In Vitro Bactericidal Activity of Biogenic Copper Oxide Nanoparticles for Neisseria gonorrhoeae with Enhanced Compatibility for Human Cells.

Resistance to antibiotics and antimicrobial compounds is a significant problem for human and animal health globally. The development and introduction of new antimicrobial compounds are urgently needed, and copper oxide nanoparticles (CuO NPs) have found widespread application across various sectors including biomedicine, pharmacy, catalysis, cosmetics, and many others. What makes them particularly attractive is the possibility of their synthesis through biogenic routes. In this study, we synthesized biogenic green tea (GT, Camellia sinensis)-derived CuO NPs (GT CuO NPs) and examined their biophysical properties, in vitro toxicity for mammalian cells in culture, and then tested them against Neisseria gonorrhoeae, an exemplar Gram-negative bacterium from the World Health Organization's Priority Pathogen List. We compared our synthesized GT CuOP NPs with commercial CuO NPs (Com CuO NPs). Com CuO NPs were significantly more cytotoxic to mammalian cells (IC50 of 7.32 µg/mL) than GT CuO NPs (IC50 of 106.1 µg/mL). GT CuO NPs showed no significant increase in bax, bcl2, il6, and il1ß mRNA expression from mammalian cells, whereas there were notable rises after treatment with Com CuO NPs. GT-CuO NPs required concentrations of 0.625 and 3.125 µg/mL to kill 50 and 100% of bacteria, respectively, whereas Com-CuO NPs needed concentrations of 15.625 and 30 µg/mL to kill 50 and 100% of bacteria, and the antibiotic ceftriaxone killed 50 and 100% with 3.125 and 30 µg/mL. Gonococci could be killed within 30 min of exposure to GT CuO NPs and the NPs could kill up to 107 within 1 h. In summary, this is the first report to our knowledge that describes the bioactivity of biogenic CuO NPs against N. gonorrhoeae. Our data suggest that biogenic nanoparticle synthesis has significant advantages over traditional chemical routes of synthesis and highlights the potential of GT-CuO NPs in addressing the challenges posed by multidrug-resistant Neisseria gonorrhoeae infections.

Nitric Oxide Plays a Dual Role in Cardiorenal Syndrome in Vitro Model.

BACKGROUND/AIMS: Nitric oxide (NO) plays a dual role, acting as both an oxidant and a reducer, with various effects depending on its concentration and environment. Acute kidney injury's (AKI) pathogenesis observed in cardiorenal syndrome 3 (CRS 3) involves inflammatory responses and the production of reactive oxygen and nitrogen species. However, the role of NO on the development of CRS 3 is still not completely understood. The study aimed to mimic CRS 3 in vitro and investigate NO signaling and inflammatory molecules. METHODS: Thus, HEK293 cells were submitted to normoxia (NX) or hypoxia (HX) protocols for 16 h followed by 3 h of reoxygenation, treated or not with L-NAME. Conditionate medium by HEK293 was transferred to H9c2 for 24 h. Cellular viability was evaluated by MTT assay, real time PCR was used to analyze gene expression and NO content were evaluated in the intra and extracellular medium by amperimetry. RESULTS: Carbonic anhydrase 9 (CA9) expression increased 2.9-fold after hypoxia. Hypoxia reduced 18 % cell viability in HEK293 that was restored by L-NAME treatment. The sum of nitrite (NO2-) and S-nitrosothiol (S-NO) fractions in HEK293 cells showed a substantial decrease on NO intracellular content (38 %). Both IL-6 and IL-10 decreased in all groups compared to NX cells. Besides TNF-α and Bax/Bcl2 ratio increased in hypoxia (approximately 120-fold and 600-fold, respectively) and L-NAME restored this effect. Regarding H9c2 cells, the S-NO fractions showed a substantial decrease in extracellular content after HX (17%) that was not restored by L-NAME. IL-1ß decreases in cardiac cells treated with conditioned medium from HX/L-NAME. CONCLUSION: In conclusion this study highlights the complex interplay of NO and inflammatory factors in hypoxia-induced renal and cardiac cell responses, with potential implications for cardiorenal syndrome.

Chronic exposure to nitric oxide sensitizes prostate cancer cells and improved ZnO/CisPt NPs cytotoxicity and selectivity.

The co-therapy of common chemotherapeutics with nitric oxide (NO), an endogenous signaling molecule, is proposed as an alternative to sensitize cancer cells and enhance treatments' efficacy. Herein, we have synthesized cisplatin-releasing zinc oxide nanoparticles (ZnO/CisPt NPs), which promoted a sustained and pH targeted release, able to release a higher amount of CisPt at tumor microenvironment conditions. This material was combined with a chronic NO treatment, at low concentration, in prostate cancer cells (PC3). NO treatment enhanced the S-NO concentration in PC3 cells, suggesting the nitrosylation or transnitrosylation processes enhancement, which are directly related to S-NO binding to proteins, function alterations and cancer cells death. Indeed, these mechanisms directly impacted the cytotoxic effect of ZnO/CisPt NPs, inducing a 30 % higher viability reduction of PC3 cells after NO treatment, along with a higher selectivity index when compared to normal human fibroblasts (FN1).

Short-term menthol treatment promotes persistent thermogenesis without induction of compensatory food consumption in Wistar rats: implications for obesity control.

In this study, we aimed to evaluate the influence of daily repeated menthol treatments on body mass and thermoregulatory effectors in Wistar rats, considering that menthol is a transient receptor potential melastatin 8 channel agonist that mimics cold sensation and activates thermoregulatory cold-defense mechanisms in mammals, promoting hyperthermia and increasing energy expenditure, and has been suggested as an anti-obesity drug. Male Wistar rats were topically treated with 5% menthol for 3 or 9 consecutive days while body mass, food intake, abdominal temperature, metabolism, cutaneous vasoconstriction, and thermal preference were measured. Menthol promoted hyperthermia on all days of treatment, due to an increase in metabolism and cutaneous vasoconstriction, without affecting food intake, resulting in less mass gain in menthol-hyperthermic animals. As the treatment progressed, the menthol-induced increases in metabolism and hyperthermia were attenuated but not abolished. Moreover, cutaneous vasoconstriction was potentiated, and an increase in the warmth-seeking behavior was induced. Taken together, the results suggest that, although changes occur in thermoeffector recruitment during the course of short-term treatment, menthol is a promising drug to prevent body mass gain. NEW & NOTEWORTHY Menthol produces a persistent increase in energy expenditure, with limited compensatory thermoregulatory adaptations and, most unexpectedly, without affecting food intake. Thus short-term treatment with menthol results in less mass gain in treated animals compared with controls. Our results suggest that menthol is a promising drug for the prevention of obesity.