Letrozole (LTZ) is a non-steroidal aromatase inhibitor that is commonly used in breast cancer therapy. It has several side effects that might lead to the drug's cessation and data of LTZ's potential adverse effects on the hepatorenal microenvironment was conflicting. In addition, searching for therapeutic interventions that could modulate its adverse effects will be very beneficial. So, this study aims to determine the impact of LTZ on the hepatorenal microenvironment in cyclic female rats with a proposed regulatory role of L-Carnitine (LC) supplementation giving molecular insights into its possible mechanism of action. LTZ (1 mg/kg using 0.5% carboxy methyl cellulose as a vehicle for 21 consecutive days orally) to assess its impact on hepatorenal microenvironment. After treatment with LC (100 mg/kg orally) for 14 days, hepatorenal redox state (lipid peroxides (MDA), reduced glutathione (GSH) and catalase enzyme (CAT)), as well as relative gene expression of nuclear factor erythroid 2-related factor 2 (), cytochrome-c ( and caspase-3 () were evaluated. Histopathological examination and immunohistochemical staining of in both liver and kidney were done. LTZ altered hepatic and renal functions. Relative gene expression of hepatorenal , and as well as redox state revealed significant deterioration. Also, the liver and kidney tissues showed several micromorphological changes and intense reaction to upon immunohistochemical staining. It can be concluded that LC alleviates LTZ induced hepatorenal oxidative stress (OS) and mitochondrial-dependent apoptotic progression through modulation of , , and signaling in female rats.

Cisplatin (Cis) is a potent chemotherapeutic agent; however, it is linked with oxidative stress, inflammation, and apoptosis, which may harmfully affect the brain. L. (HP L.) is a strong medicinal plant, but its hydrophobic polyphenolic compounds limit its activity. Therefore, our study aimed to investigate the neuroprotective action of HP L. and its nanoemulsion (NE) against Cis-induced neurotoxicity. The prepared HP.NE was subjected to characterization. The droplet size distribution, surface charge, and morphology were evaluated. In addition, an in vitro dissolution study was conducted. Compared to Cis-intoxicated rats, HP L. and HP.NE-treated rats displayed improved motor activity and spatial working memory. They also showed an increase in their antioxidant defense system and a reduction in the levels of pro-inflammatory cytokines in the brain. Moreover, they showed an increase in the expression levels of the PON-3 and GPX genes, which are associated with a reduction in the brain levels of COX-2 and TP-53. These findings were confirmed by reducing the immunohistochemical expression of nuclear factor kappa (NF-ƘB) and enhanced Ki-67 levels. In conclusion, HP L. is a promising herb and could be used as an adjuvant candidate to ameliorate chemotherapeutic-induced neurotoxicity. Moreover, HP.NE has superior activity in lessening Cis-induced oxidative stress, inflammation, and apoptosis in brain tissue.

Cisplatin (Cis) is a potent chemotherapeutic agent; however, it is linked with oxidative stress, inflammation, and apoptosis, which may harmfully affect the brain. L. (HP L.) is a strong medicinal plant, but its hydrophobic polyphenolic compounds limit its activity. Therefore, our study aimed to investigate the neuroprotective action of HP L. and its nanoemulsion (NE) against Cis-induced neurotoxicity. The prepared HP.NE was subjected to characterization. The droplet size distribution, surface charge, and morphology were evaluated. In addition, an in vitro dissolution study was conducted. Compared to Cis-intoxicated rats, HP L. and HP.NE-treated rats displayed improved motor activity and spatial working memory. They also showed an increase in their antioxidant defense system and a reduction in the levels of pro-inflammatory cytokines in the brain. Moreover, they showed an increase in the expression levels of the PON-3 and GPX genes, which are associated with a reduction in the brain levels of COX-2 and TP-53. These findings were confirmed by reducing the immunohistochemical expression of nuclear factor kappa (NF-ƘB) and enhanced Ki-67 levels. In conclusion, HP L. is a promising herb and could be used as an adjuvant candidate to ameliorate chemotherapeutic-induced neurotoxicity. Moreover, HP.NE has superior activity in lessening Cis-induced oxidative stress, inflammation, and apoptosis in brain tissue.

Bacterial vaginosis (BV) is a common condition that affects one-third of women worldwide. BV is characterized by low levels of healthy lactobacilli and an overgrowth of common anaerobes such as Gardnerella. Antibiotics for BV are administered orally or vaginally; however, approximately half of those treated will experience recurrence within 6 months. Lactobacillus crispatus present at high levels has been associated with positive health outcomes. To address the high recurrence rates following BV treatment, beneficial bacteria have been considered as an alternative or adjunct modality. This study aimed to establish proof-of-concept for a new long-acting delivery vehicle for L. crispatus. Here, it is shown that polyethylene oxide (PEO) fibers loaded with L. crispatus can be electrospun with poly(lactic-co-glycolic acid) (PLGA) fibers (ratio 1:1), and that this construct later releases L. crispatus as metabolically viable bacteria capable of lactic acid production and anti-Gardnerella activity. Probiotic-containing fibers were serially cultured in MRS (deMan, Rogosa, Sharpe) broth with daily media replacement and found to yield viable L. crispatus for at least 7 days. Lactic acid levels and corresponding pH values generally corresponded with levels of L. crispatus cultured from the fibers and strongly support the conclusion that fibers yield viable L. crispatus that is metabolically active. Cultures of L. crispatus-loaded fibers limited the growth of Gardnerella in a dilution-dependent manner during in vitro assays in the presence of cultured vaginal epithelial cells, demonstrating bactericidal potential. Exposure of VK2/E6E7 cells to L. crispatus-loaded fibers resulted in minimal loss of viability relative to untreated cells. Altogether, these data provide proof-of-concept for electrospun fibers as a candidate delivery vehicle for application of vaginal probiotics in a long-acting form.

Hepatic encephalopathy (HE) is a life-threatening disease caused by acute or chronic liver failure manifested by aberrant CNS changes. In the present study, we aimed to explore the neuroprotective effect of lactoferrin (LF) against thioacetamide (TAA)-induced HE in rats. Animals were divided into four groups, control, LF control, TAA-induced HE, and LF treatment, where LF was administered (300 mg/kg, p.o.) for 15 days in groups 2 and 4 meanwhile, TAA (200 mg/kg, i.p.) was given as two injections on days 13 and 15 for the 3rd and 4th groups. Pretreatment with LF significantly improved liver function observed as a marked decline in serum AST, ALT, and ammonia, together with lowering brain ammonia and enhancing motor coordination as well as cognitive performance. Restoration of brain oxidative status was also noted in the LF-treated group, where lipid peroxidation was hampered, and antioxidant parameters, Nrf2, HO-1, and GSH, were increased. Additionally, LF downregulated HMGB1, TLR-4, MyD88, and NF-κB signaling pathways, together with reducing inflammatory cytokine, TNF-α, and enhancing brain BDNF levels. Moreover, the histopathology of brain and liver tissues revealed that LF alleviated TAA-induced liver and brain deficits. In conclusion, the promising results of LF in attenuating HMGB1/TLR-4/MyD88 signaling highlight its neuroprotective role against HE associated with acute liver injury via ameliorating neuroinflammation, oxidative stress, and stimulating neurogenesis.