Current Pharmaceutical Design - Volume 29, Issue 28, 2023

The high levels of antibiotic resistance registered worldwide have become a serious health problem, threatening the currently available treatments for a series of infectious diseases. With antibiotics becoming less and less effective, it is becoming increasingly difficult and, in some cases, impossible to treat patients with even common infectious diseases, such as pneumonia. The inability to meet the ever-increasing demand to control microbial infection requires both the search for new antimicrobials and improved site-specific delivery. On the one hand, bacterial secondary metabolites are known for their diverse structure and antimicrobial potential and have been in use for a very long time in diverse sectors. A good deal of research is produced annually describing new molecules of bacterial origin with antimicrobial properties and varied applications. However, very few of these new molecules reach the clinical phase and even fewer are launched in the market for use. In this review article, we bring together information on these molecules with potential for application, in particular, for human and veterinary medicine, and the potential added value of the use of liposomes as delivery systems for site-specific delivery of these drugs with the synergistic effect to overcome the risk of antibiotic resistance.

LncRNA MEG3, a tumor suppressor gene, is related to reducing the proliferation, migration, and invasion as well as apoptosis abilities of gastric cancer (GC), which is a promising therapeutic target in patients. We conducted a comprehensive search of the literature on Pubmed using the keywords “lncRNA MEG3 and gas cancer” from 2014 to the present. Here, we provide a systematic and comprehensive summary of existing knowledge of the lncRNAs MEG3 and reveal its biological function and specific mechanisms in gastric cancer. MEG3 is involved in many molecular mechanisms that inhibit the development and progression of gastric cancer. For example, MEG3 can inhibit the proliferation of gastric cancer cells by inhibiting the expression of miR-21, miR-665, miR-148, miR-208, etc. MEG3 inhibits gastric carcinogenesis by inhibiting the negative regulator MDM2, regulating the expression of tumor suppressor genes p53 and Rb gene, and managing PI3K/Akt and Wnt/β-catenin signaling pathways. Additionally, gastric cancer patients with low MEG3 expression have poor prognosis, and transfection of MEG3 can improve the overall survival time of normal cells. Eventually, lncRNA MEG3 can be used as a biomarker or target for intervention, thereby providing new insights for gastric cancer therapy.

Background: The literature review reveals that NEAT1 is dysregulated in gastric cancer and plays a critical role in various aspects of tumorigenesis, including cell proliferation, invasion, metastasis, and chemotherapy resistance. NEAT1 exerts its functions through interactions with proteins, DNA, and other RNAs, acting as a scaffold or by modulating chromatin modifications and gene expression. Furthermore, NEAT1 is involved in epithelial-mesenchymal transition (EMT), angiogenesis, and immune evasion, contributing to the aggressive behavior of gastric cancer cells. The dysregulation of NEAT1 has been reported to be associated with clinicopathological features, prognosis, and therapeutic response in gastric cancer patients. Methods: A systematic literature search was performed on PubMed from September 2016 to the present using the keywords “LncRNA NEAT1” and “gastric cancer”. A total of 32 articles were identified. Studies investigating the regulatory mechanisms of NEAT1 in other tumors were excluded from this review. Additionally, to provide a more comprehensive understanding of the molecular mechanisms underlying NEAT1-mediated gastric cancer development, 27 additional articles were included. Results: LncRNA NEAT1 plays a pivotal role in gastric cancer, exerting significant effects on proliferation, invasion, metastasis, autophagy, apoptosis, drug resistance, and overall survival. The underlying molecular mechanisms involve miRNA sequestration, protein-protein interactions, transcriptional regulation, DNA methylation modifications, and activation of canonical signaling pathways. These findings underscore the multifaceted involvement of lncRNA NEAT1 in the pathogenesis and therapeutic resistance of gastric cancer, providing valuable insights into potential therapeutic targets and prognostic biomarkers. Conclusion: LncRNA NEAT1 is intricately involved in the pathogenesis of gastric cancer through various molecular mechanisms. Additionally, lncRNA NEAT1 is closely associated with radiotherapy resistance and adverse prognosis in gastric cancer patients, indicating its potential as a promising independent risk factor for clinical treatment targeting and prognostic prediction.

Undifferentiated cells, known as stem cells, have the capacity to self-renew and specialise in a variety of distinct mature and functional cell types while still retaining their original identity. For their significance in regenerative medicine, stem cells' deep potential has been widely examined, and this work has established the groundwork for cell-based therapeutics. With the potential to repair and restore specific organs or tissue injuries or chronic disease situations when the body's regenerative process is insufficient to heal, regenerative medicine is quickly advancing in healthcare. The most recent developments in stem cell-based treatments for regenerative medicine are covered in this review, focusing on mesenchymal stem cell-based treatments because these cells have received the most clinical research. The most recent applications of artificial intelligence algorithms in stem cell-based therapeutics are presented, along with their limitations and potential future applications.

