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International Journal of Nanomedicine 2024Nanoscale metal-organic frameworks (MOFs) offer high biocompatibility, nanomaterial permeability, substantial specific surface area, and well-defined pores. These... (Review)
Review
Nanoscale metal-organic frameworks (MOFs) offer high biocompatibility, nanomaterial permeability, substantial specific surface area, and well-defined pores. These properties make MOFs valuable in biomedical applications, including biological targeting and drug delivery. They also play a critical role in tumor diagnosis and treatment, including tumor cell targeting, identification, imaging, and therapeutic methods such as drug delivery, photothermal effects, photodynamic therapy, and immunogenic cell death. The diversity of MOFs with different metal centers, organics, and surface modifications underscores their multifaceted contributions to tumor research and treatment. This review is a summary of these roles and mechanisms. The final section of this review summarizes the current state of the field and discusses prospects that may bring MOFs closer to pharmaceutical applications.
Topics: Metal-Organic Frameworks; Humans; Neoplasms; Nanocomposites; Drug Delivery Systems; Animals; Photochemotherapy; Antineoplastic Agents; Nanomedicine
PubMed: 38919774
DOI: 10.2147/IJN.S463144 -
BMC Research Notes Jun 2024Asthma is an airways inflammatory disease and the most common chronic disease of childhood, which causes most hospital visits and placing a heavy financial burden on...
Asthma is an airways inflammatory disease and the most common chronic disease of childhood, which causes most hospital visits and placing a heavy financial burden on families and communities. Interleukins 4, 5 and 13, play a central role in the pathogenesis of asthma. Given the importance of oral hygiene in asthmatic patients and IL-4 and 5 are involved in the inflammatory process of periodontitis, the effect of chlorhexidine as mouthwash on asthma attacks in children on serum cytokines is necessary. In this study, 375 children with asthma were divided into two groups using or non-using chlorhexidine. Blood samples were taken and cytokines were measured by ELISA. From 375 patients, 17 patients were excluded. In this study, 171 males and 187 females participated and there were 180 patients in asthma group and 178 patients in asthma/Chlorhexidine group. The levels of IL-4, IL-5 and IL-13 had no significant difference (p > 0.05) between Asthma and Asthma/Chlorhexidine groups. Using chlorhexidine as mouthwash in children with asthma had no effect on the type 2 cytokines and may not trigger an asthma attack via allergo-inflammatory mechanism.
Topics: Humans; Chlorhexidine; Asthma; Mouthwashes; Female; Male; Child; Interleukin-4; Interleukin-13; Interleukin-5; Cytokines; Child, Preschool; Anti-Infective Agents, Local; Adolescent
PubMed: 38918842
DOI: 10.1186/s13104-024-06831-7 -
European Journal of Medical Research Jun 2024Multiple Sclerosis (MS) is a complex autoimmune disorder that significantly impacts the central nervous system, leading to a range of complications. While intracranial... (Review)
Review
Multiple Sclerosis (MS) is a complex autoimmune disorder that significantly impacts the central nervous system, leading to a range of complications. While intracranial haemorrhage (ICH) is a rare but highly morbid complication, more common CNS complications include progressive multifocal leukoencephalopathy (PML) and other CNS infections. This severe form of stroke, known for its high morbidity and mortality rates, presents a critical challenge in the management of MS. The use of disease-modifying drugs (DMDs) in treating MS introduces a nuanced aspect to patient care, with certain medications like Dimethyl Fumarate and Fingolimod showing potential in reducing the risk of ICH, while others such as Alemtuzumab and Mitoxantrone are associated with an increased risk. Understanding the intricate relationship between these DMDs, the pathophysiological mechanisms of ICH, and the individualised aspects of each patient's condition is paramount. Factors such as genetic predispositions, existing comorbidities, and lifestyle choices play a crucial role in tailoring treatment approaches, emphasising the importance of a personalised, vigilant therapeutic strategy. The necessity for ongoing and detailed research cannot be overstated. It is crucial to explore the long-term effects of DMDs on ICH occurrence and prognosis in MS patients, aiming to refine clinical practices and promote patient-centric, informed therapeutic decisions. This approach ensures that the management of MS is not only comprehensive but also adaptable to the evolving understanding of the disease and its treatments.
