International Journal of Immunopathology and Pharmacology最新文献

Background: Alteplase intravenous thrombolysis is effective for treating acute ischemic stroke (AIS) within 4.5 h. Nevertheless, the prognosis remains poor for some patients.Objective: To investigate the risk factors for poor prognosis in patients undergoing intravenous thrombolysis with alteplase following AIS based on propensity score matching and to develop a predictive model.Result: Multivariate logistic regression analysis showed that baseline blood glucose (OR = 1.20, 95%CI, 1.03-1.39), baseline NIH Stroke Scale score (OR = 1.23, 95%CI, 1.12-1.35), and hyperlipidemia (OR = 6.60, 95%CI 1.74-25.00) were risk factors for poor prognosis in patients with AIS undergoing alteplase intravenous thrombolysis. Using these factors, a nomogram model was constructed for predicting patient prognosis at 3 months. The areas under the receiver operating characteristic curve (AUCs) of the training and validation groups were 0.792 (95CI% 0.715-0.870) and 0.885 (95CI% 0.798-0.972), respectively, showing good differentiation. The Hosmer Lemeshow goodness-of-fit test showed that the model had good fit. The calibration curve fitted well with the ideal curve, and the decision curve analysis curve showed that the model had good clinical applicability when the threshold probability was between 10%-80%.Conclusion: The established nomogram could successfully predict the 3-month prognosis of patients with AIS after undergoing alteplase intravenous thrombolysis. The model thus has clinical application value.

Objective: This study investigated the raft-forming suspension of famotidine as an anti-reflux formulation to improve the oral bioavailability of narrow absorption window drugs by enhancing gastric residence time (GRT) and preventing gastro-esophageal reflux disease (GERD).

Method: Various combinations of raft-forming agents, such as Tragacanth gum (TG), guar gum (GG), and xanthan gum (XG), were evaluated alongside sodium alginate (SA) to develop an effective raft. Preformulation studies and preliminary screening were conducted to identify the most suitable raft-forming agent, and GG was chosen due to its mucilaginous properties. The formulation was optimized using a 32 full factorial design, with the quantities of GG and SA as independent factors and apparent viscosity and in-vitro drug release (%) as dependent factors. The in vivo floating behavior study was performed for optimized and stabilized formulation.

Results: Among the tested batches, F6 was selected as the optimized formulation. It exhibited desirable characteristics such as adequate raft weight for extended floating in gastric fluid, improved apparent viscosity, and a significant percentage of drug release at 12 h. A mathematical model was applied to the in-vitro data to gain insights into the drug release mechanism of the formulation. The stability of the suspension was assessed under accelerated conditions, and it demonstrated satisfactory stability. The formulation remains floating in the Rabbit stomach for more than 12 h.

Conclusion: It concludes that the developed formulation has enhanced bioavailability in the combination of GG and SA. The floating layer of the raft prevents acid reflux, and the famotidine is retained for an extended period of time in the gastric region, preventing excess acid secretion. The developed formulations are effective for stomach ulcers and GERD, with the effect of reducing acid secretion by H2 receptor antagonists.

Introduction: Corilagin possesses a diverse range of pharmacologic bioactivities. However, the specific protective effects and mechanisms of action of corilagin in the context of atherosclerosis remain unclear. In this study, we investigated the impact of corilagin on the toll-like receptor (TLR)4 signaling pathway in a mouse vascular smooth muscle cell line (MOVAS) stimulated by oxidized low-density lipoprotein (ox-LDL). Additionally, we examined the effects of corilagin in Sprague-Dawley rats experiencing atherosclerosis.

Methods: The cytotoxicity of corilagin was assessed using the CCK8 assay. MOVAS cells, pre-incubated with ox-LDL, underwent treatment with varying concentrations of corilagin. TLR4 expression was modulated by either downregulation through small interfering (si)RNA or upregulation via lentivirus transfection. Molecular expression within the TLR4 signaling pathway was analyzed using real-time polymerase chain reaction (PCR) and Western blotting. The proliferation capacity of MOVAS cells was determined through cell counting. In a rat model, atherosclerosis was induced in femoral arteries using an improved guidewire injury method, and TLR4 expression in plaque areas was assessed using immunofluorescence. Pathological changes were examined through hematoxylin and eosin staining, as well as Oil-Red-O staining.

Results: Corilagin demonstrated inhibitory effects on the TLR4 signaling pathway in MOVAS cells pre-stimulated with ox-LDL, consequently impeding the proliferative impact of ox-LDL. The modulation of TLR4 expression, either through downregulation or upregulation, similarly influenced the expression of downstream molecules. In an in vivo context, corilagin exhibited the ability to suppress TLR4 and MyD88 expression in the plaque lesion areas of rat femoral arteries, thereby alleviating the formation of atherosclerotic plaques.

