Current Pharmaceutical Biotechnology - Volume 25, Issue 16, 2024

Squamous cell carcinoma (SCC) is the second most common form of skin cancer and is typically found on sun-exposed skin. Risk factors include ultraviolet radiation exposure, older age, fairer complexion, smoking, and immunosuppression. SCC is a slow-growing tumor with the possibility of metastasis if not treated. The clinical presentation can range from a dry, scaly erythematous patch or plaque to a firm hyperkeratotic papule, plaque, or nodule, depending on the histological type via biopsy. The first-line therapies for SCC removal are standard excision and Mohs microscopic surgery; however, there are novel and alternative non-surgical options being considered for the treatment of SCC. This review summarizes the current guidelines for treating low-risk and high-risk SCC and discusses rare, experimental, and anecdotal non-surgical treatments for SCC in the literature.

Pharmaceutical design has made significant advancements in recent years, leading to the development of novel therapeutics with unprecedented efficacy and safety profiles. This review highlights the potential of these innovations to revolutionize healthcare and improve patient outcomes. The application of cutting-edge technologies like artificial intelligence, machine learning, and data mining in drug discovery and design has made it easier to find potential drug candidates. Combining big data and omics has led to the discovery of new therapeutic targets and personalized medicine strategies. Nanoparticles, liposomes, and microneedles are examples of advanced drug delivery systems that allow precise control over drug release, better bioavailability, and targeted delivery to specific tissues or cells. This improves the effectiveness of the treatment while reducing side effects. Stimuli-responsive materials and smart drug delivery systems enable drugs to be released on demand when specific internal or external signals are sent. Biologics and gene therapies are promising approaches in pharmaceutical design, offering high specificity and potency for treating various diseases like cancer, autoimmune disorders, and infectious diseases. Gene therapies hold tremendous potential for correcting genetic abnormalities, with recent breakthroughs demonstrating successful outcomes in inherited disorders and certain types of cancer. Advancements in nanotechnology and nanomedicine have paved the way for innovative diagnostic tools and therapeutics, such as nanoparticle-based imaging agents, targeted drug delivery systems, gene editing technologies, and regenerative medicine strategies. Finally, the review emphasizes the importance of regulatory considerations, ethical challenges, and future directions in pharmaceutical design. Regulatory agencies are adapting to the rapid advancements in the field, ensuring the safety and efficacy of novel therapeutics while fostering innovation. Ethical considerations regarding the use of emerging technologies, patient privacy, and access to advanced therapies also require careful attention.

Introduction: Low adherence to chronic treatment regimens is a significant barrier to improving clinical outcomes in patients with chronic diseases. Low adherence is a result of multiple factors. Methods: We review the relevant studies on the prevalence of low adherence and present some potential solutions. Results: This review presents studies on the current measures taken to overcome low adherence, indicating a need for better methods to deal with this problem. The use of first-generation digital systems to improve adherence is mainly based on reminding patients to take their medications, which is one of the reasons they fail to provide a solution for many patients. The establishment of a second-generation artificial intelligence system, which aims to improve the effectiveness of chronic drugs, is described. Conclusion: Improving clinically meaningful outcome measures and disease parameters may increase adherence and improve patients' response to therapy.

Major depressive disorder (MDD) is a common neuropsychiatric challenge that primarily targets young females. MDD as a global disorder has a multifactorial etiology related to the environment and genetic background. A balanced gut microbiota is one of the most important environmental factors involved in human physiological health. The interaction of gut microbiota components and metabolic products with the hypothalamic-pituitary-adrenal system and immune mediators can reverse depression phenotypes in vulnerable individuals. Therefore, abnormalities in the quantitative and qualitative structure of the gut microbiota may lead to the progression of MDD. In this review, we have presented an overview of the bidirectional relationship between gut microbiota and MDD, and the effect of pre-treatments and microbiomebased approaches, such as probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and a new generation of microbial alternatives, on the improvement of unstable clinical conditions caused by MDD.

Glioblastoma (GBM) is a grade-IV astrocytoma, which is the most common and aggressive type of brain tumor, spreads rapidly and has a life-threatening catastrophic effect. GBM mostly occurs in adults with an average survival time of 15 to 18 months, and the overall mortality rate is 5%. Significant invasion and drug resistance activity cause the poor diagnosis of GBM. Naringenin (NRG) is a plant secondary metabolite byproduct of the flavanone subgroup. NRG can cross the blood-brain barrier and deliver drugs into the central nervous system when conjugated with appropriate nanocarriers to overcome the challenges associated with gliomas through naringenin-loaded nanoformulations. Here, we discuss several nanocarriers employed that are as delivery systems, such as polymeric nanoparticles, micelles, liposomes, solid lipid nanoparticles (SLNs), nanosuspensions, and nanoemulsions. These naringenin-loaded nanoformulations have been tested in various in vitro and in vivo models as a potential treatment for brain disorders. This review nanoformulations of NRG can a possible therapeutic alternative for the treatment of neurological diseases are discussed.

