Background: Doxorubicin (DOX) is a potent anti-cancer agent that is widely described in cancer treatment. However, its administration is often limited by its adverse effects, particularly its testicular toxicity, which can induce infertility in male patients. DOX-induced testicular damage is due to oxidative stress, apoptosis, and inflammation. Nanocurcumin (NCR) is a nano-formulated edition of curcumin with a higher therapeutic potential. NCR has demonstrated antioxidant and anti-inflammatory properties. Methods: This study is designed to inspect the potential validity of NCR on DOX-induced testicular damage in male rats. We used thirty-two Wistar albino rats (150–200 g) and divided them into four groups. NCR (80 mg/kg/ dissolved in 1% CMC) was given orally by oral gavage for 14 days. A single dose of DOX (15 mg/kg) (i.p.) was injected on the 7th day of the experiment. Results: DOX treatment reduced the sperm viability and motility rate, cellular antioxidants, and gonadal hormones; it led to higher levels of inflammatory mediators, necrosis, and sloughing in seminiferous tubules. Conversely, NCR treatment significantly alleviated these side effects by improving sperm count/motility and reducing sperm abnormalities. The testicular function recovery was likely driven by stimulating the cytoprotective SIRT1/NF-κB pathway, depressing the testicular level of oxidative indicators such as MDA, TNF-α, iNOS, IL-1β, and NO, and increasing levels of antioxidants such as GSH and SOD. In addition, NCR contradicted the apoptotic changes by downregulating the pro-apoptotic signals Bax and caspase-3, while inducing Bcl-2 upregulation. Moreover, NCR increased levels of gonadal hormones, attenuated histological abnormalities, and preserved testicular structure when compared with the DOX group. Conclusions: NCR treatment can effectively ameliorate DOX-induced testicular toxicity.

Background: Chronic myeloid leukemia (CML) results from chromosomal translocation t(9;22) leading to the formation of the BCR-ABL fusion oncogene. CML has three stages: the chronic phase (CP), the accelerated phase (AP), and the blast crisis (BC). Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of CML. TKIs work well in CP-CML, and these patients have a survival rate similar to the normal population, but TKIs are less effective in advanced-phase CML. Even with current advances in treatment, BC-CML patients have an average overall survival of less than a year. Early recognition of CML patients at risk of disease progression can help in timely interventions with appropriate TKIs or other therapeutic modalities. Although some markers of disease progression like BCR-ABL kinase domain, ASXL1, and GATA2 mutations are available, no universal and exclusively specific molecular biomarkers exist to early diagnose CML patients at risk of CML progression for timely therapeutic interventions to delay or minimize blast crisis transformation in CML. A recent study found that all BC-CML patients harbored the FANCD2 (c.2022-5C>T) mutation. Therefore, the current study was designed to detect this FANCD2 mutant in AP-CML (early progression phase) and to clinically validate its potential as a novel molecular biomarker of early CML progression from CP to AP. Methods: Our study comprised 123 CP-CML (control group) and 60 AP-CML patients (experimental group) from 2 oncology centers, from January 2020 to July 2023. Mean hemoglobin level, WBC count, platelet count, treatment type, hepatomegaly, splenomegaly, and survival status of AP-CML patients were significantly different from those of CP-CML patients. However, as these clinical parameters cannot help in the early detection of patients at risk of CML progression, there was a need for a clinically validated biomarker of AP-CML. DNA was extracted from the patients’ blood samples, and the FANCD2 gene was sequenced using an Illumina NextSeq500 next-generation sequencer (NGS). Results: The NGS analysis revealed a unique splice-site mutation in the FANCD2 gene (c.2022-5C>T). This mutation was detected in the majority (98.3%) of AP-CML patients but in none of the CP-CML patients or healthy control sequences from genomic databases. The mutation was confirmed by Sanger sequencing. FANCD2 is a member of the Fanconi anemia pathway genes involved in DNA repair and genomic stability, and aberrations of this gene are associated with many cancers. Conclusions: In conclusion, our study shows that the somatic FANCD2 (c.2022-5C>T) mutation is a new molecular biomarker for early CML progression. We recommend further clinical validation of this biomarker in prospective clinical trials.

