Discovery Medicine[JOURNAL]
Sun
200 papers
Baicalin Plays an Anti-Osteosarcoma Role and Promotes Osteogenic Differentiation by Inhibiting NF-κB Signaling.
Zhao ZF, Cheng XF, Yu M … +2 more , Shi WF, Zhang T
Discov Med · 2024 Aug · PMID 39190380 · Publisher ↗
BACKGROUND: Osteosarcoma (OS) is commonly recognized as a malignant cancer originating from bone-forming mesenchymal stem cells, comprising approximately 20% of sarcomas. Baicalin, a bioactive flavonoid glycoside isolate...
BACKGROUND: Osteosarcoma (OS) is commonly recognized as a malignant cancer originating from bone-forming mesenchymal stem cells, comprising approximately 20% of sarcomas. Baicalin, a bioactive flavonoid glycoside isolated from , has been demonstrated to possess potent anti-inflammatory and neuroprotective properties. OBJECTIVE: To explore the potential mechanisms through which baicalin exerts anti-osteosarcoma effects and facilitates osteogenesis . METHODS: Cell Counting Kit-8 (CCK-8), scratch assay, and transwell assay were employed to assess the effects of baicalin at varying concentrations (20, 40, and 80 μM) on U2OS cell proliferation, invasion, and migration, respectively. Western blot and qRT-PCR analyses were conducted to evaluate the influence of baicalin on the osteogenic potential of OS cells by examining osteoblast markers such as osteocalcin (), osteopontin (), and runt-related transcription factor 2 (), as well as the osteoclast marker-receptor activator of nuclear factor kappa B ligand (). Additionally, the impact of baicalin on epithelial-mesenchymal transition (EMT) markers (N-cadherin, E-cadherin, Vimentin) and proteins related to the Nuclear factor κB (NF-κB) signaling pathway (p-p65, p-IκBα, p65, IκBα) in OS cells was evaluated via western blot analysis. The activity and mineralization capacity of Alkaline Phosphatase (ALP) in baicalin-treated cells were examined through ALP staining and Alizarin Red S (ARS) staining. RESULTS: Baicalin exhibited significant suppression of OS cell U2OS invasion ( < 0.01), migration ( < 0.01), and proliferation ( < 0.05) at various concentrations. Additionally, baicalin treatment notably increased the E-cadherin protein level, while decreasing the expression levels of Vimentin and N-cadherin proteins ( < 0.01), thus promoting EMT. Following baicalin treatment, there was a marked elevation in the protein and mRNA expression levels of RUNX2, OPN, and OCN, while the expression level of RANKL protein was reduced ( < 0.05), indicating enhanced osteogenic differentiation. The groups treated with baicalin exhibited higher ALP activity and mineralization ability ( < 0.01). Moreover, baicalin treatment significantly reduced the expression levels of p-IκBα and p-p65 proteins, as well as the ratios of p-IκBα/IκBα and p-p65/p65 ( < 0.01). These effects of baicalin were concentration-dependent, with higher concentrations yielding stronger effects. CONCLUSION: , baicalin demonstrates anti-OS effects and facilitates osteogenic differentiation, potentially by inhibiting NF-κB pathway activity.
Anti-Inflammatory Immunomodulatory Activity of Valacyclovir on the Activated Mammalian Macrophages.
Aydemir E
Discov Med · 2024 Aug · PMID 39190379 · Publisher ↗
BACKGROUND: Aciclovir, often known as acyclovir, is a nucleoside analog that exhibits antiviral activity against human herpesvirus 6 (HHV-6), cytomegalovirus (CMV), varicella-zoster virus (VZV), and herpes simplex virus...
BACKGROUND: Aciclovir, often known as acyclovir, is a nucleoside analog that exhibits antiviral activity against human herpesvirus 6 (HHV-6), cytomegalovirus (CMV), varicella-zoster virus (VZV), and herpes simplex virus (HSV). Valacyclovir is an amino acid ester prodrug of acyclovir. We examined valacyclovir, which is also an anti-viral agent, for its effects on inflammation. METHODS: Mammalian Macrophages were activated by lipopolysaccharide (LPS) in the presence of a concentration range of Valacyclovir. Tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-12p40 enzyme-linked immunosorbent assay (ELISA) was performed to measure the production levels of these pro-inflammatory cytokines. RESULTS: Our results suggest that Valacyclovir had anti-inflammatory activity on the LPS-activated mammalian macrophages. CONCLUSION: Valacyclovir has the potential to be utilized in the clinical setting as an anti-viral drug molecule with anti-inflammatory properties. Future studies are needed to further confirm its activities on different immune system cell types.
Overexpression Inhibits Diffuse Large B-Cell Lymphoma Progression by Promoting Autophagy through TLR4/MyD88/NF-κB Signaling Pathway.
Ning F, Wang H, Liang Z … +1 more , Lan J
Discov Med · 2024 Aug · PMID 39190378 · Publisher ↗
BACKGROUND: Tumor necrosis factor alpha induced protein 3 (TNFAIP3) is reportedly to have significant implications for autophagy regulation in various cancers. The current study aimed to decipher the role and mechanism o...
BACKGROUND: Tumor necrosis factor alpha induced protein 3 (TNFAIP3) is reportedly to have significant implications for autophagy regulation in various cancers. The current study aimed to decipher the role and mechanism of TNFAIP3 in diffuse large B-cell lymphoma (DLBCL) by modulating autophagy. METHODS: Information pertaining to the differential expression and prognostic role of in DLBCL was gleaned from the Gene Expression Omnibus (GEO) database. The expression levels in human DLBCL cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Cell counting kit-8 (CCK-8) and colony formation assays were employed to determine cell proliferation. Transwell assay and flow cytometry were applied to detect cell migration and apoptosis, respectively. Immunofluorescence and transmission electron microscope were used for the assessment of cell autophagy. The levels of apoptotic markers (caspase-3, cleaved-caspase-3, Bcl-2 Associated X (Bax), and B cell lymphoma-2 (Bcl-2)), autophagy indicators (the ratio of microtubule-associated proteins 1A/1B light chain 3 II and I (LC3II/LC3I), Sequestosome (p62)), and pathway proteins (toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), Transcription Factor NF-Kappa-B P65 Subunit (p65), and phosphorylated-p65 (p-p65)) were assessed via Western blotting. Immunohistochemistry was employed to detect Ki67 expression in tumor tissues. RESULTS: expression in DLBCL samples was downregulated, correlating with poor prognosis. expression was also downregulated in DLBCL cells. It was found that impeded cell proliferation and migration, and enhanced apoptosis of OCI-LY3 cells. Intervention with autophagy inhibitor 3-methyladenine (3-MA) markedly reversed apoptosis of OCI-LY3 cells induced by . Besides, induced autophagy via modulating the TLR4/MyD88/nuclear factor kappa B (NF-κB) signaling pathway. experiments showed that expression in DLBCL was downregulated, and upregulation of could inhibit tumor growth. CONCLUSION: inhibits DLBCL progression by inducing TLR4/MyD88/NF-κB pathway-mediated autophagy.
