Sage Publications

International Journal of Immunopathology and Pharmacology

Published by SAGE Publications Inc

Online ISSN: 2058-7384

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Print ISSN: 0394-6320

Disciplines: Immunology

Journal websiteAuthor guidelines

Top-read articles

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Mechanism of action of lecanemab.
PRISMA flow diagram showing selection process of the studies included in this review.
Pharmacokinetic parameters of IV lecanemab 10 mg/kg, biweekly.
Description of trials and characteristics of trial participants.
Key characteristics of randomized clinical trials of lecanemab.
Novel anti-amyloid-beta (Aβ) monoclonal antibody lecanemab for Alzheimer’s disease: A systematic review

October 2023

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3,281 Reads

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30 Citations

Selia Chowdhury

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A new way of the Coombs test using flow cytometry-based assay to assess erythrocytes-bound IgG antibodies in the human and rabbit model

January 2025

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24 Reads

Aims and scope


International Journal of Immunopathology and Pharmacology is a peer-reviewed, open access journal publishing original papers describing research in the fields of immunology, pathology and pharmacology. The journal reflects both the experimental and clinical aspects of immunology as well as advances in the understanding of the pathology and pharmacology of the immune system.

Recent articles


INF-γ/TGF-β1-primed umbilical cord mesenchymal stem cells boost the T-lymphocytes activity: Modulation of CD25 expression and IL-6 secretion
  • Article
  • Full-text available

February 2025

Abdulrahman H Almaeen

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Heba M Saad-Eldien

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Hala Gabr

Background Mesenchymal stromal/stem cells (MSCs) have potent immunomodulatory abilities, particularly in a milieu of hyperactive immune system, through secreting a number of cytokines, growth factors, bioactive compounds and peptides, and by cell-cell contact. During viral infection, failure of immuno-neutralization of the viral particles, recruits T-lymphocytes (T-cells) that clear the virally-infected cells. MSCs greatly potentiate T-cells anti-viral activity. Objective The objective of this study is to assess the ability of the cytokine-primed MSCs to activated T-cells, towards an antiviral application. Method Human umbilical cord MSCs (UC-MSCs) were isolated from Wharton Jelly of a consented donor. UC-MSCs were primed with interferon (INF)-γ and transforming growth factor (TGF)-β1. Peripheral blood T-cells were isolated using mini-max and CD3+ population was purified using anti-CD3 immuno-magnetic beads. Naïve or primed MSCs were co-cultured with naïve and phytohemagglutinin (PHA)-activated CD3+ T-cells. T-cell activation was evaluated by changes in their rate of proliferation by cell count, flowcytometric immuno-phenotyping for CD25 expression, and IL-6 secretion in the conditioned medium. Results The findings revealed that CD3+ T-cells count nonsignificant differed comparing the five experimental groups; Naïve MSCs, Naïve T cells, coculture with naïve MSCs, coculture with primed MSCs, and upon phytohemagglutinin-activation, despite a nonsignificant reduction of proliferation in the last two groups’ coculture. Only the coculture with the primed MSCs showed significant activation of T-cells assessed as CD25 expression compared to the other groups (p < 0.001 and p = 0.002, respectively). The undetectable levels of IL-6 in the conditioned medium of naïve MSCs, turned markedly high after their cytokine-priming (p < 0.001), reaching nonsignificant difference compared to naïve T-cells. Compared to naïve MSCs, naïve T-cells secreted considerable amounts of IL-6 (p < 0.001). Incubation of naïve MSCs with phytohemagglutinin-activated T-cells further the secretion of IL-6, to a level significantly higher than all of the aforementioned three groups; naïve MSCs, naïve T-cells and primed MSCs (p < 0.001, p = 0.0194, and p < 0.001, respectively). However, coculture of the cytokine-primed MSCs with phytohemagglutinin-activated T-cells dampened IL-6 secretion to a level that was significantly lower than that observed with naïve MSCs-phytohemagglutinin-activated T-cells coculture (p < 0.001). Conclusion The cytokine-primed UC-MSCs significantly upregulated CD25+ expression on T-cells, while hindering IL-6, without affecting their proliferation rate. This may point to potentially stronger antiviral effects, while alleviating the viral infection-induced cytokine storm.


Myricetin enhances keratinocytes differentiation via TRPV4 channel activation in mouse primary keratinocytes

February 2025

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2 Reads

The skin serves as the primary defensive barrier of the human body against external stimuli and damage. Keratinocytes, which are the predominant cell type in the human epidermis, undergo a differentiation process that is crucial for the formation of the skin barrier. Myricetin, a dietary flavonoid present in various fruits and vegetables, is known to play a significant role in maintaining intestinal barrier function; however, its impact on the skin barrier remains inadequately understood. Consequently, this study investigates the effects of myricetin on the differentiation of epidermal keratinocytes and the integrity of the skin barrier. Differentiation of primary mouse keratinocytes was induced using 1.8 mM CaCl2. tudy demonstrated that myricetin effectively suppresses cell proliferation and induces both cell cycle arrest and calcium ion (Ca²⁺) influx, without influencing apoptosis. Concurrently, myricetin enhances the expression of differentiation markers, including K10, TGase1, Filaggrin, and Involucrin, and facilitates the formation of tight junctions. Upon examining the underlying mechanisms, we discovered that myricetin activates the TRPV4 channel, and the promotion of keratinocyte differentiation by myricetin is contingent upon the activation of this channel. In summary, these findings suggested that myricetin could promote keratinocytes differentiation and have well-established skin barrier protective function.


Baicalein protects against heart failure by improving mitochondrial dysfunction and regulating endoplasmic reticulum stress to reduce apoptosis in vitro and in vivo

February 2025

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3 Reads

Objectives Baicalein, a flavonoid derived from the roots of Scutellaria baicalensis Georgi, demonstrates multifarious pharmacological effects due to its high antioxidant activity. However, the latent mechanisms remain insufficiently resolved. In the present research, we evaluated the therapeutic effects of baicalein on isoprenaline (ISO)-induced heart failure and investigated the possible underlying mechanisms. Methods Toxicity was analyzed in zebrafish embryos and mouse atrial myocytes HL-1. The MTT assay was used to evaluate the effectiveness of baicalein. DCFH-DA was used as a fluorescence probe to detect intracellular reactive oxygen species (ROS). Superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) levels were measured using SOD, MDA and GSH-Px commercial kits. Adult BALB/c mice were randomized into six groups of ten animals each. Cardiac function was analyzed by echocardiographic images. Structural changes were analyzed by hematoxylin & eosin (HE) staining, Masson staining and TUNEL staining. The mechanism of baicalein was investigated by analyzing relative signaling pathways through western blotting. Results Our studies show that baicalein both significantly reduces ISO-induced oxidative stress, apoptosis and cardiac fibrosis in vitro and vivo, this phenomenon was related to mitochondrial fusion/fission balance and inhibiting GRP78/CHOP pathway. Conclusions Our results suggested that baicalein controls mitochondrial fusion/fission balance and inhibits GRP78/CHOP pathway, thus exerting therapeutic effects in ISO-induced heart failure in HL-1 cells and BALB/c mice. These results suggested that baicalein may be a potential therapeutic agent for heart failure.


