Discovery Medicine[JOURNAL]
Sun
200 papers
Sevoflurane Activates PI3K/AKT Signaling Pathway by Upregulating Expression to Attenuate Ischemia/Reperfusion Injury in Cardiomyocytes.
Zhou RS, Xue XH, Bi Y … +4 more , Yang TT, Zhang ZQ, Zhu HY, Wang Q
Discov Med · 2024 Oct · PMID 39463227 · Publisher ↗
BACKGROUND: Myocardial ischemia/reperfusion (I/R) injury stands as a primary contributor to ischemic heart disease. Sevoflurane (SEVO), a commonly used inhalation anesthetic, has been shown to exert a direct protective e...
BACKGROUND: Myocardial ischemia/reperfusion (I/R) injury stands as a primary contributor to ischemic heart disease. Sevoflurane (SEVO), a commonly used inhalation anesthetic, has been shown to exert a direct protective effect on ischemic heart injury. However, the specific mechanism by which it exerts the protective effect remains unclear. This study was designed to investigate the role of SEVO in myocardial I/R injury and its potential molecular mechanisms. METHODS: Blood samples were collected from patients with acute myocardial infarction (AMI) (n = 20) and healthy volunteers (n = 20). The human cardiomyocytes AC16 models of I/R injury were induced by hypoxia/reoxygenation. The mRNA expression levels of growth differentiation factor 11 () in the cells and blood were determined by reverse transcription quantitative real-time PCR (RT-qPCR). The cell proliferation was detected by Cell Counting Kit-8 (CCK-8). Enzyme-Linked Immunosorbent Assay (ELISA) was utilized to detect the levels of inflammatory factors interleukin (IL)-8, IL-1β and IL-6 in the cells. And biochemical assay kits were applied for the measurement of the activity of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) as well as the malondialdehyde (MDA) level in the cells. Moreover, western blot was employed to evaluate the levels of the p-serine-threonine protein kinase (AKT), AKT, and phosphatidylinositol 3-kinase (PI3K), protein expression in the cells. RESULTS: The expression was decreased in the blood of AMI patients and cardiomyocytes induced by I/R ( < 0.01). Besides, 1% SEVO was presented to promote cardiomyocyte proliferation, inhibit apoptosis, oxidative stress and inflammation, and activate the PI3K/AKT signaling pathway through up-regulation of expression ( < 0.01). CONCLUSION: SEVO promotes proliferation and inhibits inflammatory response, apoptosis, and oxidative stress of I/R-treated cardiomyocytes by elevating expression, thereby reducing myocardial I/R injury. Notably, the mechanism underlying the alleviation of the I/R injury may involve the activation of PI3K/AKT signaling pathway.
Synergistic Inhibition of Colorectal Cancer Cells by Autocrine Motility Factor Peptide and Glycyrrhetinic Acid.
Kim SG, Duong TV, Lee S … +3 more , Ryu KJ, Kwon HK, Park HS
Discov Med · 2024 Oct · PMID 39463226 · Publisher ↗
BACKGROUND: Anti-cancer peptides are a powerful drug concept that induces cancer cell death through growth inhibition and membrane disruption, providing broad efficacy. The autocrine motility factor (AMF) interacts with...
BACKGROUND: Anti-cancer peptides are a powerful drug concept that induces cancer cell death through growth inhibition and membrane disruption, providing broad efficacy. The autocrine motility factor (AMF) interacts with the AMF receptor, regulating cancer cell motility, proliferation, metastasis, and angiogenesis through autocrine and paracrine pathways. However, studies verifying the synergistic effect of the combined use of anti-cancer drugs extracted from plants and AMF treatment are insufficient. METHODS: The effects of AMF-derived peptide sequences were evaluated in HT29 and SW620 colorectal cancer (CRC) cell lines. The study assessed the impact of AMF peptides on cell proliferation, colony formation, the Nicotinamide Adenine Dinucleotide Phosphate/Reduced Nicotinamide Adenine Dinucleotide Phosphate (NADP/NADPH) ratio, and reactive oxygen species (ROS) generation in these CRC cells. Additionally, the combined effect of AMF peptides and glycyrrhetinic acid (GA), a compound derived from licorice plants, was investigated by analyzing cell proliferation, colony formation, ROS production, and cell cycle progression in CRC cells. RESULTS: AMF peptides significantly inhibited CRC cell growth ( < 0.05), decreased colony formation ( < 0.05), and increased the NADP/NADPH ratio ( < 0.05) and ROS production ( < 0.001). When combined with GA, AMF peptides enhanced GA's effects on CRC cells, further suppressing cell growth ( < 0.05) and colony formation ( < 0.05) while increasing ROS generation ( < 0.05). CONCLUSION: The synergy between AMF peptides and GA, derived from licorice plants, suggests the potential for combined peptide-phytochemical therapy for treating CRC.
Curcumin Alleviates Airway Inflammation in Cough-Variant Asthmatic Rats by Modulating M1/M2 Macrophage Polarization.
Yang H, Xie J, Wang M … +3 more , Tang X, Wang H, Rong K
Discov Med · 2024 Oct · PMID 39463225 · Publisher ↗
BACKGROUND: With the increase of environmental pollution and atypical pathogen infections, the incidence of cough variant asthma (CVA) has been increasing annually, making it a pressing issue of the medical community. Th...
