Pharmaceuticals最新文献

Given the current global circumstances, marked by severe environmental pollution-including the contamination of food-along with daily stress and a sedentary lifestyle, many consumers choose to improve their quality of life by using, among others, minimally processed food, food supplements, and gemmo-derivatives. Recent lab and clinical studies have shown the positive impact of specific nutrients with antioxidant capacities in the treatment of several conditions generated by oxidative stress. This paper reviews antioxidant plant extracts utilized as components in various dietary supplements and gemmoderivatives, highlighting their chemical composition and biological properties in preventing diseases caused by oxidative stress. A modern approach to food science brings to the fore the concept of dietary supplements vs. functional food, nutraceuticals, and gemmo-derivatives. The definitions of these terms are not being unanimously regulated in this respect and describe each category of compound and product, also emphasizing the need to implement adequate nutrivigilance. In order to enhance the absorption and bioavailability of dietary supplements and gemmo-derivatives based on antioxidant plant extracts, some encapsulation techniques are outlined.

Objectives: As one of the important interventions to alleviate anthracycline-related cardiotoxicity (ARC), the safety assessment of dexrazoxane in clinical practice is particularly important. This study aims to evaluate the actual efficacy and potential adverse effects of dexrazoxane in clinical practice by analyzing the reports of adverse events (AEs) related to the combination with dexrazoxane and anthracyclines. Methods: We utilized four disproportionality analysis methods to analyze AE reports of the combination with dexrazoxane and anthracyclines in the Food and Drug Administration Adverse Event Reporting System (FAERS) database from the third quarter of 2014 to the first quarter of 2024. Results: Under the three backgrounds, a large number of preferred terms (PTs) such as cardiac failure disappeared in the combined group, and the PTs with significant signal values were mainly concentrated in infections and infestations. For patients under 18, some PTs associated with infections and infestations disappeared after the combination of the two drugs. Conclusions: Dexrazoxane can effectively alleviate ARC, but it may also increase the risk of infection. For infections and infestations, children under 18 years old are more likely to benefit from the combination therapy. More attention should be paid to infectious AEs in the clinical use of dexrazoxane, though disproportionality analysis is a hypothesis-generating approach.

Background: Human dental pulp stem cells (HDPSCs) with multi-lineage differentiation potential and migration ability are required for HDPSC-based bone and dental regeneration. Hispidulin is a naturally occurring flavonoid with diverse pharmacological activities, but its effects on biological properties of HDPSCs remain unknown. Therefore, we investigated the effects of hispidulin on the differentiation potential and migration ability of HDPSCs and elucidated their underlying mechanisms. Methods: The osteo/odontogenic capacity of HDPSCs was assessed using the alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. The migration ability of HDPSCs was evaluated using a scratch wound assay. Furthermore, the endothelial differentiation of HDPSCs was examined by using a capillary sprouting assay and by assessing CD31 expression. Results: Hispidulin significantly enhanced the osteo/odontogenic differentiation of HDPSCs with increased expression of osteo/odontogenic differentiation markers. Hispidulin increased the migration of HDPSCs, which was mediated by the upregulation of C-X-C chemokine receptor type 4 (CXCR4). The treatment of HDPSCs with hispidulin enhanced the differentiation of HDPSCs into endothelial cells, as evidenced by increased capillary sprouting and endothelial marker expression. In addition, we demonstrated that hispidulin activated the ERK1/2 signaling, and its inhibition by U0126 significantly suppressed the hispidulin-induced endothelial differentiation of HDPSCs. Conclusions: These findings demonstrate that hispidulin effectively promotes the osteo/odontogenic and endothelial differentiation, and migration of HDPSCs. These results suggest that hispidulin may have potential therapeutic applications in dental pulp regeneration and tissue engineering.