Clinical and immunological findings of patients with suspected APS (N = 133).
Cross-tabulation demonstrating positivity of anti-β2GPI, aCL IgG/IgM, and LA.
Association of anti-phospholipid antibodies with clinical manifestations.
Unveiling the clinical spectrum: Exploring the role of anti-β2glycoprotein-1 antibodies (anti-β2GPI) in antiphospholipid syndrome suspects

February 2025

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3 Reads

Objectives The objectives of this study were to determine the prevalence of anti-β2glycoprotein-1 antibodies (anti-β2GPI) in Pakistani patients clinically suspected to have antiphospholipid syndrome (APS) and assess their association with clinical manifestations. Introduction The antiphospholipid syndrome (APS) is a complex disorder characterized by recurrent thrombotic and obstetric complications. Methods An analytical cross-sectional study was conducted at Aga Khan University Hospital from January to June 2022, after obtaining ethical approval (ERC ID: 2021-6404-19580). A total of 133 patients aged 18–60 years, clinically suspected of having APS based on the updated international consensus (Sydney) classification criteria, were recruited. Anti-β2GPI antibodies were tested using the same blood samples provided for aCL testing, with verbal consent. Demographic, clinical, and biochemical data were collected via a structured questionnaire, while information on lupus anticoagulant testing was retrospectively obtained from prior records. Results The study included 120 females (90.2%) and 13 males (9.8%) with a mean age of 31.3 ± 8.8 years. Predominant clinical manifestations included unexplained miscarriages at >10 weeks of gestation (n = 77/120 female, 64.2%), while deep venous thrombosis (DVT) was a common non-obstetric clinical feature (n = 18/133, 13.5%). The median level of anti-β2GPI was 2.12 U/ml (1.34–7.04) and 7.5% (n = 10) were positive. Of the 10 positive patients, 2 displayed positive anti-β2GPI while concurrently testing negative for other aPL antibodies. A significant association was identified between the presence of anti-β2GPI and the occurrence of DVT and other venous thromboembolic events (VTE). Conclusion This study highlights the prevalence and diagnostic utility of anti-β2GPI in Pakistani patients suspected of APS, identifying cases missed by other aPL tests and showing significant associations with thrombotic manifestations like DVT and VTE. However, the cross-sectional design, lack of confirmatory testing, and absence of locally derived cut-offs limit causal inferences.


Aurora-A promotes lenvatinib resistance experimentally through hsa-circ-0058046/miR-424-5p/FGFR1 axis in hepatocellular carcinoma

February 2025

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7 Reads

Objective This study aimed to investigate whether the dysregulation of Aurora-A is involved in lenvatinib resistance in hepatocellular carcinoma. Methods Bioinformatics tools and drug sensitivity assays were used to investigate the association between Aurora-A expression level and lenvatinib resistance in hepatocellular carcinoma cell lines. Cell function experiments had performed after treatment with lenvatinib and/or a selective Aurora-A inhibitor (MLN-8237). CircRNA microarray, RIP, RNA pull-down, and dual-luciferace reporter assay were performed to identify the downstream molecular mechanism of Aurora-A dysregulation. Results Aurora-A expression was positively correlated with lenvatinib resistance in hepatocellular carcinoma cells. The Aurora-A selective inhibitor MLN-8237, in combination with lenvatinib, synergistically inhibited hepatocellular carcinoma cell proliferation in vitro and vivo, suggesting the Aurora-A might be a potential therapeutic target for lenvatinib resistance. Mechanistically, Aurora-A induced FGFR1 expression through the hsa-circ-0058046/miR-424-5p/FGFR1 axis. Aurora-A promotes lenvatinib resistance through hsa-circ-0058046/miR-424-5p/FGFR1 axis in hepatocellular carcinoma cells. The simultaneous inhibition of FGFR1 by the Aurora-A inhibitor MLN-8237 and lenvatinib overcame lenvatinib resistance in hepatocellular carcinoma cells. Conclusion Collectively, our findings indicate that Aurora-A promotes lenvatinib resistance through the hsa-circ-0058046/miR-424-5p/FGFR1 axis in hepatocellular carcinoma (HCC) cells. These results suggest that Aurora-A may serve as a therapeutic target for HCC patients exhibiting lenvatinib resistance. Furthermore, the combination of lenvatinib and MLN-8237 shows potential for clinical trials aimed at overcoming lenvatinib resistance.


Rapamycin ameliorates inflammatory pain via recovery of autophagy flux mediated by mammalian target of rapamycin (mTOR) signaling pathway in the rat spinal cord

February 2025

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4 Reads

Objective This study aimed to investigate the effect of rapamycin on inflammatory pain in rats. Introduction Inflammatory pain is a kind of pathological pain caused by inflammatory mediators or factors such as TNF-α (Tumor Necrosis Factor-α), IL-1β (Interleukin-1β), and IL-6 (Interleukin-6). NSAIDs and opioid analgesics are commonly used for relieving inflammatory pain, but the side effects limit their clinical application. New drugs based on new mechanisms for inflammatory pain are urgently needed. Autophagy is an evolutionarily conserved homeostatic process for lysosomal degradation of intracellular components. Recent reports indicate the involvement of autophagy in the development and maintenance of neuropathic pain, but the role of autophagy in inflammatory pain still needs to be explored. Methods The pain-related behaviors of rats were studied by paw withdrawal threshold and paw withdrawal latency. The autophagy level of the rat spinal cord was detected by western blots. The concentrations of TNF-α, IL-1β, and IL-6 were detected by ELISA. Results We found that the paw withdrawal threshold and paw withdrawal latency were both significantly decreased after CFA (Complete Freund’s Adjuvant) injection, accompanied by the activation of mTOR signaling pathway and the inhibited autophagy flux in the spinal cord. And inflammatory cytokines were increased in the spinal cord after CFA injection. Then, we studied the effect of rapamycin on CFA-induced inflammatory pain in rats, and found that rapamycin restored the autophagy flux and significantly reduced mechanical allodynia and thermal hyperalgesia. In addition, rapamycin significantly decreased the levels of TNF-α, IL-1β, and IL-6 after CFA injection in the spinal cord. Conclusion Our results suggested that rapamycin might be a promising candidate for the treatment of inflammatory pain by restoring the autophagy flux in the spinal cord.


