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  5. Volume 26, Issue 1, 2025

Current Pharmaceutical Biotechnology - Volume 26, Issue 1, 2025

Volume 26, Issue 1

Volume 26, Issue 1, 2025

    • The Emerging Roles of CircPVT1 in Cancer Progression

      https://doi.org/10.2174/0113892010282141240226112253

      CircRNA is stable due to its ring structure and is abundant in humans, which not only exists in various tissues and biofluids steadily but also plays a significant role in the physiology and pathology of human beings. CircPVT1, an endogenous circRNA, has recently been identified from the PVT1 gene located in the cancer risk region 8q24. CircPVT1 is reported to be highly expressed in many different tumors, where it affects tumor cell proliferation, apoptosis, invasion, and migration. We summarize the biosynthesis and biological functions of circPVT1 and analyze the relationship between circPVT1 and tumors as well as its significance to tumors. Further, it’s noteworthy for the diagnosis, treatment, and prognosis of cancer patients. Therefore, circPVT1 is likely to become an innovative tumor marker.

  • Biotechnology, Applied Microbiology, Pharmacology

      • Noncoding RNA Lipotherapeutics: A Promising Breakthrough in Pulmonary Hypertension Treatment

        https://doi.org/10.2174/0113892010302590240321073509

        Pulmonary Hypertension (PH) is a complex cardiovascular disorder characterized by elevated blood pressure in the pulmonary arteries. Current therapeutic approaches for PH have limitations in addressing the underlying molecular mechanisms. This article explores the potential of noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), delivered through Lipid-Based Nanoparticles (LNPs) as a novel treatment strategy. These ncRNAs play critical roles in regulating vascular function and are implicated in PH pathogenesis. LNPs provide a promising method for the efficient and targeted delivery of ncRNAs. Advances in LNP technology, including the incorporation of R8 peptide modification, have shown promise in enhancing the delivery and efficacy of ncRNAs in PH models. Challenges such as biocompatibility, toxicity, and precise targeting must be addressed as these therapies move toward clinical application. The potential of personalized medicine and the integration of artificial intelligence in LNP design are discussed as prospects. In conclusion, ncRNA lipotherapeutics delivered LNPs offer a transformative approach to treating PH, potentially leading to more effective management and improved patient outcomes in the future. However, continued research and clinical trials are necessary to fully realize their therapeutic potential in the field of PH treatment.

    • Exploring the Therapeutic Potential of Flavonoids in the Management of Cancer

      Authors: Sonia Singh and Riya Verma
      https://doi.org/10.2174/0113892010297456240327062614

      Flavonoids are a class of polyphenolic compounds that can be classified into six distinct categories, namely isoflavonoids, flavanones, flavanols, flavonols, flavones, and anthocyanidins. These compounds are naturally occurring and can be found in a diverse range of plant species. Flavonoids, a class of bioactive compounds, are mostly obtained through the consumption of vegetables, fruits and plant-derived beverages such as wine, cocoa-based products and green tea. Flavonoids have been demonstrated to exhibit a diverse range of anticancer properties. These include the modulation of activities of enzymes involved in scavenging reactive oxygen species, involvement in cell cycle arrest, induction of apoptosis and autophagy, as well as suppression of cancer cell proliferation and invasiveness. Flavonoids exhibit a dual role in maintaining reactive oxygen species balance. They function as antioxidants in regular physiological conditions, while also demonstrating significant pro-oxidant properties in cancer cells. This pro-oxidant activity induces apoptotic pathways and downregulates pro-inflammatory signalling pathways. The paper explores the biochemical characteristics, bioavailability, anticancer efficacy, and modes of action of flavonoids.

    • Unveiling FDA-approved Drugs and Formulations in the Management of Bladder Cancer: A Review

      https://doi.org/10.2174/0113892010314650240514053735

      Urological cancers are one of the most prevalent malignancies around the globe. Specifically, bladder cancer severely threatens the health of humans because of its heterogeneous and aggressive nature. Extensive studies have been conducted for many years in order to address the limitations associated with the treatment of solid tumors with selective substances. This article aims to provide a summary of the therapeutic drugs that have received FDA approval or are presently in the testing phase for use in the prevention or treatment of bladder cancer. In this review, FDA-approved drugs for bladder cancer treatment have been listed along with their dose protocols, current status, pharmacokinetics, action mechanisms, and marketed products. The article also emphasizes the novel preparations of these drugs that are presently under clinical trials or are in the approval stage. Thus, this review will serve as a single point of reference for scientists involved in the formulation development of these drugs.