Designing and standardizing drug formulations are crucial for ensuring the safety and efficacy of medications. Nanomedicine utilizes nano drug delivery systems and advanced nanodevices to address numerous critical medical challenges. Currently, oral and intranasal aerosol drug delivery (OIADD) is the primary method for treating respiratory diseases worldwide. With advancements in disease understanding and the development of aerosolized nano drug delivery systems, the application of OIADD has exceeded its traditional boundaries, demonstrating significant potential in the treatment of non-respiratory conditions as well. This study provides a comprehensive overview of the applications of oral and intranasal aerosol formulations in disease treatment. It examines the key challenges limiting the development of nanomedicines in drug delivery systems, formulation processes, and aerosol devices and explores the latest advancements in these areas. This review aims to offer valuable insights to researchers involved in the development of aerosol delivery platforms.

Late-onset Alzheimer's disease (LOAD) is a chronic, multifactorial, and progressive neurodegenerative disease that associates with aging and is highly prevalent in our older population (≥65 years of age). This hypothesis generating this narrative review will examine the important role for the use of sodium thiosulfate (STS) as a possible multi-targeting treatment option for LOAD. Sulfur is widely available in our environment and is responsible for forming organosulfur compounds that are known to be associated with a wide range of biological activities in the brain. STS is known to have (i) antioxidant and (ii) anti-inflammatory properties; (iii) chelation properties for calcium and the pro-oxidative cation metals such as iron and copper; (iv) donor properties for hydrogen sulfide production; (v) possible restorative properties for brain endothelial-cell-derived bioavailable nitric oxide. Thus, it becomes apparent that STS has the potential for neuroprotection and neuromodulation and may allow for an attenuation of the progressive nature of neurodegeneration and impaired cognition in LOAD. STS has been successfully used to prevent cisplatin oxidative-stress-induced ototoxicity in the treatment of head and neck and solid cancers, cyanide and arsenic poisoning, and fungal skin diseases. Most recently, intravenous STS has become part of the treatment plan for calciphylaxis globally due to vascular calcification and ischemia-induced skin necrosis and ulceration. Side effects have been minimal with reports of metabolic acidosis and increased anion gap; as with any drug treatment, there is also the possibility of allergic reactions, possible long-term osteoporosis from animal studies to date, and minor side-effects of nausea, headache, and rhinorrhea if infused too rapidly. While STS poorly penetrates the intact blood-brain barrier(s) (BBBs), it could readily penetrate BBBs that are dysfunctional and disrupted to deliver its neuroprotective and neuromodulating effects in addition to its ability to penetrate the blood-cerebrospinal fluid barrier of the choroid plexus. Novel strategies such as the future use of nano-technology may be helpful in allowing an increased entry of STS into the brain.

Chinese scorpion (CS), a traditional animal-based medicine used for over a millennium, has been documented since AD 935-960. It is derived from the scorpion Buthus martensii Karsch and is used to treat various ailments such as stroke, epilepsy, rheumatism, and more. Modern research has identified the pharmacological mechanisms behind its traditional uses, with active components like venom and proteins showing analgesic, antitumor, antiepileptic, and antithrombotic effects. Studies reveal that CS affects ion channels, crucial for cellular functions, through interactions with sodium, potassium, and calcium channels, potentially explaining its therapeutic effects. Future research aims to elucidate the precise mechanisms, target specific ion channel subtypes, and validate clinical efficacy and safety, paving the way for novel therapies based on these natural compounds.

Background: At present, the complexity that governs the associations between different biological entities is understood better than ever before, owing to high-throughput techniques and systems biology. Networks of interactions are necessary not only for the visualization of these complex relationships but also because their analysis tends to be valuable for the extraction of novel biological knowledge. Methods: For this reason, we constructed a disease-protein-drug network, focusing on a category of rare protein-misfolding diseases, known as amyloidoses, and on other pathological conditions also associated with amyloid deposition. Apart from the amyloidogenic proteins that self-assemble into fibrils, we also included other co-deposited proteins found in amyloid deposits. Results: In this work, protein-protein, protein-drug, and disease-drug associations were collected to create a heterogenous network. Through disease-based and drug-based analyses, we highlighted commonalities between diseases and proposed an approved drug with prospects of repurposing. Conclusions: The identified disease associations and drug candidates are proposed for further study that will potentially help treat diseases associated with amyloid deposition.

Background: COVID-19 became a global health crisis in early 2020, and the way out of the crisis was the rapid development of vaccines by Sinopharm, Pfizer, and Sputnik, among others, which played a crucial role in controlling the pandemic. Therefore, this study aims to investigate the long-term immune response by measuring the levels of anti-S1 IgG antibodies induced by homologous and heterologous vaccination regimens. Methods: We investigated the titer of the anti-S1 IgG antibody produced for the viral surface antigen 3, 6 months after the second dose, before the third dose, and 1, 3, and 6 months after the third dose. Results: Anti-S1 IgG antibody levels significantly increased three/six months after the second dose and following the booster in individuals without prior COVID-19 infection who received all three homologous vaccine doses. The group that initially responded poorly to Sinopharm showed a significant and sustained increase after receiving the Pfizer booster. Additionally, prior SARS-CoV-2 infection between primary and booster vaccination boosted anti-S1 antibody titers in all individuals, regardless of the vaccine used. The highest vaccine efficacy was observed during the primary vaccination period and declined over time, especially during the omicron-dominant period. Conclusions: The results suggest that while homologous and heterologous booster doses can significantly enhance anti-S1 IgG antibody levels, prior SARS-CoV-2 infection and the type of vaccine administered influence the duration and magnitude of the immune response.

Background/objectives: Films in the mouth offer a promising alternative drug delivery system for oral administration, with several advantages over traditional oral formulations. Furthermore, their non-invasive nature and easy administration make them conducive to increasing patient compliance. The use of active agents in these films can further improve their drug delivery properties, making them an even more useful drug delivery system.

Methods: In this research, carrageenan was used as a polymer, while glycerine was added as a plasticizer, furthermore, lidocaine hydrochloride and diclofenac sodium were used as the active agents. The prepared films were characterized by analytical techniques.

Results: The results showed that glycerine reduced the mucoadhesivity and breaking hardness of the films and increasing the temperature made the films brittle. These results are also confirmed by the statistical analysis. Based on the FTIR results, glycerine can be used in films without structural changes.

Conclusions: Based on the findings, films prepared from a solution with a concentration of 1.5% carrageenan and 1.5% glycerine at 70 °C are suitable as a drug delivery system for use on the buccal mucosa when combined with active agents. Carrageenan was successfully used as a carrier for two different types of active agents.

Background: Luteolin-7-O-glucuronide (L7Gn) is a flavonoid isolated from numerous traditional Chinese herbal medicines that exerts anti-inflammatory effects. Previous research has revealed that aerosol inhalation is the most straightforward way of administration for the delivery of respiratory agents. Thus far, the impact of aerosol inhalation of L7Gn on lung inflammation and the underlying mechanisms remain unknown. Methods: The real-time particle size for L7Gn aerosol inhalation was detected by the Spraytec spray droplet size measurement system, including transmission and size diameters. The acute lung injury (ALI) rat model was induced by aerosol inhalation of LPS to evaluate the protective effect of L7Gn. The inhibitory effect of NLRP3 inflammasome activation assays was conducted in LPS-induced MH-S cells. Elisa, Western blotting, and RT-PCR were utilized to investigate the expression of NLRP3 inflammasome-relevant proteins and genes. Results: In this study, we found that inhalation of L7Gn aerosol significantly reduced pulmonary injury by inhibiting inflammatory infiltration and enhancing lung function. Meanwhile, the NLR family pyrin domain containing 3 (NLRP3) inflammasome was activated dramatically, accompanied by upregulated expression of IL-1β and IL-18, both in the ALI rat model and in LPS-induced MH-S cells. Moreover, L7Gn was found to significantly downregulate the expression of NLRP3, ASC, caspase-1, and cleaved caspase-1, which are critical components of the NLRP3 inflammasome, as well as the expression of IL-1β and IL-18. Conclusions: Based on our findings, L7Gn could exert anti-inflammatory effects by inhibiting NLRP3 inflammasome activation, which may emerge as potential therapeutic agents for the treatment of ALI.