USP7 Promotes TGF-β1 Signaling by De-Ubiquitinating Smad2/Smad3 in Pulmonary Fibrosis.
Tang F, Gong H, Ke T … +3 more , Yang W, Yang Y, Liu Z
Discov Med · 2024 Aug · PMID 39190377 · Publisher ↗
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a long-term, progressive, and irreversible pulmonary interstitial disease. The activation of Smad family member 2 (Smad2) and Smad3 transcription factors by transforming...
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a long-term, progressive, and irreversible pulmonary interstitial disease. The activation of Smad family member 2 (Smad2) and Smad3 transcription factors by transforming growth factor β-1 (TGF-β1) is a critical event in the pathogenesis of IPF. However, there is still a lack of understanding regarding the molecular mechanisms governing Smad2 and Smad3 proteins. Ubiquitin-specific protease 7 (USP7) is a deubiquitinase that plays a vital role in regulating protein stability within cells. However, its regulation of the TGF-β signaling pathway and its significance in IPF remain undiscovered. This study aims to clarify the function of USP7 in the TGF-β signaling pathway, while simultaneously exploring the specific molecular mechanisms involved. Additionally, this study seeks to evaluate the therapeutic potential of targeted USP7 inhibitors in IPF, thereby providing novel insights for the diagnosis and management of IPF. METHODS: We first detected the expression of USP7 in lung tissues of mice with Bleomycin (BLM)-induced pulmonary fibrosis and in Beas-2B cells treated with or without TGF-β1 through Western blot analysis. Subsequently, we explored the influence of USP7 on fibrotic processes and the TGF-β1 signaling pathway, utilizing and studies. Finally, we assessed the effectiveness of USP7-specific inhibitors in an IPF murine model. RESULTS: In the present study, USP7 was found to de-ubiquitinate Smad2 and Smad3, consequently increasing their stability and promoting the TGF-β1-induced production of profibrotic proteins including α-smooth muscle actin (α-SMA) and fibronectin 1 (FN-1). Inhibition or knockdown of USP7 resulted in decreased levels of Smad2 and Smad3 proteins, leading to reduced expression of FN-1, Collagen Type I Alpha 1 Chain (Col1A1), and α-SMA induced by TGF-β1 in human pulmonary epithelial cells. These findings demonstrate that overexpression of USP7 reduces Smad2/3 ubiquitination, whereas inhibition or knockdown of USP7 enhances their ubiquitination. USP7 is abundantly expressed in IPF lungs. The expressions of USP7, Smad2, and Smad3 were upregulated in bleomycin-induced lung injury. The USP7 inhibitor P22077 reduced the expression of FN-1 and type I collagen as well as Smad2/3 and collagen deposition in lung tissue in a model of pulmonary fibrosis induced by bleomycin. CONCLUSIONS: This study demonstrates that USP7 promotes TGF-β1 signaling by stabilizing Smad2 and Smad3. The contribution of USP7 to the progression of IPF indicates it may be a viable treatment target.
Data Analysis of Heart Rate Variability and Arrhythmia in Patients with Paroxysmal Atrial Fibrillation.
Jin H, Ding L, Li B … +1 more , Zhang J
Discov Med · 2024 Aug · PMID 39190376 · Publisher ↗
BACKGROUND: Atrial fibrillation (AF) is the most common type of arrhythmia. Heart rate variability (HRV) may be associated with AF risk. The aim of this study was to test HRV indices and arrhythmias as predictors of paro...
BACKGROUND: Atrial fibrillation (AF) is the most common type of arrhythmia. Heart rate variability (HRV) may be associated with AF risk. The aim of this study was to test HRV indices and arrhythmias as predictors of paroxysmal AF based on 24-hour dynamic electrocardiogram recordings of patients. METHODS: A total of 199 patients with paroxysmal AF (AF group) and 204 elderly volunteers over 60 years old (Control group) who underwent a 24-hour dynamic electrocardiogram from August 2022 to March 2023 were included. Time-domain indices, frequency-domain indices, and arrhythmia data of the two groups were classified and measured. Binary logistic regression analysis was performed on variables with significant differences to identify independent risk factors. A nomogram prediction model was established, and the sum of individual scores of each variable was calculated. RESULTS: Gender, age, body mass index and low-density lipoprotein (LDL) did not differ significantly between AF and Control groups ( > 0.05), whereas significant group differences were found for smoking, hypertension, diabetes, and high-density lipoprotein (HDL) ( < 0.05). The standard deviation of all normal to normal (NN) R-R intervals (SDNN), standard deviation of 5-minute average NN intervals (SDANN), root mean square of successive NN interval differences (rMSSD), 50 ms from the preceding interval (pNN50), low-frequency/high-frequency (LF/HF), LF, premature atrial contractions (PACs), atrial tachycardia (AT), T-wave index, and ST-segment index differed significantly between the two groups. Logistic regression analysis identified rMSSD, PACs, and AT as independent predictors of AF. For each unit increase in rMSSD and PACs, the odds of developing AF increased by 1.0357 and 1.0005 times, respectively. For each unit increase in AT, the odds of developing AF decreased by 0.9976 times. The total score of the nomogram prediction model ranged from 0 to 110. CONCLUSION: The autonomic nervous system (ANS) plays a pivotal role in the occurrence and development of AF. The individualized nomogram prediction model of AF occurrence contributes to the early identification of high-risk patients with AF.
