Exploring the anti-cancer potential of SGLT2 inhibitors in breast cancer treatment in pre-clinical and clinical studies.

The link between type 2 diabetes mellitus (T2DM) and an increased risk of breast cancer (BC) has prompted the exploration of novel therapeutic strategies targeting shared metabolic pathways. This review focuses on the emerging evidence surrounding the potential anti-cancer effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors in the context of BC. Preclinical studies have demonstrated that various SGLT2 inhibitors, such as canagliflozin, dapagliflozin, ipragliflozin, and empagliflozin, can inhibit the proliferation of BC cells, induce apoptosis, and modulate key cellular signaling pathways. These mechanisms include the activation of AMP-activated protein kinase (AMPK), suppression of mammalian target of rapamycin (mTOR) signaling, and regulation of lipid metabolism and inflammatory mediators. The combination of SGLT2 inhibitors with conventional treatments, including chemotherapy and radiotherapy, as well as targeted therapies like phosphoinositide 3-kinases (PI3K) inhibitors, has shown promising results in enhancing the anti-cancer efficacy and potentially reducing treatment-related toxicities. The identification of specific biomarkers or genetic signatures that predict responsiveness to SGLT2 inhibitor therapy could enable more personalized treatment selection and optimization, particularly for challenging BC subtypes [e, g., triple negative BC (TNBC)]. Ongoing and future clinical trials investigating the use of SGLT2 inhibitors, both as monotherapy and in combination with other agents, will be crucial in elucidating their translational potential and guiding their integration into comprehensive BC care. Overall, SGLT2 inhibitors represent a novel and promising therapeutic approach with the potential to improve clinical outcomes for patients with various subtypes of BC, including the aggressive and chemo-resistant TNBC.

Nanotechnology and nano-sized tools: Newer approaches to circumvent oncolytic adenovirus limitations.

Oncolytic adenoviruses (OAds), engineered Ads preferentially infect and lyse tumor cells, have attracted remarkable attention as immunotherapy weapons for the treatment of various malignancies. Despite hopeful successes in preclinical investigations and translation into clinical phases, they face some challenges that thwart their therapeutic effectiveness, including low infectivity of cancer cells, liver sequestration, pre-existing neutralizing antibodies, physical barriers to the spread of Ads, and immunosuppressive TME. Nanotechnology and nano-sized tools provide several advantages to overcome these limitations of OAds. Nano-sized tools could improve the therapeutic efficacy of OAds by enhancing infectivity and cellular uptake, targeting and protecting from pre-existing immune responses, masking and preventing liver tropism, and co-delivery with other therapeutic agents. Herein, we reviewed the constructs of various OAds and their application in clinical trials, as well as the limitations they have faced. Furthermore, we emphasized the potential applications of nanotechnology to solve the constraints of OAds to improve their anti-tumor activities.

Exploring the microplastic pollution: Unveiling origins and varieties in coastal sediments and waters of the Bushehr Province, Persian Gulf, Iran.

In this study, microplastic (MP) pollution in the coastal sediments and tidal waters of Bushehr province in the Persian Gulf was comprehensively investigated. The sampling stations were selected based on their proximity to various human activities in January and February 2022, such as tourism, fishing, urban development and industry. The results showed that the abundance of MP associated with different human activities varied. The highest concentrations were observed near the petrochemical industry in Asaluyeh, followed by the densely populated Bushehr and the fishing port of Dayyer. Other areas such as Ganaveh, Deylam and Mand also showed varying levels of MP contamination. The average MP concentration was 1.67 × 104 particles/km2 in surface water and 1346.67 ± 601.69 particles/kg in dry sediment. Fiber particles were in the majority in both sediment and water samples, mainly black. The sediment samples had a size range of 100-500 µm (41.34 %), while the water samples were between 500 and 1000 µm (33.44 %). The main polymers found were polyethylene (PE) and polypropylene (PP). This assessment highlights the widespread problem of microplastic pollution in the coastal and intertidal zones of Bushehr province in the Persian Gulf.