Pain has long been defined as an unpleasant sensory and emotional experience originating from any region of the body in the presence or absence of tissue injury. Physicians involved in acute medicine commonly undertake a variety of invasive and painful procedures that prompt procedural sedation and analgesia (PSA), which is a condition sparing the protective airway reflexes while depressing the patient’s awareness of external stimuli. This state is achieved following obtaining the patient’s informed consent, necessary point-ofcare monitoring, and complete recording of the procedures. The most commonly employed combination for PSA mostly comprises short-acting benzodiazepine (midazolam) and a potent opioid, such as fentanyl. The biggest advantage of opioids is that despite all the powerful effects, upper airway reflexes are preserved and often do not require intervention. Choices of analgesic and sedative agents should be strictly individualized and determined for the specific condition. The objective of this review article was to underline the characteristics, effectiveness, adverse effects, and pitfalls of the relevant drugs employed in adults to facilitate PSA in emergency procedures.

Background: Despite widespread application of drug-eluting stents in coronary intervention, in-stent restenosis (ISR) is still a daunting complication in clinical practice. Panax notoginseng saponins (PNS) are considered to be effective herb compounds for preventing ISR. Objective: This study aimed to elucidate the targets and mechanisms of PNS in ISR prevention using network pharmacology approaches and experimental verification. Methods: Relevant targets of PNS active compounds were collected from the HERB database and PharmMapper. The ISR-related targets were obtained from the GeneCards database and the Comparative Toxicogenomics Database. The GO and KEGG enrichment analysis was performed using R software. The String database and Cytoscape software were employed to build the PPI and compounds-targets-pathways-disease networks. Finally, Molecular docking performed by Autodock Vina and cellular experiments were used to validate network pharmacology results. Results: There were 40 common targets between PNS targets and ISR targets. GO analysis revealed that these targets focused on multiple ISR-related biological processes, including cell proliferation and migration, cell adhesion, inflammatory response, and anti-thrombosis and so on. The KEGG enrichment results suggested that PNS could regulate multiple signaling pathways to inhibit or delay the development and occurrence of ISR. The molecular docking and cellular experiments results verified the network pharmacology results. Conclusion: This study demonstrated that the potential molecular mechanisms of PNS for ISR prevention involved multiple compounds, targets, and pathways. These findings provide a theoretical reference and experimental basis for the clinical application and product development of PNS for the prevention of ISR.

Background: Chemoresistance is a major cause of relapse or death in ovarian cancer (OC) patients. New evidence suggests the crucial role of myeloid-derived suppressor cells (MDSCs) in mediating chemoresistance of cancer cells. We aimed to dissect the way MDSCs affect the cisplatin resistance phenotype of OC and the related mechanisms. Methods: MDSCs were isolated from the spleen of OC mice isograft. CCK-8 and colony formation assays revealed the effects of an MDSC-conditioned medium with dysregulated CD39 on the proliferation and cisplatin sensitivity of OC cells. Fluorescence assay was used to reveal the effects of MDSCs with dysregulated CD39 on adenosine triphosphate (ATP) hydrolysis and adenosine (ADO) synthesis. Results: MDSCs with highly expressed CD39 could facilitate the proliferation and cisplatin resistance of OC cells, while MDSCs with downregulated CD39 caused the opposite results. In addition, MDSCs with upregulated CD39 could facilitate the hydrolysis of immunogenic ATP to immunosuppressive ADO, while the introduction of CD39 inhibitor could repress such hydrolysis of ATP and generation of ADO, thereby abating the proliferation and cisplatin resistance of OC cells. Conclusion: CD39+MDSC could promote the proliferation and cisplatin resistance of OC cells by generating high concentrations of ADO, which indicates that targeting CD39+MDSC might be a feasible way to improve cisplatin resistance in OC.

Background: In the recent decade, there has been increasing interest in preventing ovarian toxicity after chemotherapy exposure. It has been documented that ginger (Zingiber officinale) might normalize the hormonal balance and control the menstrual cycle.. Objective: This study has analyzed whether ginger extract protects against cyclophosphamide (CP)-induced ovarian failure in rats. Methods: Rats were distributed into four groups consisting of vehicle, CP, ginger, and CP + ginger. At the end of the treatment, all rats were killed under anesthesia to obtain ovarian tissues and blood samples for histological, molecular, and biochemical experiments. Results: Our results indicated that ginger improves CP-caused histological changes in ovarian tissues and significantly restores serum hormonal abnormalities. Ginger also showed unique antioxidant, anti-inflammatory, and antiapoptotic properties in the ovarian tissues of CP-induced rats. Further, our findings indicated that ginger might activate the Nrf2 and SIRT and inhibit the PI3K/AKT pathway in the ovaries of CP-treated rats. In conclusion, ginger was found to protect against CP-caused ovarian toxicity in rats. Conclusion: The protective impacts of ginger may mediate, at least partly, by alleviating the oxidant state, inhibiting pro-inflammatory conditions, and exhibiting antiapoptotic activities.