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Frontiers in Immunology 2023Immunotherapy has been emerging as a powerful strategy for cancer management. Recently, accumulating evidence has demonstrated that bacteria-based immunotherapy... (Review)
Review
Immunotherapy has been emerging as a powerful strategy for cancer management. Recently, accumulating evidence has demonstrated that bacteria-based immunotherapy including naive bacteria, bacterial components, and bacterial derivatives, can modulate immune response various cellular and molecular pathways. The key mechanisms of bacterial antitumor immunity include inducing immune cells to kill tumor cells directly or reverse the immunosuppressive microenvironment. Currently, bacterial antigens synthesized as vaccine candidates by bioengineering technology are novel antitumor immunotherapy. Especially the combination therapy of bacterial vaccine with conventional therapies may further achieve enhanced therapeutic benefits against cancers. However, the clinical translation of bacteria-based immunotherapy is limited for biosafety concerns and non-uniform production standards. In this review, we aim to summarize immunotherapy strategies based on advanced bacterial therapeutics and discuss their potential for cancer management, we will also propose approaches for optimizing bacteria-based immunotherapy for facilitating clinical translation.
Topics: Humans; Immunotherapy; Bacteria; Neoplasms; Antigens, Bacterial; Bacterial Vaccines; Tumor Microenvironment
PubMed: 37600773
DOI: 10.3389/fimmu.2023.1140463 -
Pharmacology & Therapeutics Apr 2024Melanoma is the most aggressive form of skin cancer, representing approximately 4% of all cutaneous neoplasms and accounting for up to 80% of deaths. Advanced stages of... (Review)
Review
Melanoma is the most aggressive form of skin cancer, representing approximately 4% of all cutaneous neoplasms and accounting for up to 80% of deaths. Advanced stages of melanoma involve metastatic processes and are associated with high mortality and morbidity, mainly due to the rapid dissemination and heterogeneous responses to current therapies, including immunotherapy. Immune checkpoint inhibitors (ICIs) are currently used in the treatment of metastatic melanoma (MM) and despite being linked to an increase in patient survival, a high percentage of them still do not benefit from it. Accordingly, the number of therapeutic regimens for MM patients using ICIs either alone or in combination with other therapies has increased, together with the need for reliable biomarkers that can both predict and monitor response to ICIs. In this context, circulating biomarkers, such as DNA, RNA, proteins, and cells, have emerged due to their ability to reflect disease status. Moreover, blood tests are minimally invasive and provide an attractive option to detect biomarkers, avoiding stressful medical procedures. This systematic review aims to evaluate the possibility of a non-invasive biomarker signature that can guide therapeutic decisions. The studies reported here offer valuable insight into how circulating biomarkers can have a role in personalized treatments for melanoma patients receiving ICIs therapy, emphasizing the need for rigorous clinical trials to confirm findings and establish standardized procedures.
Topics: Humans; Melanoma; Skin Neoplasms; Immunotherapy; Biomarkers
PubMed: 38367867
DOI: 10.1016/j.pharmthera.2024.108613 -
European Neuropsychopharmacology : the... Nov 2023Azapirones have been proposed as anxiety and mood modulators. We assessed azapirones' viability in anxiety disorders via systematic review and random-effects... (Meta-Analysis)
Meta-Analysis
Azapirones have been proposed as anxiety and mood modulators. We assessed azapirones' viability in anxiety disorders via systematic review and random-effects meta-analysis, inquiring PubMed/MEDLINE/CENTRAL/WHO-ICTRP/WebOfScience/VIP up-to 05/01/2023. We conducted sensitivity, and subgroup analyses assessing heterogeneity, publication bias, risk of bias, and confidence in the evidence within the GRADE framework. Symptom reduction (mean difference/MD), study-defined response (risk ratios/RRs), and acceptability were co-primary outcomes. Adverse events and withdrawal were secondary. Seventy studies were included. In generalized anxiety disorder (GAD), azapirones largely outperformed placebo (MD=-4.91, 95%C.I.[-5.91, -3.90], Hedges'g -1.37 [-1.02, -0.73]), k = 22, n = 2,567; RR=1.64, 95%C.I.[1.45, 1.86], k = 9, n = 1,346). While azapirones overlapped benzodiazepines in symptom reduction (MD=-0.12, 95%C.I.[-0.70, 0.45], k = 34, n = 3,160), they were slightly outperformed in response rate (RR=0.94, 95%C.I.[0.90, 0.99], k = 18, n = 2,423). Azapirones overlapped SRIs (MD=0.09, 95%C.I.[-0.49, 0.67], k = 8, n = 747; RR=0.97, 95%C.I.[0.89, 1.07], k = 7, n = 737). Confidence in estimates was high/moderate vs. placebo, moderate/low vs. benzodiazepine, very-low vs. SRIs. Azapirones failed to outperform the placebo in panic and social anxiety disorders. Azapirones overlapped placebo and SRIs in drop-out rates, while they showed higher treatment discontinuation rates than benzodiazepines (RR=1.33, 95%C.I.[1.16, 1.53], k = 23, n = 2,768). Azapirones caused less sedation/fatigue/drowsiness/weakness/cognitive issues than benzodiazepines, resembling placebo. They caused more nausea and dizziness than placebo, more headache and nausea than benzodiazepines, and less nausea and xerostomia than SRIs. Azapirones proved effective and relatively well-tolerated for GAD. They should be preferred over benzodiazepines, especially in the long-term, considering their lower sedation and addiction potential, representing a potential SRI alternative. Further research is warranted to prove efficacy in panic and social anxiety.
