Current pharmaceutical design最新文献

Oxidative stress is a biological stress response produced by the destruction of redox equilibrium in aerobic metabolism in organisms, which is closely related to the occurrence of many diseases. Mesenchymal stem cells (MSCs) have been found to improve oxidative stress injury in a variety of diseases, including lung injury, liver diseases, atherosclerotic diseases, diabetes and its complications, ischemia-reperfusion injury, inflammatory bowel disease. The antioxidant stress capacity of MSCs may be a breakthrough in the treatment of these diseases. This review found that MSCs have the ability to resist oxidative stress, which may be achieved through MSCs involvement in mediating the Nrf2, MAPK, NF-κB, AMPK, PI3K/AKT and Wnt4/β-catenin signaling pathways.

Hepatocellular carcinoma (HCC) is influenced by several factors, among which genetic polymorphisms play a key role. Polymorphisms in various genes affect key pathways involved in HCC development, including metabolism, expression of inflammatory cytokines, cell proliferation, and apoptosis regulation. These polymorphisms induce differential effects on susceptibility to HCC, disease progression, and treatment outcomes. Understanding the effect of genetic variations on HCC pathogenesis is essential to elucidate underlying mechanisms and identify potential therapeutic targets. This review explores the diverse roles of genetic polymorphisms in HCC, providing insights into the complex interplay between genetic factors and disease development.

Nowadays, the usage of probiotics in the food industry has become common. It has been proven that probiotics have many health benefits, such as adjusting the intestinal microbiome, boosting the immune system, and enhancing anti-inflammatory and anti-cancer activities. However, in recent years, some concerns have arisen about the consumption of probiotics, especially in vulnerable populations such as elderly, infants, and people with underlying diseases. As a result, finding a new alternative to probiotics that has the same function as probiotics and is safer has been prioritized. In recent years, postbiotics have been introduced as a great replacement for probiotics. However, the safety of these compounds is not exactly confirmed due to the limited in vivo research. In this review, the definition, classification, activities, limitations, and some advantages of postbiotics over probiotics are discussed. Finally, the limited published data about the safety of postbiotics is summarized.

Introduction: The role of glutamate in the development of some brain pathological conditions, such as multiple sclerosis, has been well described. Levetiracetam (LEV), a new broad-spectrum antiseizure medicine, is widely used to control certain types of seizures. Apart from its anti-seizure activity, LEV exerts neuroprotection via anti-inflammatory, antioxidant, and antiapoptotic effects. The current study was designed to evaluate the protective potential of LEV against glutamate-induced injury in OLN-93 oligodendrocytes.

Methods: At first, the potential negative impact of LEV on OLN-93 viability was evaluated. After that, the cells were concurrently treated with LEV (0-100 μM) and glutamate (8 mM) for 24 h. The viability, redox status, and the rate of apoptosis of OLN-93 cells were then assessed using 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyl-2H-tetrazolium bromide (MTT), 2',7' dichlorodihydrofluorescein diacetate (H2DCFDA), 2-thiobarbituric acid reactive substances (TBARS) and annexin V/propidium iodide (PI) assays, respectively. Moreover, caspase-3 expression, as a marker of cell apoptosis, was evaluated by Western blotting.

Results: LEV at 1-800 μM did not have any negative effect on cell survival. Treatment with LEV (50 and 100 μM) substantially enhanced the cell viability following glutamate insult. The cytoprotective activity of LEV (50 and 100 μM) against glutamate toxicity was accompanied by reduced reactive oxygen species (ROS) accumulation and malondialdehyde (MDA) level. Moreover, 100 μM of LEV inhibited apoptosis and decreased the expression level of cleaved caspase-3 following glutamate exposure.

Conclusion: Taken together, the results suggested that LEV has protective effects against glutamate-mediated cytotoxicity in OLN-93 cells. The oligoprotective action of LEV was shown to be exerted via inhibition of oxidative stress and cellular apoptosis.

A double bond between the nitrogen and carbon atoms characterizes a wide class of compounds known as Schiff bases. The flexibility of Schiff bases is formed from several methods and may be combined with alkyl or aryl substituents. The group is a part of organic compounds, either synthetic or natural, and it serves as a precursor and an intermediate in drugs that have therapeutic action. The review focuses on molecular docking and structure-activity relationship (SAR) analysis for antidiabetic effects of the different nonmetal Schiff bases. Many studies have found that Schiff bases are used as linkers in an extensive range of synthesized compounds and other activities. Thus, this current study aims to give the scientific community a thoughtful look at the principal ideas put forward by investigators regarding antidiabetic actions exhibited by certain Schiff-based derivatives, as this review covered many aspects, including docking and SAR analysis. For individuals who intend to create novel antidiabetic compounds with Schiff bases as pharmacophores or physiologically active moieties, it will be an invaluable informational resource.

Background: Psychosis, marked by detachment from reality, includes symptoms like hallucinations and delusions. Traditional herbal remedies like kratom are gaining attention for psychiatric conditions. This was aimed at comprehending the molecular mechanisms of Kratom's antipsychotic effects utilizing a multi-modal computational approach.

Materials and methods: This study employed network pharmacology followed by molecular docking and molecular dynamics simulation study to investigate the potential antipsychotic properties of kratom compounds by identifying their key molecular targets and interactions.

Results: Compounds present in kratom interact with a variety of receptors and proteins that play a pivotal role in neurotransmission, neurodevelopment, and cellular signaling. These interactions, particularly with dopamine and serotonin receptors, various proteins, and pathways, suggest a complex influence on psychiatric conditions. Both mitragynine and zotepine (an atypical antipsychotic drug) display significant binding affinities for 5HTR2A receptors, suggesting their potential for modulating related physiological pathways. Mitragynine displayed higher flexibility in binding compared to zotepine, which showed a more stable interaction. Hydrogen bond analysis revealed a more variable interaction profile for mitragynine than zotepine.

Conclusion: The research findings suggest that the interaction between kratom compounds and essential brain receptors could influence psychiatric conditions. Notably, both mitragynine (a key kratom component) and zotepine (an antipsychotic) bind to the 5HTR2A receptor, suggesting the potential for kratom to modulate similar pathways. Interestingly, mitragynine's flexible binding mode compared to zotepine might indicate a more diverse range of effects. Overall, the findings suggest complex interactions between kratom and the brain's signaling system, warranting further investigation into its potential therapeutic effects.

Chitosan is a kind of natural material with many unique physicochemical and biological properties related to antibacterial, antioxidant, and chelating. In recent years, chitosan-based nano gels (CS-NG) have been widely used in the field of cancer nanomedicine due to their excellent characteristics including biodegradability, biocompatibility, flexibility, large surface area, controllability, high loading capacity, and especially it can be engineered to become stimuli-responsive to tumor environments. In this review, we summarized the main synthesis approaches of CS-NGs including radical polymerization, self-assembly, microemulsion, and ionic gelation methods. These novel CS-NGs are applied in cancer nanomedicine serving as drug delivery, gene delivery, and bioimaging. Besides, we proposed our perspectives regarding the clinical development of CS-NGs cancer nanomedicine applications.

Introduction: Sepsis, like neutropenic sepsis, is a medical condition in which our body overreacts to infectious agents. It is associated with damage to normal tissues and organs by the immune system, which leads to the spread of inflammation throughout our body. Of note, microRNAs (miRNAs) have been found to have a critical role in the sepsis progression. Such miRNAs are registered in the miRNA databases, such as Gene Expression Omnibus (GEO), with a specific identifier and unique characteristics. There is also computational software, such as TargetScan, that are broadly employed for the analysis of miRNAs, including their identification, target prediction, and functional analysis.

Methods: The current In-silico study aimed to predict miRNAs involved in sepsis progression. To this end, the GEO database was employed to find the sepsis-related genome profile. Afterward, down-regulated genes were selected for further bioinformatics analysis with the assumption that their decreased expression is associated with an increased sepsis progression. The miRNAs complementary to the selected genes were then predicted using TargetScan software. Based on the current In-silico analysis, seven miRNAs, including hsa-miR-325-3p, hsa-miR-146a-3p, hsa-miR-126-5p, hsa-miR-22-3p, hsa-miR-223-3p, hsa-miR-145-5p, and has-miR-181 family, were predicted to participate in sepsis pathogenesis. Among the predicted miRNAs, hsa-miR-325-3p has not been previously predicted or validated to be involved in septic conditions.

Results: Our prediction results showed that hsa-miR-325-3p may target genes implicating in both anti- (ETFB gene) and pro-inflammatory (TCEA1 and PTPN1 genes) responses, suggesting it is an immune hemostasis regulator during sepsis inflammation. Although the role of other predicted miRNAs has been already validated in the sepsis pathogenesis, the current study predicted new targets of these miRNAs, which have not been reported by previous In-silico or experimental studies on sepsis and other pathogenic conditions. Notably, other miRNAs, including hsa-miR-146a-3p, hsa-miR-126-5p, hsa-miR-22-3p, hsa-miR-223-3p, and hsa-miR-145-5p were predicted to target genes participating in inflammatory responses, including BLOC1S1, POLR2G, PTPN1, TCEA1, and CCT3.

Conclusion: In conclusion, the results of the present study can provide promising targets as therapeutic and diagnostic tools to treat and manage inflammation sepsis, such as neutropenic sepsis. However, these findings should be further evaluated in experimental studies to find their exact effects and underlying mechanisms.

Inflammation is a universal response of mammalian tissue to harm, comprising reactions to injuries, pathogens, and foreign particles. Liver inflammation is commonly associated with hepatocyte necrosis and apoptosis. These forms of liver cell injury initiate a sequence of events independent of the etiological basis for the inflammation and can result in hepatic disorders. It is also common for liver cancer. This review fundamentally focuses on the molecular pathways involved in hepatic inflammation. This review aims to explore the molecular pathways involved in hepatic inflammation, focusing on arachidonic acid, NF-κB, MAPK, PI3K/Akt, and JAK/STAT pathways. It investigates active compounds in herbal plants and their pharmacological characteristics. The review proposes a unique therapeutic blueprint for managing hepatic inflammation and diseases by modifying these pathways with herbal remedies.

Implementing lifestyle interventions as a primary prevention strategy is a cost-effective approach to reducing the occurrence of cancer, which is a significant contributor to illness and death globally. Recent advanced studies have uncovered the crucial role of nutrients in safeguarding women's health and preventing disorders. Genistein is an abundant isoflavonoid found in soybeans. Genistein functions as a chemotherapeutic drug against various forms of cancer, primarily by modifying apoptosis, the cell cycle, and angiogenesis and suppressing metastasis. Furthermore, Genistein has demonstrated diverse outcomes in women, contingent upon their physiological characteristics, such as being in the early or postmenopausal stages. The primary categories of gynecologic cancers are cervical, ovarian, uterine, vaginal, and vulvar cancers. Understanding the precise mechanism by which Genistein acts on ovarian cancer could contribute to the advancement of anti-breast cancer treatments, particularly in situations where no specific targeted therapies are currently known or accessible. Additional investigation into the molecular action of Genistein has the potential to facilitate the development of a plant-derived cancer medication that has fewer harmful effects. This research could also help overcome drug resistance and prevent the occurrence of ovarian cancers.