Current Pharmaceutical Biotechnology - Volume 24, Issue 12, 2023

Vesicular delivery systems are a kind of drug delivery system that is gaining popularity due to its sustained release nature. This article was designed to understand the characteristics of a drug carrier called multivesicular liposomes, which have the potential to be the future of sustainedrelease drug delivery systems. Multivesicular liposomes have a honeycomb-like structure made up of non-concentric aqueous polyhedral compartments separated by continuous lipid membranes. Because of their unusual structure, they can encapsulate both hydrophilic and lipophilic pharmaceuticals and release them in a prolonged and controlled manner. They also have high encapsulation efficiency, bioavailability, biocompatibility, and stability, and are biodegradable by nature, making them suitable for treating chronic disorders. Encapsulating drugs into multivesicular liposomes is called DepoFoam^® technology, which has the capability to release them in a timely manner, lowering the drug administration frequency. As a result, the FDA has approved several various approaches for this technology to treat chronic conditions. Multivesicular liposomes in the form of DepoFoam® technology hold a promising future as a novel drug delivery system. Much research needs to be done to extend their use across various aspects of the therapeutic field.

Background: Esophageal cancer (EC), including esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), is a highly prevalent malignancy that occurs predominantly in the Asian region and is related to ethnicity, genetics, diet, and lifestyle. The nuclear receptor (NR) superfamily consists of 48 members of the human body. It is a collection of a large class of transcription factors, including Peroxisome proliferator-activated receptors (PPARs), Farnesol X receptor (FXR), Vitamin D receptor (VDR), Retinoic acid receptor (RAR), Pregnane X receptor (PXR), Androgen receptor (AR) and so on. Several NRs have been detected as oncogenes or tumor suppressors in EC progression. Objectives: NRs are associated with the progression of many cancers, including EC. Some NRs, such as PPARs and FXR, play an important role in EC. Studying the molecular mechanism of NRs in EC is helpful for further understanding the development of EC. Preclinical research and development of small molecule compound drugs targeting NRs have provided new ideas for the potential targeted therapy of EC. Methods: This review summarizes the studies on NRs in EC in recent years, mainly including in vitro cell experiments and in vivo animal experiments. Results: NRs influence EC progress in a variety of ways. They mainly affect the proliferation, migration and drug resistance of EC cells by affecting key cancer cell signaling pathways. Activation or inhibition of NRs inhibits or promotes EC progression, depending on EC types and tumor stages. Preclinical studies mainly focus on the development of small molecule drugs for targeting NRs (such as PPARγ agonists, PPARδ inhibitors, and FXR agonists), and agonists or inhibitors of NRs will become a potential therapeutic regimen for EC. Conclusion: The studies on the roles of NRs in EC have provided a theoretical basis for us to further understand the pathogenesis of EC and develop potential therapeutic drugs targeting NRs for the treatment of different diseases.

Background: Preclinical and clinical evidence implies that destructive therapies in local and malignant tissue are frequently used on patients with head and neck cancer. Consequently, the microbiome of the treated and adjacent regions is affected. Disruption of the normal microbiome plays an important role not only in the disease progression but also in its emergence, therefore new therapies involving probiotics, prebiotics, and synbiotics have been developed to control or regulate this microbial disruption. Objective: This review aims to describe the current and potential uses of probiotics at different stages of development of head and neck squamous cell carcinoma, as an adjuvant therapy to prevent common complications such as radiation-induced oral mucositis (RIOM) and its role in other areas. Methods: Currently, there is no widely effective strategy to treat or prevent this kind of cancer. Surgery, radiation therapy, and chemotherapy are the three main treatments for head and neck cancer. Some therapies can also cause long-term health problems, or complications which might change the way you eat, talk, hear and breathe. Results: The main uses for which probiotics have been studied are: Prevention and reduction of severity of RIOM, change in dental plaque to reduce dysbiosis, and reduction of complications in post-operated patients. Potential uses of probiotics include the reduction of disease initiation and progression by reducing local inflammation caused by bacteria and other organisms. Conclusion: The incidence and severity of RIOM may be lessened by probiotics. To establish its uses in additional clinical settings, though, more studies are necessary.