Circulating cell-free DNA as a potential biomarker for prediction of disease activity and prognosis among Egyptian rheumatoid arthritis patients

January 2025

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12 Reads

Cell-free DNA (cfDNA) has emerged as a potential biomarker for assessing disease activity and prognosis in rheumatoid arthritis (RA). However, the association between cfDNA levels and the established RA markers of inflammation and disease severity remains unclear. The current study aimed to detect plasma levels of cfDNA in patients with RA and to investigate their association with RA activity indicators (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity score-28 (DAS28)), prognostic markers (rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA)), and the musculoskeletal ultrasonographic (US7) scores. This controlled cross-sectional study included 108 RA patients and 108 healthy controls. Plasma levels of cfDNA were quantified by real-time PCR using ALU repeats. Levels of ESR, CRP, RF, and ACPA were measured using routine laboratory assays. Synovial inflammation and joint damage evaluation was performed using the US7 scoring system. Plasma levels of cfDNA were higher in RA patients than controls (P < 0.001) and significantly increased with higher DAS28 scores among all RA activity groups. Also, cfDNA levels were significantly positively correlated with ESR, CRP, RF, and ACPA levels (P-values <0.001). Regarding US7, cfDNA was significantly positively correlated with synovitis and erosion scores (P-values <0.05) but did not correlate significantly with tenosynovitis scores (P-values >0.05). In addition, plasma cfDNA was significantly higher in seropositive RA patients than in seronegative patients (P = 0.007). The odds ratio for cfDNA as a risk factor for erosions was 2.254. This study revealed that cfDNA levels are elevated in RA patients and positively associated with disease activity indicators and prognosis markers. Further research is warranted to validate these findings in larger cohorts and explore the clinical implications of cfDNA measurement in RA management.


Analysis of total RNA as a potential biomarker of Parkinson’s disease in silico

January 2025

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14 Reads

Knowledge about total RNA molecules in Parkinson’s disease is limited. This gene expression profiling study was conducted with a preclinical experimental design using a mouse model to examine the molecular-biological characteristics and the pathological implication of total RNA gene interaction in Parkinson’s disease in silico. In silico analysis of total RNA molecules, the Gene Expression Omnibus database, published results, and preliminary findings of available patient samples apply. The potential signaling network and the effect of the interaction of molecules with total RNA was predicted and confirmed. The research consists of four parts. At first, we analyzed the control and MPTP groups. In the second part, we analyzed FVB-N control and MPTP. In the third part, we analyzed controls. In the fourth part, we analyzed MTPT separately. The constructed network contains total RNA, where the Kyoto Encyclopedia of Genes and Genomes database analysis showed that genes from the signaling pathway are involved in the development and complications of Parkinson’s disease in male and female rats. Identified total RNA and genes are involved in altered signaling. There is direct interconnection and interdependence of interactions in the signaling network. Results identified the significant total-RNA molecules of the signaling pathway that connect other molecules. In silico analysis shows upregulated and downregulated genes in Parkinson’s disease rats. Preliminary data shows that total RNA molecules interact with other genes, and they are applicable in Parkinson’s disease course monitoring, shedding light on how factors impact the expression of genes and offering strategies for management.


A new way of the Coombs test using flow cytometry-based assay to assess erythrocytes-bound IgG antibodies in the human and rabbit model

January 2025

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24 Reads

The Coombs test is important in hematology for detecting erythrocyte-bound IgG antibodies or in serm through agglutination methods, but its sensitivity and specificity are limited. Flow cytometry provides a more precise and sensitive alternative for quantitatively assessing RBC-bound IgG antibodies. This assessment is crucial for evaluating the risk of hemolytic reactions and ensuring safe transfusions. This study aimed to explore a new method for the detection of RBC-bound IgG antibodies in rabbits following the injection of human red blood cells. Rabbits serum treated with 2-mercaptoethanol (2-ME) were serially diluted at ratios of 1:1, 1:2, 1:4, 1:8, 1:16, 1:32, 1:64, 1:128, 1:256, 1:512, 1:1024, and 1:2048. These diluted samples were then reacted with O-type red blood cells (RBCs). Serum samples from healthy individuals were used as the control group. The tubes were kept in a water bath at 37°C for 30 min incubation. After incubation, the samples were analyzed using a flow cytometry-based assay. Additionally, the traditional Coombs tube method was used and the strength of IgG antibody and agglutination was graded. The results were analyzed using a flow cytometry-based assay, and the agglutination strength was determined using the Coombs traditional tube method for RBC-bound IgG antibodies. A significant difference was found between the rabbits serum and normal control groups (p < 0.001). IgG titers increased significantly after 1 month of immunization in rabbits compared to the titers observed after 1 week. The serum Anti-D stability test showed a coefficient of variation (CV) of 7.74%, indicating good stability of the test results. In this study, we concluded that the flow cytometry-based assay for detecting RBC-bound IgG antibodies was accurate, sensitive, and had positional value in clinical laboratories and research centers.