Remimazolam Alleviates Ventilator-Induced Lung Injury by Activating TSPO to Inhibit Macrophage Pyroptosis.
Zhang L, Zhao D, Lv H … +1 more , Jiang X
Discov Med · 2024 Aug · PMID 39190375 · Publisher ↗
BACKGROUND: Macrophages are activated in ventilator-induced lung injury (VILI), accompanied by macrophage pyroptosis. Remimazolam (Re) plays a role in inhibiting macrophage activation. In this study, we aimed to investig...
BACKGROUND: Macrophages are activated in ventilator-induced lung injury (VILI), accompanied by macrophage pyroptosis. Remimazolam (Re) plays a role in inhibiting macrophage activation. In this study, we aimed to investigate the mechanism of Re in VILI. METHODS: A VILI model (20 mL/kg mechanical ventilation) was created using C57BL/6 mice. Alveolar macrophages were isolated from bronchoalveolar lavage fluid (BALF) and received mechanical stretching to simulate the mechanical ventilation . VILI model mice were treated with Re (16 mg/kg) to assess the alveolar structure, wet/dry (W/D) weight ratio, endothelial barrier antigen (EBA) permeability index, BALF protein content, inflammatory factors, macrophage pyroptosis, pyroptosis-related factors, and translocator protein (TSPO) level using a series of biological experiments. Whether Re alleviated macrophage pyroptosis by regulating TSPO was determined by rescue experiments. RESULTS: Re alleviated VILI, as evidenced by improvement of abnormal morphology of lung tissues during VILI and decreases in the lung W/D weight ratio, lung EBA permeability index, and BALF protein content. Re attenuated pulmonary inflammation and macrophage pyroptosis during VILI via down-regulation of inflammatory factors (myeloperoxidase, malondialchehyche, 8-hydroxy-2 deoxyguanosine, interleukin-6, tumor necrosis factor-α, macrophage inflammatory protein-2, interleukin-1β, and interleukin-18), and pyroptosis factors (cleaved gasdermin D (GSDMD)/GSDMD value, NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and caspase-1). Re activated TSPO in macrophages. TSPO overexpression rescued the cell stretch-inhibited macrophage viability and cell stretch-induced macrophage pyroptosis. CONCLUSION: Re alleviates VILI by activating TSPO to inhibit macrophage pyroptosis.
The Effect of Riboflavin on Neurological Rehabilitation after Traumatic Brain Injury in Children.
Cai Q, Zhao B, Ke Y
Discov Med · 2024 Aug · PMID 39190374 · Publisher ↗
BACKGROUND: Traumatic brain injury (TBI), which is the brain impairment and lesion caused by the external force injuring the head and the underlying brain, can cause pediatric death, disability, neurological disorders, a...
BACKGROUND: Traumatic brain injury (TBI), which is the brain impairment and lesion caused by the external force injuring the head and the underlying brain, can cause pediatric death, disability, neurological disorders, and even lifelong disability. This study was to explore the effect of riboflavin (RF) on neurological rehabilitation and functional recovery after TBI. METHODS: The rat models of TBI were constructed by treating rats with controlled cortical impact (CCI). By treating TBI rats with RF, we investigated whether the administration of RF would affect the sensorimotor function and cognitive ability recovery through adhesive removal test, modified neurological severity score (mNSS), corner test, wire-grip test and the Morris water maze. The effects of RF on lesion volume and water content were investigated using hematoxylin and eosin (H&E) staining and wet-dry method. The Nissl staining and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) staining were used to demonstrate the effect of RF on neural apoptosis. Inflammation-related cytokines of interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and transforming growth factor (TGF)-β1 were measured by enzyme-linked immunosorbent assay (ELISA) to evaluate the effect of RF on neuroinflammation. The impact of RF on oxidative stress was assessed by measuring malondialdehyde (MDA) content and superoxide dismutase (SOD) activity, and the platelet endothelial cell adhesion molecule-1 (CD31) staining for observing vessel density, the reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) for measuring vascular endothelial growth factor () mRNA expression and western blot for VEGF protein expression were used for evaluated angiogenesis. RESULTS: The administration of RF could facilitate the recovery of neurological function by promoting the recovery of sensorimotor function and cognitive ability ( < 0.05). Furthermore, RF could reduce the lesion volume and water content after TBI and ameliorate neural apoptosis, neuroinflammation, and oxidative stress ( < 0.05). Finally, RF increased vessel density ( < 0.01) and levels ( < 0.01) in brain tissues after TBI, promoting angiogenesis. CONCLUSION: RF benefits neurological rehabilitation after TBI by promoting neurological function recovery, ameliorating the pathogenesis after TBI, and facilitating brain vascular remodeling. These findings provide a novel mechanism for RF treating pediatric TBI.
Idebenone-Loaded Nanocomposite Microspheres for Nasal Administration-A Perspective in the Treatment of Alzheimer's Disease.
Boyuklieva R, Katsarov P, Zagorchev P … +3 more , Abarova S, Hristozova A, Pilicheva B
Discov Med · 2024 Aug · PMID 39190373 · Publisher ↗
BACKGROUND: Alzheimer's disease results in neurodegeneration and is characterized by an accumulation of abnormal neuritic lesions and intracellular aggregates of hyperphosphorylated Tau proteins in the cerebrum. That lea...