BACKGROUND: With the increase of environmental pollution and atypical pathogen infections, the incidence of cough variant asthma (CVA) has been increasing annually, making it a pressing issue of the medical community. This study aims to observe the ameliorative effect of curcumin on a rat model of cough variant asthma. METHODS: A rat model of cough variant asthma was induced by sensitization with ovalbumin combined with aluminum hydroxide (Al(OH)), followed by repeated excitations. The drug was administered on the day of the initial nebulized attack, and gavage was administered for 14 d. Pathological changes in the lung tissues were observed, along with the assessment of cough susceptibility and airway resistance. The number of inflammatory cell eosinophils and leukocytes were determined in alveolar lavage fluid. Additionally, serum inflammatory factors and lung tissues Matrix Metalloproteinase-9 (MMP-9) protein were assessed. The level of M1/M2 macrophages was also detected. RESULTS: Following the administration of curcumin, there was reduced inflammatory infiltration, less disordered arrangement of the lung tissue, and decreased abnormal proliferation of lung tissues in cough variant asthma rats compared to the model group. Curcumin treatment led toa notable reduction in cough frequency, a significant decrease in pro-inflammatory factor concentration levels in serum and inflammatory cell counts in the alveolar lavage fluid, and a marked increase in anti-inflammatory factor levels ( < 0.05). Additionally, curcumin administration led to a significant increase in M2-type macrophage levels, while simultaneously decreasing the levels of M1-type macrophages ( < 0.05). CONCLUSIONS: The administration of curcumin effectively ameliorates ovalbumin-induced airway inflammation in cough-variant asthma rats. This effect is attributed to modulating macrophage polarization towards the anti-inflammatory M2 phenotype, thereby reducing airway inflammation, airway hyperresponsiveness, and lung tissue injury.
Alleviates Inflammatory Response, Apoptosis, and ECM Degradation in Osteoarthritic Chondrocytes by Stabilizing .
Zhong F, Cen S, Long C … +2 more , Teng L, Zhong G
Discov Med · 2024 Oct · PMID 39463224 · Publisher ↗
BACKGROUND: It has been reported that Sirtuin 2 () prevents phosphoenolpyruvate carboxykinase 1 () degradation, which can be involved in aging-induced osteoarthritis (OA), but the molecular mechanism of / in chondrocytes...
BACKGROUND: It has been reported that Sirtuin 2 () prevents phosphoenolpyruvate carboxykinase 1 () degradation, which can be involved in aging-induced osteoarthritis (OA), but the molecular mechanism of / in chondrocytes has not been clarified. Therefore, this study aims to explore the mechanism of / in chondrocyte inflammation. METHOD: To establish the OA model , chondrocytes cultured with interleukin-1β (IL-1β, 10 ng/mL) and manipulation of and expression in the constructed cells to elucidate the interaction between the two genes. 1,9-Dimethyl-Methylene Blue (DMMB) was used to detect cellular glycosaminoglycan (GAG) content. Inflammatory factor levels were assessed using Enzyme-linked Immunosorbent Assay (ELISA). Apoptosis was detected by osmotic dye. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2 Associated X (Bax), Wnt Family Member 1 (Wnt1), catenin Beta 1 (β-catenin), Aggrecan, Collagen II, matrix metallopeptidase 13 (MMP-13) proteins in cells were analyzed using Western blot. RESULTS: gained lower expressions in OA cell models. Overexpression of or S in the IL-1β chondrocyte model of inflammation promoted GAG content, inhibited apoptosis and Wnt/β-catenin protein expression, and lowered the levels of inflammatory factors. silencing was proved to have the opposite effect. overexpression rescued the increased inflammation, MMP-13 expression, and apoptosis and the decreased Aggrecan and Collagen II expression caused by silencing. silencing also reversed the positive effects of overexpression on chondrocytes. CONCLUSION: inhibits articular chondrocyte extracellular matrix (ECM) degradation, inflammatory factor expression, and apoptosis via .
The Evaluation of Gastric Cancer Lymphovascular Invasion Using CT Volume Perfusion.
Li Y, Huang L, Li L … +3 more , Chen L, Chen P, Chen X
Discov Med · 2024 Oct · PMID 39463223 · Publisher ↗
BACKGROUND: The best treatment option for patients with resectable gastric cancer is radical gastric cancer surgery. However, the postoperative overall survival rate is low. Lymphovascular invasion (LVI) is a risk factor...
