Enhancing pressure ulcer healing and tissue regeneration by using N-acetyl-cysteine loaded carboxymethyl cellulose/gelatin/sodium alginate hydrogel.

Prolonged pressure on the skin can result in pressure ulcers, which may lead to serious complications, such as infection and tissue damage. In this study, we evaluated the effect of a carboxymethyl cellulose/gelatin/sodium alginate (CMC/Gel/Alg) hydrogel containing N-acetyl-cysteine (NAC) on the healing of pressure ulcers. Pressure ulcers were induced by applying a magnet to the dorsum of rat skin. The wounds were then treated with sterile gauze, ChitoHeal Gel®, and CMC/Gel/Alg hydrogel dressings with or without NAC for the other groups. We evaluated the morphology, weight loss, swelling, rheology, blood compatibility, cytocompatibility, antioxidant capacity, and wound scratch of the prepared hydrogel. MTT assay revealed that the optimum concentration of NAC was 5 mg/ml, which induced higher cell proliferation and viability. Results of the histopathological evaluation showed increased wound closure, and complete re-epithelialization in the hydrogel-containing NAC group compared to the other groups. The CMC/Gel/Alg/5 mg/ml NAC hydrogel dressing showed 84% wound closure at 14 days after treatment. Immunohistochemical results showed a decrease in the level of TNF-α on day 14 compared day 7. Results of the qPCR assay revealed that NAC hydrogel increased the expression of Collagen type I and TGF-ß1 and decreased MMP2 and MMP9 mRNA on the 14th day. The results suggest that the CMC/Gel/Alg/5 mg/ml NAC hydrogel with antioxidant properties is an appropriate dressing for wound healing.

Isolation and Characterization of Extracellular Vesicles of Chick Embryo Blood.

Exosomes from plants or animals are a cheap, available, and promising option in medicine, which can be used for the detection or treatment of various diseases. This study aims to evaluate the antitoxic and antioxidant properties of Extracellular vesicle (EVs) extracted from chicken embryo blood using a fibroblast cell line (NIH/3T3). EVs from chick embryos were extracted in this experimental investigation using the sedimentation method and examined using dynamic light scattering (DLS) and field emission electron microscopy (FE-SEM). The protein concentration and overall antioxidant capacity of the EVs were determined using bicinchoninic acid (BCA) and antioxidant capacity (FRAP). EVs were added to NIH/3T3 cells at varying concentrations (1, 2, and 10 mg/ml), and the MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay test was used to measure cell survival. The size of the isolated EVs was confirmed to be less than 100 nm by electron microscopy and DLS. The quantity of protein in these EVs was 3200 µg/ml, and their total antioxidant capacities were 3130.17, 1914.122, and 976.9 µMol/L. The MTT test findings demonstrated that NIH/3T3 cells survived treatment with EVs (P ≤ 0.001) compared to the control group. Antioxidant-rich and protein-rich exosomes in chicken embryos may be valuable in managing oxidative stress.

Optical coherence tomography angiography measurements in systemic lupus erythematosus: A systematic review and meta-analysis.

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting various organs. Ocular involvement, particularly retinopathy, is common, emphasizing the significance of early detection. Optical coherence tomography angiography (OCTA), a non-invasive imaging technique, reveals microvascular changes, aiding SLE diagnosis and monitoring. This study evaluates OCTA's effectiveness in detecting SLE-related retinal alterations. A systemic search was undertaken across PubMed, Embase, and Scopus databases to identify studies presenting OCTA measurements in SLE patients compared to healthy controls. The meta-analysis, employing either fixed-effects or random-effects models based on heterogeneity levels, was conducted. Additionally, subgroup and sensitivity analyses, meta-regression, and quality assessments were carried out. Thirteen studies of 565 eyes in the SLE group and 560 eyes in the control group were included. The meta-analyses revealed that SLE patients had a significantly lower retinal vessel density in the superficial and deep capillary plexus layers, choriocapillaris flow area, and foveal avascular zone (FAZ) circularity index compared to healthy controls, but that there were no significant differences in the FAZ area and perimeter. These findings highlight how OCTA can provide a noninvasive assessment of SLE effects on the retinal microvasculature, potentially presenting a reliable biomarker for more precise detection of SLE and disease activity monitoring.

Development of novel low-cost readout electronics for large field-of-view gamma camera detectors.