Prisma flow chart summary of selection process.
Thematic mechanism of SARS-CoV2 induced cytokine storm in infected lungs. 31
Source: Corrado Pelaia, Caterina Tinello, Alessandro Vatrella, Giovambattista De Sarro and Girolamo Pelaia. “Lung under attack by COVID-19-induced cytokine storm: pathogenic mechanisms and therapeutic implications.” Therapeutic Advances in Respiratory Disease, vol. 14. 2020, https://doi.org/10.1177/1753466620933508. Licensed under [https://creativecommons.org/licenses/by-nc/4.0/].
IL: interleukin; IFN: interferon; COVID-19: coronavirus disease 2019; ARDS: acute respiratory distress syndrome; Th: T helper; GM-CSF: granulocyte macrophage-colony stimulating factor; SARS-CoV-2: severe acute respiratory syndrome coronavirus-2; ACE2: angiotensin-converting enzyme 2; APC: Antigen presenting cells.
Pathophysiological mechanism alveolar epithelial and vascular endothelial injury by SARS-CoV2 infection.
(Left) SARS-CoV-2 enter into the host through the host alveolar epithelium that depends mainly on TMPRSS2 (transmembrane serine protease 2) and ACE2 (angiotensin-converting enzyme-2) expression. Initially, the CoV binds via spike glycoprotein on alveolar type 2 (AT2) cells to ACE2, initiating the virus and host cell membranes fusion. At the same time, TMPRSS2 cleaves the ACE2 resulting in the enhancement of cell surface clearance of ACE2 and spike glycoprotein of the virus into S1 and S2 subunits leading to the uncoating and viral genome release into the cytoplasm. This is followed by the viral replication, viral core proteins (S, M, N, and E) translation, viral particles assembly in the ER-Golgi-intermediate compartment and finally small wallet vesicle packaging to cell membrane for exocytosis. The dysfunction or loss of AT2 cell induced by the SARS-CoV-2 infection is harmful to injured lungs for a variety of reasons: (1) increased risk of atelectasis and alveolar collapse due to the decrease in surfactant, (2) impaired replacement of alveolar type 1 (AT1) cell caused by the decrease in AT2 progenitor cells, (3) release of viral induced cytokine by AT1/AT2 cells resulting in the infiltration of alveolar interstitial immune cell and capillary leak. (Right) Endothelial cells infection by SARS-CoV-2 might occur from alveolar or luminal interstitial side, triggering the cytokine release from the endothelium resulting in increased capullary permeability, thus allowing the extravasation and adhesion of monocytes and neutrophils into the alveolar interstitial space. PAMPs and DAMPs (Pathogen and damage associated molecular patterns) stimulated the macrophages and neutrophils to secret cytokines, complement and procoagulants, promoting the attack and clearance of virus, but induces further injury to the vessels increasing the risk for thrombosis. Intravascular thrombus formation is promoted by several factors which include: (1) Complement and NETs (neutrophil extracellular traps) secretion mediated by neutrophil increases platelet aggregation. (2) Secretion of TF (tissue factor) by macrophages and endothelial cells triggered by the cytokines stimulates the coagulation pathways and enhances the formation of fibrin clot. (3) Decreased secretion of anticothrombotic mediators, like TFPI (Tissue Factor pathway inhibitor) and AT (antithrombin) caused by endothelial damage. (4) Megakaryocytes residing in the lungs produce the locally available platelets for aggregation. (5) ACE2 overactivation increases the PAI1 (plasminogen activator inhibitor 1) production, decraesing the activation of plasmin and fibrinolysis.
Mechanism of COVID-19 associated pulmonary fibrosis. 56
Source: Zhen Zheng, Fei Peng, Yong Zhou. “Pulmonary fibrosis: A short- or long-term sequelae of severe COVID-19?” Chinese Medical Journal Pulmonary and Critical Care Medicine. Vol. 2023. No. 1. 2023, https://doi.org/10.1016/j.pccm.2022.12.002. Licensed under [http://creativecommons.org/licenses/by-nc-nd/4.0/]).
MV: Mechanical ventilation; TGFβ1: Transforming growth factor -β1; Ang-(1-7): Angiotensin 1–7; CTGF: Connective tissue growth factor; Ang II: Angiotensin II; ACE2: Angiotensin-converting enzyme 2; RGD: Arginine (Arg)-glycine (Gly)-aspartic acid (Asp); TNF: Tumor necrosis factor; IL: Interleukin; Gal-3: Galectin-3.
An overview of selected clinical trials registered for COVID-19 treatment. 79 .
COVID-19: A threat to the respiratory system

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causes acute coronavirus disease-19 (COVID-19) that has emerged on a pandemic level. Coronaviruses are well-known to have a negative impact on the lungs and cardiovascular system. SARS-CoV-2 induces a cytokine storm that primarily targets the lungs, causing widespread clinical disorders, including COVID-19. Although, SARS-CoV-2 positive individuals often show no or mild upper respiratory tract symptoms, severe cases can progress to acute respiratory distress syndrome (ARDS). Novel CoV-2 infection in 2019 resulted in viral pneumonia as well as other complications and extrapulmonary manifestation. ARDS is also linked to a higher risk of death. Now, it is essential to develop our perception of the long term sequelae coronavirus infection for the identification of COVID-19 survivors who are at higher risk of developing the chronic lung fibrosis. This review study was planned to provide an overview of the effects of SARS-CoV-2 infection on various parts of the respiratory system such as airways, pulmonary vascular, lung parenchymal and respiratory neuromuscular system as well as the potential mechanism of the ARDS related respiratory complications including the lung fibrosis in patients with severe COVID-19.


Curcumin suppresses metastasis, invasion, and proliferation in osteosarcoma cells by regulating the EGFR/Src signaling axis

December 2024

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12 Reads

We explored the biological mechanisms by which curcumin (Cur) confronts osteosarcoma (OS) tumorigenesis and potential drug gene targets based on network pharmacology and in vitro cell experiments. Cur has been recognized for its significant role in combating various types of tumors. However, the intrinsic molecular mechanisms through which it affects OS remain uncharted. In this study, we performed network pharmacology methods including protein-protein interaction (PPI) and core target screening, Functional Enrichment Analysis and Network Construction, Molecular Docking, which obtained the potential target of Cur. Meanwhile, cell experiments (wound healing assay, Transwell assay, Western blots, immunofluorescence, et al.) in vitro were performed to verify the targets, and reveal the biological mechanisms. A total of 18 hub genes were identified through our network pharmacological analysis. In vitro studies show that Cur inhibits the proliferation, migration, invasion capabilities of MG63 and U2OS cells. Western blot reveals a down-regulation of p-PI3K, PI3K, p-Akt, Akt, EGFR, Src, p-Src (Tyr416) and STAT3 expression when treated with Cur. Additionally, Cur upregulated epithelial proteins (E-cadherin and Occludin) while decreasing the expression of the mesenchymal protein (N-cadherin). In addition, Cur treatment decreases the EGFR/Src signaling pathway in the presence of active Src overexpression. Cur inhibits the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) by down-regulating EGFR/Src signaling axis, also resulting in coordinated weakening of its downstream regulatory genes, including Akt, STAT3, Bcl2, ERK1/2, among others signal axis (PI3K/Akt signaling pathway).


Hesperidin ameliorates thioacetamide-induced liver fibrosis via antioxidative and anti-inflammatory mechanisms targeting TGF-β/α-SMA pathways in rats

December 2024

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16 Reads

Our study intended to explore Hesp antioxidant and anti-inflammatory effects against TAA hepatic fibrosis in rats. Hesperidin (Hesp), is a pharmacologically active flavonoid, found abundantly in citrus species. Our present research attempts to inspect the potential hepatoprotective role of Hesp against thioacetamide (TAA)-induced hepatic fibrosis. Thirty-two male albino rats were split up into four equal groups, each with eight rats: Cont group was treated with ip saline. Every other day, the TAA group was injected 100 mg/kg BW ip TAA, Hesp group received every day oral Hesp 200 mg/kg BW as well as TAA + Hesp group received both therapies (TAA, Hesp) for eight successive weeks. Hesp in TAA treated group reduces ALT, AST, and ALP activities, total, direct bilirubin, total cholesterol, and triglycerides, meanwhile TP, Alb, globulin, A/G ratio levels were insignificantly differed. The antioxidant capacity of Hesp was pronounced by a marked reduction in MDA level. While the antioxidant markers (SOD, CAT, GSH) were insignificantly changed after Hesp treatment. A strong significant correlation in treated rats between fibrosis score and CD34 and FGF23 gene expression. Liver sections from dual-treated rats showed a moderately decreased hepatic lesion and the dense, bluish-stained fibrous tissue by Masson’s trichrome. Elevated gene expressions of CD34 and FGF23 after TAA hepatotoxicity were diminished by the antifibrotic effect of Hesp. Also, immunohistochemical expression showed reduction of TGF-β and α-SMA in hepatocytes in the dual therapy group. Hesp possesses a potent antioxidant, and antifibrotic activities against TAA induced hepatic fibrosis by modulating TGF-β/α-SMA pathways.


