Amir Ghorbanihaghjo

Purpose Non-small cell lung cancer (NSCLC) is among the most lethal cancers globally, partly due to dysregulated STAT3 signaling, which is related to tumor growth. Combination strategies involving STAT3 inhibitors with chemotherapeutic agents may improve therapeutic efficacy. Therefore, the current study assessed the effects of Stattic (a STAT3 inhibitor) in combination with vinblastine (a microtubule-destabilizing agent) against A549 lung cancer cells. Methods The antiproliferative effect was examined using MTT assay, apoptosis by Annexin V–FITC/PI and DAPI staining, cell cycle distribution by flow cytometry, and cell migration by wound-healing assay. Molecular changes in apoptosis-related genes were evaluated by qRT-PCR, and alterations in fatty acid profiles were analyzed via gas–liquid chromatography. Results The IC₅₀ values for vinblastine and Stattic were 11.3 nM and 1.8 µM, respectively. Co-treatment of Stattic with vinblastine significantly inhibited cell migration, increased the percentage of apoptotic cells, elevated the mRNA expression of the pro-apoptotic gene Bak, and reduced the expression of anti-apoptotic genes Bcl-2 and Mcl-1. In addition, vinblastine treatment elevated saturated fatty acid levels, while Stattic increased monounsaturated fatty acid levels; their combination produced an intermediate lipid profile, indicating treatment-associated changes in cellular fatty acid composition. Conclusion These findings suggest that the vinblastine–Stattic combination enhances anticancer activity in A549 cells and warrants further mechanistic and in vivo studies.

Cancer is one of the major public health challenges worldwide, and the STAT3 signaling pathway is recognized as one of the most important signaling pathways in the progression of this disease. This pathway can increase the survival and proliferation of cancer cells and their resistance to treatment by regulating lipid and carbohydrate metabolism, apoptosis, and inflammatory processes. Therefore, STAT3 inhibition is considered an effective therapeutic approach in the fight against cancer. Two main strategies (direct and indirect) have been considered to inhibit this protein, with direct inhibition being more effective due to its more specific properties. Extensive research is also underway to design and develop effective inhibitors for STAT3, and in this regard, SH2 domain inhibitors have reached clinical trial phases.

Background & Aims: Remdesivir (REM) has been widely used to treat subjects affected by COVID-19 due to its broad-spectrum activity. The aim was to assess the REM effect on liver histopathology, enzymes, and alterations in oxidative stress markers. Methods: Forty-eight Wistar rats were separated into eight groups as follows: Group A (Control) received normal saline intraperitoneally (IP) for 10 days; Group B (Low-dose REM) received REM (2.8 mg/kg for the first day and 1.4 mg/kg for days 2 to 10, IP); Group C (High-dose REM) received REM (8.5 mg/kg IP for the first 17 days and days 2 to 10); Group D (High-dose REM+DEX (Dexamethasone)+ HEP (Heparin) received DEX (7 mg/kg intramuscularly for 10 days) and HEP (333 IU/kg subcutaneously on the first day and 250 IU/kg subcutaneously every 12 hours from day 2 to day 10); Group E (High-dose REM+ DEX); Group F (High-dose REM+ HEP); Group G (DEX); Group H (HEP). For statistical analysis, non-parametric tests (Kruskal-Wallis H and Mann-Whitney U) were used for pathological lesions (semi-quantitative data) between the different groups, and a p < 0.05 was considered significant. Results: There were mild to severe pathological changes in the treated groups, including cell swelling, vascular congestion. Also, the D and G groups showed similar pathological lesions, which were more severe than in other treated groups with a significant difference (p < 0.05). Conclusions: This study identified Remdesivir-induced liver toxicity and oxidative stress alterations in rats, underscoring the need for careful liver function monitoring, especially in patients with hepatic dysfunction. The findings recommend caution in using Remdesivir as a first-line treatment in such cases, and further studies are required to validate these effects and explore broader clinical implications.