PURPOSE: Large scintillation crystals-based gamma cameras play a crucial role in nuclear medicine imaging. In this study, a large field-of-view (FOV) gamma detector consisting of 48 square PMTs developed using a new readout electronics, reducing 48 (6 × 8) analog signals to 14 (6 + 8) analog sums of each row and column, with reduced complexity and cost while preserving image quality. METHODS: All 14 analog signals were converted to digital signals using AD9257 high-speed analog to digital (ADC) converters driven by the SPARTAN-6 family of field-programmable gate arrays (FPGA) in order to calculate the signal integrals. The positioning algorithm was based on the digital correlated signal enhancement (CSE) algorithm implemented in the acquisition software. The performance characteristics of the developed gamma camera were measured using the NEMA NU 1-2018 standards. RESULTS: The measured energy resolution of the developed detector was 8.7 % at 140 keV, with an intrinsic spatial resolution of 3.9 mm. The uniformity was within 0.6 %, while the linearity was within 0.1 %. CONCLUSION: The performance evaluation demonstrated that the developed detector has suitable specifications for high-end nuclear medicine imaging.

Recent advances in enhances peripheral nerve orientation: the synergy of micro or nano patterns with therapeutic tactics.

Several studies suggest that topographical patterns influence nerve cell fate. Efforts have been made to improve nerve cell functionality through this approach, focusing on therapeutic strategies that enhance nerve cell function and support structures. However, inadequate nerve cell orientation can impede long-term efficiency, affecting nerve tissue repair. Therefore, enhancing neurites/axons directional growth and cell orientation is crucial for better therapeutic outcomes, reducing nerve coiling, and ensuring accurate nerve fiber connections. Conflicting results exist regarding the effects of micro- or nano-patterns on nerve cell migration, directional growth, immunogenic response, and angiogenesis, complicating their clinical use. Nevertheless, advances in lithography, electrospinning, casting, and molding techniques to intentionally control the fate and neuronal cells orientation are being explored to rapidly and sustainably improve nerve tissue efficiency. It appears that this can be accomplished by combining micro- and nano-patterns with nanomaterials, biological gradients, and electrical stimulation. Despite promising outcomes, the unclear mechanism of action, the presence of growth cones in various directions, and the restriction of outcomes to morphological and functional nerve cell markers have presented challenges in utilizing this method. This review seeks to clarify how micro- or nano-patterns affect nerve cell morphology and function, highlighting the potential benefits of cell orientation, especially in combined approaches.

Diagnostic Performance of Artificial Intelligence in Detection of Hepatocellular Carcinoma: A Meta-analysis.

Due to the increasing interest in the use of artificial intelligence (AI) algorithms in hepatocellular carcinoma detection, we performed a systematic review and meta-analysis to pool the data on diagnostic performance metrics of AI and to compare them with clinicians' performance. A search in PubMed and Scopus was performed in January 2024 to find studies that evaluated and/or validated an AI algorithm for the detection of HCC. We performed a meta-analysis to pool the data on the metrics of diagnostic performance. Subgroup analysis based on the modality of imaging and meta-regression based on multiple parameters were performed to find potential sources of heterogeneity. The risk of bias was assessed using Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) and Prediction Model Study Risk of Bias Assessment Tool (PROBAST) reporting guidelines. Out of 3177 studies screened, 44 eligible studies were included. The pooled sensitivity and specificity for internally validated AI algorithms were 84% (95% CI: 81,87) and 92% (95% CI: 90,94), respectively. Externally validated AI algorithms had a pooled sensitivity of 85% (95% CI: 78,89) and specificity of 84% (95% CI: 72,91). When clinicians were internally validated, their pooled sensitivity was 70% (95% CI: 60,78), while their pooled specificity was 85% (95% CI: 77,90). This study implies that AI can perform as a diagnostic supplement for clinicians and radiologists by screening images and highlighting regions of interest, thus improving workflow.

Magnesium-oxide-enhanced bone regeneration: 3D-printing of gelatin-coated composite scaffolds with sustained Rosuvastatin release.