The severe respiratory infections in the current pandemic coronavirus disease-19 (COVID-19) have influenced more or less every human life. The first person to get infected with this virus was reported in the capital of Hubei province (Wuhan), China, in late December 2019. Since the disease has been declared a pandemic, research scholars and experts have been manufacturing new vaccines or targeted therapies to curb the spread of SARS-CoV-2. However, only limited options have emerged so far, which yet require complete scientific validation by long-term data collection regarding safety and efficacy. In the wake of the recent emerging wave of the pandemic viz omicron variant, changing facets of the viral genome and dearth of preventative and therapeutic possibilities for the management of COVID-19, the usage of Convalescent Plasma Therapy (CPT) may be looked at as a potentially viable option of treatment in the existing situation. Earlier, immune plasma has been used with success in the management of H1N1 influenza virus, MERS-CoV, and SARS-CoV-1 epidemics. In the present unpredictable situation created by the COVID-19 pandemic, the CPT is used with a positive outcome amongst many infected individuals in different parts of the world with acceptable efficacy. This article aimed to present an up-to-date evaluation of existing literature on the efficacy of convalescent plasma as a potential therapy, its safety and effectiveness and the challenges in treating COVID-19.

Background: Knema (the Myristicaceae family) is a large genus of small-medium trees found in Southeast Asia, Africa, and Australia. Historical records dealt with the uses of Knema species as medicinal plants against various diseases, especially cancer remedies, or their application as tonic agents in Asian communities Objective: The aim of this review is to provide the most current knowledge on the traditional uses, chemical profiles, as well as pharmacological values of Knema plants. Methods: Through electronic search, the literature materials on Knema plants were acquired from scholarly journals, books, and internationally recognized scientific databases, such as PubMed, ScienceDirect, Sci-Finder, Web of Science, and Google Scholar. All full-text articles and abstracts on Knema were screened. Genus Knema, traditional use, phytochemistry, and pharmacology were the first selective keywords to search for references. Results: Since the 1970s, more than 185 metabolites have been isolated from Knema plants and structurally elucidated. Among them, phenolic lipids, flavonoids, and lignans are the principal metabolites. Crude extracts, fractions, and isolated compounds of Knema species possess a wide variety of pharmacological properties, such as antioxidative, antidiabetic, antimicrobial, antiinflammatory, antimalarial, neuroprotective, and hepatoprotective activities, but cytotoxicity is the most striking feature. Phenolic lipids containing long alkyl side chains and polar hydroxyl or acyl groups are found as the most active molecules in cytotoxic assays. Conclusion: Further studies on phytochemistry and pharmacological activities, toxicological assessments, pharmacological mechanisms, and pharmacokinetics are urgently needed.

Colorectal cancer (CRC) is considered a lethal cancer all around the world, and its incidence has been reported to be increasing. Chemotherapeutic drugs commonly used for treating this cancer have shown some drawbacks, including toxicity to healthy cells and non-precise delivery. Thus, there is a necessity for discovering novel diagnostic and therapeutic options to increase the survival rate of CRC patients. Chitosan, as a natural polymer, has attracted a lot attention during the past years in different fields, including cancer. Studies have indicated that chitosan-based materials play various roles in prevention, diagnosis, and treatment of cancers. Chitosan nanoparticles (NPs) have been shown to serve as anti-cancer agents, which provide sustained drug release and targeted delivery of drugs to the tumor site. In this paper, we review available literature on the roles of chitosan in CRC. We discuss the applications of chitosan in designing drug delivery systems as well as anti-cancer activities of chitosan and involved signaling pathways.

Background: Alzheimer’s disease (AD) is an age-related neurodegenerative disease and is featured by cognitive impairment. Procyanidins have been shown to have a potential protective effect against neurodegenerative diseases, but the underlying mechanism is not comprehensive enough. Objective: To further investigate the effects of procyanidins from lotus seedpod (LSPC) on cognition in AD. Methods: The APP/PS1 transgenic mice were administered with LSPC (100 mg/kg body weight) for five months. The Morris water maze test was used to assess learning and memory function, the long-term potentiation (LTP) was measured, and the expressions of Aβ, pCREB/CREB and BDNF were quantified by western blot. Results: LSPC significantly ameliorated cognitive dysfunction, reduced Aβ deposition and reversed the remarkable reduction of the phosphorylation of CREB and the expression of BDNF, and then enhanced the effect of LTP in APP/PS1 mice. Conclusion: These results revealed that LSPC could ameliorate cognitive impairment through the CREB-BDNF pathway that mediates the enhancement of LTP in APP/PS1 transgenic mice.