Diabetes mellitus (DM) is a global health challenge marked by chronic hyperglycemia, which can result in complications such as diabetic cardiomyopathy. Sitagliptin, an oral anti-hyperglycemic drug, has demonstrated efficacy in alleviating cardiovascular complications associated with DM. This study explored the impact of Sitagliptin’s potential as a therapeutic agent, functioning not only to control blood sugar levels but also to enhance vascular health and strengthen cardiac resilience in diabetes. The investigation focused on alterations in the vascular endothelial growth factor (VEGF) and its receptor-1 (FLT-1) signaling pathways, as well as its potential to suppress inflammation and oxidative stress. A number of rats received a single dose of streptozotocin (STZ) 55 mg/kg (i.p.) to induce DM. Sitagliptin was administered orally (100 mg/kg/90 days) to normal and diabetic rats, after which samples were collected for investigation. Sitagliptin significantly mitigated weight loss in diabetic rats. Its administration significantly reduced blood glucose levels and improved serum troponin I and CK-MB levels. Heart sections from diabetic rats showed a marked increase in mTOR, VEGF, and FLT-1 immune reaction, while sitagliptin-treated diabetic rats’ heart sections showed moderate immune reactions. Sitagliptin’s protective effect was also associated with reduced inflammation, and apoptotic markers. In conclusion, Sitagliptin is suggested to offer beneficial effects on the vascular health of cardiac blood vessels, thereby potentially reducing myocardial stress in diabetic patients.

Diabetes mellitus (DM) represents a pressing public health challenge globally, with profound implications in both developed and developing nations. It stands as one of the most pervasive and severe chronic conditions worldwide. This study delves into the potential therapeutic effects of naringin on H9c2 cardiac cells subjected to elevated glucose levels, specifically exploring its viability as a treatment for diabetic cardiomyopathy. Methods: For our experiment, we prepared a final concentration of 80.0 μM of NAR in distilled water, subsequently stored at 4.0°C. H9c2 cardiac cells, derived from embryonic rat ventricles, were cultured in DMEM supplemented with FBS, D-Glucose. In this study we simulated Diabetic Cardiomyopathy by exposing the cells to high D-Glucose concentrations. Viability was assessed using the AlamarBlue assay, while ROS production was detected using the DCFH–DA dye. RNA from treated and control cells was isolated to test different genes. Results and discussion: In summary, pre-treatment of H9c2 cardiomyocytes with 80.0 μM concentrations of both Naringenin and Naringin, prior to high glucose exposure, proved most effective, especially concerning the upregulation of the Bcl-2 anti-apoptotic gene. The present study explored the adverse impacts of high glucose (HG) on H9c2 cardiomyocyte cells, evidenced by symptoms like cytotoxicity, apoptosis, oxidative stress, and mitochondrial malfunctions, further underlined by a reduced cell viability. We discovered a pronounced linkage between the surge in reactive oxygen species (ROS) production and HG-driven cardiomyocyte damage. Conclusion: Naringenin (NAR) at 80.0 μM concentration, when pre-treated on H9c2 cardiomyocytes prior to high glucose exposure, effectively upregulates the Bcl-2 anti-apoptotic gene, offering protection against hyperglycemia-triggered cardiac damages by reducing ROS activity and cell apoptosis. The study reaffirms previous findings linking elevated HG levels to cardiomyocyte damage, emphasizing that an 80.0 μM NAR treatment for 2.0 hours is the most potent countermeasure against diabetic cardiomyopathy.

Introduction: Mesenchymal stem cell (MSCs) are multipotent stem cells and can differentiate into different cell types and can proliferate for long time. These two characteristics make MSCs an excellent source for regenerative medicine to treat various diseases and injuries. Objectives: The objectives of the present study are to find the effects of date seed extraction (roasted and non-roasted) as a potential to inhibit adipogenesis of bone marrow MSCs. Materials and Methods: Bone marrow mesenchymal stem cell lines (human MSCS) is a gift from our collaborator from Denmark Professor Mousta Kassems lab in Odense. Cells were cultured in Dulbecco’s Modified Eagle Medium (DMEM) that includes D-glucose 4500 mg/L, 110 mg/L sodium pyruvate, 4 mM L-glutamine, 10% fetal bovine serum (FBS), non-essential amino acids (Gibco-Invitrogen, USA), and 1x penicillin–streptomycin (Pen–strep). Results: The viability of the cells grown has been evaluated using the AlmarBlue according to the standard protocol described. A total of six plates were divided between roasted and non-roasted date seed extracts. The cell viability of these plates was measured on day 1, day 2 and day 3 using AlmarBlue. Moreover, we measured the cell viability of the remaining two plates of the 24 well-plate on day 9 for cells incubated with different concentrations of roasted and non-roasted date seed extract with or without adipocyte induction medium CNT. The intensity of fluorescence is proportional to the number of living cells in treated samples and CNT. AlmarBlue assay showed that roasted date extract manifested high cell viability on day 1 and day 2 compared to day 3 which showed a reduction in cell viability. The cell viability of extract from roasted date seed showed high metabolic activity showed at 50, 500 and 1000 concentrations on day two. Conclusion:The present study showed that roasted and non-roasted date seed extract were significantly reducing adipocyte differentiation compared to the control group. We observed that non-roasted date seed extract significantly reduces adipocyte with 100 g/ml concentration and above. Practical Implications: These results may have clinical implications for diabetic patients since date seed extract has anti-adipogenic, anti-oxidants, anti-bacterial and anti-viral effects. Further studies are needed to determine the correct dose of date seed extract.