Discovery Medicine

The Pathophysiology, Diagnosis and Management of Chronic Inflammatory Skin Diseases
Tong LZ, Desai RM, Olsen R and Davis M
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.
Vitamin D's Role in Cardiovascular Diseases
Islam H, Hassaan SM, Islam R, Islam T, Zaidi F, Rehman HU, Haque MMU, Turabee Z, Asim M, Ahmad I and Naveed AK
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, Wang X, Ma H, Fang Q, Xia J, Tao P and Zhang D
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.
Focal Adhesion Kinase (FAK) and c-Src Dependent Signal Transduction in Cell Adhesion
Katoh K
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 and Houreld NN
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.
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, Yang S and Zhang Q
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.
The Regulatory Effect of Remifentanil on JNK Signaling during Remission of Flap Ischemia-Reperfusion Injury
Feng W, Feng X and Wu S
The impact of remifentanil on hypogastric flap function following ischemia-reperfusion (I/R) injury remains largely unknown, limiting its potential clinical application in flap surgery. This study investigated the therapeutic effects of remifentanil on hypogastric flap I/R injury.
Alleviates Inflammatory Response, Apoptosis, and ECM Degradation in Osteoarthritic Chondrocytes by Stabilizing
Zhong F, Cen S, Long C, Teng L and Zhong G
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.
The Evaluation of Gastric Cancer Lymphovascular Invasion Using CT Volume Perfusion
Li Y, Huang L, Li L, Chen L, Chen P and Chen X
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.
Synergistic Inhibition of Colorectal Cancer Cells by Autocrine Motility Factor Peptide and Glycyrrhetinic Acid
Kim SG, Duong TV, Lee S, Ryu KJ, Kwon HK and Park HS
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.
Curcumin Alleviates Airway Inflammation in Cough-Variant Asthmatic Rats by Modulating M1/M2 Macrophage Polarization
Yang H, Xie J, Wang M, Tang X, Wang H and Rong K
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.
Sevoflurane Activates PI3K/AKT Signaling Pathway by Upregulating Expression to Attenuate Ischemia/Reperfusion Injury in Cardiomyocytes
Zhou RS, Xue XH, Bi Y, Yang TT, Zhang ZQ, Zhu HY and Wang Q
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.
Upregulation of MFAP5 Enhances COL1A1 Expression, Promoting Epithelial-Mesenchymal Transition in Gastric Cancer Cells
Shi Y, E J, Wu X and Wang F
Gastric cancer (GC) is one of the most common types of cancer. Earlier research has suggested an association of microfibril-associated protein 5 (MFAP5) and collagen type I alpha 1 (COL1A1) with the progression of various tumors. However, the specific roles and mechanisms of action of MFAP5 and COL1A1 in the context of GC are yet to be fully elucidated. Thus, the objective of this study is to investigate the functions of MFAP5 and COL1A1 in the epithelial-mesenchymal transition (EMT) of GC and to unravel the associated molecular mechanisms.
Propofol Ameliorates Sepsis-Induced Myocardial Dysfunction via Anti-Apoptotic, Anti-Oxidative Properties, and mTOR Signaling
Xie L, Zhao M, Zong L and Yue Y
Sepsis often leads to cardiomyopathy, contributing to increased mortality rates. 2,6-Diisopropylphenol (propofol), an anesthetic, has demonstrated efficacy in protecting cardiomyocytes from cell death caused by hypoxia and reoxygenation. This study examined the effects of propofol on sepsis-associated myocardial dysfunction and explored the underlying mechanism of action.
Role of Apolipoprotein E in Alzheimer's Disease Pathogenesis, Prognosis and Treatment
Reiss AB, Housny M, Gulkarov S, Hossain T, Locke B, Srivastava A, Pinkhasov A, Gomolin IH, Wisniewski T and De Leon J
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.
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, Tang J, Li K, Yang R, Fan Z, Sun N and Ge J
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.
HERV-Derived Syncytin-1 and Syncytin-2 as Sources of Linear and Discontinuous Epitopes in Antiphospholipid Syndrome: A Pivotal Computational Study
Di Palma L and Talotta R
To date, no studies have investigated the potential reactivation of human endogenous retroviruses (HERVs) in the pathogenesis of antiphospholipid syndrome (APS). HERV-derived syncytin-1 and syncytin-2 are localized in the plasma membrane of cells and physiologically expressed during pregnancy. The current study aimed to determine whether the epitopes of syncytins can trigger an immune response leading to APS in genetically predisposed individuals.
A Comparison between Demyelinating and Omicron Variant Infection-Associated Optic Neuritis
Zhang J, Wang L, Chen C, Ren H, Jin M, Liu H, Yang B, Huang Z, Jiang L and Chen FK
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.
Antimicrobial Resistance: A Global Public Health Concern that Needs Perspective Combating Strategies and New Talented Antibiotics
Algammal AM and Behzadi P
No abstract present.
METTL3 Regulates the Translation of Oncogene Myc through mA Modification and Promotes the Occurrence and Development of Cervical Cancer
Ma Y, Shi H and Zheng W
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.
Reaction Times in Modern Virology: "This is not a Drill"
Focosi D and Maggi F
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.