Vol 25, No 15 (2024)

Biotechnology

Role of Nutraceuticals in Treating Erectile Dysfunction via Inhibition of Phosphodiesterase-5 Enzyme: A Mini Review

Kulshrestha R., Singla N., Afzal O., Goyal A., Saini M., Altamimi A., Almalki W., Kazmi I., Al-Abbasi F., Alzarea S., Gupta G.

Abstract

:Erectile Dysfunction (ED) is a prevalent sexual health condition affecting a significant portion of the male population worldwide. The conventional therapeutic approaches for ED often involve the use of pharmaceutical agents targeting the phosphodiesterase-5 (PDE5) enzyme. Currently, treatment with PDE-5 inhibitors is the standard approach for ED, and four PDE-5 inhibitors, namely sildenafil, vardenafil, tadalafil, and avanafil, are in use. However, these pharmaceutical interventions may be associated with adverse effects and limitations. As a result, there has been a growing interest in exploring alternative and complementary treatment options for ED, such as nutraceuticals, which are bioactive compounds derived from natural sources. Nutraceuticals, which include vitamins, minerals, herbs, and other dietary supplements, have gained popularity for their potential health benefits. Certain nutraceuticals have demonstrated the ability to modulate various physiological pathways, including those involved in erectile function. A notable mechanism of action is the inhibition of the PDE5 enzyme, which plays a pivotal role in the regulation of cGMP levels. By inhibiting PDE5, nutraceuticals can promote the accumulation of cGMP, leading to enhanced penile blood flow and improved erectile function. A comprehensive analysis of the literature showcases various nutraceutical agents, including plant-derived compounds like flavonoids, polyphenols, and amino acids which have exhibited PDE5 inhibitory effects. Mechanistic insights into their action involve modulation of NO release, cGMP elevation, and relaxation of penile smooth muscles, all critical factors for achieving and sustaining erections. This review focuses on elucidating the role of nutraceuticals in treating erectile dysfunction through the inhibition of the PDE5 enzyme.

Current Pharmaceutical Biotechnology. 2024;25(15):1905-1914
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Single Nucleotide Polymorphisms (SNPs) in the Shadows: Uncovering their Function in Non-Coding Region of Esophageal Cancer

Saikia S., Postwala H., Athilingam V., Anandan A., Padma V., Kalita P., Chorawala M., Prajapati B.

Abstract

:Esophageal cancer is a complex disease influenced by genetic and environmental factors. Single nucleotide polymorphisms [SNPs] in non-coding regions of the genome have emerged as crucial contributors to esophageal cancer susceptibility. This review provides a comprehensive overview of the role of SNPs in non-coding regions and their association with esophageal cancer. The accumulation of SNPs in the genome has been implicated in esophageal cancer risk. Various studies have identified specific locations in the genome where SNPs are more likely to occur, suggesting a location-specific response. Chromatin conformational studies have shed light on the localization of SNPs and their impact on gene transcription, posttranscriptional modifications, gene expression regulation, and histone modification. Furthermore, miRNA-related SNPs have been found to play a significant role in esophageal squamous cell carcinoma [ESCC]. These SNPs can affect miRNA binding sites, thereby altering target gene regulation and contributing to ESCC development. Additionally, the risk of ESCC has been linked to base excision repair, suggesting that SNPs in this pathway may influence disease susceptibility. Somatic DNA segment alterations and modified expression quantitative trait loci [eQTL] have also been associated with ESCC. These alterations can lead to disrupted gene expression and cellular processes, ultimately contributing to cancer development and progression. Moreover, SNPs have been found to be associated with the long non-coding RNA HOTAIR, which plays a crucial role in ESCC pathogenesis. This review concludes with a discussion of the current and future perspectives in the field of SNPs in non-coding regions and their relevance to esophageal cancer. Understanding the functional implications of these SNPs may lead to the identification of novel therapeutic targets and the development of personalized approaches for esophageal cancer prevention and treatment.

Current Pharmaceutical Biotechnology. 2024;25(15):1915-1938
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Advances in Aerogels Formulations for Pulmonary Targeted Delivery of Therapeutic Agents: Safety, Efficacy and Regulatory Aspects

Verma S., Sharma P., Malviya R., Das S.

Abstract

:Aerogels are the 3D network of organic, inorganic, composite, layered, or hybrid-type materials that are used to increase the solubility of Class 1 (low solubility and high permeability) and Class 4 (poor solubility and low permeability) molecules. This approach improves systemic drug absorption due to the alveoli's broad surface area, thin epithelial layer, and high vascularization. Local therapies are more effective and have fewer side effects than systemic distribution because inhalation treatment targets the specific location and raises drug concentration in the lungs.

:The present manuscript aims to explore various aspects of aerogel formulations for pulmonary targeted delivery of active pharmaceutical agents. The manuscript also discusses the safety, efficacy, and regulatory aspects of aerogel formulations. According to projections, the global respiratory drug market is growing 4–6% annually, with short–term development potential. The proliferation of literature on pulmonary medicine delivery, especially in recent years, shows increased interest.