Topics: Humans; Randomized Controlled Trials as Topic; Anxiety Disorders; Anxiety; Benzodiazepines; Nausea
PubMed: 37544075
DOI: 10.1016/j.euroneuro.2023.07.008 -
Phytotherapy Research : PTR Sep 2023Sepsis and septic shock are still one of the most important medical challenges. Sepsis is an extreme and uncontrolled response of the innate immune system to invading... (Review)
Review
Sepsis and septic shock are still one of the most important medical challenges. Sepsis is an extreme and uncontrolled response of the innate immune system to invading pathogenesis. Resveratrol (3,5,4'-trihydroxytrans-stilbene), is a phenolic and non-flavonoid compound naturally produced by some plants and fruits. The object of the current study is to systematically review the impacts of resveratrol and its mechanisms of function in the management of sepsis and its related complications. The guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements were applied to perform the study (PROSPERO: CRD42021289357). We searched Embase, Web of Science, Google Scholar, Science Direct, PubMed, ProQuest, and Scopus databases up to January 2023 by using the relevant keywords. Study criteria were met by 72 out of 1415 articles screened. The results of this systematic review depict that resveratrol can reduces the complications of sepsis by affecting inflammatory pathways, oxidative stress, and modulating immune responses. Future human randomized clinical trials are necessary due to the promising therapeutic effects of resveratrol on sepsis complications and the lack of clinical trials in this regard.
Topics: Humans; Antioxidants; Oxidative Stress; Resveratrol; Sepsis
PubMed: 37405908
DOI: 10.1002/ptr.7917 -
Biomolecules Nov 2023Neutrophil extracellular traps (NETs) represent a recently discovered polymorphonuclear leukocyte-associated ancient defence mechanism, and they have also been... (Review)
Review
Neutrophil extracellular traps (NETs) represent a recently discovered polymorphonuclear leukocyte-associated ancient defence mechanism, and they have also been identified as part of polytrauma patients' sterile inflammatory response. This systematic review aimed to determine the clinical significance of NETs in polytrauma, focusing on potential prognostic, diagnostic and therapeutic relevance. The methodology covered all major databases and all study types, but was restricted to polytraumatised humans. Fourteen studies met the inclusion criteria, reporting on 1967 patients. Ten samples were taken from plasma and four from whole blood. There was no standardisation of methodology of NET detection among plasma studies; however, of all the papers that included a healthy control NET, proxies were increased. Polytrauma patients were consistently reported to have higher concentrations of NET markers in peripheral blood than those in healthy controls, but their diagnostic, therapeutic and prognostic utility is equivocal due to the diverse study population and methodology. After 20 years since the discovery of NETs, their natural history and potential clinical utility in polytrauma is undetermined, requiring further standardisation and research.
Topics: Humans; Extracellular Traps; Prognosis; Neutrophils; Multiple Trauma
PubMed: 38002307
DOI: 10.3390/biom13111625 -
Molecular Biology Reports May 2024Treatment-resistant depression (TRD) is a condition in a subset of depressed patients characterized by resistance to antidepressant medications. The global prevalence of... (Review)
Review
BACKGROUND
Treatment-resistant depression (TRD) is a condition in a subset of depressed patients characterized by resistance to antidepressant medications. The global prevalence of TRD has been steadily increasing, yet significant advancements in its diagnosis and treatment remain elusive despite extensive research efforts. The precise underlying pathogenic mechanisms are still not fully understood. Epigenetic mechanisms play a vital role in a wide range of diseases. In recent years, investigators have increasingly focused on the regulatory roles of miRNAs in the onset and progression of TRD. miRNAs are a class of noncoding RNA molecules that regulate the translation and degradation of their target mRNAs via interaction, making the exploration of their functions in TRD essential for elucidating their pathogenic mechanisms.