Critical-size bone defects are one of the main challenges in bone tissue regeneration that determines the need to use angiogenic and osteogenic agents. Rosuvastatin (RSV) is a class of cholesterol-lowering drugs with osteogenic potential. Magnesium oxide (MgO) is an angiogenesis component affecting apatite formation. This study aims to evaluate 3D-printed Polycaprolactone/ß-tricalcium phosphate/nano-hydroxyapatite/ MgO (PCL/ß-TCP/nHA/MgO) scaffolds as a carrier for MgO and RSV in bone regeneration. For this purpose, PCL/ß-TCP/nHA/MgO scaffolds were fabricated with a 3D-printing method and coated with gelatin and RSV. The biocompatibility and osteogenicity of scaffolds were examined with MTT, ALP, and Alizarin red staining. Finally, the scaffolds were implanted in a bone defect of rat's calvaria, and tissue regeneration was investigated after 3 months. Our results showed that the simultaneous presence of RSV and MgO improved biocompatibility, wettability, degradation rate, and ALP activity but decreased mechanical strength. PCL/ß-TCP/nHA/MgO/gelatin-RSV scaffolds produced sustained release of MgO and RSV within 30 days. CT images showed that PCL/ß-TCP/nHA/MgO/gelatin-RSV scaffolds filled approximately 86.83 + 4.9 % of the defects within 3 months and improved angiogenesis, woven bone, and osteogenic genes expression. These results indicate the potential of PCL/ß-TCP/nHA/MgO/gelatin-RSV scaffolds as a promising tool for bone regeneration and clinical trials.

Brain-based sex differences in schizophrenia: A systematic review of fMRI studies.

Schizophrenia is a chronic psychiatric disorder with characteristic symptoms of delusions, hallucinations, lack of motivation, and paucity of thought. Recent evidence suggests that the symptoms of schizophrenia, negative symptoms in particular, vary widely between the sexes and that symptom onset is earlier in males. A better understanding of sex-based differences in functional magnetic resonance imaging (fMRI) studies of schizophrenia may provide a key to understanding sex-based symptom differences. This study aimed to summarize sex-based functional magnetic resonance imaging (fMRI) differences in brain activity of patients with schizophrenia. We searched PubMed and Scopus to find fMRI studies that assessed sex-based differences in the brain activity of patients with schizophrenia. We excluded studies that did not evaluate brain activity using fMRI, did not evaluate sex differences, and were nonhuman or in vitro studies. We found 12 studies that met the inclusion criteria for the current systematic review. Compared to females with schizophrenia, males with schizophrenia showed more blood oxygen level-dependent (BOLD) activation in the cerebellum, the temporal gyrus, and the right precuneus cortex. Male patients also had greater occurrence of low-frequency fluctuations in cerebral blood flow in frontal and parietal lobes and the insular cortex, while female patients had greater occurrence of low-frequency fluctuations in the hippocampus, parahippocampus, and lentiform nucleus. The current study summarizes fMRI studies that evaluated sex-based fMRI brain differences in schizophrenia that may help to shed light on the underlying pathophysiology and further understanding of sex-based differences in the clinical presentation and course of the disorder.

Fabrication of Rosuvastatin-Incorporated Polycaprolactone -Gelatin Scaffold for Bone Repair: A Preliminary In Vitro Study.

OBJECTIVE: Rosuvastatin (RSV) is a hydrophilic, effective statin with a long half-life that stimulates bone regeneration. The present study aims to develop a new scaffold and controlled release system for RSV with favourable properties for bone tissue engineering (BTE). MATERIALS AND METHODS: In this experimental study, high porous polycaprolactone (PCL)-gelatin scaffolds that contained different concentrations of RSV (0 mg/10 ml, 0.1 mg/10 ml, 0.5 mg/10 ml, 2.5 mg/10 ml, 12.5 mg/10 ml, and 62.5 mg/10 ml) were fabricated by the thermally-induced phase separation (TIPS) method. Mechanical and biological properties of the scaffolds were evaluated by Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), compressive strength, porosity, MTT, alkaline phosphatase (ALP) activity, water contact angle, degradation rate, pH alteration, blood clotting index (BCI), and hemocompatibility. RESULTS: SEM analysis confirmed that the porous structure of the scaffolds contained interconnected pores. FTIR results showed that the RSV structure was maintained during the scaffold's fabrication. RSV (up to 62.5 mg/10 ml) increased compressive strength (16.342 ± 1.79 MPa), wettability (70.2), and degradation rate of the scaffolds. Scaffolds that contained 2.5 mg/10 ml RSV had the best effect on the human umbilical cord mesenchymal stem cell (HUC-MSCs) survival, hemocompatibility, and BCI. As a sustained release system, only 31.68 ± 0.1% of RSV was released from the PCL-Gelatin-2.5 mg/10 ml RSV scaffold over 30 days. In addition, the results of ALP activity showed that RSV increased the osteogenic differentiation potential of the scaffolds. CONCLUSION: PCL-Gelatin-2.5 mg/10 ml RSV scaffolds have favorable mechanical, physical, and osteogenic properties for bone tissue and provide a favorable release system for RSV. They can mentioned as a a promising strategy for bone regeneration that should be further assessed in animals and clinical studies.