It is becoming more and harder in today's climate to disregard the impact of cancer on social health. Even though a significant amount of money is spent annually on cancer research, it still ranks as the second leading cause of death worldwide. Additionally, only about half of the patients suffering from complex forms of cancer survive a year after receiving traditional cancer therapies. A method for silencing genes is called RNA interference (RNAi). Such a method is very effective in focusing on genes linked to cancer. Most gene products implicated in cancer have recently been used as RNA interference (RNAi) therapeutic targets. According to the findings from this research, RNAi application is necessary for today's cancer treatment to target functioning carcinogenic molecules and tumor resistance to chemotherapy and radiation. Proapoptotic and antiproliferative activity has been reported from previous research studies on cell culture systems, animal models, and clinical trials through the knockdown of gene products from RNAi technology. Numerous novel RNAi-based medications are now in the clinical trial stages thanks to the discovery of the RNAi mechanism and advancements in the area. In the future, genomic-based personalized medicines can be developed through this RNAi therapy. Hopefully, cancer sufferers will find this sort of therapy to be one of the most effective ones. Various kinds of RNA-based treatments, such as aptamers, small interfering RNAs, microRNAs, antisense oligonucleotides, and messenger RNA, are covered in broad terms in this study. We also present an overview of the RNA-based therapies that have received regulatory approval in the past or are now undergoing clinical studies.

Background: Ischemia-reperfusion injury (IRI) is a well-known ailment that can disturb organ function. Objectives: This systematic review study investigated fisetin's effects and possible mechanisms in attenuating myocardial, cerebral, renal, and hepatic IRIs. Methods: This systematic review included studies earlier than Sep 2023 by following the PRISMA statement 2020. After determining inclusion and exclusion criteria and related keywords, bibliographic databases, such as Cochrane Library, PubMed, Web of Science, Embase, and Scopus databases, were used to search the relevant studies. Studies were imported in End- Note X8, and the primary information was recorded in Excel. Results: Fisetin reduced reactive oxygen species (ROS) generation and upregulated antioxidant enzymes, such as superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and glutathione peroxidase (GPx), in ischemic tissues. Moreover, fisetin can attenuate oxidative stress by activating phosphoinositide-3-kinase–protein kinase B/Akt (PI3K/Akt) and nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. Fisetin has been indicated to prevent the activation of several pro-inflammatory signaling pathways, including NF-ΚB (Nuclear factor kappa-light-chain-enhancer of activated B cells) and MAPKs (Mitogen-activated protein kinases). It also inhibits the production of pro-inflammatory cytokines and enzymes like tumor necrosis factor-a (TNF-α), inducible-NO synthase (iNOS), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), interleukin-1β (IL-1β), IL-1, and IL-6. Fisetin attenuates IRI by improving mitochondrial function, anti-apoptotic effects, promoting autophagy, and preserving tissues from histological changes induced by IRIs. Conclusion: Fisetin, by antioxidant, anti-inflammatory, mitochondrial protection, promoting autophagy, and anti-apoptotic properties, can reduce cell injury due to myocardial, cerebral renal, and hepatic IRIs without any significant side effects.

Background: Quassinoids are degraded triterpene compounds that can be obtained from various species of the Simaroubaceae plant family, including Eurycoma longifolia. Quassinoids are the major compounds in E. longifolia, and they are known to have various medicinal potentials, such as anticancer and antimalarial properties. Dihydrofolate reductase (DHFR) was reported to be one of the important targets for certain anticancer and antimalarial drugs. Twelve quassinoids from E. longifolia were identified to have anticancer effects based on their IC50 values. This study aimed to evaluate the interactions of these twelve quassinoids with DHFR via Autodock 4.2 software and Biovia Discovery Studio Visualiser. Methods: Twelve quassinoids from E. longifolia and their interactions with DHFR were evaluated via Autodock 4.2 software and Biovia Discovery Studio Visualiser. Their drug-likeness and pharmacokinetic properties were also assessed using the ADMETlab 2.0 program. Results: The molecular docking results showed that eleven quassinoids showed better docking scores than methotrexate, in which the binding energy (BE) of these quassinoids ranged from - 7.87 to -9.58 kcal/mol. Their inhibition constant (Ki) ranged from 0.095 to 1.71 μM. At the same time, the BE and Ki values for methotrexate were -7.80 kcal/mol and 1.64 μM, respectively. Conclusion: From the analysis, 6-dehydrolongilactone and eurycomalide B are among the twelve compounds that showed great potential as hit-to-lead compounds based on the docking score on DHFR, drug-likeness, and ADMET properties. These results suggest a great potential to pursue validation studies via in vitro and in vivo models.

Background: Long non-coding RNAs (LncRNAs) are generally reported to participate in the development of Osteoarthritis (OA) by acting as competing endogenous RNAs (ceRNAs). However, the molecular mechanism is largely unknown. This study aimed to investigate the possible mechanisms contributing to osteoarthritis (OA). Methods: Four gene expression profiles from patients with OA were downloaded from a public database and integrated to screen important RNAs associated with OA. Differentially expressed (DE) lncRNAs, microRNAs (miRNAs), and mRNAs were filtered, and a ceRNA network was constructed. An in vitro OA model was established by treating chondrocytes with IL-1β. The expression levels of MMP-13, COL2A1, aggrecan, and RUNX2 were detected by qRT-PCR and western blot. Cell proliferation ability was detected by CCK-8 assay. Flow cytometry was used for apoptosis assay. A dual luciferase reporter gene was used to confirm the relationship between DLEU1, miR-492, and TLR8. Results: An OA-related ceRNA network, including 11 pathways, 3 miRNAs, 7 lncRNAs, and 16 mRNAs, was constructed. DLEU1 and TLR8 were upregulated, and miR-492 was downregulated in IL-1β-induced chondrocytes. Overexpression of DLEU1 suppressed viability and promoted apoptosis and extracellular matrix (ECM) degradation in IL-1β induced chondrocytes. Luciferase reporter assay validated the regulatory relations among DLEU1, miR-492, and TLR8. Further study revealed that the effects of DLEU1 on chondrocytes could be reversed by miR-492. Conclusion: DLEU1 may be responsible for the viability, apoptosis, and ECM degradation in OA via miR-492/TLR8 axis.