METHODS AND RESULTS
A systematic search was conducted in four databases, namely PubMed, Web of Science, Cochrane Library, and Embase, focusing on studies related to treatment-resistant depression and miRNAs. The search was performed using terms individually or in combination, such as "treatment-resistant depression," "medication-resistant depression," and "miRNAs." The selected articles were reviewed and collated, covering the time period from the inception of each database to the end of February 2024. We found that miRNAs play a crucial role in the pathophysiology of TRD through three main aspects: 1) involvement in miRNA-mediated inflammatory responses (including miR-155, miR-345-5p, miR-146a, and miR-146a-5p); 2) influence on 5-HT transport processes (including miR-674,miR-708, and miR-133a); and 3) regulation of synaptic plasticity (including has-miR-335-5p,has-miR- 1292-3p, let-7b, and let-7c). Investigating the differential expression and interactions of these miRNAs could contribute to a deeper understanding of the molecular mechanisms underlying TRD.
CONCLUSIONS
miRNAs might play a pivotal role in the pathogenesis of TRD. Gaining a deeper understanding of the roles and interrelations of miRNAs in TRD will contribute to elucidating disease pathogenesis and potentially provide avenues for the development of novel diagnostic and therapeutic strategies.
Topics: Humans; MicroRNAs; Depressive Disorder, Treatment-Resistant; Antidepressive Agents; Gene Expression Regulation; Epigenesis, Genetic
PubMed: 38727891
DOI: 10.1007/s11033-024-09554-x -
A Systematic Review on the Continuous Cropping Obstacles and Control Strategies in Medicinal Plants.International Journal of Molecular... Aug 2023Continuous cropping (CC) is a common practice in agriculture, and usually causes serious economic losses due to soil degeneration, decreased crop yield and quality, and... (Review)
Review
Continuous cropping (CC) is a common practice in agriculture, and usually causes serious economic losses due to soil degeneration, decreased crop yield and quality, and increased disease incidence, especially in medicinal plants. Continuous cropping obstacles (CCOs) are mainly due to changes in soil microbial communities, nutrient availability, and allelopathic effects. Recently, progressive studies have illustrated the molecular mechanisms of CCOs, and valid strategies to overcome them. Transcriptomic and metabolomics analyses revealed that identified DEGs (differently expressed genes) and metabolites involved in the response to CCOs are involved in various biological processes, including photosynthesis, carbon metabolism, secondary metabolite biosynthesis, and bioactive compounds. Soil improvement is an effective strategy to overcome this problem. Soil amendments can improve the microbial community by increasing the abundance of beneficial microorganisms, soil fertility, and nutrient availability. In this review, we sum up the recent status of the research on CCOs in medicinal plants, the combination of transcriptomic and metabolomics studies, and related control strategies, including uses of soil amendments, crop rotation, and intercropping. Finally, we propose future research trends for understanding CCOs, and strategies to overcome these obstacles and promote sustainable agriculture practices in medicinal plants.
Topics: Plants, Medicinal; Soil Microbiology; Agriculture; Soil; Carbon
PubMed: 37569843
DOI: 10.3390/ijms241512470 -
Journal of Affective Disorders Sep 2023Patients with Post-traumatic stress disorder (PTSD) exposed to traumatic reminders show hyperreactivity in brain areas (e.g., amygdala) belonging or related to the... (Meta-Analysis)
Meta-Analysis Review
Patients with Post-traumatic stress disorder (PTSD) exposed to traumatic reminders show hyperreactivity in brain areas (e.g., amygdala) belonging or related to the Innate Alarm System (IAS), allowing the rapid processing of salient stimuli. Evidence that IAS is activated by subliminal trauma-reminders could shed a new light on the factors precipitating and perpetuating PTSD symptomatology. Thus, we systematically reviewed studies investigating neuroimaging correlates of subliminal stimulation in PTSD. Twenty-three studies were selected from the MEDLINE and Scopus® databases for a qualitative synthesis, 5 of which allowed a further meta-analysis of fMRI data. The intensity of IAS responses to subliminal trauma-related reminders ranged from a minimum in healthy controls to a maximum in the PTSD patients with the most severe (e.g., dissociative) symptoms or the least responsiveness to treatment. Comparisons with other disorders (e.g., phobias) revealed contrasting results. Our findings demonstrate the hyperactivation of areas belonging or related to IAS in response to unconscious threats that should be integrated in diagnostic as well as in therapeutic protocols.