The process of bibliographic retrieval in PubMed.
Schematic illustration of microglial regulations of central post-stroke pain via multiple mechanisms at the supraspinal and spinal levels, which was categorized and described in detail in Table 1.
Recent findings of microglial signaling in CPSP mediation.
Progress of research into microglial mediation of central post-stroke pain

Central post-stroke pain (CPSP) is a chronic neuropathic pain syndrome that commonly occurs after cerebral stroke, and it severely impairs the daily activities of stroke patients. A number of fundamental and clinical studies support the theory that CPSP is mainly caused by ischemic and hemorrhagic injury of the spinal-thalamic-cortical neural pathway. However, the underlying reasons of CPSP genesis and development are far from clear. In recent years, the majority of research focused on microglia, the main resident immune cells of the central nervous system, which highlighted its critical role in the regulation of CPSP. The present article concentrated on exciting discoveries of microglia in mediating CPSP from the perspectives of their bioactive factors, cellular receptors, and signaling pathways, in order to offer a convenient and easy-to-digest overview. In addition, the potential and challenges of several agents in clinical translation of CPSP treatment was discussed based on recent preclinical studies.


Use of CRP/lymphocyte ratio as a predictor of treatment selection and mortality in COVID-19 patients in the intensive care unit

December 2024

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20 Reads

This study primarily aimed to examine the significance of the C-reactive protein to lymphocyte ratio (CLR), a key marker of inflammation, in relation to the disease progression and management of COVID-19 patients admitted to the intensive care unit (ICU). A total of 464 patients aged 18 years or older, diagnosed with COVID-19 and admitted to the ICU between April 1, 2021, and February 1, 2022, were included in the study. Sociodemographic, laboratory, radiological, and clinical data were collected for each patient. The cohort was then divided into two groups—those who survived and those who did not—and analyzed accordingly. Among the patients included in the study, 58.2% were male, and the mean age was 62.39 ± 15.65 years. The mortality rate was 42%. The analysis revealed that the need for high-flow oxygen and mechanical ventilation increased the risk of death by 9.64 times. Furthermore, for each 1-point increase in the SOFA Score, Charlson Comorbidity Index, and Nutric Score, the risk of death increased by 1.27, 1.18, and 1.40 times, respectively. Intravenous immunoglobulin, administered to a select group of patients, reduced the risk of death by 23.8 times. The optimal threshold value for CLR was identified as 103.05, with values above this increasing the risk of death by 1.84 times. Critically ill patients with CLR values exceeding the identified threshold should receive more intensive monitoring and timely adjustments in treatment. Given that CLR is a simple, accessible, and cost-effective marker, it holds particular value in managing aggressive diseases like COVID-19.


Pancreatic tissue impairment and recovery in SAP rats. (a) H&E staining pictures in CON group of rats. (b) H&E staining pictures in SAP group of rats. (c) H&E staining in SAP+PHI group of rats. (d) Pancreatic histological scores in each group of rats. (e–f) Serological indicators in each group of rats. Data shown are means ± SEM. Compared with CON group. ****P < 0.0001; compared with SAP group, #P < 0.05, ####P < 0.0001.
Autophagy impairment and recovery. (a- 1-9) Immunohistochemistry analysis of LC3-II, LAMP-2 and p62 protein expression levels in each group of rats (400×). (b–d) Quantitative analysis of protein expression in each group of rats. (e) Transmission electron microscope observation in CON group of rats (15000×). (f) Transmission electron microscope observation in SAP group of rats (15000×). (g) Transmission electron microscope observation in SAP+PHI group of rats (15000×). Data shown are means ± SEM. Compared with CON group. *P < 0.05, **P < 0.01, ****P < 0.0001 ; compared with SAP group, #P < 0.05, ####P < 0.0001.
Protein expression of the PI3K/Akt/mToR signalling pathway. (a) Western blot analysis of p-PI3K, p-Akt, p-mToR, PI3K, Akt and mToR protein expression levels in each group of rats. (b–g) Quantitative analysis of protein expression in each group of rats. Data shown are means ± SEM. Compared with CON group. **P < 0.01, ***P < 0.001. Compared with SAP group, #P < 0.05, ##P < 0.01.
Immunohistochemical quantification analysis table.
Phillygenin rescues impaired autophagy flux by modulating the PI3K/Akt/mToR signaling pathway in a rat model of severe acute pancreatitis

December 2024

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4 Reads

To investigate the mechanism of pancreatic alveolar cell autophagy in rats with severe acute pancreatitis (SAP) by phillygenin (PHI) based on the PI3K/Akt/mToR pathway. Rats were randomly divided into control group (CON group), SAP model group (SAP group) and PHI treatment group (SAP+PHI group), with 10 rats in each group. 5% sodium taurocholate was injected retrogradely into the biliopancreatic duct to establish a SAP rat model, and PHI was injected intraperitoneally into the pancreas after successful establishment of the model. The colorimetric assay was used to determine serum amylase and lipase activity levels. Pancreatic morphology and histological changes were assessed by H&E staining. Autophagy-related indices were determined by immunohistochemistry: LC3-II, P62, LAMP. Autophagy pathway-related indices were determined by western blotting assay: p-PI3K, PI3K, p-Akt, Akt, p-mToR, mToR. Autophagy vesicle alteration. Compared with the SAP group, the SAP+PHI group showed a decrease in amylase, lipase and pathological score, an increase in the expression of LAMP-2, and a decrease in the expression of p62, p-PI3K, p-Akt and p-mToR, with a statistically significant difference (p < 0.05). Electron microscopy showed that autophagic flux was restored and accumulated autophagic vehicles were relatively reduced by PHI intervention. PHI can rescue the impaired autophagic flux by inhibiting the PI3K/Akt/mToR pathway, allowing abnormal autophagic vesicles to complete autophagy to protect the rat.