Topics: Humans; Multiple Sclerosis; Cerebral Hemorrhage; Immunosuppressive Agents; Mitoxantrone; Fingolimod Hydrochloride; Dimethyl Fumarate
PubMed: 38918831
DOI: 10.1186/s40001-024-01945-x -
Journal of Neuroinflammation Jun 2024The microglia-mediated neuroinflammation have been shown to play a crucial role in the ocular pathological angiogenesis process, but specific immunotherapies for...
The microglia-mediated neuroinflammation have been shown to play a crucial role in the ocular pathological angiogenesis process, but specific immunotherapies for neovascular ocular diseases are still lacking. This study proposed that targeting GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) might be a novel immunotherapy for these angiogenesis diseases. We found a significant upregulation of CGAS and STING genes in the RNA-seq data derived from retinal tissues of the patients with proliferative diabetic retinopathy. In experimental models of ocular angiogenesis including laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), the cGAS-STING pathway was activated as angiogenesis progressed. Either genetic deletion or pharmacological inhibition of STING resulted in a remarkable suppression of neovascularization in both models. Furthermore, cGAS-STING signaling was specifically activated in myeloid cells, triggering the subsequent RIP1-RIP3-MLKL pathway activation and leading to necroptosis-mediated inflammation. Notably, targeted inhibition of the cGAS-STING pathway with C-176 or SN-011 could significantly suppress pathological angiogenesis in CNV and OIR. Additionally, the combination of C-176 or SN-011 with anti-VEGF therapy led to least angiogenesis, markedly enhancing the anti-angiogenic effectiveness. Together, our findings provide compelling evidence for the importance of the cGAS-STING-necroptosis axis in pathological angiogenesis, highlighting its potential as a promising immunotherapeutic target for treating neovascular ocular diseases.
Topics: Nucleotidyltransferases; Membrane Proteins; Animals; Humans; Mice; Neuroinflammatory Diseases; Mice, Inbred C57BL; Choroidal Neovascularization; Signal Transduction; Mice, Knockout; Diabetic Retinopathy
PubMed: 38918759
DOI: 10.1186/s12974-024-03155-y -
BMC Psychiatry Jun 2024Children and adolescents, after natural and man-made disasters, often exhibit various psychological, emotional, and behavioral issues, showing a range of clinical... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Children and adolescents, after natural and man-made disasters, often exhibit various psychological, emotional, and behavioral issues, showing a range of clinical symptoms related to post-traumatic stress disorder (PTSD) and depression. This review used a network meta-analysis (NMA) approach to compare and rank psychological interventions for PTSD and depression in children and adolescents after exposure to natural and man-made disasters.
METHODS
Randomized studies of psychosocial interventions for PTSD and depression in children and adolescents exposed to natural and man-made disasters were identified. PTSD and depression symptoms at postintervention and 1-12 month follow-up are the outcomes. The standardized mean differences (SMDs) between pairs of interventions at postintervention and follow-up were pooled. Mean effect sizes with 95% credible intervals (CI) were calculated, and the ranking probabilities for all interventions were estimated using the surface under the cumulative ranking curve. Study quality was assessed with version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2).
RESULTS
In total, 26 studies with 4331 participants were included in this NMA. Eye movement desensitization and reprocessing therapy (EMDR) (SMD = - 0.67; 95% CI - 1.17 to - 0.17), exposure therapy (ET) (SMD = - 0.66; 95% CI - 1.11 to - 0.22), and cognitive behavioral therapy (CBT) (SMD = - 0.62; 95% CI - 0.90 to - 0.34) were significantly more effective for PTSD at postintervention than inactive intervention. EMDR (SMD = - 0.72; 95% CI - 1.11 to - 0.33) and ET (SMD = - 0.62; 95% CI - 0.97 to - 0.27) were associated with a higher reduction in PTSD symptoms at follow-up than inactive intervention. EMDR (SMD = - 0.40; 95% CI - 0.78 to - 0.03) and play therapy (PT) (SMD = - 0.37; 95% CI - 0.62 to - 0.12) were significantly more effective for depression at postintervention than inactive intervention. For all psychological interventions in reducing depression symptoms at follow-up compared with inactive intervention, the differences were not significant.