Effects of Tumor Microenvironment on the Primo Vascular Pattern in the Mouse Model of Metastatic Breast Cancer.

Background: : Tumor survival, promotion, and metastatic functions are regulated by the tumor microenvironment (TME). The primo vascular system (PVS), the third circulatory system in animals, is currently thought to be a highly effective pathway for the spread of cancer cells. Objectives: : In the present study, we intend to determine the TME effects on the PVS pattern in breast cancer for the first time. Methods: : Heterotopic and orthotopic metastatic triple-negative breast cancer (TNBC) mice models were created. After 35 days, the skin was retracted, and a 2 cm skin incision was made up and down from the surface of the tumor tissue. In preparation for PVS staining, the dyes (trypan blue and alamarBlue) were injected throughout the tumor tissues. Under a stereomicroscope, PVS in heterotopic and orthotopic tumors was seen. Results: : According to our data, there are no appreciable variations in PVS patterns and density between heterotopic and orthotopic animal models. Furthermore, alamarBlue is a good option for tumor PVS staining, as demonstrated by our research. Conclusion: : For the first time, our data gave significant new information about the PVS in TNBC. Creating new anti-cancer treatments may be made possible by a better understanding of the biological characteristics of the TME and PVS.

Biological study of skin wound treated with Alginate/Carboxymethyl cellulose/chorion membrane, diopside nanoparticles, and Botox A.

A hydrogel-based wound dressing with desirable properties is necessary for achieving functional skin integrity post-injury. This study focuses on preparing a hydrogel using Alginate/Carboxymethyl cellulose (Alg/CMC) as a base material. To evaluate its regenerative effects on full-thickness wounds, diopside nanoparticles and Botulinum toxin A (BTX-A) were incorporated into the hydrogel along with chorion membrane. The diopside nanoparticles (DNPs) act as a proangiogenic factor, promoting proliferation and regulating inflammation, while the chorion membrane facilitates these processes. Additionally, BTX-A prevents scar formation and aids in wound closure. The nanoparticles and hydrogel were characterized using various techniques, and their cytocompatibility was assessed. In vivo studies and quantitative polymerase chain reaction analysis showed that wound area reduction was significant after two weeks of treatment with the Alg/CMC/ChNPs/DNPs/BTX-A hydrogel. Overall, this scaffold demonstrated potential for promoting tissue regeneration and new epithelization formation, making it a promising candidate for enhancing skin restoration in wound treatments.

Choroidal thickness in eyes of rheumatoid arthritis patients measured using optical coherence tomography: A systematic review and meta-analysis.

Rheumatoid arthritis (RA), an autoimmune disease, affects eyes in 25% of cases. Retinal alterations in RA can function as biomarkers as early risk indicators for developing sight-threatening conditions. Optical coherence tomography (OCT) provides high-resolution images of the retina and its component's thickness measures. The purpose of this review is to compare the choroidal thickness (CT) of RA patients and healthy controls. We examined the databases of PubMed, Scopus, and Embase. Depending on the heterogeneity, an appropriate model was used for the meta-analysis. Additionally, meta-regression, publication bias, subgroup analyses, and quality evaluation were carried out. We evaluated 8 studies involving 363 RA patients and 343 healthy controls. Our findings demonstrated that RA participants had significantly lower CT at 500 and 1500 µm nasal and temporal to the fovea compared to controls. The subfoveal, 1000 µm temporal and nasal to the fovea, and average CT, however, did not demonstrate statistical significance. The results of this study demonstrate that choroidal thickness is different in RA patients from healthy controls in several areas. OCT measurements may be related to both the visual acuity and the possibility of developing several rheumatic-ophthalmic problems. Future research is thus needed to get more firm findings.