Calcitriol ameliorates cisplatin-induced hepatorenal toxicity via regulation of Nrf2-Mrp2/p38 MAPK signaling in mice

December 2024

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8 Reads

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1 Citation

Despite being one of the most frequently used chemotherapy agents, cisplatin exhibits substantial hepatorenal injury by triggering oxidative stress, inflammation, and apoptosis pathways. The current investigation studied the possible protective effects of calcitriol on cisplatin-induced hepatorenal toxicity. Mice were divided randomly as follows: control group, calcitriol group (received calcitriol 5 µg/kg, p.o. for 14 days), cisplatin group (received a single i.p. injection of cisplatin 10 mg/kg on the 10th day), and calcitriol + cisplatin group (received calcitriol 5 µg/kg, p.o. for 14 days and cisplatin 10 mg/kg, i.p. on the 10th day). The possible interaction between calcitriol and cisplatin on cell viability was tested in HepG2 cells by MTT assay. Hepatorenal toxicity induced by cisplatin was reversed by calcitriol, as evidenced by improved histological examinations and liver and kidney function tests. In addition, calcitriol counteracted oxidative stress and enhanced Nrf2 and Mrp2 expression in the liver and kidney while suppressing levels of p38 MAPK in cisplatin-treated mice. Calcitriol also inhibited cisplatin-induced hepatic and renal inflammation, as determined by suppressing TNF-α and enhancing IL-10 levels. By downregulating caspase-3, calcitriol also promoted liver and kidney tissue survival in mice treated with cisplatin. Moreover, cisplatin’s cytotoxic effects were significantly potentiated when calcitriol was combined with cisplatin. The current study showed that calcitriol protects against cisplatin-induced hepatorenal injury by suppressing oxidative stress, inflammation, and apoptosis, which the Nrf2-Mrp2/p38 MAPK pathway might regulate.


Case timeline: diagnosis and treatment overview.
In CTU, both coronal (A) and transverse sections (B) show a solid mass located in the middle near the upper pole of the left kidney, next to the renal pelvis.
Macroscopic view shows the tumor located at mid-upper pole of kidney, adjacent to the renal collecting system.
The tubules and cysts are delineated by a uniform layer of epithelial cells, displaying a variety of morphologies including flat and hobnail to cuboidal and columnar. The majority of cells feature copious eosinophilic cytoplasm. (Haematoxylin and Eosin staining (HE), magnification ×400 (A), magnification ×100 (B).).
of studies on adjuvant treatment for TC-RCC cases.
Coexistence of tubulocystic renal cell carcinoma and polycythemia vera: A rare case report

December 2024

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6 Reads

Tubulocystic Renal Cell Carcinoma (TC-RCC) and Polycythemia Vera (PV) are both infrequent medical conditions. TC-RCC was recognized as a distinct subtype of kidney cancer by the World Health Organization in 2016, while PV is a rare myeloproliferative neoplasm distinguished by the excessive production of red blood cells. The coexistence of these two conditions is exceptionally uncommon and lacks comprehensive documentation. This study presents a case report of a 35-year-old male patient who has been diagnosed with PV for the past 20 years. The patient underwent a radical nephrectomy to remove the renal tumor, and subsequent histopathological analysis confirmed the presence of TC-RCC. Throughout the 6-month follow-up period, the patient exhibited no signs of abnormalities. The rarity of the coexistence of TC-RCC and PV highlights the intricate nature of managing such instances, necessitating a cautious approach to diagnosis and treatment, particularly in surgical interventions. The present study serves as a valuable resource for diagnosing and treating individuals presenting with concurrent renal neoplasms and PV.


Adverse reactions of immune checkpoint inhibitors combined with angiogenesis inhibitors: A pharmacovigilance analysis of drug–drug interactions

December 2024

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14 Reads

The combination of immune checkpoint inhibitors (ICIs) and angiogenesis inhibitors (AGIs) is widely used in cancer treatment; however, drug–drug reactions (DDIs) remain unknown. We aimed to identify interaction signals for the concomitant use of ICIs and AGIs. Data were obtained from the US FDA Adverse Event Reporting System (FAERS) from January 1, 2015, to December 31, 2023. Disproportionality analysis was used for data mining by calculating the reporting odds ratio (ROR) and 95% confidence interval (95% CI). Adjusted RORs were analysed using logistic regression analysis, considering age, sex and reporting year. Further confirmation was assessed via additive and multiplicative models. We identified 75,936 reports on ICIs combined with AGIs. Significant interaction signals were observed for hepatobiliary disorders (RORcrude: 5.25, 95% CI: 5.07–5.44, RORadj: 5.01, 95% CI: 4.82–5.22, additive models: 0.2323), investigations (RORcrude: 1.66, 95% CI: 1.62–1.70, RORadj: 1.63, 95% CI: 1.58–1.67, additive models: 0.2187, multiplicative models: 1.1265), renal and urinary disorders (RORcrude: 1.87, 95% CI: 1.80–1.95, RORadj: 1.72, 95% CI: 1.64–1.79, additive models: 0.3239, multiplicative models: 1.1799) and vascular disorders (RORcrude: 1.94, 95% CI: 1.87–2.02, RORadj: 1.87, 95% CI: 1.80–1.95, additive models: 0.5823, multiplicative models: 1.5676). Subset data analysis showed positive interaction signals for PDL-1/CTLA-4 inhibitors + AGI in hepatobiliary disorders, PD-1 inhibitors + AGI in investigations, or PD-1/PDL-1 inhibitors + AGI in renal and urinary/ vascular disorders. Based on FAERS data, four systemic disorders were identified as having DDIs related to the combined use of ICIs and AGIs. Pre-clinical trials are required to explore the mechanisms underlying these interactions.


Receiver operating characteristic curves for prediction capacity of MMP-2 and MMP-9: (a) non-metastatic versus healthy controls, (b) metastatic versus healthy controls, (c) non-metastatic versus metastatic.
MMP: matrix metalloproteinase; AUC: area under curve.
Patients’ general characteristics and clinicopathological features of the disease.
Comparison of MMP-2 and MMP-9 concentrations among the study groups.
Association of serum MMP-2 and MMP-9 and clinicopathological features of the study groups.
Prognostic impact of matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) in Egyptian breast cancer patients

December 2024

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35 Reads

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1 Citation

This study aims to investigate the diagnostic and prognostic relevance of MMP-2 and MMP-9 as biomarkers for breast cancer, as well as their association with clinicopathological factors. Breast cancer is a leading contributor to cancer-related deaths among women worldwide. The discovery of biomarkers is crucial for early diagnosis, outcome prediction, and effective treatment. Matrix metalloproteinases (MMPs) play a significant role in various physiological and pathological activities, including development, tissue repair, inflammation, cancer spread, and metastasis. While the prognostic significance of MMP-2 and MMP-9 levels in breast cancer has been studied, the findings remain inconclusive. Participants were divided into three groups, with each group consisting of 62 individuals: Group I comprised healthy controls, Group II consisted of newly diagnosed breast cancer patients (stage I-III), and Group III included patients with metastatic breast cancer. Levels of MMP-2 and MMP-9 were evaluated in these groups using the ELISA method. An evident increase in MMP-2 and MMP-9 levels was noted when comparing the control group with both the breast cancer and metastatic groups. Furthermore, a notable correlation was identified between serum MMP-9 levels and the pathological diagnosis of breast cancer (P < 0.001) as well as tumor size (P < 0.01). MMP-2 and MMP-9 have emerged as promising biomarkers for breast cancer, with MMP-9 specifically associated with disease prognosis. Continued investigation into the anti-tumor mechanisms of MMPs may yield significant advancements in the development of targeted therapeutic strategies for the management of breast cancer.