The protective effect of hydroalcoholic extract of Ephedra pachyclada leaves on ovarian damage induced by cyclophosphamide in rat: An experimental study.

Background: Cyclophosphamide (CP) is an anticancer drug that acts as an alkylation agent after metabolism in the liver. CP has toxic effects on the body's cells, especially the reproductive system's function, and causes infertility. Moreover, medicinal plants have few side effects and are psychologically acceptable to patients. Objective: This study aimed to investigate the impact of Ephedra pachyclada hydroalcoholic extract (EPHE) on ovarian tissue and hypothalamic-pituitary-gonadal axis in rats treated with CP. Materials and Methods: In this experimental study, 48 adult female Wistar rats (180-200 gr, 9-10 wk) were randomly assigned to 6 experimental groups (n = 8/each): (a) control; (b) sham; (c) CP; (d) CP+250 mg/kg EPHE; (e) CP+500 mg/kg EPHE; (f) CP+1000 mg/kg EPHE. On the 29th day of the experiment, serum was collected; serum concentration of the luteinizing hormone, follicle-stimulating hormone, estrogen, progesterone, and antioxidant activity were measured. The number of ovarian follicles were also counted. Results: In the CP groups, serum concentrations of follicle-stimulating hormone and luteinizing hormone significantly increased, and estrogen and progesterone significantly decreased (p ≤ 0.05). EPHE significantly compensated for the complications caused by CP and 1000 mg/kg had the greatest effect. Antioxidant reduction by CP was significantly enhanced by EPHE, especially at higher doses (p ≤ 0.05). The number of primordial, primary, secondary, and Graafian follicles showed a significant decrease in CP groups and EPHE groups showed a significant increase compared to the CP. EPHE showed that the concentration of 1000 mg/kg was more effective than other doses (p ≤ 0.05). Conclusion: In addition to proving the effect of EPHE on the hypothalamic-pituitary-gonadal axis, our investigation showed antioxidant properties, which can be an effective factor in CP-treated rats.

Biomedical applications of PLGA nanoparticles in nanomedicine: advances in drug delivery systems and cancer therapy.

INTRODUCTION: During the last decades, the ever-increasing proportion of patients with cancer has been led to serious concerns worldwide. Therefore, the development and use of novel pharmaceuticals, like nanoparticles (NPs)-based drug delivery systems (DDSs), can be potentially effective in cancer therapy. AREA COVERED: Poly lactic-co-glycolic acid (PLGA) NPs, as a kind of bioavailable, biocompatible, and biodegradable polymers, have approved by the Food and Drug Administration (FDA) for some biomedical and pharmaceutical applications. PLGA is comprised of lactic acid (LA) and glycolic acid (GA) and their ratio could be controlled during various syntheses and preparation approaches. LA/GA ratio determines the stability and degradation time of PLGA; lower content of GA results in fast degradation. There are several approaches for preparing PLGA NPs that can affect their various aspects, such as size, solubility, stability, drug loading, pharmacokinetics, and pharmacodynamics, and so on. EXPERT OPINION: These NPs have indicated the controlled and sustained drug release in the cancer site and can use in passive and active (via surface modification) DDSs. This review aims to provide an overview of PLGA NPs, their preparation approach and physicochemical aspects, drug release mechanism and the cellular fate, DDSs for efficient cancer therapy, and status in the pharmaceutical industry and nanomedicine.

Abundance and characteristics of microplastic in some commercial species from the Persian Gulf, Iran.