BACKGROUND: Alzheimer's disease results in neurodegeneration and is characterized by an accumulation of abnormal neuritic lesions and intracellular aggregates of hyperphosphorylated Tau proteins in the cerebrum. That leads to progressive decline in memory, thinking, and learning skills. Oxidative stress has been shown to play a significant role in the pathogenesis of Alzheimer's disease. Antioxidants are identified as part of therapeutic strategy to prevent or reduce the disease. Idebenone is a synthetic analogue of coenzyme Q with potent antioxidant properties, originally developed for the treatment of Alzheimer's disease and other cognitive disorders. After oral administration idebenone undergoes excessive first-pass metabolism and has a very low bioavailability of only about 1%. The use of an alternative route of administration such as the nasal and its incorporation into a novel carrier (nanocomposite microspheres) will eliminate the problems associated with reduced absorption, stability, and rapid biotransformation and will increase the opportunity for idebenone to realize its therapeutic potential in Alzheimer's disease. METHODS: Idebenone-loaded nanocomposite microspheres were obtained by spray drying. The structures were characterized using laser diffraction, scanning electron microscopy, high-performance liquid chromatography, Fourier-transform infrared spectroscopy, and differential scanning calorimetry. The ability of nanocomposite microspheres to bind human serum albumin was investigated by fluorescence spectroscopy. The mucoadhesive properties of the carrier were also determined. RESULTS: Bioadhesive nanocomposite microparticles with spherical shape, smooth surface, size of 7.37 ± 2.4 μm, and with high production yield, good drug entrapment efficiency, and loading values were obtained. Infrared spectra demonstrated no chemical interactions between idebenone and structure-forming polymers. The ability of particles to bind to human serum albumin depends on their drug loading. CONCLUSIONS: Nanocomposite microspheres were developed as the novel delivery system of idebenone for target nose-to-brain delivery. The obtained carrier may increase the therapeutic potential of idebenone by providing higher concentrations in brain tissue and reducing systemic exposure and side effects.
The Role of RNA m5C Modification in Central Nervous System Diseases.
Wu P, Gao J, Lan G … +1 more , Wang Y
Discov Med · 2024 Aug · PMID 39190372 · Publisher ↗
As advances in RNA modification research progress, the significance of 5-methylcytosine (m5C) modification is being increasingly acknowledged. m5C undergoes modification by the methyltransferase NOP2/Sun domain (NSUN) fa...
As advances in RNA modification research progress, the significance of 5-methylcytosine (m5C) modification is being increasingly acknowledged. m5C undergoes modification by the methyltransferase NOP2/Sun domain (NSUN) family/DNA methyltransferase (DNMT) family (writer) and is removed by demethylases (eraser), including the ten-eleven translocation (TET) family and Alkb homolog 1 (ALKBH1). Moreover, m5C interacts with RNA-binding proteins (reader), such as Y-box-binding protein 1 (YBX1) and Aly/REF export factor (ALYREF). Expanding on this structural framework, m5C modification possesses the capacity to regulate various physiological and pathological processes. Recent studies indicate that m5C plays a pivotal regulatory role in the central nervous system, and its dysregulation may correlate with the onset and progression of various central nervous system diseases. In this review, we summarize recent research on m5C components and delve into the potential mechanisms of m5C involvement in central nervous system disorders, such as Alzheimer's disease, brain tumors, epilepsy, and stroke.
Tailored-Biomaterials Based Potential Strategies for Cardiovascular Disease.
Bhullar SK, Mondal H, Thomas J … +5 more , Ruzgar DG, Chandrasekaran N, Mukherjee A, Jun MBG, Willerth SM
Discov Med · 2024 Aug · PMID 39190371 · Publisher ↗
Cardiovascular disease is a significant health concern worldwide, and varied effective treatment and prevention methods have been developed. Among these, tailored biomaterials-based strategies such as stents, scaffolds,...
Cardiovascular disease is a significant health concern worldwide, and varied effective treatment and prevention methods have been developed. Among these, tailored biomaterials-based strategies such as stents, scaffolds, patches, and drug delivery systems have emerged as a promising avenue. These devices are designed to match the mechanical and biological mechanisms of the cardiovascular system, ensuring optimal performance and compatibility. By effectively treating or preventing cardiovascular diseases, these devices have the potential to improve patient health outcomes significantly. They can restore blood flow by addressing blocked arteries and regenerate damaged cardiac tissue by delivering bioactive agents or cells directly to the affected area in a targeted, sustained, and controllable manner. Therefore, the objective of this article is to summarize the available evidence on these tailored biomaterial-based tunable cardiovascular devices. This knowledge can help to transform cardiovascular medicine for the treatment or prevention of cardiovascular disease and restore cardiac function to improve patients' quality of life.
Dietary Diversity and Associated Factors among Children 6-23 Months Old in Ethiopia: Systematic Review and Meta-Analysis.
Mulatu S, Mekonnen GB, Tsehay YT … +6 more , Mamo ST, Messelu MA, Belay AE, Belayneh AG, Adal O, Tafere C
Discov Med · 2024 Jul · PMID 39054722 · Publisher ↗
BACKGROUND: Feeding diversified food for children is the major indicator of nutritional quality and adequacy that is crucial during the complementary feeding period for infants and young children aged 6-23 months. Ensuri...