Diagnostic Performance of Artificial Intelligence in Detection of Primary Malignant Bone Tumors: a Meta-Analysis.

We aim to conduct a meta-analysis on studies that evaluated the diagnostic performance of artificial intelligence (AI) algorithms in the detection of primary bone tumors, distinguishing them from other bone lesions, and comparing them with clinician assessment. A systematic search was conducted using a combination of keywords related to bone tumors and AI. After extracting contingency tables from all included studies, we performed a meta-analysis using random-effects model to determine the pooled sensitivity and specificity, accompanied by their respective 95% confidence intervals (CI). Quality assessment was evaluated using a modified version of Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) and Prediction Model Study Risk of Bias Assessment Tool (PROBAST). The pooled sensitivities for AI algorithms and clinicians on internal validation test sets for detecting bone neoplasms were 84% (95% CI: 79.88) and 76% (95% CI: 64.85), and pooled specificities were 86% (95% CI: 81.90) and 64% (95% CI: 55.72), respectively. At external validation, the pooled sensitivity and specificity for AI algorithms were 84% (95% CI: 75.90) and 91% (95% CI: 83.96), respectively. The same numbers for clinicians were 85% (95% CI: 73.92) and 94% (95% CI: 89.97), respectively. The sensitivity and specificity for clinicians with AI assistance were 95% (95% CI: 86.98) and 57% (95% CI: 48.66). Caution is needed when interpreting findings due to potential limitations. Further research is needed to bridge this gap in scientific understanding and promote effective implementation for medical practice advancement.

The effects of physical activity on pediatric eyes: A systematic review and meta-analysis.

INTRODUCTION: Examining the retina represents a non-invasive method to evaluate abnormalities pertaining to the nervous and cardiovascular systems. Evidence indicates that physical activity is a non-pharmacological intervention to enhance the nervous and cardiovascular systems. However, little is unknown about its effects on ocular characteristics in children and adolescents. The purpose of this study was to examine the effects of physical activity interventions on ocular characteristics in children and adolescents. METHOD: The electronic bases Web of Science, Embase, Cochrane Library, PubMed, SPORTDiscus, CINAHL, and ERIC were searched from inception to May 2023. Incorporated were randomized controlled trials or quasi-experimental designs that had implemented acute or chronic physical activity interventions among children and adolescents to evaluate various eye-related attributes via clinical examinations or surveys. Two authors independently performed the data extraction and risk of bias assessment, utilizing the Physiotherapy Evidence Database checklist. RESULTS: A total of 474 articles were identified, of which eight articles underwent a systematic review, and six were chosen for meta-analysis. Chronic physical activity interventions positively impacted central retinal artery equivalent (CRAE) with a small to moderate effect (SMD = 0.21; 95% CI 0.04 to 0.39, p = 0.034, I2 = 0%) and central retinal venular equivalent (CRVE) with a small effect (SMD = 0.098; 95% CI 0.08 to 0.11; p = 0.008, I2 = 0%). Intraocular pressure, kinetic visual acuity, and eye strain also improved significantly after physical activity interventions. DISCUSSION: Participating in chronic physical activity programs appear to impact children and adolescents' eye-related attributes positively.

Artificial intelligence in osteoarthritis detection: A systematic review and meta-analysis.

OBJECTIVES: As an increasing number of studies apply artificial intelligence (AI) algorithms in osteoarthritis (OA) detection, we performed a systematic review and meta-analysis to pool the data on diagnostic performance metrics of AI, and to compare them with clinicians' performance. MATERIALS AND METHODS: A search in PubMed and Scopus was performed to find studies published up to April 2022 that evaluated and/or validated an AI algorithm for the detection or classification of OA. We performed a meta-analysis to pool the data on the metrics of diagnostic performance. Subgroup analysis based on the involved joint and meta-regression based on multiple parameters were performed to find potential sources of heterogeneity. The risk of bias was assessed using Prediction Model Study Risk of Bias Assessment Tool reporting guidelines. RESULTS: Of the 61 studies included, 27 studies with 91 contingency tables provided sufficient data to enter the meta-analysis. The pooled sensitivities for AI algorithms and clinicians on internal validation test sets were 88% (95% confidence interval [CI]: 86,91) and 80% (95% CI: 68,88) and pooled specificities were 81% (95% CI: 75,85) and 79% (95% CI: 80,85), respectively. At external validation, the pooled sensitivity and specificity for AI algorithms were 94% (95% CI: 90,97) and 91% (95% CI: 77,97), respectively. CONCLUSION: Although the results of this meta-analysis should be interpreted with caution due to the potential pitfalls in the included studies, the promising role of AI as a diagnostic adjunct to radiologists is indisputable.