  • Biotechnology, Applied Microbiology, Pharmacology

      • Exploring Marine Alkaloids: A Natural Approach to Cancer Treatment

        https://doi.org/10.2174/0113892010316791240611093022

        Cancer is one of the most complicated and prevalent diseases in the world, and its incidence is growing worldwide. Natural products containing pharmacological activity are widely used in the pharmaceutical industry, especially in anticancer drugs, due to their diverse structures and distinctive functional groups that inspire new drug results by means of synthetic chemistry. Terrestrial medicinal plants have traditionally been the primary source for developing natural products (NPs). However, over the past thirty years, marine organisms such as invertebrates, plants, algae, and bacteria have revealed many new pharmaceutical compounds known as marine NPs. This field constantly evolves as a discipline in molecular targeted drug discovery, incorporating advanced screening tools that have revolutionised and become integral to modern antitumor research. This review discusses recent studies on new natural anticancer alkaloids obtained from marine organisms. The paper illustrates the structure and origin of marine alkaloids and demonstrates the cytotoxic action of new alkaloids from several structural families and their synthetic analogs. The most recent findings about the potential or development of some of them as novel medications, together with the status of our understanding of their current mechanisms of action, are also compiled.

    • Intestinal Epithelial Cell-specific Knockout of METTL3 Aggravates Intestinal Inflammation in CLP Mice by Weakening the Intestinal Barrier

      https://doi.org/10.2174/0113892010271970240202054245
      Background

      Many studies have demonstrated that the expression of methyltransferase-like 3 (METTL3) is altered in various inflammatory diseases. Its specific mechanistic role in the intestinal inflammatory response during sepsis remains limited and requires further investigation.

      Objectives

      Explore the potential mechanism of METTL3 in the intestinal inflammatory response during sepsis.

      Materials and Methods

      Immunohistochemical analysis was utilized to detect the expression of METTL3 in the necrotic intestine of patients with intestinal necrosis and the small intestine of cecal ligation and puncture (CLP) mice. Mice were subjected to the CLP and Sham surgeries, intestine tissue was harvested and performed HE staining, and ELISA to examine intestinal inflammatory responses, while TUNEL staining was applied to detect intestinal cell apoptosis. Additionally, ELISA was used to detect diamine oxidase (DAO) and intestinal fatty acid binding protein (I-FABP) levels in intestinal tissue. Immunohistochemistry and RT-qPCR were also employed to examine the mRNA and protein expression levels of Zona Occludens 1 (ZO-1) and Claudin-1. Finally, transcriptomic sequencing was performed on the small intestine tissues of METTL3 Knock-out (KO) and Wild-type (WT) mice in response to sepsis.

      Results

      METTL3 exhibited lower expression level in the necrotic intestine of patients and the small intestine of CLP mice. Loss of METTL3 in CLP mice triggered significantly higher expression of TNF-α and IL-18, down-regulated expression of ZO-1 and claudin-1, and decreased expression of DAO and I-FABP in the intestinal tissue. KEGG enrichment analysis showed that the differential genes were significantly enriched in immune-related pathways.

      Conclusion

      This study reveals a novel mechanism responsible for exacerbated intestinal inflammation orchestrated by METTL3. Particularly, METTL3 null mice displayed decreased ZO-1 and Claudin-1 expression, which largely hampered intestinal epithelial barrier function, resulting in bacterial and toxin translocation and intestinal immune activation and inflammation against sepsis.

  • Biotechnology, Applied Microbiology, Pharmacology

      • Optimization of Phloretin-loaded Nanospanlastics for Targeting of Signaling Pathway in HFD-induced Obesity

        https://doi.org/10.2174/0113892010278684240105115516
        Objectives

        Obese patients are at increased risk for CVD, which is the main cause of premature death and has been a major cause of disability and ill health in recent years. PTN, a natural dihydrochalcone flavonoid, has a variety of pharmacological characteristics. This article aimed to prepare PTN-NSLs to evaluate their anti-obesity activity.