Topics: Humans; Stress Disorders, Post-Traumatic; Subliminal Stimulation; Brain; Amygdala; Brain Mapping; Magnetic Resonance Imaging
PubMed: 37236272
DOI: 10.1016/j.jad.2023.05.047 -
Global Mental Health (Cambridge,... 2023Trauma exposure is prevalent globally and is a defining event for the development of posttraumatic stress disorder (PTSD), characterised by intrusive thoughts, avoidance... (Review)
Review
Trauma exposure is prevalent globally and is a defining event for the development of posttraumatic stress disorder (PTSD), characterised by intrusive thoughts, avoidance behaviours, hypervigilance and negative alterations in cognition and mood. Exposure to trauma elicits a range of physiological responses which can interact with environmental factors to confer relative risk or resilience for PTSD. This systematic review summarises the findings of longitudinal studies examining biological correlates predictive of PTSD symptomology. Databases (Pubmed, Scopus and Web of Science) were systematically searched using relevant keywords for studies published between 1 January 2021 and 31 December 2022. English language studies were included if they were original research manuscripts or meta-analyses of cohort investigations that assessed longitudinal relationships between one or more molecular-level measures and either PTSD status or symptoms. Eighteen of the 1,042 records identified were included. Studies primarily included military veterans/personnel, individuals admitted to hospitals after acute traumatic injury, and women exposed to interpersonal violence or rape. Genomic, inflammation and endocrine measures were the most commonly assessed molecular markers and highlighted processes related to inflammation, stress responding, and learning and memory. Quality assessments were done using the Systematic Appraisal of Quality in Observational Research, and the majority of studies were rated as being of high quality, with the remainder of moderate quality. Studies were predominantly conducted in upper-income countries. Those performed in low- and middle-income countries were not broadly representative in terms of demographic, trauma type and geographic profiles, with three out of the four studies conducted assessing only female participants, rape exposure and South Africa, respectively. They also did not generate multimodal data or use machine learning or multilevel modelling, potentially reflecting greater resource limitations in LMICs. Research examining molecular contributions to PTSD does not adequately reflect the global burden of the disorder.
PubMed: 37854422
DOI: 10.1017/gmh.2023.53 -
Endocrine Jun 2024Plenty of evidence suggests that dysregulated microRNAs are linked to developing autoimmune thyroid diseases. In this study, we aimed to identify commonly linked... (Review)
Review
BACKGROUND
Plenty of evidence suggests that dysregulated microRNAs are linked to developing autoimmune thyroid diseases. In this study, we aimed to identify commonly linked dysregulated microRNAs in Hashimoto's thyroiditis(HT) and explore microRNA-targeted genes and the involved pathways.
METHODS
Embase, PubMed, Web of Science, and Scopus databases were searched using the MeSH terms and free text terms, which yielded 11879 articles published up to July 2023. Two-step screening(first for titles and second for abstracts) was completed according to inclusion and exclusion criteria. The search strategy was formulated using the PEO format(Population, Exposure, and Outcome) for observational studies. The corresponding target genes and relevant signaling pathways were also identified using web servers of Diana Tools/its mirPath v.3 software, miRNA Enrichment Analysis, Mirpath DB2, miRPathDB 2.0, and miRmap.
RESULTS
Review inclusion criteria were met by 16 studies. Thirty-three microRNAs were identified as differentially expressed in HT patients compared to a healthy control after qRT-PCR or RNA sequencing confirmation. Only three miR-146a, miR-142, and miR-301 showed significant results in more than two studies comparing HT cases with healthy controls.
CONCLUSION
Three key microRNAs in HT were identified by systematic review; the corresponding target genes and signaling pathways involved in the target genes were also identified. These microRNAs regulate the immune response and inflammation and may favor the development and progression of HT. These data may be beneficial to make a step forward to understand the exact etiology of HT and use of these MicroRNAs as possible diagnostic and prognostic biomarkers and as target therapy.
Topics: Hashimoto Disease; Humans; MicroRNAs
PubMed: 38212462
DOI: 10.1007/s12020-023-03673-4