Background: Rhizopus delemar, the main causative pathogen for the lethal mucormycosis and a severe threat during the COVID-19 pandemic, is resistant to most antifungals, including fluconazole, a known selective antifungal drug. On the other hand, antifungals are known to enhance fungal melanin synthesis. Rhizopus melanin plays an important role in fungal pathogenesis and in escaping the human defense mechanism, thus complicating the use of current antifungal drugs and fungal eradication. Because of drug resistance and the slow discovery of effective antifungals, sensitizing the activity of older ones seems a more promising strategy. Methods: In this study, a strategy was employed to revive the use and enhance the effectiveness of fluconazole against R. delemar. UOSC-13, a compound synthesized in-house to target the Rhizopus melanin, was combined with fluconazole either as is or after encapsulation in poly (lactic-coglycolic acid) nanoparticles (PLG-NPs). Both combinations were tested for the growth of R. delemar, and the MIC50 values were calculated and compared. Results: The activity of fluconazole was found to be enhanced several folds following the use of both combined treatment and nanoencapsulation. The combination of fluconazole with UOSC-13 caused a 5-fold reduction in the MIC50 value of fluconazole. Furthermore, encapsulating UOSC-13 in PLG-NPs enhanced the activity of fluconazole by an additional 10 folds while providing a wide safety profile. Conclusion: Consistent with previous reports, the encapsulation of fluconazole without sensitization showed no significant difference in activity. Collectively, sensitization of fluconazole represents a promising strategy to revive the use of outdated antifungal drugs back in the market.

Aims: We linked phenotypes and genotypes by PheGe-Net, a unified operation frame. Background: Genotype refers to the general name of all gene combinations of an individual. It reflects the genetic composition of organisms. Phenotype refers to the macroscopic characteristics of an organism that can be observed. Objective: Identifying the phenotype-genotype association assists in the explanation of the pathogenesis and the progress of genomic medicine. Methods: PheGe-Net exploited the similarity net of phenotypes and genotypes and recognized phenotype-genotype relationships to discover their hidden interactions. Results: By conducting experiments with a real-world dataset, the validity of our PheGe-Net is verified. Our method outperformed the second-best one by around 3% on Accuracy and NMI when clustering the phenotype/genotype; it also successfully detected phenotype-genotype associations, for example, the association for obesity (OMIM ID: 601665) was analyzed, and among the top ten scored genes, two known ones were assigned with scores more than 0.75, and other eight predicted ones are also explainable. Conclusion: PheGe-Net is not only able to discover latent phenotype or genotype clusters but also can uncover the hidden relationships among them, as long as there are known similarity networks of phenotype, genotype, and acknowledged pheno-genotype relationships.

Objectives: The nuclear factor-ΚB (NF-ΚB) signaling pathway plays an important role in regulating tubular epithelial-mesenchymal transition (EMT), an indispensable cellular programme for driving organ fibrosis and tumor progression. Liuwei Dihuang Decoction (LWD) is an effective Chinese formula for treating chronic renal failure. Methods: First, by using morphological examination, immunofluorescence staining assay, RTqPCR, and Western blot analysis, in vitro experiments were designed to analyze NF-ΚB and EMT markers (including Snail, α-SMA, and E-cadherin) in transforming growth factor-β1 (TGF-β1) induced renal tubular epithelial cells (HK-2) and to detect the expression levels of LWD-CS cotreatment. Then, the recombinant lentiviral vector was overexpressed and knocked down by NF- ΚB and transfected into HK-2 cells. Cells were treated with TGF-β1 (10 ng/ml) with blank serum or LWD-containing serum, respectively, and the expression of these molecules in the NF-ΚB/Snail signaling pathway was further evaluated. Results: Our results confirmed that TGF-β1 could induce EMT, nuclear translocation of NF-ΚB p65, and activate the NF-ΚB/Snail signaling pathway in HK-2 cells. Furthermore, NF-ΚB knocked-down dramatically increases the TGF-β1-induced mRNA and protein expression level of E-cadherin and reduces the level of Snail and α-SMA; this is reversed by NF-ΚB overexpression. LWD can decrease the EMT levels through the NF-ΚB/Snail signaling activation in TGF-β1-induced EMT of HK-2 cells. Conclusion: The present study provides evidence suggesting a novel mechanism that LWD exerts anti-fibrosis effects through inhibiting activation of the NF-ΚB/Snail signaling pathway and consequently downregulating the TGF-β1-induced EMT in renal tubular epithelial cells.