BACKGROUND: Feeding diversified food for children is the major indicator of nutritional quality and adequacy that is crucial during the complementary feeding period for infants and young children aged 6-23 months. Ensuring diversified food is highly essential for the normal growth and development of the infant and young children. In Ethiopia, malnutrition and food insecurity remain prevalent, underscoring the need to understand and improve dietary diversity among children. The primary objective of this review was to determine the pooled prevalence of dietary diversity and its associated factors among children aged 6-23 months in Ethiopia. METHODS: We thoroughly searched some electronic databases, including Pub Med, Africa Index Medicus, Science Direct, Hinari, and Google Scholar, to perform a meta-analysis. Excel was used to extract and combine the data, while Stata 17 was used for statistical analysis. To estimate pooled prevalence rates and related associated factors, we used a random-effect model and the Der Simonian-Laird technique. The I-test was utilized to examine heterogeneity, and funnel plots, in conjunction with Egger's and Begg's tests, were employed to investigate publication bias. RESULT: This review analyzed 42 full-text studies, finding a pooled prevalence of 26.78% (95% confidence interval (CI): 23.35-30.21) with significant heterogeneity (I = 98.95%). Maternal education levels-college & above Adjusted Odds Ratio (AOR: 5.377, 95% CI: 3.116-9.279), secondary and above (AOR: 3.324, 95% CI: 1.939-5.700), primary (AOR: 3.065, 95% CI: 2.275-3.129), and formal education (AOR: 2.484, 95% CI: 1.722-3.583)-showed higher odds than counterparts. Similarly, fathers' education-secondary and above (AOR: 2.837, 95% CI: 1.981-4.065) and primary (AOR: 2.082, 95% CI: 1.016-4.266)-and father's occupation as merchant (AOR: 2.739, 95% CI: 1.355-5.539), and mother's occupation as housewife (AOR: 3.636, 95% CI: 2.457-5.381) showed higher odds. Additionally, male child sex (AOR: 1.877, 95% CI: 1.185-2.972), child age 18-23 months (AOR: 2.470, 95% CI: 1.568-3.987), and 12-17 months (AOR: 2.460, 95% CI: 1.914-3.163) indicated higher odds than counterparts. Having Postnatal Care (PNC) follow-up, counseling on infant and young child feeding (IYCF) practices, and no history of child illness were associated with higher odds (AOR: 3.155, 95% CI: 2.104-4.732), (AOR: 2.960, 95% CI: 2.288-3.829), and (AOR: 2.420, 95% CI: 1.765-3.318), respectively. Maternal knowledge of dietary diversity, urban residency, Antenatal Care (ANC) follow-up, child growth monitoring, and media exposure also showed higher odds. Similarly, maternal age groups 25-34 years and 35-44 years had higher odds compared to those aged 15-24 years. Other factors associated with higher odds included home grading, food security, institutional delivery, availability of cow milk, and household wealth index. CONCLUSION: Among Ethiopian children aged 6-23 months, the prevalence of recommended dietary diversity feeding practices was remarkably low, with only about 25% meeting the minimum recommended diversified food. The scientific predictors factor affecting dietary diversity included maternal media exposure, place of delivery, food security, urban residency, availability of cow milk, child growth monitoring, age, and knowledge of IYCF practices; paternal factors like education and occupation; child-related variables like age, sex, and history of illness; and history of ANC and PNC.
Whole-Exome Sequencing Detecting a Recurrent Pathogenic Mutation, p.His63Asp (H63D) in COVID-19 Patients and Its Effect on Mortality.
Mir R, Elfaki I, Alanazi MA … +11 more , Algehainy NA, Altemani FH, Alsayed BA, Mohamed EI, Mustafa SK, Moawadh MS, Tayeb FJ, Alfaifi J, Alatawi SM, Mir MM, Ullah MF
Discov Med · 2024 Jul · PMID 39054721 · Publisher ↗
BACKGROUND: In recent years, various coronaviruses have caused severe respiratory illnesses worldwide. For example the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections of COVID-19 outbreak in 2019...
BACKGROUND: In recent years, various coronaviruses have caused severe respiratory illnesses worldwide. For example the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections of COVID-19 outbreak in 2019 in Wuhan, China. Genome-wide association studies (GWAS) have significantly expanded our comprehension of how specific genetic variations are linked to diseases. Research has demonstrated the existence of genetic factors influencing susceptibility to coronaviruses. The objective of this study was to examine the association of certain loci with the COVID-19 in Saudi population. METHODS: In the present study we have examined the link between the COVID-19 disease and certain genetic variants in hospitalized COVID-19 patients (n = 16) in Tabuk and Bisha, Kingdom Saudi Arabia. We used the genome Analysis Toolkit (GATK) and Comprehensive variant annotation was performed different databases and tools such as Search Tool for the Retrieval of Interacting Genes (STRING), PanelApp and PolyPhen-2. RESULTS: The study showed that the genetic variants associated with genes such as Homeostatic Iron Regulator () (found in 7 patients, representing 44%), complement factor H () (6 patients, 38%), cadherin 23 () (4 patients, 25%), cytotoxic T-lymphocyte associated protein 4 () (3 patients, 19%), Transforming Growth Factor Beta 1 () (3 patients, 19%), CREB-binding protein () (2 patients, 13%), E1A Binding Protein P300 () (2 patients, 13%), hemoglobin subunit beta () (2 patients, 13%), interferon regulatory factor 7 () (2 patients, 13%), and unc-119 lipid binding chaperone () (2 patients, 13%) might be associated with susceptibility to coronavirus. We also identified mutations in the COVID-19 patient that are pathogenic or likely pathogenic. CONCLUSION: A recurrent pathogenic mutation, p.His63Asp (H63D), was identified in 7 patients, suggesting its potential contribution to disease severity. Additionally, a likely pathogenic variant, p.Glu7Val (E7V), was present in 2 patients, highlighting its potential role in disease susceptibility. Our results shed light on the key genetic mechanisms of COVID-19 pathogenesis and help to identify and stratify the individuals or populations that are at risk to corona virus infection. The identification of susceptible individuals or populations assist in prevention and/or in treatment programs.
Local Anesthetic Bupivacaine Inhibits Melanoma Proliferation and Metastasis by Targeting PAPSS2.
Guan E, Zhang J, Zhou J … +2 more , Liu Y, Xu N
Discov Med · 2024 Jul · PMID 39054720 · Publisher ↗
BACKGROUND: Melanoma is a highly invasive skin cancer with limited treatment strategies. Bupivacaine, a commonly used local anesthetic recognized for its safety, has shown promise in combating tumors. 3'-phosphoadenosine...
BACKGROUND: Melanoma is a highly invasive skin cancer with limited treatment strategies. Bupivacaine, a commonly used local anesthetic recognized for its safety, has shown promise in combating tumors. 3'-phosphoadenosine 5'-phosphosulfate synthase 2 (PAPSS2) is a key enzyme in the sulfation process and is associated with the development and metastasis of various tumors. This study aimed to explore the mechanism by which bupivacaine inhibits melanoma proliferation and metastasis by targeting PAPSS2. METHODS: The effects of bupivacaine on the proliferation of A375 and A2058 melanoma cells were evaluated using Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) labeling, and clonogenic assays. Cell migration, invasion, and PAPSS2 expression were evaluated using Transwell experiments and Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) analysis. Additionally, an melanoma tumor model in nude mice was constructed to evaluate the impact of bupivacaine on melanoma growth and metastasis. Immunohistochemistry was used to assess tumor metastasis and PAPSS2 expression levels in the nude mouse model. RESULTS: Experimental results demonstrated that bupivacaine significantly inhibited melanoma proliferation and invasion compared to the control group. Notably, this inhibitory effect was partially reversed by PAPSS2 overexpression. experiments demonstrated that bupivacaine-treated nude mice exhibited reduced tumor volumes, weights, and fewer lung metastatic foci. Molecular analysis via qRT-PCR and immunohistochemistry analysis further indicated that bupivacaine significantly reduced PAPSS2 in tumor tissues. CONCLUSION: This study confirms that bupivacaine, a local anesthetic, can inhibit melanoma proliferation and metastasis by targeting the PAPSS2 signaling pathway. These findings suggest its potential as an anti-tumor medication and present new treatment strategies for melanoma.
