The endoplasmic reticulum (ER), the center of protein folding, also controls the cell's life-and-death signaling mechanisms. ER stress caused by unfolded or misfolded proteins leads to the activation of the unfolded protein response (UPR) in the cell. The UPR utilizes three main signaling pathways to restore disrupted ER homeostasis. These signaling pathways are protein kinase R-like endoplasmic reticulum kinase, inositol-requiring enzyme 1, and activating transcription factor 6. Studies have reported that ER stress (ERS) plays a role in the pathogenesis of metabolic disorders such as diabetes, obesity, atherosclerosis, and nonalcoholic liver disease. This review will briefly discuss the ERS response in these metabolic diseases.

Autoimmune diseases are complex clinical conditions that present significant therapeutic challenges due to their intricate immunological mechanisms. Conventional treatment strategies, such as immunosuppressive drugs and anti-inflammatory therapies, often demonstrate limited efficacy and are associated with considerable side effects. Recently, mesenchymal stem cells (MSCs) have attracted growing interest as a promising therapeutic approach, owing to their immunomodulatory properties and ability to promote tissue repair. However, the direct application of MSCs faces several limitations, including the risk of immunogenicity and difficulties in large-scale production. In this context MSC-derived exosomes (MSC-Exos), nano-sized extracellular vesicles secreted by MSCs, have emerged as a compelling alternative to cell-based therapies. Enriched with proteins, lipids, and nucleic acids, these exosomes exhibit potent anti-inflammatory and immunomodulatory effects. Their primary mechanisms of action include enhancing the population of regulatory T cells, modulating macrophage polarization, and suppressing proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α. The therapeutic potential of MSC-Exos extends beyond individual conditions, encompassing a wide range of autoimmune diseases. For instance in Behçet’s disease, they have been shown to regulate vasculitis and inflammatory processes by inhibiting proinflammatory cytokines and promoting endothelial cell regeneration. Moreover, MSC-Exos have demonstrated promising immunomodulatory effects in other autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis. Through mechanisms such as inflammation suppression, vascular repair, and the restoration of immune homeostasis, MSC-Exos represent a versatile and innovative approach to autoimmune disease therapy. This review explored the molecular and therapeutic effects of MSCs and MSC-Exos in autoimmune diseases, with particular emphasis on their clinical potential in Behçet’s disease, systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis.

Objectives: Psoriasis is a widespread immunological disease characterised by inflammation and primarily associated with skin and joint symptoms. The kynurenine pathway significantly influences inflammation and immune system activity. The aim of this study is to determine serum concentrations of kynurenine metabolites in patients with psoriasis and investigate their correlation with disease severity. Methods: This study included 30 participants with psoriasis and 30 individuals without the disease as healthy controls. Serum levels of tryptophan, kynurenine, 3-OH anthranilic acid, quinolinic acid, 3-OH kynurenine, and kynurenic acid were determined by liquid chromatography-mass spectrometry (LC-MS/MS). Results: Serum levels of kynurenic acid (p<0.001), tryptophan (p<0.001) and the tryptophan/kynurenine ratio (TKR) (p<0.001) were statistically significantly lower in psoriasis patients than in healthy controls, while levels of quinolinic acid (p=0.007) and kynurenine (p=0.001) were significantly higher. The psoriasis area severity index (PASI) correlated positively with 3-hydroxykynurenine and kynurenic acid. Conclusions: Kynurenine metabolites are associated with the pathophysiology of psoriasis and could serve as valuable candidate markers for monitoring inflammation.

Objective: In this study, the antioxidant and chemotherapy-modulating effects of shilajit, a natural humic substance, on the human lung adenocarcinoma cell line (A549) were investigated. Material-Method: Shilajit extracts (water and DMEM solvent) were applied to A549 cells alone and in combination with etoposide (IC₅₀ = 42.54 µg/mL) and cisplatin (IC₅₀ = 6.44 µg/mL). Cell viability was measured by the MTT method, and the antioxidant activity was evaluated using the DPPH radical scavenging assay. Results: As a result of the MTT test, shilajit alone was found to significantly increase cell viability, while in combination with etoposide and cisplatin it reduced the cytotoxic effects of these agents. This may be related to the mitochondrial activity enhancing and oxidative stress suppressing properties of shilajit. The IC₅₀ value for antioxidant activity was calculated as 1.10 mg/ml for the water extract and 1.32 mg/ml for the methanol extract of shilajit. The IC₅₀ values for the positive controls BHA and BHT were 0.023 and 1.88 mg/mL, respectively. Both extract forms of shilajit showed a dose-dependent antioxidant effect, but exhibited lower activity compared to synthetic antioxidants. Conclusion: The results suggest that shilajit has cell-protective and antioxidant properties, but caution is advised when used in combination with chemotherapeutic agents. There is a possibility that in some cases shilajit activates cellular resistance mechanisms to chemotherapy.

Digoxin is a drug commonly used to achieve rate control in heart failure and atrial fibrillation with some form of arrhythmia. It shows a positive inotropic effect by inhibiting the Na + / K + ATPase pump in the myocardial cell membrane. Since digoxin is a drug with a narrow therapeutic range, the therapeutic dose range should be monitored and the individual dose regimen should be established, taking care of plasma concentrations. Factors such as patient's age, renal dysfunction, abnormal electrolyte values, drug-drug or drug-plant interactions increase the risk of intoxication. Patients may present with nausea and vomiting in digoxin intoxication and may present with ventricular arrhythmias with fatal rhythm disorders. Although digoxin should be discontinued as treatment, accompanying electrolyte imbalances should be treated. In patients with malignant arrhythmias, digoxin-specific antibodies should be considered in treatment. In this review, various drug-drug interactions that are frequently observed and easily prevented in patients taking digoxin are discussed with a case report.