The preventive effects of antioxidants against the reduction in skin water content in skin barrier–disrupted mice treated with or without PM10. An increase in skin water content was observed after treatment with dieckol, punicalagin, epigallocatechin gallate (EGCG), and resveratrol, while PM10 treatment decreased skin water content in tape stripping–induced skin barrier–disrupted mouse models. Data in the bar graphs represent the mean ± standard deviation from three independent experiments (*P < 0.05, **P < 0.001, ***P < 0.005, ****P < 0.0001).
The preventive effect of antioxidants on the amplification of inflammatory cytokines in PM10-exposed, tape stripping–induced skin barrier–disrupted mice was examined. Initially, the expression levels of genes associated with IL-1β, IL-4, IL-6, IL-8, and TNF-α were found to be elevated in the tape stripping–induced skin barrier–disrupted mice relative to those in the control group. Upon treatment with PM10, the skin barrier–disrupted mice exhibited greater increases in gene expression levels than the group treated solely with vehicle. These findings suggested that PM10 has the potential to exacerbate inflammation and disrupt the skin barrier by further stimulating gene expression. Additionally, subsequent administration of antioxidants resulted in a significant reduction in the expression levels of IL-1β, IL-4, IL-6, IL-8, and TNF-α relative to those observed following exclusive PM10 exposure. The data depicted in the bar graphs represent the mean ± standard deviation derived from three independent experiments (*P < 0.05, **P < 0.001, ***P < 0.005, ****P < 0.0001).
The protein levels of IL-1β, IL-4, IL-6, IL-8, and TNF-α exhibited an elevation in tape stripping–induced skin barrier–disrupted mice relative to those observed in the control group. Upon treatment with PM10, these skin barrier–disrupted mice demonstrated a more pronounced increase in protein expression levels compared with those subjected solely to vehicle treatment. These findings demonstrated the exacerbating effects of PM10 on inflammation and barrier disruption through further augmentation of protein expression. Additionally, following antioxidant treatment, a significant decrease in the protein expression levels of IL-1β, IL-4, IL-6, IL-8, and TNF-α was observed compared with those after exclusive PM10 exposure. The data presented in the bar graphs represent the mean ± standard deviation derived from three independent experiments (*P < 0.05, **P < 0.001, ***P < 0.005, ****P < 0.0001).
Preventive effects of antioxidants on the downregulation of keratinocyte differentiation markers in tape stripping–induced skin barrier–disrupted mice after PM10 treatment. Antioxidants increased the levels of loricrin, involucrin, and filaggrin in the PM10-treated, skin barrier–disrupted mice.
Real-time PCR primers used in this study.
Effects of antioxidants on skin hydration, inflammatory cytokines, and keratinocyte differentiation markers in a PM10-exposed skin barrier–disrupted mouse model

December 2024

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16 Reads

Given that particulate matter (PM) has an established role in inducing oxidative stress, inflammation, and skin aging, it is plausible that PM could exacerbate inflammatory skin conditions such as xerosis. Xerosis represents a significant dermatological concern among older adults within aging populations. We conducted an investigation into the efficacy of antioxidants, such as dieckol, punicalagin, epigallocatechin gallate (EGCG), and resveratrol, against PM10 in a skin barrier–disrupted mouse model. A skin barrier–disrupted mouse model was induced by tape stripping. This study investigated the antioxidative and anti-inflammatory properties of antioxidants on PM-induced changes using the skin barrier–disrupted mouse model. Tape strips were attached to the back of 7-week-old nude mice and removed quickly. To investigate variations in skin hydration, levels of inflammatory cytokines, and indicators of keratinocyte differentiation, mice underwent treatment with several compounds: a control vehicle (100 μL), PM10 100 μL (100 μg/mL), PM10 100 μL (100 μg/mL) with antioxidants 100 μL (Punicalagin 5 μM, Dieckol 5 μM, EGCG 1 μM, resveratol 1 μM) for 1 week. To assess their effects, different analysis were conducted using measurements of skin moisture, real-time polymerase chain reaction, enzyme-linked immunosorbent assay for detecting inflammatory cytokines, and immunofluorescence staining to identify markers of keratinocyte differentiation. While PM10 decreased water content in disrupted skin, all antioxidants preserved skin hydration in the skin barrier–disrupted mice, regardless of the presence of PM10. All antioxidants also inhibited the upregulation of inflammatory cytokines, such as interleukin (IL)-1β, IL-4, IL-6, IL-8, and tumor necrosis factor-alpha and normalized the downregulation of keratinocyte differentiation markers against PM10 in skin barrier–disrupted mice. This study elucidated the protective effects of antioxidants-namely, punicalagin, dieckol, EGCG, and resveratrol-in mitigating the impact of PM10 on skin barrier integrity and inflammation in a disrupted skin barrier mouse model, highlighting their potential utility in dermatological treatments.


(a) The patient presented with ulcers on both lower limbs, with deep ulcers with irregular edges on all four limbs. The edges of the lower limb ulcers are purplish-red, which is consistent with the clinical manifestations of pyoderma gangrenosum (PG). (b) Photos of the patient’s lower limbs at discharge. (c) Follow-up visit in June shows the condition of the patient’s lower limbs; as seen in the images, the ulcers have completely healed, forming scar changes resembling “cigarette paper.” (d) Gulliver’s sign in pyoderma gangrenosum. Note the new epithelial growth connecting the ulcer bed to the surrounding normal skin.
(a) ×20 magnification and (b) ×200 magnification skin biopsy of the lower limbs showing neutrophil infiltration, pyogenic dermatitis, and epidermal vesicles.
Treatment of systemic sclerosis complicated with pyoderma gangrenosum with adalimumab: A case report of a rare disease

November 2024

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2 Reads

Pyoderma gangrenosum (PG) is a rare noninfectious neutrophilic dermatosis characterized by recurrent, painful ulcers that commonly affect the lower extremities but can also involve other parts of the body. Over half of patients with PG have concomitant systemic immune diseases, with the association of PG with systemic sclerosis (SSc) being extremely rare. Treatment of PG primarily involves local therapy, steroids, and immunosuppressants, with an increasing emphasis on biologic agents. Among these, tumor necrosis factor-alpha (TNF-α) antagonists are considered effective. The patient in this report was an elderly female with a history of systemic sclerosis for many years and initially presented with gangrenous ulcers on the fingertips. After inconclusive conventional treatment, adalimumab was added for 5 weeks, resulting in disease suppression, a reduction in ulcer size, and re-epithelialization of the skin lesions after 6 months.


