alleviated T-cell exhaustion, heightened T-cell activation, and minimized toxicity. The integration of CAR-T therapy, which targets tumor-associated antigens, with PD-1 blockade augments T-cell function and mitigates immune suppression within the tumor microenvironment. To assess the impact of combination therapy on various tumors and lymphomas, we categorized them based on six major tumor-associated antigens: mesothelin, disialoganglioside GD-2, CD-19, CD-22, CD-133, and CD-30, which are present in different tumor types. We evaluated the efficacy, complete and partial responses, and progression-free survival in both pre-clinical and clinical models. Additionally, we discussed potential implications, including the feasibility of combination immunotherapies, emphasizing the importance of ongoing research to optimize treatment strategies and improve outcomes for cancer patients. Overall, we believe combining CAR-T therapy with PD-1 blockade holds promise for the next generation of cancer immunotherapy.
Topics: Humans; Programmed Cell Death 1 Receptor; Immunotherapy, Adoptive; Lymphoma; Immune Checkpoint Inhibitors; Receptors, Chimeric Antigen; Animals; Neoplasms; Combined Modality Therapy; Tumor Microenvironment; Antigens, Neoplasm; T-Lymphocytes
PubMed: 38799440
DOI: 10.3389/fimmu.2024.1389971 -
Arthroscopy : the Journal of... May 2024To assess the current scientific literature on the microbiome's relationship with knee osteoarthritis (OA), with specific focuses on the gut microbiome-joint axis and... (Review)
Review
PURPOSE
To assess the current scientific literature on the microbiome's relationship with knee osteoarthritis (OA), with specific focuses on the gut microbiome-joint axis and joint microbiome-joint axis.
METHODS
A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, searching PubMed, Embase, and Cochrane databases for relevant English-language clinical studies on the gut and/or joint microbiomes' association with knee OA in humans. Bias was evaluated using the methodological index for non-randomized studies score.
RESULTS
Thirty-five thousand bacterial species comprise the gut microbiome; approximately 90% are members of the phyla Bacteroides and Firmicutes. Symbiosis between the gut microbiome and host under normal physiological conditions positively affects host growth, development, immunity, and longevity. Gut microbiome imbalance can negatively influence various physiological processes, including immune response, inflammation, metabolism, and joint health including development of knee OA. In addition, next generation gene sequencing suggests the presence of microorganisms in the synovial fluid of osteoarthritic knees, and distinct microbiome profiles detected are presumed to play a role in the development of OA. With regard to the gut microbiome, consistent alterations in microbial composition between OA patients and controls are noted, in addition to several associations between certain gut bacteria with OA-related knee pain, patient-reported outcome measure performance, imaging findings, and changes in metabolic and inflammatory pathways. Regarding the joint microbiome, studies revealed increased levels of lipopolysaccharide (LPS) and LPS-binding protein in synovial fluid are associated with activated macrophages, and correlated with worsened osteophyte severity, joint space narrowing, and pain scores in knee OA patients. In addition, studies demonstrated various microbial composition differences in OA patients compared to control, with certain joint microbes directly associated with OA pathogenesis, inflammation, and metabolic dysregulation.
CONCLUSIONS
The gut microbiome-joint axis and joint microbiome shows alterations in microbial composition between osteoarthritic patients and controls. These alterations are associated with perturbations of metabolic and inflammatory pathways, imaging findings, osteoarthritis-related pain, and patient reported outcome measure performance.
LEVEL OF EVIDENCE
Systematic Review; Level III.
PubMed: 38797504
DOI: 10.1016/j.arthro.2024.05.010 -
Human Vaccines & Immunotherapeutics Dec 2024Solid cancer patients, compared to their healthy counterparts, are at a greater risk of contracting and suffering from severe complications and poorer prognosis after... (Meta-Analysis)
Meta-Analysis
Solid cancer patients, compared to their healthy counterparts, are at a greater risk of contracting and suffering from severe complications and poorer prognosis after COVID-19 infections. They also have different immune responses after doses of COVID-19 vaccination, but limited evidence is available to reveal the effectiveness and help to guide immunization programs for this subpopulation; MEDLINE, Embase, Web of Science, Cochrane Library databases, and clinicaltrials.gov were used to search literature. The pooled seroconversion rate was calculated using a random-effects model and reported with a 95% confidence interval (CI); The review includes 66 studies containing serological responses after COVID-19 vaccination in 13,050 solid cancer patients and 8550 healthy controls. The pooled seropositive rates after the first dose in patients with solid cancer and healthy controls are 55.2% (95% CI 45.9%-64.5% = 18) and 90.2% (95% CI 80.9%-96.6% = 13), respectively. The seropositive rates after the second dose in patients with solid cancer and healthy controls are 87.6% (95% CI 84.1%-90.7% = 50) and 98.9% (95% CI 97.6%-99.7% = 35), respectively. The seropositive rates after the third dose in patients with solid cancer and healthy controls are 91.4% (95% CI 85.4%-95.9% = 21) and 99.8% (95% CI 98.1%-100.0% = 4), respectively. Subgroup analysis finds that study sample size, timing of antibody testing, and vaccine type have influence on the results; Seroconversion rates after COVID-19 vaccination are significantly lower in patients with solid malignancies, especially after the first dose, then shrinking gradually after the following two vaccinations, indicating that subsequent doses or a booster dose should be considered for the effectiveness of this subpopulation.
Topics: Humans; Neoplasms; COVID-19 Vaccines; COVID-19; Antibodies, Viral; Seroconversion; SARS-CoV-2; Vaccination
PubMed: 38785118
DOI: 10.1080/21645515.2024.2357424