Knockdown of YAP1 Reduces YTHDF3 to Stabilize and thus Inhibit Bladder Cancer Stem Cell Stemness.
Qiu D, Gao L, Yu X
Discov Med · 2024 Jul · PMID 39054719 · Publisher ↗
BACKGROUND: The previous study has proved the oncogenic role of Yes-associated protein 1 (YAP1) in bladder cancer (BLCA), thus this study focused on its impact on bladder cancer stem cells (BCSCs) and underlying mechanis...
BACKGROUND: The previous study has proved the oncogenic role of Yes-associated protein 1 (YAP1) in bladder cancer (BLCA), thus this study focused on its impact on bladder cancer stem cells (BCSCs) and underlying mechanism. METHOD: BCSCs were obtained by treating human BLCA cells UMUC3 with cisplatin and identified by measuring CD133 in UMUC3/BCSCs via flow cytometry. YAP1 interaction proteins and mothers against decapentaplegic homolog 7 () N6-methyladenosine (m6A) site were analyzed by bioinformatics. BCSCs were transfected. m6A level, YTH domain-containing family proteins 3 (YTHDF3)- interaction, YAP1/YTHDF3 expression in BCSCs were assessed by methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation (RIP) or quantitative reverse transcription PCR (qRT-PCR), respectively. BCSC proliferation was detected by 5-Bromo-2-deoxyuridine (BrdU) staining. UMUC3/BCSC migration/invasion and tumour sphere formation were determined by Transwell or tumour sphere formation assays. YAP1/YTHDF3//transforming growth factor (TGF)-β1/stemness marker expressions in UMUC3/BCSCs were measured by Western blot assay. RESULT: BCSCs showed higher CD133 ratio, expressions of stemness marker/YAP1/YTHDF3/TGF-β1, lower expression and greater invasion/migration/tumour sphere formation capabilities than UMUC3 cells. YAP1 knockdown decreased m6A level and impaired YTHDF3- interaction in BCSCs. YAP1 silencing inhibited cell growth/invasiveness/migration/tumour sphere formation and stemness-associated protein/YTHDF3/TGF-β1 expressions while upregulating expression in BCSCs, which was offset by YTHDF3 overexpression. CONCLUSION: The silencing of YAP1 in BCSCs impedes the YTHDF3-mediated degradation of m6A-modified , culminating in diminished cell stemness.
Genomic Alterations and Clinical Characterization in Chinese Patients with Metastatic Colorectal Cancer.
Zhang XH, Zhou JQ, Wei Q … +5 more , Li J, Xu T, Bai CM, Zhou JF, Wang XC
Discov Med · 2024 Jul · PMID 39054718 · Publisher ↗
BACKGROUND: Metastatic colorectal cancer (mCRC) is increasingly characterized by myriad genomic alterations beyond the well-known factors such as , , and microsatellite instability (MSI). Novel genomic changes, including...
BACKGROUND: Metastatic colorectal cancer (mCRC) is increasingly characterized by myriad genomic alterations beyond the well-known factors such as , , and microsatellite instability (MSI). Novel genomic changes, including amplifications, mutations, and gene fusions, are now recognized as potential targets for precision therapy. This study aims to explore the genomic landscape of a Chinese cohort with mCRC to identify potentially targetable genetic alterations for personalized treatment strategies. METHODS: A total of 500 mCRC patients in China were enrolled, based on which genomic profiling was performed using capture-based targeted sequencing across a panel of 520 genes on tumor tissues to identify prevalent genomic alterations. The mutations were analyzed by optimized proprietary algorithms. MSI and mismatch repair deficiency status were analyzed using the read-count-distribution approach. Besides, the overall survival (OS) related to these molecular changes was estimated. RESULTS: The cohort's genomic profiling revealed mutations in 78%, in 60%, and in 47% of the patients. MSI-High status was confirmed in 5.8% of cases via a next-generation sequencing (NGS)-based algorithm. / amplifications were found in 12% (60/500) of patients, with potential therapeutic implications for those without concurrent mutations. A subset of patients (1.2%; 6/500) showed fusions and DNA damage response (DDR) gene mutations (except ) that could be targeted therapeutically. The (G12C) variant was detected in 14 patients (2.8%), and 61 (12.2%) had a mutation. Notably, survival analysis showed no significant differences in OS between mutant loci and mutations ( = 0.436). However, mutations were associated with a poorer prognosis than wild-type and non- mutations (16.3 months vs. 29.5 and 31.1 months, respectively; < 0.001). CONCLUSIONS: This study validates the feasibility of using NGS to detect prognostic and therapeutically actionable genetic variants in Chinese mCRC patients, contributing to understanding the genomic variation within this population and highlighting the potential for personalized medicine in managing mCRC.
Synergistic Effects of I Seed Implantation Brachytherapy and Gemcitabine in Pancreatic Tumors.
Li Q, Li Y, Liu J … +2 more , Huang X, Li Z
Discov Med · 2024 Jul · PMID 39054717 · Publisher ↗
BACKGROUND: Monotherapy consisting of radiotherapy or chemotherapy has limited efficacy in pancreatic tumors. This study aims to investigate whether the combination of I brachytherapy and gemcitabine (GEM) chemotherapy h...