The senomorphic impact of astaxanthin on irradiated rat spleen: STING, TLR4 and mTOR contributed pathway

October 2024

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15 Reads

Objectives: Exposure of spleen tissues to ionizing radiation during radiotherapy can induce cellular stress and immune-dysfunction leading to cellular senescence. Introduction: The process of a cancerous development is facilitated by the accumulation of senescent cells. This justifies the incorporation of anti-senescent medications during splenic irradiation (SI). Methods: In this study senescence was induced in the spleen of male albino rats by radiation exposure (5Gy-single whole body gamma-irradiation) then after 2 weeks, oral astaxanthin regimen was started once daily in a dose of 25 mg/kg for 7 consecutive days. Concurrent control groups were carried out. Results: the present data reflected that irradiation provoked an increase in the oxidative stress biomarkers (nitric oxide, lipid peroxidation and total reactive oxygen species levels)and the inflammatory biomarkers (Myeloperoxidase and interleukin-6). In addition irradiation led to the over expression of stimulator of interferon genes (cGAS-STING), mammalian target of rapamycin (mTOR) and Toll-like receptor 4 (TLR4) along with the lactate dehydrogenase (LDH), cyclin-dependent kinase inhibitor 1 (p21) cyclin-dependent kinase inhibitor 2A (p16) increment with elevation of tumor suppressor protein (p53) level. However, reduced glutathione contents and catalase activity were reduced post irradiation in spleen tissues, all these changes reflecting induction of cellular senescence. Astaxanthin treatment showed an improvement in the antioxidant/oxidative stress balance, inflammatory biomarkers, histopathological examination and immunohistochemical expressions of the tested proteins in the irradiated rats. Conclusion: the current findings offer a new insight into the senomorphic effect of astaxanthin following radiation-induced spleen senescence via STING, mTOR, and TLR4 signalling pathways.


Association of HLA class II alleles and haplotypes with bullous and mucus membrane pemphigoid risk: A systematic review, a meta-analysis and a meta-regression

Although, several studies have assessed the association of HLA Class II and genes with bullous pemphigoid (BP) and mucous membrane pemphigoid (MMP), results were inconsistent and between-studies heterogeneity needs to be investigated. An electronic literature search for eligible studies among all papers published prior to May 31, 2024, was conducted through PubMed, EMBASE, Web of science and Scopus databases. Meta-analyses together with subgroup analyses and meta-regressions were performed for the three following HLA genes: DRB1, DQA1 and DQB1. Combined analyses revealed a significant increase in pemphigoid risk conferred by the following alleles: DQB1*0301, DRB1*11, DRB1*1101 subtype and DQA1*0505, all p-values <.001. However, there was a moderate to high level of between-studies heterogeneity. Subgroup analyses revealed that the risk conferred by the aforementioned alleles was significantly higher in case of dipeptidyl peptidase-4 inhibitors induced BP (DBP) comparatively to idiopathic BP and MMP. In addition, the risk conferred by the DQB1*0301 was significantly higher in MMP (OR [95% CI] = 5.25 [4.03–6.84]) than in BP (OR [95% CI] = 2.22 [1.87–2.65]), p = .007. Besides, the DRB1*1101-DQB1*0301 and DRB1*11-DQA1*05-DQB1*0301 haplotypes were significantly associated with an increased pemphigoid risk, both p-values <.001. Conversely, the DQA1*0201 allele was significantly associated with reduced pemphigoid risk (OR [95% CI] = 0.3 [0.17–0.52]), with no between-studies heterogeneity (I² = 0%, p = .76). This meta-analysis demonstrated that the DRB1*1101, DQA1*0505 and DQB1*0301 were significantly associated with increased pemphigoid risk. These associations were found to be significantly stronger in case of DBP comparatively to idiopathic pemphigoid. The DQA1*0201 allele seems to play a protective role against pemphigoid. Registration: This review has been registered on PROSPERO: CRD42024552821, Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024552821.


SMC4 serves as a potential marker for the diagnosis and prognosis of colon adenocarcinoma

October 2024

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6 Reads

Objective We aimed to explore the role of structural maintenance of chromosomes 4 (SMC4) in malignant progression and immunology of colon adenocarcinoma (COAD). Methods The expression, genetic and protein features, and immune cell infiltration of SMC4 in pan-cancer were provided by public databases and websites. The protein expression of SMC4 in COAD tissues was screened by immunohistochemical assay. Si-RNA-mediated transfection was performed in COAD cells and the proliferation viability was measured using MTT, colony formation and EdU assays. Cell autophagy was detected by AO staining, western blots, and immunofluorescence staining. The migratory ability was determined using scratch and transwell assays. The expression of epithelial-to-mesenchymal transition (EMT) markers and transcriptional factors were detected using western blots. Results The expression of SMC4 was upregulated in pan-cancer and had relationships with prognosis, TMB, and MSI of cancer patients. Particularly, SMC4 protein was highly expressed in COAD tissues and correlated with poor prognosis of patients. Depletion of SMC4 inhibited cell proliferation, induced autophagy, and decreased migration through EMT progression in COAD cells. In addition, SMC4 was associated with infiltration of neutrophils, M2 macrophages, and CD4 + T cells in COAD, and had positive association with M2 macrophage markers and immune checkpoints. Conclusion SMC4 was correlated with patients’ poor prognosis, proliferation, metastasis, and immune cell infiltrates, and might function as a potential diagnosis and prognostic biomarker in COAD.


Magnetic resonance imaging (MRI) in August 2015. Diffuse subcortical lesions showed on axial T2 turbo inversion recovery magnitude (TIRM) Dark Fluid MRI scans (A–C). Spinal cord lesion at the level of C7 visible on a sagittal TIRM MRI scan.
Laboratory analysis of the patient.
Serum levels of immunoglobulin of the patient.
Lymphocyte phenotype of the patient.
Complications of untreated hypogammaglobulinemia in a patient with common variable immunodeficiency – A case report

October 2024

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29 Reads

Common variable immunodeficiency (CVID) is a primary immunodeficiency disorder characterized by decreased or undetectable serum levels of immunoglobulin G (IgG), decreased levels of IgA isotypes, and poor specific antibody production in response to vaccines and pathogens. Owing to hypogammaglobulinemia, patients have increased susceptibility to infections and a higher risk of malignancies. Here we present a case study of patient with a diagnosis of CVID, who refused immunoglobulin replacement therapy despite plenty of complications. Patient suffered from recurrent respiratory and digestive tract infections, diarrhea, malnutrition, infection of the central nervous system, and autoimmune complications. The complications of untreated hypogammaglobulinemia eventually led to the death of the patient at the age of 63 years. Patients with CVID have an increased susceptibility to chronic infections and subsequent complications; hence, proper treatment with immunoglobulin replacement therapy should be administered. Owing to the increased risk of autoimmunity and malignancy, regular surveillance should be conducted in patients with CVID. Understanding the natural history of untreated hypogammaglobulinemia emphasizes the need for early diagnosis, appropriate treatment, and vigilant follow-up in patients with CVID.


Journal metrics


3.0 (2023)

Journal Impact Factor™


21%

Acceptance rate


4.0 (2023)

CiteScore™


0.581 (2023)

SNIP


$2,800

Article processing charge

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