BACKGROUND: The best treatment option for patients with resectable gastric cancer is radical gastric cancer surgery. However, the postoperative overall survival rate is low. Lymphovascular invasion (LVI) is a risk factor for cancer recurrence and a stand-alone predictor of a poor post-operative prognosis for gastric cancer (GC) patients. Current evaluation of tumor LVI performed on histological specimens, which can only be assessed after surgery, is also limited by intra-tumoural heterogeneity via biopsy. This study explored the value of CT volume perfusion in assessing tumors' lymphovascular invasion of gastric cancer. METHODS: 59 gastric cancer patients confirmed by pathology who underwent both computed tomography (CT) volume perfusion examinations and gastrectomy surgery were prospectively included. Tumour lymphovascular invasion (LVI, positive or negative) was evaluated. The relationship between clinicopathological variables associated with LVI and CT perfusion parameters was analyzed by univariate analysis, followed by multivariate logistic regression analysis and receiver operating characteristic (ROC) analysis. RESULTS: The LVI-positive and LVI-negative groups differed significantly in terms of time to start (TTS), mean transit time (MTT), Tmax, and flow extraction product (FEP). Both FEP (odds ratio (OR), 1.048; 95% confidence interval (CI): 1.005-1.092) and MTT (OR, 0.549; 95% CI: 0.351-0.858) have the potential to be employed as independent predictors of LVI (both < 0.05). There were different correlations between LVI, lower MTT and greater FEP. The specificity of MTT (87.88%) was higher than that of FEP (72.73%), while the sensitivity of MTT (53.85%) was lower than that of FEP (57.69%). Compared to MTT and FEP alone, the combination demonstrated a comparatively higher area under the curve (AUC) (0.797) and sensitivity (84.62%). CONCLUSIONS: CT volume perfusion helps evaluate LVI in gastric cancer before surgery. MTT and FEP are independent predictors for LVI, and the combination variation has better diagnostic performance. Clinical Trial Register: Jiangmen Central Hospital, https://www.chictr.org.cn/showproj.html?proj=24375, ChiCTR1800014455.
BML-111 Modulates and Alleviates p38/MAPK Signaling Pathway and Th1/Th2/Th17 Cytokine Response in Murine Psoriasis-Like Dermatitis.
An Y, Zhang Q, Ren Y … +2 more , Yang S, Zhang Q
Discov Med · 2024 Oct · PMID 39463222 · Publisher ↗
BACKGROUND: Psoriasis is a prevalent cutaneous inflammatory disorder characterized by elevated keratinocyte inflammation. 5(S)-6(R)-7-trihydroxyheptanoic-acid-methyl-ester (BML-111), an established analogue of lipoxin A4...
BACKGROUND: Psoriasis is a prevalent cutaneous inflammatory disorder characterized by elevated keratinocyte inflammation. 5(S)-6(R)-7-trihydroxyheptanoic-acid-methyl-ester (BML-111), an established analogue of lipoxin A4, is known for its potent anti-inflammatory properties. However, the precise role of BML-111 within a murine psoriasis-like dermatitis model requires further clarification. This research aims to investigate the modulatory effects of BML-111 on inflammatory responses, the p38/mitogen-activated protein kinase (MAPK) signaling cascade, and T helper type 1 (Th1), Th2, and Th17 cell responses within the context of a murine psoriasis-like dermatitis model. METHODS: A psoriasis-like dermatitis model was established by applying 5% imiquimod (IMQ) cream to the backs of C57BL/6 mice, which were pretreated intraperitoneally with or without BML-111 prior to IMQ application. Hematoxylin-eosin staining was utilized to detect the pathological alterations of the murine dorsal skin tissue. Furthermore, the psoriasis area and severity index (PASI) scoring system was used to assess the dynamic cutaneous alterations in the mice. The levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin (IL)-1β, IL-6, IL-4, and IL-17A in the murine serum samples were quantified by means of enzyme-linked immunosorbent assays (ELISA). Western blotting was conducted to detect the proteins of TNF-α, IL-1β, IL-6, phospho-p38 (p-p38), and p38 in murine skin tissues. Lastly, a flow cytometry analysis was executed to evaluate the expression of peripheral blood Th1/Th2/Th17 cell subsets. RESULTS: BML-111 attenuated IMQ-induced pathological changes in skin tissue of psoriasis-like dermatitis mice. BML-111 treatment substantially reduced TNF-α, IL-1β, IL-6, IFN-γ and IL-17A levels and elevated IL-4 levels in serum and skin lesion tissues of IMQ-induced mice ( < 0.01, < 0.01, < 0.01, < 0.05, < 0.05, < 0.05, respectively). The ratio of Th1/Th17 cells in the peripheral blood of BML-111-treated mice was substantially diminished and the ratio of Th2 cells was substantially augmented ( < 0.05, < 0.01, < 0.001, respectively). Mechanistically, p-p38 protein level was substantially reduced in the skin tissues of BML-111-treated mice ( < 0.05). While, dehydrocorydaline (DHC, a p38/MAPK pathway agonists) reversed the reduction of p-p38 protein level induced by BML-111 treatment in psoriasis-like mice ( < 0.05). CONCLUSION: BML-111 modulates the p38/MAPK signaling pathway and Th1/Th2/Th17 cytokine response, and alleviates psoriasis-like dermatitis in mice.
Establishment of a Disease Model Using Patient-Specific Induced Pluripotent Stem Cells-Derived Trabecular Meshwork Cells in a Chinese Primary Open-Angle Glaucoma Mega-Pedigree.
Rong H, Luo Z, Tang M … +6 more , Tang J, Li K, Yang R, Fan Z, Sun N, Ge J
Discov Med · 2024 Oct · PMID 39463221 · Publisher ↗
BACKGROUND: Primary open-angle glaucoma (POAG) is one of the most common insidious blinding eye diseases. Understanding the pathogenic mechanisms of it is extremely important. It is accepted that POAG attacks specific oc...