BACKGROUND: Monotherapy consisting of radiotherapy or chemotherapy has limited efficacy in pancreatic tumors. This study aims to investigate whether the combination of I brachytherapy and gemcitabine (GEM) chemotherapy has a synergistic effect on pancreatic cancer (PC). METHODS: , PANC-1 cells in the exponential phase were treated with I radioactive seeds (6 Gy) and GEM (30 nM). Cell proliferation, apoptosis, and mitochondrial membrane potential were measured using the Cell Counting Kit-8 (CCK-8) assay, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, and flow cytometry, respectively. , we examined the inhibitory effect of three different treatment regimens on tumor growth in mice when combined with I brachytherapy and GEM. Next, we investigated the effects of the optimal scheme among the three on the tumor microenvironment, tumor tissue morphology, tumor cell apoptosis, systemic inflammatory response, and levels of apoptosis-related proteins in the tumor. Changes in the tumor microenvironment and levels of apoptosis-related proteins were measured by Western blot. The extent of damage to tumor tissue morphology was assessed by Hematoxylin and Eosin (HE) staining. Tumor cell apoptosis was measured by TUNEL staining. Changes in inflammation-related factors were determined by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: The results of cell experiments demonstrated that the combination of I radioactive seeds (6 Gy) and GEM (30 nM) had a stronger inhibitory effect on PANC-1 cells than either alone ( < 0.05). , data showed that the GEM (after 3 d) + I treatment group had the strongest tumor inhibition effect on PC ( < 0.05). Western blot analysis showed that the combined treatment of I brachytherapy and GEM caused changes in the expression of collagen and connexin in the tumor microenvironment, promoted tumor cell apoptosis, upregulated the expression of pro-apoptotic proteins, and helped to restore pancreatic function ( < 0.01). CONCLUSION: Our research results suggest that the strategy of I seed implantation surgery in mice after 3 days of GEM treatment has a more pronounced synergistic effect on the treatment of PC.
Levosimendan Ameliorates Hypoxia-Induced Brain Injury in Rats by Modulating PTEN/Akt Signaling Pathway-Mediated Ferroptosis.
Meng W, Shu C, Gao H
Discov Med · 2024 Jul · PMID 39054716 · Publisher ↗
BACKGROUND: Levosimendan (Levo) is a drug commonly used to treat heart failure. Recent studies have suggested that Levo may have neuroprotective effects, but it is still unknown how exactly it contributes to hypoxia-indu...
BACKGROUND: Levosimendan (Levo) is a drug commonly used to treat heart failure. Recent studies have suggested that Levo may have neuroprotective effects, but it is still unknown how exactly it contributes to hypoxia-induced brain damage. Thus, the aim of this study was to investigate how Levo affects hypoxia-induced brain damage and to clarify any possible underlying mechanisms. METHODS: One group of rats (Levo group) was pretreated with Levo via oral force-feeding for four weeks. Another group (Ferrostatin-1 (Fer-1) group) was pretreated with intraperitoneal injections of Fer-1 for four weeks. A rat model of chronic hypoxia was created by treating rats with 13% O for 14 days in a closed hypoxia chamber. For each group (Control, Model, Levo, Fer-1), we evaluated learning and memory capacity and the morphology and structure of neurons in the rats' brain tissue. Other measurements included tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6); malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px); Fe; apoptosis; cleaved caspase-3, caspase-3; phosphatase and tensin homolog (PTEN), protein kinase B (Akt), phosphorylated Akt (p-Akt); and ferroptosis-related proteins Nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11). RESULTS: The Model group rats had considerably fewer neurons than the Control group, with loosely arranged cells, and markedly impaired learning and memory abilities ( < 0.05). Oxidative damage and inflammation in brain tissues of the Model group were significantly intensified, accompanied by a substantial increase in neuronal apoptosis ( < 0.05). PTEN protein, Fe concentration, and cleaved caspase-3 expression were all significantly upregulated, whereas p-Akt, Nrf2, GPX4, and SLC7A11 proteins were dramatically downregulated ( < 0.05). Both the Levo and Fer-1 groups demonstrated significantly more neurons and closely arranged cells than the Model group, along with a notable improvement in learning and memory abilities ( < 0.05). Oxidative damage and inflammation in brain tissues of the Levo and Fer-1 groups were markedly alleviated, and neuronal apoptosis was suppressed ( < 0.05). p-Akt, Nrf2, GPX4, and SLC7A11 proteins were dramatically upregulated, whereas the expression of cleaved caspase-3, PTEN protein, and Fe content was considerably downregulated ( < 0.05). CONCLUSIONS: Levo effectively mitigates brain injury in rats with chronic hypoxia, likely by regulating ferroptosis via the PTEN/Akt signaling pathway.
Gastrodin Ameliorates the Inflammation, Oxidative Stress, and Extracellular Matrix Degradation of IL-1β-Mediated Fibroblast-Like Synoviocytes via Suppressing the Gremlin-1/NF-κB Pathway.
Hu Y, Li M, Chen XY … +4 more , Huang CH, Cao HY, Wang GJ, Du XF
Discov Med · 2024 Jul · PMID 39054715 · Publisher ↗
BACKGROUND: Synovial inflammation plays a crucial role in osteoarthritis (OA). Gastrodin (GAS), an active ingredient derived from the Gastrodia elata Blume rhizome, possesses antioxidant and anti-inflammatory pharmacolog...