CONCLUSION
EMDR appears to be most effective in reducing PTSD and depression in children and adolescents exposed to natural and man-made disasters. In addition, ET and CBT are potentially effective in reducing PTSD symptoms at postintervention, while PT is beneficial in managing depression symptoms at the treatment endpoint.
Topics: Humans; Stress Disorders, Post-Traumatic; Adolescent; Child; Network Meta-Analysis; Psychosocial Intervention; Disasters; Eye Movement Desensitization Reprocessing; Depression; Natural Disasters; Randomized Controlled Trials as Topic; Cognitive Behavioral Therapy
PubMed: 38918741
DOI: 10.1186/s12888-024-05924-8 -
Asian Pacific Journal of Cancer... Jun 2024The alterations of EGFR and HER2/neu as growth factor receptors and the cytoplasmic signal transduction proteins of RAS/RAF/MAP kinases including its end effector...
Evaluation of the Expression EGFR, HER2/NEU and the End Effector ERK of the RAS/RAF/MAP Kinase Pathway in Prostatic Adenocarcinoma for a Possible Role as New Target Therapy.
UNLABELLED
The alterations of EGFR and HER2/neu as growth factor receptors and the cytoplasmic signal transduction proteins of RAS/RAF/MAP kinases including its end effector molecule (ERK) are important in the carcinogenesis of many tumors. The activation of these protooncogenes in prostate cancer is still under investigation. The aim of this work was to study EGFR, HER2- neu, inactive (non-phosphorylated) and active (phosphorylated) ERK expression in prostatic adenocarcinomas in correlation to the clinical and pathological parameters.
METHODS
Immunohistochemistry- using tissue microarrays- for EGFR, HER2/neu, non-phosphorylated, and phosphor-ERK, was performed on tissues from 166 patients- with primary prostatic adenocarcinoma with no prior treatment-. The results of different markers expression were correlated with the clinical and pathological parameters and were analyzed statistically.
RESULTS
The prostatic tissue showed EGFR, HER2 neu, phosphorylated and non-phosphorylated ERK expression in 8.4%, 1.4%, 78.2%, and 83.4% respectively whether low (patchy) or high expression (diffuse). There were no significant correlations found between patient characteristics and expression of the tested markers. The negative immune reactivity for non-phosphorylated ERK and EGFR- was significantly correlated with high tumor stage (p values 0.03 and 0.01, respectively).
CONCLUSION
EGFR and HER2/neu may play a limited role in prostatic adenocarcinoma as they showed positive expression in a limited number of the examined tissues specifically HER2neu. The expression of non-phosphorylated ERK (mostly weak to moderate) and phosphorylated ERK (mostly moderate to strong)- was appreciated in most cases. Thus, we suggest that anti-EGFR drugs may have a limited role in the treatment of castrate-resistant prostate cancer, but anti-MEK/ERK drugs may have more promising role as a target therapy. It is recommended to perform further molecular testing to elucidate the exact mechanism and significance of these markers.
Topics: Humans; Male; Prostatic Neoplasms; ErbB Receptors; Receptor, ErbB-2; Adenocarcinoma; Biomarkers, Tumor; Aged; Middle Aged; Prognosis; Phosphorylation; raf Kinases; Follow-Up Studies; MAP Kinase Signaling System; ras Proteins; Aged, 80 and over; Extracellular Signal-Regulated MAP Kinases; Signal Transduction
PubMed: 38918683
DOI: 10.31557/APJCP.2024.25.6.2193 -
Asian Pacific Journal of Cancer... Jun 2024This study aimed to discover the cytotoxic effect of YH239-EE and YH239 alone and their enantiomer potency in cytotoxic effect on the MCF7 cell line.