BACKGROUND: Primary open-angle glaucoma (POAG) is one of the most common insidious blinding eye diseases. Understanding the pathogenic mechanisms of it is extremely important. It is accepted that POAG attacks specific ocular tissue, such as trabecular meshwork and optic nerve damage, which causes elevated intraocular pressure and optic nerve damage. This study aimed to develop a preliminary prediction model for this disease by establishing the patient-specific induced pluripotent stem cells (iPSCs)-derived trabecular meshwork cells (TMCs) (p-iPSCs-TMCs) in the largest POAG family named "GZ.1" in China and preliminarily analyze the pathogenic mechanisms. METHODS: Peripheral blood of patients in GZ.1 and healthy individuals not belonging to the family were collected and reprogrammed into iPSCs. Then, the iPSCs were differentiated into iPSCs-TMCs. Next, their morphology and function were compared. Finally, their pathogenic mechanisms were analyzed. RESULTS: The patient-specific iPSCs (p-iPSCs) and healthy individual-specific iPSCs (n-iPSCs) were all successfully generated. Their morphology was quite similar to each other. However, p-iPSCs-TMCs exhibited compromised morphology and function. p-iPSCs-TMCs displayed the morphology of heterogeneous distribution and accumulation in clusters, while n-iPSCs-derived TMCs (n-iPSCs-TMCs) showed a uniformly distributed and homogenous appearance. Moreover, p-iPSCs-TMCs showed greater cell apoptosis ( < 0.01), impaired proliferating ability (24-h and 48-h time points: < 0.05, 72-h and 96-h time points: < 0.001), production of reactive oxygen species ( < 0.05), and impaired phagocytosis ability than n-iPSCs-TMCs (24-h, 48-h, and 72-h time points: < 0.0001, 96-h time point: < 0.001). CONCLUSION: The p-iPSCs-TMCs can be successfully differentiated from peripheral blood, while the cells show impaired morphology and function compared with n-iPSCs-TMCs. Given this, p-iPSCs-TMCs can serve as an ideal disease model for POAG in GZ.1. Our study on the morphology and function of iPSCs-TMCs in GZ.1 may provide a valuable tool for elucidating the pathogenesis of POAG.
Focal Adhesion Kinase (FAK) and c-Src Dependent Signal Transduction in Cell Adhesion.
Katoh K
Discov Med · 2024 Oct · PMID 39463220 · Publisher ↗
This review predominantly acquaints the role of focal adhesion kinase (FAK) and cellular-Src (c-Src) in cell adhesion. Cell adhesion is a crucial phenomenon that causes the cells to interact with the extracellular matrix...
This review predominantly acquaints the role of focal adhesion kinase (FAK) and cellular-Src (c-Src) in cell adhesion. Cell adhesion is a crucial phenomenon that causes the cells to interact with the extracellular matrix (ECM) or with each other. There are different proteins involved in cell adhesion including cell adhesion molecules (CAMs)/receptors that are present on the cell surface and various cytoplasmic proteins. FAK and c-Src are two proteins in the cytoplasm, which serve as regulators of different proteins involved in cell adhesion. They activate talin, vinculin and paxillin in turn connect the integrins with the cytoskeleton and in this way strengthen the integrin interaction with ECM. FAK-Src signalling also modulates cell-cell adhesion by regulating actin interactions. Being a key modulator of cell adhesion, FAK and c-Src signalling are linked with different pathological conditions like cancer, cardiovascular diseases, and embryonic developmental disorders. Thus, comprehensive research into FAK-Src signalling is of great importance in the exploration of different signalling targets for therapeutic interpretations. Different inhibitors and antibodies against various cell adhesion proteins, such as FAK, c-Src, and integrins, have already been used in preclinical and clinical trials to treat a variety of diseases, including cancer and chronic inflammatory conditions. Furthermore, this review presents different challenges to FAK-Src and cell adhesion signalling targeted drug development, which include, cytotoxicity and cell resistance to the drug. Finally, this review remarks that FAK and c-Src are important regulators of cell adhesion and are linked to various pathologies, nevertheless, more comprehensive research on these proteins would be a significant step forward in the development of effective therapies for the diseases associated with them.
Therapeutic Potential of Photobiomodulation in Diabetic Complications.
Hadebe L, Houreld NN
Discov Med · 2024 Oct · PMID 39463219 · Publisher ↗
Diabetes mellitus (DM) and its associated complications, including diabetic kidney disease, neuropathy, and retinopathy, impose significant challenges on healthcare systems due to their high morbidity, mortality, and ass...