BACKGROUND: Synovial inflammation plays a crucial role in osteoarthritis (OA). Gastrodin (GAS), an active ingredient derived from the Gastrodia elata Blume rhizome, possesses antioxidant and anti-inflammatory pharmacological effects. This research aimed to evaluate the function and molecular mechanism of GAS on human fibroblast-like synoviocytes of osteoarthritis (HFLS-OA) induced by interleukin (IL)-1β. METHODS: The impact of GAS on the viability of IL-1β-treated HFLS-OA cells was assessed using the cell counting kit-8 (CCK-8). Quantitative real-time reverse transcription PCR (qRT-PCR) was employed to detect changes in , , monocyte chemotactic protein-1 (), tumor necrosis factor ()-α, and mRNA expression in each group. Corresponding kits were utilized to measure the catalase (CAT) and superoxide dismutase (SOD) activities, as well as the nitric oxide (NO) level. Western blot analysis was conducted to examine the expression of extracellular matrix degradation-associated proteins and nuclear factor kappa-B (NF-κB) pathway-correlated proteins in each group. RESULTS: GAS significantly promoted the proliferation of IL-1β-induced HFLS-OA cells and concurrently down-regulated mRNA expression ( < 0.05). Through the down-regulation of expression, GAS exhibited the following effects: decreased , , and mRNA expression, as well as NO levels ( < 0.05); increased SOD and CAT activities ( < 0.05); down-regulated matrix metallopeptidase 13 (MMP-13) and MMP-1 protein expression levels ( < 0.01); and up-regulated collagen II protein expression level ( < 0.01) in IL-1β-treated HFLS-OA cells. Additionally, GAS decreased phospho-inhibitory kappa B (p-IκB)/IκB, phospho-inhibitory kappa B kinase (p-IKK)/IKK, and p-p65/p65 ratios in IL-1β-induced HFLS-OA cells by inhibiting Gremlin-1 expression ( < 0.01). CONCLUSION: GAS demonstrates a positive impact on inflammation, oxidative stress, and extracellular matrix degradation in IL-1β-mediated HFLS-OA cells. This effect is achieved by suppressing Gremlin-1 expression and reducing NF-κB pathway activity.
SIRT6 Inhibits the Proliferation and Collagen Synthesis of Keloid Fibroblasts through MAPK/ERK Pathway.
Zhou T, Chen Y, Wang C … +3 more , Huang Z, Tan Z, Ma Y
Discov Med · 2024 Jul · PMID 39054714 · Publisher ↗
BACKGROUND: Keloid, a fibroproliferative disorder, significantly impacts patients' quality of life, yet effective therapies remain elusive. This study explored the role of silent information regulator 6 (SIRT6) in modula...
BACKGROUND: Keloid, a fibroproliferative disorder, significantly impacts patients' quality of life, yet effective therapies remain elusive. This study explored the role of silent information regulator 6 (SIRT6) in modulating the proliferation, invasion, and collagen synthesis of keloid fibroblasts. METHODS: Keloid and normal skin specimens were collected, and fibroblasts were isolated from the keloid tissue. SIRT6 recombinant adenovirus (Ad) was constructed to infect keloid fibroblasts to overexpress SIRT6. This study entails three groups: Control group, adenovirus-Negative Control (Ad-NC) group, and Ad-SIRT6 group. SIRT6 protein and mRNA levels were measured via Western blotting and Quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively. Cell viability was determined using 5-ethynyl-2'-deoxyuridine (EdU) assay. Flow cytometry was exploited to measure cell apoptosis. To investigate cell migration, wound healing assay and Transwell assay were employed. Western blotting was also utilized to study the expression levels of apoptotic proteins, collagen deposition-related proteins, and Mitogen-Activated Protein Kinases (MAPK)/extracellular regulated protein kinases (ERK) pathway-related proteins. RESULTS: Compared to the control and Ad-NC groups, the Ad-SIRT6 group exhibited significantly elevated SIRT6 level; diminished cell proliferation, migration and invasion; reduced protein levels of α-smooth muscle actin (α-SMA), collagen I, collagen III, phospho SMAD Family Member 3 (p-Smad3), transforming growth factor-β 1 (TGF-β1), and MAPK/ERK pathway proteins (phospho extracellular signal-regulated protein kinase 1/2 (p-ERK1/2), phospho MAP kinase-ERK kinase (p-MEK) and phospho-c-Raf (p-c-Raf)). Treatment with epidermal growth factor (EGF), an MAPK/ERK pathway agonists, reversed the inhibitory effect of SIRT6 on cell activity and inhibited apoptosis in keloid fibroblasts. CONCLUSION: SIRT6 overexpression in keloid fibroblasts attenuates proliferation, invasion, and collagen synthesis, while fostering apoptosis, likely through the suppression of MAPK/ERK pathway activity. This suggests a potential therapeutic target for keloid treatment.
The Role of Intra-Articular Delivery of BM-MSCs-Derived Exosomes in Improving Osteoarthritis: Implication of // Axis.
El-Din SS, Aboulhoda BE, Hassouna A … +9 more , Shakweer MM, Alghamdi MA, Essam D, Essam M, AlRakaf NA, Elzahed HM, Selmy A, Sabry D, Mekawy DM
Discov Med · 2024 Jul · PMID 39054713 · Publisher ↗
BACKGROUND: Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently attracted great attention due to their crucial anti-inflammatory and regenerative properties. This work aims to examine the curative impact o...
BACKGROUND: Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently attracted great attention due to their crucial anti-inflammatory and regenerative properties. This work aims to examine the curative impact of intra-articular injection of BM-MSCs-derived exosomes in ameliorating osteoarthritis (OA) progression in rats and to explore the interaction between circular RNA of Yes-associated protein 1 () and microRNA-21 () in the rat knee joints. METHODOLOGY: Gene expression , , toll-like receptor-7 (), aggrecan, and collagen type II were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in the rat articular tissues. In addition, the Enzyme-linked immunosorbent assay (ELISA) technique was used to estimate the level of the inflammatory markers interleukin 4 (IL-4), interleukin 10 (IL-10), interleukin 1β (IL-1β), and tumor necrosis factor-alpha (TNF-α); and the oxidative markers glutathione (GSH), malondialdehyde (MDA) and total reactive oxygen species (ROS). Histopathological examination using Hematoxylin and Eosin (H&E) staining of the rat articular tissue was also performed along with an estimation of the articular cartilage thickness. RESULTS: Our results showed that BM-MSCs-derived exosomes significantly elevated gene expression level ( < 0.05) along with subsequent downregulation of and ( < 0.05). These effects impacted the inflammatory milieu of rat articular surfaces, where there was a significant reduction ( < 0.05) of the pro-inflammatory and oxidative markers with significantly increased production of the anti-inflammatory and antioxidative markers ( < 0.05). Marked elevation in aggrecan and collagen type II gene expression was also found in the treated groups ( < 0.05). CONCLUSION: Those data suggest that BM-MSCs-derived exosomes have a crucial role in mitigating OA symptoms and pathology progression and might be regarded as an effective as well as acceptable treatment option for OA.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe