Studying the effects of secondary metabolites isolated from Cycas thouarsii R.Br. leaves on MDA-MB-231 breast cancer cells.

The various therapeutic drugs that are currently utilized for the management of cancer, especially breast cancer, are greatly challenged by the augmented resistance that is either acquired or de novo by the cancer cells owing to the long treatment periods. So, this study aimed at elucidating the possible anticancer potential of four compounds 7, 4', 7'', 4'''-tetra-O-methyl amentoflavone, hesperidin, ferulic acid, and chlorogenic acid that are isolated from Cycas thouarsii leaves n-butanol fraction for the first time. The MTT assay evaluated the cytotoxic action of four isolated compounds against MDA-MB-231 breast cancer cells and oral epithelial cells. Interestingly, ferulic acid revealed the lowest IC50 of 12.52 µg/mL against MDA-MB-231 cells and a high IC50 of 80.2 µg/mL against oral epithelial cells. Also, using an inverted microscope, the influence of ferulic acid was studied on the MDA-MB-231, which revealed the appearance of apoptosis characteristics like shrinkage of the cells and blebbing of the cell membrane. In addition, the flow cytometric analysis showed that the MDA-MB-231 cells stained with Annexin V/PI had a rise in the count of the cells in the early and late apoptosis stages. Moreover, gel electrophoresis detected DNA fragmentation in the ferulic acid-treated cells. Finally, the effect of the compound was tested at the molecular level by qRT-PCR. An upregulation of the pro-apoptotic genes (BAX and P53) and a downregulation of the anti-apoptotic gene (BCL-2) were observed. Consequently, our study demonstrated that these isolated compounds, especially ferulic acid, may be vital anticancer agents, particularly for breast cancer, through its induction of apoptosis through the P53-dependent pathway.

Potential Therapeutic Benefits of Metformin Alone and in Combination with Sitagliptin in the Management of Type 2 Diabetes Patients with COVID-19.

Type 2 diabetes mellitus (T2DM) is a potential risk factor for the development of COVID-19 and is associated with higher severity and mortality rates. T2DM patients are commonly treated with metformin monotherapy or metformin plus sitagliptin. In the present case-control, single-center cohort study, a total number of 112 T2DM patients suffering from COVID-19 and aged 44−62 years old were compared with 78 T2DM patients without COVID-19 and aged 42−56 years old. Both the patient group and the control group were allocated into four groups. Group A: T2DM patients with COVID-19 on metformin treatments plus standard therapy (n = 60); group B: T2DM patients with COVID-19 on metformin plus sitagliptin plus standard therapy (n = 52); group C: T2DM patients without COVID-19 on metformin treatments (n = 40); and group D: T2DM patients without COVID-19 on metformin plus sitagliptin (n = 38). The investigation duration was 2−3 weeks. Anthropometric measurements, serological and biochemical investigations, pulmonary radiological findings, and clinical outcomes were evaluated. Only 101 T2DM patients with COVID-19 continued the study, 71 (70.29%) with mild-moderate COVID-19 and 30 (29.7%) with severe COVID-19 were compared with 78 T2DM patients as a control. Inflammatory biomarkers (C reactive protein, ferritin, and procalcitonin), a lung injury biomarker (lactate dehydrogenase), and a coagulopathy biomarker (D-dimer) were elevated in severe COVID-19 patients compared with mild-moderate COVID-19 (p < 0.05) and T2DM patients (p < 0.05). However, metformin plus sitagliptin was more effective than metformin monotherapy in T2DM patients with COVID-19, as evidenced by the mitigation of oxidative stress, CT scan score, and clinical outcomes. The present study confirmed the protective effects of this combination against the development of COVID-19 severity, as most T2DM COVID-19 patients develop mild-moderate forms. Herein, the combination of metformin and sitagliptin may lead to more beneficial effects than metformin monotherapy.

Gentiopicroside PLGA Nanospheres: Fabrication, in vitro Characterization, Antimicrobial Action, and in vivo Effect for Enhancing Wound Healing in Diabetic Rats.

Purpose: Gentiopicroside (GPS), an adequate bioactive candidate, has a promising approach for enhancing wound healing due to its antioxidant and antimicrobial properties. Its poor aqueous solubility negatively affects oral absorption accompanied by low bioavailability due to intestinal/hepatic first-pass metabolism. Our aim in this study is to fabricate GPS into appropriate nanocarriers (PLGA nanospheres, NSs) to enhance its solubility and hence its oral absorption would be improved. Methods: Normal and ODS silica gel together with Sephadex LH20 column used for isolation of GPS from Gentiana lutea roots. Crude GPS would be further processed for nanospheres fabrication using a single o/w emulsion solvent evaporation technique followed by in vitro optimization study to examine the effect of two formulation variables: polymer (PLGA) and stabilizer (PVA) concentrations on the physical characterizations of prepared NSs. Possible GPS-PLGA chemical and physical interactions have been analyzed using Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The optimum GPS-PLGA NSs have been chosen for antimicrobial study to investigate its inhibitory action on Staphylococcus aureus compared with unloaded GPS NSs. Also, a well-designed in vivo study on streptozotocin-induced diabetic rats has been performed to examine the wound healing effect of GPS-PLGA NSs followed by histological examination of wound incisions at different day intervals throughout the study. Results: The optimum GPS PLGA NSs (F5) with well-controlled particle size (250.10±07.86 nm), relative high entrapment efficiency (83.35±5.71), and the highest % cumulative release (85.79±8.74) have increased the antimicrobial activity as it exhibited a higher inhibitory effect on bacterial growth than free GPS. F5 showed a greater enhancing impact on wound healing and a significant stimulating effect on the synthesis of collagen fibers compared with free GPS. Conclusion: These findings demonstrate that loading GPS into PLGA NSs is considered a promising strategy ensuring optimum GPS delivery for potential management of wounds.