Diabetes mellitus (DM) and its associated complications, including diabetic kidney disease, neuropathy, and retinopathy, impose significant challenges on healthcare systems due to their high morbidity, mortality, and associated costs. Existing treatments often yield unsatisfactory clinical outcomes, underscoring the need for innovative approaches to mitigate debilitating effects on patients' health-related quality of life. Photobiomodulation (PBM) is a non-invasive treatment that utilizes specific wavelengths of light in the treatment of various medical complications associated with DM. The specific wavelength used during PBM is critical in determining the therapeutic outcomes for managing diabetic complications. This paper aimed to explore the therapeutic potential of PBM in the management of diabetic complications, focusing on blue, red, and near-infrared (NIR) wavelengths. Relevant literature from Google Scholar, PubMed and ClinicalTrials databases from inception to date was searched using the keywords 'photobiomodulation', 'diabetes', 'diabetic complications', 'wound healing', 'neuropathy', 'retinopathy', and 'chronic wounds'. Red and NIR wavelengths are commonly used for a range of complications, while blue light has primarily been explored for treating diabetic wounds due to its antimicrobial nature. PBM treatment parameters for the same diabetic complication vary across clinical trials and preclinical research, with minimal clinical trials conducted on most diabetic complications. This inconsistency hinders the establishment of standardized PBM parameters, particularly concerning the optimal application setting.
Vitamin D's Role in Cardiovascular Diseases.
Islam H, Hassaan SM, Islam R … +8 more , Islam T, Zaidi F, Rehman HU, Haque MMU, Turabee Z, Asim M, Ahmad I, Naveed AK
Discov Med · 2024 Oct · PMID 39463218 · Publisher ↗
This article explores the correlation between vitamin D levels and cardiovascular health, focusing on hypertension, atherosclerosis, and cardiac dysfunction. Cardiovascular diseases (CVDs) rank as the leading global caus...
This article explores the correlation between vitamin D levels and cardiovascular health, focusing on hypertension, atherosclerosis, and cardiac dysfunction. Cardiovascular diseases (CVDs) rank as the leading global cause of death, underscoring the significance of exploring vitamin D's potential role in maintaining a healthy cardiovascular system. It discusses vitamin D's mechanisms of action, including genomic and non-genomic pathways, and explores risk factors like smoking, obesity, and hypertension, linked to vitamin D deficiency. Additionally, it delves into its role in regulating the renin-angiotensin system, cardiac hypertrophy, and inflammation. The link between vitamin D supplementation and a lower risk of cardiovascular events, including hypertension, atherosclerosis, and heart failure, is considered. However, inconsistent results from supplementation trials call for further research to establish efficacy for cardiovascular health. In conclusion, the article emphasizes the importance of vitamin D for cardiovascular well-being and calls for comprehensive studies to explore its therapeutic potential in treating cardiovascular disease (CVD).
Gut-Liver Axis: Modulating the Gut Microbiota and Its Metabolic Products as a Potential Therapeutic Strategy for the Treatment of Hepatic Ischemia-Reperfusion Injury.
Wang J, Yun Y, Dong X … +6 more , Wang X, Ma H, Fang Q, Xia J, Tao P, Zhang D
Discov Med · 2024 Oct · PMID 39463217 · Publisher ↗
Hepatic ischemia-reperfusion injury (HIRI) is a major complication reported in various clinical scenarios such as liver transplantation (LTx), hepatectomy, and acute hepatic insult. This condition affects the restoration...
Hepatic ischemia-reperfusion injury (HIRI) is a major complication reported in various clinical scenarios such as liver transplantation (LTx), hepatectomy, and acute hepatic insult. This condition affects the restoration of hepatic functionalities post-LTx. Contemporary scientific inquiries have highlighted the involvement of intestinal microbiota and their metabolic by-products in the initiation and progression of HIRI. Perturbations in the gut microbiome, instigated by external stressors such as inflammatory processes, ischemic conditions, and reperfusion events, affect the biosynthesis of metabolites such as short-chain fatty acids (SCFAs), bile acids (BAs), and lipopolysaccharides (LPS). SCFAs can exert anti-inflammatory effects, modulate cellular apoptosis, and attenuate oxidative stress, thereby ameliorating hepatic injury. Other studies have shown that the intestinal microbiota confers hepatoprotective effects by modulating the host's immune response and synthesis of cytokines, controlling inflammation, and enhancing liver protection. This review comprehensively describes the mechanisms underlying the association of gut microbiota and its metabolites with hepatic disease and ischemia-reperfusion injury. The findings from recent studies investigating the gut-liver axis are reviewed to identify therapeutic avenues for the prevention and treatment of liver dysfunction and ischemia-reperfusion injury. In-so-doing, novel pathways and perspectives can be exploited to develop therapies for the control of inflammatory hepatic ischemia-reperfusion injury, particularly following liver transplantation or surgical intervention.
The Pathophysiology, Diagnosis and Management of Chronic Inflammatory Skin Diseases.
Tong LZ, Desai RM, Olsen R … +1 more , Davis M
Discov Med · 2024 Oct · PMID 39463216 · Publisher ↗
Atopic dermatitis, psoriasis, rosacea, seborrheic dermatitis, allergic contact dermatitis, and irritant contact dermatitis comprise a large proportion of chronic inflammatory dermatoses. This paper reviews the clinical p...