Conclusion: Corilagin can inhibit the TLR4 signaling pathway in VSMCs, possibly by downregulating TLR4 expression and, consequently, relieving atherosclerosis.

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.

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.

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.

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.

Objectives: Tuberostemonine has several biological activity, the aim of study examined the impact of tuberostemonine on the proliferation of TGF-β1 induced cell model, and its ability to alleviate pulmonary fibrosis stimulated by bleomycin in mice.

Methods: In vitro, we assessed the effect of tuberostemonine (350, 550 and 750 µM) on the proliferation of cells stimulated by TGF-β1 (10 μg/L), as well as on parameters such as α-SMA vitality, human fibronectin, collagen, and hydroxyproline levels in cells. In vivo, we analyzed inflammation, hydroxyproline, collagen activity and metabolomics in the lungs of mice. Additionally, a comprehensive investigation into the TGF-β/smad signaling pathway was undertaken, targeting lung tissue as well as HFL cells.

Results: Within the confines of an in vitro setup, the tuberostemonine manifested a discerned IC50 of 1.9 mM. Furthermore, a significant reduction of over fifty percent was ascertained in the secretion levels of hydroxyproline, fibronectin, collagen type I, collagen type III and α-SMA. In vivo, tuberostemonine obviously improved the respiratory function percentage over 50% of animal model and decreased the hydroxyproline, lung inflammation and collagen deposition. A prominent decline in TGF-β/smad pathway functioning was identified within both the internal and external cellular contexts.

Conclusions: Tuberostemonine is considered as a modulator to alleviate fibrosis and may become a new renovation for pulmonary fibrosis.

Background: Clear cell renal cell carcinoma (ccRCC) is the most invasive type of cancer, with a high risk of metastasis and recurrence. Therefore, there is an urgent need to identify novel prognostic predictors and therapeutic targets of ccRCC. Activating transcription factor 3 (ATF3), a tumor oncogene or repressor, has rarely been examined in ccRCC. In the present study, we comprehensively elucidate the prognostic value and potential functions of ATF3 in ccRCC.Methods: Several TCGA-based online databases were used to analyze ATF3 expression in ccRCC and determine ccRCC prognosis. The upstream-binding micro (mi) RNAs of ATF3 and long non-coding (lnc)RNAs were predicted using the StarBase database.Results: Analysis of several TCGA-based online databases showed that ATF3 expression is decreased in ccRCC, suggesting a significant association with the prognosis of patients with ccRCC. Furthermore, we found hsa-miR-221-3p to be potential regulatory miRNA of ATF3 in ccRCC. Prediction and analysis of the upstream lncRNAs indicated that PAXIP1-AS2 and OIP5-AS1 were the most potent upstream lncRNAs of the hsa-miR-221-3p/ATF3 axis in ccRCC. The results of the GO and KEGG analyses implied that ATF3 is likely involved in the regulation of apoptotic signaling in response to endoplasmic reticulum (ER) stress in ccRCC. Correlation analysis revealed a positive relationship between ATF3 expression and ER stress.Conclusions: Our in silico findings highlighted that ATF3 expression was low in ccRCC and negatively correlated with poor prognosis. Furthermore, PAXIP1-AS2 and the OIP5-AS1/hsa-miR-221-3p/ATF3 axis were identified as significant potential regulators of ER stress-mediated apoptosis in ccRCC.

Objectives: This study aims to systematically explore the role of chemokine CXC ligand 13 (CXCL13) in head and neck squamous cell carcinoma (HNSCC). Methods: The Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases provided the RNA-seq data for cancer and normal tissues, respectively. Gene set enrichment analysis was applied to search the cancer hallmarks associated with CXCL13 expression. TIMER2.0 was the main platform used to investigate the immune cell infiltration related to CXCL13. Immunohistochemistry was applied to explore the relationship between CXCL13 and patients' prognosis and the relationship between CXCL13 and tertiary lymphoid structures (TLSs). Results: The expression of CXCL13 was upregulated in most tumors, including HNSCC. The higher expression of CXCL13 was closely related to the positive prognosis of HNSCC. CXCL13 was mainly expressed in B cells and CD8 + T cells, revealing the relationship between its expression and immune activation in the tumor microenvironment. Furthermore, immunohistochemistry and multiple fluorescence staining analysis of HNSCC samples showed a powerful correlation between CXCL13 expression, TLSs formation, and positive prognosis. Finally, CXCL13 significantly increased the response to cancer immunotherapy. Conclusions: CXCL13 may function as a potential biomarker for predicting prognosis and immunotherapy response and associate with TLSs in HNSCC.