International Journal of Immunopathology and Pharmacology最新文献

Objectives: Alantolactone (AL) is a compound extracted from the roots of Inula Racemosa that has shown beneficial effects in cardiovascular disease. However, the cardioprotective mechanism of AL against hypoxic/ischemic (H/I) injury is still unclear. This research aimed to determine AL's ability to protect the heart against isoproterenol (ISO)-induced MI injury in vivo and cobalt chloride (CoCl₂) induced H/I injury in vitro.

Methods: Electrocardiography (ECG), lactate dehydrogenase (LDH), creatine kinase (CK), and cardiac troponin I (cTnI) assays in addition to histological analysis of the myocardium were used to investigate the effects of AL in vivo. Influences of AL on L-type Ca²⁺ current (I_Ca-L) in isolated rat myocytes were observed by the patch-clamp technique. Furthermore, cell viability, apoptosis, oxidative stress injury, mitochondrial membrane potential, and intracellular Ca²⁺ concentration were examined in vitro.

Results: The results indicated that AL treatment ameliorated the morphological and ECG changes associated with MI, and decreased levels of LDH, CK, and cTnI. Furthermore, pretreatment with AL elevated antioxidant enzyme activity and suppressed ROS production. AL prevented H/I-induced apoptosis, mitochondria damage, and calcium overload while reducing I_Ca-L in a concentration and time dependent fashion. The 50% inhibiting concentration (IC₅₀) and maximal inhibitory effect (E_max) of AL were 17.29 μmol/L and 57.73 ± 1.05%, respectively.

Conclusion: AL attenuated MI-related injury by reducing oxidative stress, apoptosis, calcium overload, and mitochondria damage. These cardioprotective effects may be related to the direct inhibition of I_Ca-L.

Objective: LPS-responsive beige-like anchor (LRBA) deficiency is one of the most common monogenic disorders causing common variable immunodeficiency (CVID) and CVID-like disorders. However, the clinical spectrum of compound heterozygous (CHZ) LRBA variation should be extended. In this study, we presented five cases of compound heterozygous LRBA with various refractory cytopenias.

Materials and methods: Retrospective analysis of the clinical manifestations, management, and outcomes of five cases (from five pedigrees) with LRBA gene CHZ variants which initially manifested as single/multilineage immune cytopenias was performed.

Results: 1. Gene variations: All five patients inherited the compound heterozygous LRBA variations from their parents which were thought to be pathogenic. BEACH, DUF4704, and LamG were the main affected domains of LRBA gene in this case series. 2. Immune dysregulation of clinic: (1) Hypogammaglobulinemia were recorded in four patients, and the proportion of Treg was decreased in two patients. Only one patient had been with increased TCRαβ+CD4/CD8 double-negative T cells (DNT). (2) Lymphoproliferative manifestations were seen in three patients. (3) All five patients were complained with cytopenia, although they showed different clinical manifestations. None of the parents was asymptomatic. (4) Other immune disorders: P5 also had relapsed infections and autoimmune endocrinopathy. 3. Management and outcomes: P1 and P5 responded well to immunomodulatory therapy and P3 was effectively treated with hemophagocytic lymphohistiocytosis (HLH) first-line regimen chemotherapy. P4 showed no responses to steroids and IVIG. However, TPO-R agonist was effective.

Conclusion: Unlike homozygous mutations, compound heterozygous LRBA variation should always be kept in mind for the various phenotypes and different treatment responses.

Background: In gastric cancer, a malignant condition with a dismal prognosis, long non-coding RNAs (LncRNAs) play a significant regulatory role. They often compete with microRNAs through the ceRNA mechanism to affect the expression of target mRNA. However, the specific clinical value and mechanism of action of LncRNA in gastric cancer are still unclear. Methods: This study detected the expression and clinical value of LINC01088 in gastric cancer tissues. Furthermore, the biological functions of LINC01088 and the regulation mechanism of the miR-95/LATS2 pathway were explored.Results: LINC01088 and LATS2 mRNA expression decreased, and miR-95 increased in gastric cancer tissues. LINC01088 has an excellent positive correlation with LATS2 mRNA, which may be a ceRNA pair; LINC01088 has binding sites with miR-95. Gene interference tests on gastric cancer cell lines revealed that LINC01088 could prevent gastric cancer cells from proliferating, invading, and migrating. The function of LINC01088 is achieved by regulating the miR-95/LATS2 pathway through the ceRNA mechanism.Conclusion: The results of this study show that LINC01088 expression is significantly reduced in gastric cancer tissues and cell lines. LINC01088 inhibits gastric cancer cells' proliferation, invasion, and migration by regulating the miR-95/LATS2 pathway via the ceRNA mechanism.

Objectives: To investigate the underlying mechanisms of how the basic fibroblast growth factor monoclonal antibody (bFGFmAb) attenuates cisplatin (DDP) resistance in lung cancer using A549 cells and cisplatin-resistant A549 cells (A549/DDP). Methods: Cancer cell proliferation, cell viability, and 50% inhibitory concentration (IC50) of cisplatin were assessed. Transwell assays were utilized to evaluate the invasion activity of tumor cells in response to treatment. Epithelial-to-mesenchymal transition markers and drug resistance proteins were analysed using Western blots. Results: We demonstrate that the bFGFmAb inhibits the proliferation and invasion of both A549 and A549/DDP cells. The bFGFmAb increases cisplatin sensitivity of both A549 and A549/DDP cells as evidenced by an increase in the IC50 of cisplatin in A549 and A549/DDP cells. Furthermore, bFGFmAb significantly increases the expression of E-cadherin, whilst decreasing the expression of N-cadherin and bFGF in both cell lines, thereby showing inhibition of epithelial-to-mesenchymal transition. In addition, we demonstrate that bFGFmAb significantly reduces the expression of the lung resistance protein. Conclusions: Our data suggests that the humanized bFGFmAb is a promising agent to attenuate cisplatin resistance in NSCLC. The underlying mechanism for this effect of bFGFmAb may be associated with the inhibition of epithelial-to-mesenchymal transition and reduced expression of lung resistance protein.