Atopic dermatitis, psoriasis, rosacea, seborrheic dermatitis, allergic contact dermatitis, and irritant contact dermatitis comprise a large proportion of chronic inflammatory dermatoses. This paper reviews the clinical presentations, pathophysiology, and therapeutics of inflammatory dermatoses, highlighting recent drug developments such as lebrikizumab for atopic dermatitis as well as deucravacitinib and spesolimab for psoriasis. Chronic inflammatory dermatoses significantly impact patient quality of life and contribute to substantial healthcare costs. Effective management of severe cases often requires systemic therapies and biological therapies. A thorough clinical evaluation with a tailored therapeutic approach is essential for delivering optimal care to individuals with chronic inflammatory skin diseases.
Role of Apolipoprotein E in Alzheimer's Disease Pathogenesis, Prognosis and Treatment.
Reiss AB, Housny M, Gulkarov S … +7 more , Hossain T, Locke B, Srivastava A, Pinkhasov A, Gomolin IH, Wisniewski T, De Leon J
Discov Med · 2024 Oct · PMID 39463215 · Publisher ↗
Alzheimer's disease (AD) is an incurable and progressive neurodegenerative disease with increasing prevalence worldwide. Previous trials of anti-amyloid and anti-tau immunotherapy indicate that additional research needs...
Alzheimer's disease (AD) is an incurable and progressive neurodegenerative disease with increasing prevalence worldwide. Previous trials of anti-amyloid and anti-tau immunotherapy indicate that additional research needs to be conducted on other mechanisms to find curative or disease-modifying therapy. This review focuses on apolipoprotein E (ApoE), a critical protein in brain lipid metabolism that acts specifically in the clearance and transport of lipids and cholesterol. The ApoE4 allele confers substantial gene dose-dependent risk of developing AD and lowers the age of onset of AD, although the mechanisms of influence remain incompletely understood. The other isoforms bring different levels of AD risk. ApoE2 is protective while ApoE3 is the most common isoform and is considered neutral. An overview is presented of the latest information on the role of ApoE in AD pathogenesis with an emphasis on pathways that are involved in AD development and interactions with crucial processes in different cell types in the brain. Elucidating the key interactions of ApoE with multiple aspects of brain function can be useful for designing novel ApoE-targeted therapeutic approaches.
Reaction Times in Modern Virology: "This is not a Drill".
Focosi D, Maggi F
Discov Med · 2024 Sep · PMID 39327255 · Publisher ↗
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of interest BA.2.87.1 has not driven any Coronavirus disease 2019 (COVID-19) pandemic wave. Nevertheless, it has served to test the reaction times...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of interest BA.2.87.1 has not driven any Coronavirus disease 2019 (COVID-19) pandemic wave. Nevertheless, it has served to test the reaction times of modern virology laboratories. In this commentary, we highlight how fast the reaction has been at characterizing this sublineage, leading at an unprecedented pace to almost as many papers as the number of viral sequences.
Antimicrobial Resistance: A Global Public Health Concern that Needs Perspective Combating Strategies and New Talented Antibiotics.
Algammal AM, Behzadi P
Discov Med · 2024 Sep · PMID 39327254 · Publisher ↗
Abstract loading — click title to view on PubMed.
METTL3 Regulates the Translation of Oncogene Myc through mA Modification and Promotes the Occurrence and Development of Cervical Cancer.
Ma Y, Shi H, Zheng W
Discov Med · 2024 Sep · PMID 39327253 · Publisher ↗
BACKGROUND: Cervical cancer (CC) is one of the major types of gynecological cancer, with a high global incidence and mortality rate. Methyltransferase-like 3 (METTL3), a key constituent of methyltransferase, plays a cruc...
BACKGROUND: Cervical cancer (CC) is one of the major types of gynecological cancer, with a high global incidence and mortality rate. Methyltransferase-like 3 (METTL3), a key constituent of methyltransferase, plays a crucial role in various biological processes. Still, only a rare report has been made on its involvement in the progression of CC. Therefore, this study aims to investigate the impact of METTL3 in CC and its molecular mechanisms. METHODS: Gene expression datasets about CC were obtained from the Gene Expression Omnibus (GEO) database, and the expression of and was analyzed. Cell viability was detected after knockdown in HeLa and SiHa cells, followed by cell counting Kit-8 (CCK-8) assays. The relative expression of and was detected via real-time quantitative PCR (qPCR) assays, and the protein expression was determined using Western blot. Meanwhile, cell invasion and migration capabilities were assessed utilizing transwell assays, and cell proliferation was detected using the EdU experiment. Furthermore, RNA methylation immunoprecipitation-qPCR detection was performed to determine the expression of after N-methyladenosine (mA) modification. RESULTS: Analysis of the GEO database indicated elevated expression of METTL3 and Myc in CC tissues. Patients with high METTL3 expression had shorter disease-free survival, and patients with high Myc expression had shorter overall survival. Following the knockdown of , there was a significant reduction in the viability, proliferation, invasion, and migration abilities of HeLa and SiHa cells. Besides, the expression of and mRNAs and proteins was greatly reduced. The level of mA decreased significantly after knockdown. CONCLUSIONS: plays an important role in regulating cervical cancer cells. promotes CC development through mA modification to regulate the expression of the oncogene .
A Comparison between Demyelinating and Omicron Variant Infection-Associated Optic Neuritis.
Zhang J, Wang L, Chen C … +7 more , Ren H, Jin M, Liu H, Yang B, Huang Z, Jiang L, Chen FK
Discov Med · 2024 Sep · PMID 39327252 · Publisher ↗
BACKGROUND: The connection between viral infection and the onset of demyelination has garnered considerable attention. Omicron, the most recent prevalent strain of the severe acute respiratory syndrome coronavirus 2 (SAR...
BACKGROUND: The connection between viral infection and the onset of demyelination has garnered considerable attention. Omicron, the most recent prevalent strain of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised concerns. Optic neuritis (ON) associated with Omicron infection and spontaneous demyelinating ON may manifest distinct disease progressions. This study aims to contrast the features of these two distinct etiologies of ON. METHODS: This case-control study comprised fifteen patients (21 eyes) diagnosed with Omicron infection-related ON and fifteen patients (24 eyes) with demyelinating ON serving as the control group. Clinical characteristics, cerebrospinal fluid (CSF) analysis, treatment protocols, and outcomes were compared between the two groups. RESULTS: The Omicron-infected group exhibited a higher incidence of pain upon ocular movement ( = 0.023) and peripapillary hemorrhages ( = 0.046). In CSF analysis, there was an elevation in white cell counts (WCCs) ( = 0.004), with lymphocytes being the predominant cell type in the Omicron-related ON group. However, oligoclonal bands (OCBs), indicative of intrathecal synthesis, were significantly lower and lagged behind those of the demyelinating ON group ( = 0.021). SARS-CoV-2 RNA was not directly detected in the CSF of the Omicron-related ON group, and the degree of WCC elevation was closely linked with peripapillary hemorrhages (odds ratio = 0.029, = 0.02). Additionally, the Omicron-related ON group displayed more pronounced ganglion cell loss following 3-month treatment ( = 0.02). CONCLUSION: Omicron-related ON is distinguished by more pronounced clinical symptoms and distinct CSF characteristics compared to spontaneous demyelinating ON. The absence of viral RNA sequence in the CSF of Omicron-associated ON supports the use of steroid monotherapy; however, varying treatment options and prognoses should be considered for these two types of ON.
Berberine Alleviates Sevoflurane Anesthesia-Induced Cognitive Dysfunction in Neonatal Mice via Regulating CREB1.
Wang H, Wu W, Zheng Q … +4 more , Yu F, Zhang H, Yu G, Huang L
Discov Med · 2024 Sep · PMID 39327251 · Publisher ↗
BACKGROUND: Sevoflurane has been shown to stimulate neurotoxicity and lead to cognitive impairment. Berberine is known for its role in regulating nervous system diseases, including cognitive dysfunction. This study aimed...
BACKGROUND: Sevoflurane has been shown to stimulate neurotoxicity and lead to cognitive impairment. Berberine is known for its role in regulating nervous system diseases, including cognitive dysfunction. This study aimed to investigate the effects of berberine on cognitive dysfunction induced by sevoflurane anesthesia and its potential mechanisms. METHODS: In the study, neonatal mice were subjected to sevoflurane anesthesia to induce cognitive dysfunction. The cognitive function of the neonatal mice was evaluated using the Morris water maze test, open field test, and tail suspension test. Enzyme-linked immunosorbent assay (ELISA) was utilized to assess the levels of inflammatory factors. Immunohistochemistry (IHC) was conducted to detect ionized calcium-binding adaptor molecule 1 (IBA-1)-positive cells and cleaved caspase-3-positive cells in the hippocampus of the neonatal mice. Western blotting was used to measure the levels of cyclic adenosine monophosphate (cAMP) response element-binding protein 1 (CREB1) in hippocampal tissues and neurons. Hippocampal neurons were isolated from the hippocampus of neonatal mice. These neurons were treated with berberine or subjected to cell transfection. The cell counting kit-8 (CCK-8) assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay were conducted to measure cell viability and apoptosis of hippocampal neurons . RESULTS: Berberine significantly attenuated sevoflurane-induced cognitive impairment and inflammation in neonatal mice ( < 0.05 or < 0.01). Additionally, berberine reduced sevoflurane-triggered neuronal apoptosis in the hippocampus of neonatal mice ( < 0.01). Sevoflurane markedly decreased CREB1 expression in the hippocampus of neonatal mice ( < 0.01), which was elevated by berberine treatment ( < 0.01). Mechanistically, sevoflurane significantly suppressed cell viability and promoted cell apoptosis of hippocampal neurons ( < 0.0001 or < 0.01), which were mitigated by berberine ( < 0.05, < 0.01, or < 0.001). Furthermore, berberine significantly elevated CREB1 expression in sevoflurane-treated hippocampal neurons ( < 0.01). The beneficial effects of berberine on cell viability and apoptosis in sevoflurane-treated hippocampal neurons were blocked by CREB1 depletion ( < 0.001). CONCLUSION: Our results demonstrated that CREB1 was significantly decreased in the hippocampus of sevoflurane-treated neonatal mice and in sevoflurane-treated hippocampal neurons . This decrease was mitigated by berberine treatment. Moreover, berberine improved sevoflurane anesthesia-induced cognitive impairment in neonatal mice by attenuating neuronal inflammation and apoptosis . The inhibitory effects of berberine on sevoflurane-induced cell apoptosis were reversed by CREB1 downregulation. These findings indicate that berberine protects against sevoflurane anesthesia-induced cognitive impairment by reducing apoptosis of hippocampal neurons, partially through increasing CREB1 expression.