        Methods

        Morphology, Particle size, zeta potential, UV-vis, entrapment efficiency, FT-IR spectra, and an release study of PTN-NSLs were described. PTN-NSLs were also tested for their anti-obesity properties in obese rats. The LD of PTN-NSLs was calculated, as was the 1/20 LD prepared for the treatment of obese rats. Also, the level of glycemic, oxidative stress and inflammatory biomarkers were estimated in the obese rat’s model.

        Results

        The synthesized PTN-NSLs were uniform, spherically shaped, and well dispersed with no aggregation noted, with a size range of 114.06 ± 8.35 nm. The measured zeta potential value of PTN-NSLs was -32.50.8 mv. Also, the UV spectra of PTN and PTN-NSLs have strong absorption at 225 and 285 nm. Also, the LD of PTN-NSLs was found to be 2750 mg/kg.b.w. Moreover, administrating obese rats with PTN-NSLs resulted in improved glycemic features as well as GSH, SOD, GPx, GR, IL10, TBARs, and IL-6 levels, as well as attenuated and gene expression.

        Conclusion

        Administration of PTN-NSLs significantly attenuated the levels of glycemic, oxidative stress, and inflammatory biomarkers. The biochemical and PCR findings are aided by histological investigations. Also, the present findings imply that PTN-NSLs might be a promising pharmacological tool for the treatment of obesity-related diseases.

    • LncRNA LINC00466 Promotes the Progression of Breast Cancer miR-4731-5p/EPHA2 Pathway

      https://doi.org/10.2174/0113892010290582240419051056
      Background

      Breast Cancer (BC) is a female malignancy with a high mortality rate. Novel diagnostic and prognostic biomarkers are valuable for reducing BC mortality. Our study is designed to undrape the precise role of the LINC00466/miR-4731-5p/EPHA2 axis in BC.

      Methods

      The Cancer Genome Atlas (TCGA) sequencing dataset was utilized to compare the levels of LINC00466. The levels of LINC00466, miR-4731-5p, and EPHA2 were tested by qRT-PCR. Cell proliferation and cycle were detected by CCK-8 assay and flow cytometer. role of LINC00466 was tested by Xenograft nude models. Binding sites were predicted by TargetScan and Starbase. The binding relationship was employed by Dual-luciferase reporter gene assay and RNA pull-down assay.

      Results

      LINC00466 was increased in human breast cancer tissues. LINC00466 was negatively associated with miR-4731-5p and positively correlated with EPHA2 in human breast cancer tissues. Down-regulation of LINC00466 suppressed the proliferation and arrested the cell cycle of breast cancer cells, and inhibited tumor growth .

      Conclusion

      LINC00466 promoted BC development mediating the miR-4731-5p/EPHA2 axis, which has the potential value as a promising therapeutic target in BC.

  • Biotechnology, Applied Microbiology, Pharmacology

      • The Role of Cuproptosis Key Factor FDX1 in Gastric Cancer

        https://doi.org/10.2174/0113892010301997240527162423
        Background

        Gastric cancer is a common malignant tumor of the digestive tract, both domestically and internationally. It has high incidence and mortality rates, posing a significant threat to human health. The levels of blood copper are elevated in patients with gastric cancer. However, the exact relationship between copper overload and the malignant phenotype of gastric cancer is still unclear. This study aims to investigate the role of the Cuproptosis-related factor FDX1 in the conversion of gastric cancer to a malignant phenotype.

        Methods

        Firstly, the relative mRNA and protein expression levels of FDX1 in gastric cancer were detected. Secondly, lentiviral transfection of gastric cancer cell lines was performed, and the effects of FDX1 functional intervention on the proliferation, invasion and migration of gastric cancer cells were assessed by CCK-8, colony formation, EdU proliferation, cell scratch and Transwell assays. Thirdly, the differential alteration of genes after overexpression of FDX1 was also analyzed by transcriptome sequencing. Finally, we assessed the tumour-forming capacity by the xenograft model.

        Results

        FDX1 is significantly upregulated in gastric cancer. The inhibition of FDX1 function results in the suppression of malignant phenotypic transformation in gastric cancer cells. Conversely, overexpression of FDX1 function leads to alterations in tumor-related signaling pathways and the tumor microenvironment.

        Conclusion

        FDX1 plays a significant role in the malignant phenotypic transformation of gastric cancer cells. Further investigation into the regulatory mechanism of FDX1 in the malignant transformation of gastric cancer will enhance our understanding of the involvement of Cuproptosis in gastric cancer.

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