Drought trends projection under future climate change scenarios for Iran region.

The study highlights the potential characteristics of droughts under future climate change scenarios. For this purpose, the changes in Standardized Precipitation Evapotranspiration Index (SPEI) under the A1B, A2, and B1 climate change scenarios in Iran were assessed. The daily weather data of 30 synoptic stations from 1992 to 2010 were analyzed. The HadCM3 statistical model in the LARS-WG was used to predict the future weather conditions between 2011 and 2112, for three 34-year periods; 2011-2045, 2046-2079, and 2080-2112. In regard to the findings, the upward trend of the potential evapotranspiration in parallel with the downward trend of the precipitation in the next 102 years in three scenarios to the base timescale was transparent. The frequency of the SPEI in the base month indicated that 17.02% of the studied months faced the drought. Considering the scenarios of climate change for three 34-year periods (i.e., 2011-2045, 2046-2079, and 2080-2112) the average percentages of potential drought occurrences for all the stations in the next three periods will be 8.89, 16.58, and 27.27 respectively under the B1 scenario. While the predicted values under the A1B scenario are 7.63, 12.66, and 35.08%respectively. The relevant findings under the A2 scenario are 6.73, 10.16, 40.8%. As a consequence, water shortage would be more serious in the third period of study under all three scenarios. The percentage of drought occurrence in the future years under the A2, B1, and A1B will be 19.23%, 17.74%, and 18.84%, respectively which confirms the worst condition under the A2 scenario. For all stations, the number of months with moderate drought was substantially more than severe and extreme droughts. Considering the A2 scenario as a high emission scenario, the analysis of SPEI frequency illustrated that the proportion of dry periods in regions with humid and cool climate is more than hot and warm climates; however, the duration of dry periods in warmer climates is longer than colder climates. Moreover, the temporal distribution of precipitation and potential evapotranspiration indicated that in a large number of stations, there is a significant difference between them in the middle months of the year, which justifies the importance of prudent water management in warm months.

Treatment for Severe Class II Open Bite Using a Bonded Hyrax Expander, IZC Mini-Implants, and MEAW Technique in an Adolescent Patient.

This case report describes the successful 3D treatment of a patient with a narrow maxilla and a severe class II open bite using a combination of a bonded hyrax expander, infrazygomatic crest mini-implants, and the multiloop edgewise arch-wire (MEAW) technique. A 14-year-old female with a thumb-sucking habit in childhood, presented with a severe open bite, a convex profile, and an obtuse nasolabial angle. Diagnosis revealed a skeletal Class II open bite with moderate crowding in the maxillary and mild crowding in the mandibular arch. Treatment objectives included eliminating the open bite, achieving normal overbite and overjet, and improving upper incisor visibility. Treatment involved the use of a bonded rapid palatal expansion device, mini-implants for maxillary intrusion, fixed appliances, vertical elastics, and a MEAW. Treatment results showed resolution of the open bite, improvement in overbite and overjet, achievement of Class I molar and canine relationships, and improved upper incisors visibility. Fixed appliances were used for the whole 22-month therapy period, and post-treatment records demonstrated that the treatment's objectives were met.

Upregulation of C-X-C chemokine receptor type 4 (CXCR4) in the breast cancer stem like cells.

BACKGROUND AND OBJECTIVES: Breast cancer stem like cells (CSCs) as a subset of cancer cells exhibit similar properties with normal stem cells. These cells are responsible for cancer metastasis and recurrence. Pivotal roles of CXCR4 in metastasis, chemoresistance and stemness of tumor cells have been showed previously. Here, we aim to explore the relationship between CXCR4 and CSCs in primary and metastatic breast tumor cells. METHODS AND RESULTS: Primary and highly metastatic breast tumor cells were isolated in our laboratory. Spheroid formation was used to confirm the presence of CSCs and their self-renewal capability. CXCR4 expression was evaluated using real-time polymerase chain reaction in monolayer culture and multicellular spheroids. Our data showed that in all tested cells, CXCR4 expression was significantly increased in CSCs. In parallel, compared with primary tumor cells, downregulation of CXCR4 in metastatic tumor cells was confirmed. CONCLUSION: These results provided new insights related to significant alteration of CXCR4 expression in multicellular spheroids. Analysis of molecular properties of spheroids could be used to detect molecular and genetic aspects of CSCs and also created a targeted therapeutic strategy against breast CSCs.

Upregulation of Matrix Metalloproteinases in the Metastatic Cascade of Breast Cancer to the Brain.

BACKGROUND: In patients with triple-negative breast cancer (TNBC), brain metastasis is a fatal consequence. Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9 as the major members of the MMP family, are involved in many different facets of breast cancer metastasis. AIMS: In this study, we sought the MMPs expression in the metastatic cascade of TNBC. METHODS AND RESULTS: Primary breast cancer cells known as 4T1T were extracted from the tumor mass following the creation of an animal model of TNBC. The brain metastasis lesions of malignant mice were used to extract highly brain metastatic tumor cells known as 4T1B. Gelatinase zymography and real-time polymerase chain reaction (RT-PCR) were used to examine the expression of MMPs at the proteomic and transcriptomic levels in 4T1T and 4T1B. Our results indicated; brain metastatic tumor cells greatly increased their expression of MMPs. In 4T1B, MMP-2 and MMP-9 gene expression were upregulated by 4 and 3.4 folds respectively. Zymographic analysis found MMP activity only in 4T1B. CONCLUSION: These results offer significant information about the massive alteration of MMPs expression in the brain metastasis of TNBC. By analyzing the molecular characteristics of brain metastatic tumor cells, we can understand the molecular and genetic features of brain metastasis and develop tailored therapeutic strategies to combat TNBC brain metastasis.

The efficacy of physical exercise interventions on mental health, cognitive function, and ADHD symptoms in children and adolescents with ADHD: an umbrella review.

Background: A considerable number of published reviews have addressed the effects of physical exercise on mental health, cognitive function, or attention-deficit hyperactivity (ADHD) symptoms as outcomes in children and adolescents with ADHD. Their findings have often conflicted, therefore, there is an urgent need to synthesise a hierarchy of the evidence and examine the credibility of previous meta-analyses. To establish the robustness of these findings, we conducted an additional meta-analysis on a number of individual studies that were not covered in previous reviews but were suitable for inclusion in our own study. Methods: Three reviewers independently searched Web of Science, Psych INFO, Embase, Cochrane Library, PubMed, SPORTDiscus, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) for meta-analyses published between database inceptions to December 1, 2022. The individual studies were also screened from 1 January 2015 to 1 December 2022. We included meta-analyses and eligible individual studies that addressed the effects of exercise on at least one outcome of mental health, cognitive function, or ADHD symptoms in children and adolescents with ADHD. We excluded systematic reviews and articles that lacked sufficient data for a meaningful second analysis. The effect estimates (Hedges' g), 95% confidence interval (95% CI), 95% prediction interval (95% PI), small study effects, and excess significance bias were calculated. Finally, we categorised the meta-analyses based on the credibility of the evidence criteria and their quality using a Measurement Tool to Assess Systematic Reviews 2 checklist. This umbrella review was registered with PROSPERO, CRD42022361331. Findings: Of 181 listed review articles and 60 individual papers, 10 reviews and 12 individual articles were included in the meta-analyses. This yielded 37 meta-analyses based on 106 study estimates. Evidence was highly suggestive for the effectiveness of exercise (class II) for improving inattention (G = 0.92, 95% CI: 0.44-1.39, 95%), inhibitory control (G = 0.82, 95% CI: 0.52-1.13), and cognitive flexibility (G = 0.52, 95% CI: 0.32-0.72). However, evidence for the effectiveness of exercise on emotional, social, and working memory outcomes was weak, and these results were not significant for hyperactivity and behavioural functioning. Interpretation: Improvement of cognitive flexibility, inhibitory control, and inattention in children and adolescents with ADHD was highly suggested by exercise interventions. However, results were weak for other outcomes (emotional functioning, social functioning, and working memory). Further high-quality randomised controlled trials are, therefore, warranted to determine the effectiveness of exercise on weak outcomes. Funding: None.