Association of Microbleeds on Susceptibility-Weighted Imaging with Ferroptosis and Prognosis in Rabbits with Spinal Cord Injury.
Liu XZ, Wang BC, Shen KP … +2 more , Jin WJ, Zhao J
Discov Med · 2024 Sep · PMID 39327250 · Publisher ↗
BACKGROUND: Susceptibility-weighted imaging (SWI) is a common imaging technique used to identify cerebral microbleeds. Given that spinal cord injury (SCI) often creates an environment that favors ferroptosis, a type of c...
BACKGROUND: Susceptibility-weighted imaging (SWI) is a common imaging technique used to identify cerebral microbleeds. Given that spinal cord injury (SCI) often creates an environment that favors ferroptosis, a type of cell death driven by iron, this study aimed to explore the relationship between microbleeds on SWI and ferroptosis, and explore the effect of deferoxamine on SCI. METHODS: Thirty-six rabbits were divided into three groups: sham, SCI, and SCI with deferoxamine (DFO, a ferroptosis inhibitor) treatment (SCI+DFO). Following 48 hours of SCI modeling, the rabbits underwent magnetic resonance imaging (MRI) and SWI examinations. Ferroptosis markers and spinal cord tissue morphology were examined, and the modified Tarlov's score was used to assess neurological function. RESULTS: SWI analysis revealed that rabbits in the SCI group exhibited lower signal intensities and larger microbleed areas compared to the those in the SCI+DFO group ( < 0.05). The SCI+DFO group demonstrated significantly decreased iron and malondialdehyde (MDA) levels, coupled with increased glutathione (GSH) and glutathione peroxidase 4 (GPX4) levels, along with attenuated ferroptosis ( < 0.05). This group also displayed greater Neuronal Nuclei (NeuN) expression, Tarlov's scores, and neurological recovery rates (all < 0.05). A significant positive correlation was found between the microbleed area and iron content (r = 0.59, = 0.04), MDA (r = 0.75, = 0.01), and mitochondrial damage (r = 0.90, < 0.01). Conversely, a negative correlation was established between the microbleed area and GPX4 levels (r = -0.87, < 0.01), as well as neurological function recovery (r = -0.62, = 0.03). CONCLUSION: The extent of microbleeds on SWI following SCI is closely correlated with ferroptosis, and the inhibition of ferroptosis could improve neurologic function. These findings suggest that the area of microbleeds on SWI could potentially serve as a predictive marker for ferroptosis in spinal cord injury.
KLHDC8A Regulates M1/M2 Macrophage Polarization Through the PD-1/STAT3 Pathway to Promote Papillary Thyroid Cancer Development.
Peng Y, Wen M, Yu J … +2 more , He C, Yu J
Discov Med · 2024 Sep · PMID 39327249 · Publisher ↗
BACKGROUND: Papillary thyroid cancer (PTC) is one of the most frequent endocrine malignancies. Kelch domain containing 8A (KLHDC8A) is reported as an epigenetically driven oncogene, but the role of KLHDC8A in PTC is stil...
BACKGROUND: Papillary thyroid cancer (PTC) is one of the most frequent endocrine malignancies. Kelch domain containing 8A (KLHDC8A) is reported as an epigenetically driven oncogene, but the role of KLHDC8A in PTC is still unclear. This study aimed to explore the function of KLHDC8A in PTC progression. METHODS: KLHDC8A expression was analyzed by the Gene Expression Profiling Interactive Analysis (GEPIA) website, quantitative real-time PCR (qRT-PCR), and western blot. The viability of PTC cells (TPC-1 and BCPAP) was assessed by cell counting kit-8 (CCK-8) kit. A transwell assay was carried out to evaluate the invasion and migration of PTC cells. Macrophage polarization-associated markers were determined by qRT-PCR and western blot. Mice tumor xenograft models were established to analyze the role of KLHDC8A . Pathway-related proteins (programmed cell death protein 1 (PD-1) and signal transducer and activator of transcription 3 (STAT3)) were determined by western blot. RESULTS: GEPIA demonstrated that KLHDC8A was highly expressed in PTC ( < 0.05). Knockdown of KLHDC8A hindered cell viability, invasion, and migration of PTC cells ( < 0.0001). Additionally, KLHDC8A knockdown inhibited M2 polarization while promoting M1 polarization ( < 0.0001). Meanwhile, KLHDC8A silencing inhibited tumor growth in mice xenografted models ( < 0.0001). Moreover, the PD-1/STAT3 pathway was suppressed by KLHDC8A silencing ( < 0.01), and the STAT3 activator (colivelin) attenuated the inhibitory effects of KLHDC8A silencing on PTC progression ( < 0.01). CONCLUSIONS: Through and experiments, KLHDC8A silencing could restrain PTC cell viability, migration, and invasion, inhibit tumor growth, and promote M1 polarization via the PD-1/STAT3 axis, providing a new therapeutic idea for PTC clinical treatment.
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