OBJECTIVE
This study aimed to discover the cytotoxic effect of YH239-EE and YH239 alone and their enantiomer potency in cytotoxic effect on the MCF7 cell line.
METHODS
We used the cytotoxic study on MDM2 cell lines by detecting the percentage of apoptosis and necrosis by annexin v methods.
RESULT
This result shows that YH239-EE causes more apoptosis and necrosis 40% in comparison to YH239 without ethyl ester, about 4.92 %, and The (+) enantiomer of YH239-EE demonstrated a markedly higher induction of apoptosis and necrosis (84.48%) in MCF7 cells compared to the (-) enantiomer (48.71%).
CONCLUSION
The ethyl ester group in YH239-EE might play a crucial role in enhancing the compound's ability to induce cell death, and The high efficacy of the (+) enantiomer of YH239-EE in inducing cell death in MCF7 cells suggests it may be a more promising therapeutic candidate for breast cancer treatment, specifically for subtypes represented by MCF7 cells.
Topics: Humans; Apoptosis; Breast Neoplasms; MCF-7 Cells; Female; Cell Proliferation; Tumor Cells, Cultured; Antineoplastic Agents; Stereoisomerism
PubMed: 38918676
DOI: 10.31557/APJCP.2024.25.6.2133 -
Asian Pacific Journal of Cancer... Jun 2024The miR-451 has been reported to play an important role in colorectal cancer (CRC) pathogenesis and can be a pivotal diagnosis biomarker of CRC. Given the contradictions... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The miR-451 has been reported to play an important role in colorectal cancer (CRC) pathogenesis and can be a pivotal diagnosis biomarker of CRC. Given the contradictions in the diagnosis value of the miR-451 in patients with CRC, deciphering the diagnostic/prognostic role of this miRNA in CRC will support the identification of a novel therapeutic target for CRC. Therefore, in the present meta-analysis, we evaluated the diagnostic value of miR-451 in CRC patients.
MATERIALS AND METHODS
The electronic databases of Embase, PubMed, ISI Web of Science, and Scopus systematically searched for relevant studies. The odds ratio (OR) with a 95% confidence interval (CI) was calculated to evaluate the association between miR-451 family expression and diagnosis of colorectal cancer. The parameters including sensitivity, specificity, and area under the curve (AUC) were obtained. The quality of evidence was evaluated using the Newcastle-Ottava Scale (NOS).
RESULTS
This study involved 510 patients (45% female and 55% male) with CRC. The pooled analysis of the studies showed a significant association between low expression levels of miR-451 in patients with CRC (OR = 7.59; 95% CI 2.39 - 24.07; p = 0.001). The overall sensitivity and specificity were 0.95 (0.61 - 1) and 0.83 (0.43 - 0.99), respectively. The pooled AUC was 0.97 (0.88 - 1; p < 0.006). Results showed if the pre-test probability is 50% for a patient, the post-test probability will be 85%. The indices demonstrated the high potency of miR-451 as a diagnostic biomarker in patients with CRC. No publication bias was observed using the Begg's (p=0.85) and Egger's tests (p=0.45).
CONCLUSION
A strong relationship between the low expression levels of miR-451 and CRC progression was observed. This finding suggests the miR-451 family may be helpful as a potential biomarker for the earlier diagnosis of colorectal cancer.
Topics: Humans; Colorectal Neoplasms; MicroRNAs; Prognosis; Biomarkers, Tumor; Female
PubMed: 38918650
DOI: 10.31557/APJCP.2024.25.6.1903 -
Cureus May 2024Supraspinatus tears are a common injury, particularly among athletes who engage in sports that include repetitive overhead motions, such as baseball players. Standard...