Background & Aims: Remdesivir (REM) has been widely used to treat subjects affected by COVID-19 due to its broad-spectrum activity. The aim was to assess the REM effect on liver histopathology, enzymes, and alterations in oxidative stress markers.Methods Forty-eight Wistar rats were separated into eight groups as follows: Group A (Control) received normal saline intraperitoneally (IP) for 10 days; Group B (Low-dose REM) received REM (2.8 mg/kg for the first day and 1.4 mg/kg for days 2 to 10, IP); Group C (High-dose REM) received REM (8.5 mg/kg IP for the first 17 days and days 2 to 10); Group D (High-dose REM + DEX (Dexamethasone) + HEP (Heparin) received DEX (7 mg/kg intramuscularly for 10 days) and HEP (333 IU/kg subcutaneously on the first day and 250 IU/kg subcutaneously every 12 hours from day 2 to day 10); Group E (High-dose REM + DEX); Group F (High-dose REM + HEP); Group G (DEX); Group H (HEP). For statistical analysis, non-parametric tests (Kruskal-Wallis H and Mann-Whitney U) were used for pathological lesions (semi-quantitative data) between the different groups, and a p < 0.05 was considered significant.Results There were mild to severe pathological changes in the treated groups, including cell swelling, vascular congestion. Also, the D and G groups showed similar pathological lesions, which were more severe than in other treated groups with a significant difference (p < 0.05).Conclusions Remdesivir causes hepatic toxicity and alterations in oxidative stress markers, and therefore monitoring is required during treatment.

The dose‐dependent adverse effects of anticancer agents need new methods with lesser toxicity. The objective of the current research was to evaluate the efficacy of GLUT1 inhibitor, as an inhibitor of glucose consumption in cancer cells, in augmenting the efficiency of docetaxel with respect to cytotoxicity and apoptosis. Cell cytotoxicity was assessed by using methylthiazolyldiphenyl‐tetrazolium bromide (MTT) assay. Annexin V/PI double staining was employed to evaluate apoptosis percentage. Quantitative real‐time polymerase chain reaction (RT‐PCR) analysis was accomplished to detect the expression of genes involved in the apoptosis pathway. The IC₅₀ values for docetaxel and BAY‐876 were 3.7 ± 0.81 and 34.1 ± 3.4 nM, respectively. The severity of synergistic mutual effects of these agents on each other was calculated by synergy finder application. It showed that the percentage of apoptotic cells following co‐administration of docetaxel and BAY‐876 increased to 48.1 ± 2.8%. In comparison without GLUT1 co‐administration, the combined therapy decreased significantly the transcriptome levels of the Bcl‐2 and Ki‐67 and a remarkable increase in the level of the Bax as proapoptotic protein(p < 0.05). Co‐treatment of BAY‐876 and docetaxel depicted a synergistic effect which was calculated using the synergy finder highest single agent (HSA) method (HSA synergy score: 28.055). These findings recommend that the combination of GLUT‐1 inhibitor and docetaxel can be considered as a promising therapeutic approach for the treatment of patients with lung cancer.

Background. Lichen planus is considered a potentially malignant condition with an unknown etiology. This study aimed to determine the carcinoembryonic antigen (CEA) and IgG serum levels in different oral lichenoid lesions before and after treatment with local corticosteroids. Methods. Two groups of 23 individuals, including oral ulcerative lichenoid lesions patients and healthy ones, were evaluated. Toluidine blue staining and biopsy examinations were carried out while visual analog scale (VAS) was used to evaluate symptoms. By applying corticosteroids, CEA and IgG serum levels were determined before and three weeks after intervention and at the end of the study (9 weeks) with ELISA and turbidimetry methods, respectively. Results. Before the intervention, there was no significant difference in CEA serum levels between the control and case groups (P=0.19). Moreover, the CEA serum levels indicated no significant difference before and after treatment in the case group (P=0.30). While IgG serum level was significantly higher before the intervention (P=0.01), it decreased significantly in the case group after treatment (P=0.02). In addition, pain intensity reduced significantly in the case group (P=0.05). According to statistics, 8.2% out of 21.7% of patients with positive staining results exhibited dysplasia signs. Conclusion. However, neither CEA nor IgG serum levels were different in patients diagnosed with or without dysplasia and positive or negative staining results (P>0.05). IgG serum levels and pain severity effectively decreased in the oral ulcerative lichenoid lesions patients treated with local corticosteroids. Therefore, this treatment can be considered an effective and low-complication treatment modality for lichenoid lesions.