Global production of plastics has increased dramatically in recent decades and is considered a major threat to marine life and human health due to their stability, persistence, and potential to move through food chains. The study was conducted to detect, identify and quantify microplastics (MP) in the gastrointestinal tract (GI) of some commercial fish species in the North Persian Gulf in Bushehr Province: Psettodes erumei, Sphyraena jello, Sillago sihama, Metapenaeus affinis and Portunus segnis. A total of 216 plastic particles were collected from 102 individuals (72.68% of all sampled individuals; MP prevalence of 85.1% for M. affinis, 80% for P. segnis, 70% for P.erumei, 60.3% for S.sihama, 45.2% for S.jello). The average number of microplastics per organism was 2.26 ± 0.38 MP/ind (considering only species that ingested plastic, n = 102) and 1.51 ± 0.40 pieces/ind (considering all species studied, n = 140). Microfibers accounted for 58.49% of the total microplastics, followed by fragments (33.02%) and pellets (8.49%). The most common color of microplastic was black (52.83%), followed by blue (22.64%) and transparent (15.09%). The length of microplastic ranged from 100 to 5000 µm with an average of 854 ± 312 µm. Microplastics were significantly (p < 0.05) abundant in two shrimp studied: M. affinis and P. segnis (plastic in 80% of individuals studied) and to a lesser extent in the pelagic barracuda fish S. jello (plastic in 45% of individuals studied). The main synthetic polymers identified by Fourier transform infrared spectroscopy (FTIR) were polyethylene (38%), polypropylene (24%), polystyrene (17%), polyethylene terephthalate (11%) and polyamide (10%). The pollutant load index and lifetime accumulation index were calculated to identify the most polluted species and their toxicity to human health. The white shrimp M. affinis was identified as the most polluted and toxic species for MP based on PLI. The present study can provide valuable data for further research and a background for the control and monitoring of this pollutant in the coastal environment of Bushehr province.

Nanovaccines for cancer immunotherapy: Focusing on complex formation between adjuvant and antigen.

As an interesting cancer immunotherapy approach, cancer vaccines have been developed to deliver tumor antigens and adjuvants to antigen-presenting cells (APCs). Although the safety and easy production shifted the vaccine designing platforms toward the subunit vaccines, their efficacy is limited due to inefficient vaccine delivery. Nanotechnology-based vaccines, called nanovaccines, address the delivery limitations through co-delivery of antigens and adjuvants into lymphoid organs and APCs and their intracellular release, leading to cross-presentation of antigens and induction of potent anti-tumor immune responses. Although the nanovaccines, either as encapsulating agents or biomimetic nanoparticles, exert the desired anti-tumor activities, there is evidence that the mixing formulation to form nanocomplexes between antigens and adjuvants based on the electrostatic interactions provokes high levels of immune responses owing to Ags' availability and faster release. Here, we summarized the various platforms for developing cancer vaccines and the advantages of using delivery systems. The cancer nanovaccines, including nanoparticle-based and biomimetic-based nanovaccines, are discussed in detail. Finally, we focused on the nanocomplexes formation between antigens and adjuvants as promising cancer nanovaccine platforms.

In vitro calcium availability in bakery products fortified with tuna bone powder as a natural calcium source.

Avoidance of dairy products due to lactose intolerance can lead to insufficiency of calcium (Ca) in the body. In an approach to address this problem, tuna bone powder (TBP) was formulated as a calcium supplement to fortify bakery products. In a study, TBP recovered by alkaline treatment contained 38.16 g/100 g of calcium and 23.31 g/100 g of phosphorus. The ratio of Ca:P that was close to 2:1 was hence comparable to that in human bones. The availability of calcium in TBP was 53.93%, which was significantly higher than most calcium salts, tricalcium phosphate (TCP) being the exception. In vitro availability of calcium in TBP-fortified cookies or TCP-fortified cookies were comparable at 38.9% and 39.5%, respectively. These values were higher than the readings from TBP-fortified bread (36.7%) or TCP-fortified bread (37.4%). Sensory evaluation of bakery products containing TBP or TCP elicited comparable scores for the two additives from test panels. Hence, TBP could be used in the production of high calcium bakery products that would enjoy consumer acceptance.