Supraspinatus tears are a common injury, particularly among athletes who engage in sports that include repetitive overhead motions, such as baseball players. Standard conservative therapies include rest and activity modification, physical therapy, non-steroidal anti-inflammatory drugs (NSAIDs), cold/heat therapy, and corticosteroid injections. Ongoing research and anecdotal evidence support using platelet-rich plasma (PRP) for supraspinatus/rotator cuff tears. Platelet releasate is obtained from PRP via the activation of platelets, subsequently releasing bioactive substances. Activation can be achieved through various methods, some of which include the addition of calcium chloride, thrombin, or exposure to low-level lasers. Platelet releasate has the potential to assist in the healing of tears by releasing growth factors that facilitate muscle and tendon repair. This case presentation discusses the outcomes of platelet releasate paired with extracorporeal shock wave therapy (ESWT) for the treatment of a partial-thickness supraspinatus tear in an 18-year-old male baseball athlete. After exploring conservative treatment options, the patient opted for a single platelet releasate injection along with a four-part series with ESWT. Four weeks post-procedure, the patient reported a 25% improvement. He was able to fully return to play for the entire baseball season. Although the effectiveness of platelet releasate is still a topic of debate and further investigation, this case demonstrates how platelet releasate shows promising results in accelerating the treatment recovery for a partial supraspinatus tear. Further investigation and research could support the benefit of this procedure for accelerated recovery of injuries compared to PRP.
PubMed: 38915987
DOI: 10.7759/cureus.61057 -
Frontiers in Endocrinology 2024Diabetes and its complications cause a heavy burden of disease worldwide. In recent years, Mendelian randomization (MR) has been widely used to discover the pathogenesis...
PURPOSE
Diabetes and its complications cause a heavy burden of disease worldwide. In recent years, Mendelian randomization (MR) has been widely used to discover the pathogenesis and epidemiology of diseases, as well as to discover new therapeutic targets. Therefore, based on systematic "druggable" genomics, we aim to identify new therapeutic targets for diabetes and analyze its pathophysiological mechanisms to promote its new therapeutic strategies.
MATERIAL AND METHOD
We used double sample MR to integrate the identified druggable genomics to evaluate the causal effect of quantitative trait loci (eQTLs) expressed by druggable genes in blood on type 1 and 2 diabetes (T1DM and T2DM). Repeat the study using different data sources on diabetes and its complications to verify the identified genes. Not only that, we also use Bayesian co-localization analysis to evaluate the posterior probabilities of different causal variations, shared causal variations, and co-localization probabilities to examine the possibility of genetic confounding. Finally, using diabetes markers with available genome-wide association studies data, we evaluated the causal relationship between established diabetes markers to explore possible mechanisms.
RESULT
Overall, a total of 4,477 unique druggable genes have been gathered. After filtering using methods such as Bonferroni significance (P<1.90e-05), the MR Steiger directionality test, Bayesian co-localization analysis, and validation with different datasets, Finally, 7 potential druggable genes that may affect the results of T1DM and 7 potential druggable genes that may affect the results of T2DM were identified. Reverse MR suggests that C4B may play a bidirectional role in the pathogenesis of T1DM, and none of the other 13 target genes have a reverse causal relationship. And the 7 target genes in T2DM may each affect the biomarkers of T2DM to mediate the pathogenesis of T2DM.
CONCLUSION
This study provides genetic evidence supporting the potential therapeutic benefits of targeting seven druggable genes, namely MAP3K13, KCNJ11, REG4, KIF11, CCNE2, PEAK1, and NRBP1, for T2DM treatment. Similarly, targeting seven druggable genes, namely ERBB3, C4B, CD69, PTPN22, IL27, ATP2A1, and LT-β, has The potential therapeutic benefits of T1DM treatment. This will provide new ideas for the treatment of diabetes and also help to determine the priority of drug development for diabetes.
Topics: Humans; Mendelian Randomization Analysis; Genome-Wide Association Study; Diabetes Mellitus, Type 2; Quantitative Trait Loci; Genetic Predisposition to Disease; Bayes Theorem; Diabetes Mellitus, Type 1; Genomics; Hypoglycemic Agents; Polymorphism, Single Nucleotide
PubMed: 38915894
DOI: 10.3389/fendo.2024.1366290