Background. Oral lichen planus (OLP) is a multifactorial chronic inflammatory condition with unknown etiology. This condition has been associated with Helicobacter pylori. This study aimed to investigate the relationship between the treatment of H. pylori infection and improvements in OLP lesions. Methods. In this cohort study, 42 patients with erosive or ulcerative OLP lesions were evaluated in terms of H. pylori infection using the H. pylori stool antigen (HpSA) test. The patients were divided into three groups. The first group consisted of 12 H. pylori-negative patients. The second group consisted of 21 H. pylori-positive patients receiving antibacterial treatment. The third group included nine H. pylori-positive patients not willing to receive treatment. All the three groups underwent the usual OLP treatment. Patients in the second and third groups were re-evaluated by the HpSA test after two months. The efficacy indexes and visual analog scale were used to evaluate clinical improvements. Results. The efficiency index and pain scores were affected by the intervention (P0.05) was obtained. Conclusion. Pain intensity was higher in patients with H. pylori than in those without H. pylori before treatment. Also, in patients with H. pylori, the treatment affects the complete recovery rate.

Cisplatin is a therapeutic drug widely used to treat various solid tumors. Nephrotoxicity is a well-known side effect in patients treated with cisplatin. Falcarindiol (FAD), natural polyacetylene compound greatly found in Apiaceae family, has anti-cancer, -bacterial, -inflammatory and -oxidant activity which is utilized in the present study. Thirty male C57BL/6 mice were randomly divided into five groups of six each; sham, cisplatin (15 mg/kg), cisplatin + FAD (50 and 100 mg/kg/day), and FAD (100 mg/kg/day). Cisplatin administration elevated the concentrations of BUN and creatinine, as well as kidney histopathologic damage. On the other hand, FAD treatment attenuated cisplatin-induced injury, and also down-regulated mRNA levels of TNF-α and IL-1β together with protein expression of p-NF-kB p65. Moreover, FAD induced the protein expression of p-AMPK and nuclear Nrf2 accompanied by its respective target genes such as NQO-1 and HO-1 in a dose-dependent manner. In conclusion, the findings collectively characterize FAD as a drug candidate to treat cisplatin-induced nephrotoxicity thorough down-regulation of NF-kB signaling pathway in mice

Inflammatory bowel disease (IBD) is a chronic inflammatory condition that may emerge at a young age and often lasts for life. It often goes through phases of recurrence and remission and has a devastating effect on quality of life. The exact etiology of the disease is still unclear, but it appears that an inappropriate immune response to intestinal flora bacteria in people with a genetic predisposition may cause the disease. Managing inflammatory bowel disease is still a serious challenge. Oxidative stress and free radicals appear to be involved in the pathogenesis of this disease, and a number of studies have suggested the use of antioxidants as a therapeutic approach. The antioxidant and anti-inflammatory properties of some trace elements have led some of the research to focus on studying these trace elements in inflammatory bowel disease. Zinc and selenium are among the most important trace elements that have significant anti-inflammatory and antioxidant properties. Some studies have shown the importance of these trace elements in inflammatory bowel disease. In this review, we have attempted to provide a comprehensive overview of the findings of these studies and to gather current knowledge about the association of these trace elements with the inflammatory process and inflammatory bowel disease.