:Aerogels come in various technologies and compositions, but any aerogel used in a biological system must be constructed of a material that is biocompatible and, ideally, biodegradable. Aerogels are made via \"supercritical processing\". After many liquid phase iterations using organic solvents, supercritical extraction, and drying are performed. Moreover, the sol-gel polymerization process makes inorganic aerogels from TMOS or TEOS, the less hazardous silane. The resulting aerogels were shown to be mostly loaded with pharmaceutically active chemicals, such as furosemide-sodium, penbutolol-hemisulfate, and methylprednisolone. For biotechnology, pharmaceutical sciences, biosensors, and diagnostics, these aerogels have mostly been researched. Although aerogels are made of many different materials and methods, any aerogel utilized in a biological system needs to be made of a substance that is both biocompatible and, preferably, biodegradable.

:In conclusion, aerogel-based pulmonary drug delivery systems can be used in biomedicine and non-biomedicine applications for improved sustainability, mechanical properties, biodegradability, and biocompatibility. This covers scaffolds, aerogels, and nanoparticles. Furthermore, biopolymers have been described, including cellulose nanocrystals (CNC) and MXenes. A safety regulatory database is necessary to offer direction on the commercialization potential of aerogelbased formulations. After that, enormous efforts are discovered to be performed to synthesize an effective aerogel, particularly to shorten the drying period, which ultimately modifies the efficacy. As a result, there is an urgent need to enhance the performance going forward.

Current Pharmaceutical Biotechnology. 2024;25(15):1939-1951
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The Astonishing Accomplishment of Biological Drug Delivery using Lipid Nanoparticles: An Ubiquitous Review

Kapoor D., Chilkapalli S., Prajapati B., Rodriques P., Patel R., Singh S., Bhattacharya S.

Abstract

:Biotech drugs, including proteins, hormones, enzymes, DNA/RNA therapies, and cell-based treatments, are gaining popularity due to their effectiveness. However, effective delivery systems are needed to overcome administration challenges. Lipid nanoparticles (LNPs) have emerged as promising carriers for various therapies. LNPs are biocompatible, less likely to cause adverse reactions, and can stabilize delicate biological drugs, enhancing their stability and solubility. Scalable and cost-effective manufacturing processes make LNPs suitable for largescale production. Despite recent research efforts, challenges in stability, toxicity, and regulatory concerns have limited the commercial availability of LNP-based products. This review explores the applications, administration routes, challenges, and future directions of LNPs in delivering biopharmaceuticals.

Current Pharmaceutical Biotechnology. 2024;25(15):1952-1968
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Recent Approaches on Molecular Markers, Treatment and Novel Drug Delivery System Used for the Management of Colorectal Cancer: A Comprehensive Review

Chauhan S., Sharma S.

Abstract

:Colorectal cancer affects 1 in 25 females and 1 in 24 males, making it the third most frequent cancer with over 6,08,030 deaths worldwide, despite advancements in detection and treatments, including surgery, chemotherapeutics, radiotherapy, and immune therapeutics. Novel potential agents have increased survival in acute and chronic disease conditions, with a higher risk of side effects and cost. However, metastatic disease has an insignificant long-term diagnosis, and significant challenges remain due to last-stage diagnosis and treatment failure. Early detection, survival, and treatment efficacy are all improved by biomarkers. The advancement of cancer biomarkers' molecular pathology and genomics during the last three decades has improved therapy. Clinically useful prognostic biomarkers assist clinical judgment, for example, by predicting the success of EGFR-inhibiting antibodies in the presence of KRAS gene mutations. Few biomarkers are currently used in clinical settings, so further research is still needed. Nanocarriers, with materials like Carbon nanotubes and gold nanoparticles, provide targeted CRC drug delivery and diagnostics. Light-responsive drugs with gold and silica nanoparticles effectively target and destroy CRC cells. We evaluate the potential use of the long non-coding RNA (non-coding RNA) oncogene plasmacytoma variant translocation 1 (PVT1) as a diagnostic, prognostic, and therapeutic biomarker, along with the latest nanotech breakthroughs in CRC diagnosis and treatment.

Current Pharmaceutical Biotechnology. 2024;25(15):1969-1985
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Extrusion and Co-extrusion: A Technology in Probiotic Encapsulation with Alternative Materials

Homayouni-Rad A., Mortazavian A., Pourjafar H., Moghadam S.

Abstract

:Encapsulation, in particular extrusion and co-extrusion, is a common practice to protect probiotics from the harsh conditions of the digestive tract as well as processing. Hydrocolloids, including proteins and carbohydrates, natural or modified, are a group of ingredients used as the wall material in extrusion. Hydrocolloids, due to their specific properties, can significantly improve the probiotic survivability of the final powder during the microencapsulation process and storage. The present article will discuss the different kinds of hydrocolloids used for microencapsulation of probiotics by extrusion and co-extrusion, along with new sources of novel gums and their potential as wall material.

Current Pharmaceutical Biotechnology. 2024;25(15):1986-2000
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Harnessing Chimeric Antigen Receptor-engineered Invariant Natural Killer T Cells: Therapeutic Strategies for Cancer and the Tumor Microenvironment

Wang Y., Li Y.

Abstract

:Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy has emerged as a revolutionary approach for cancer treatment, especially for hematologic cancers. However, CAR-T therapy has some limitations, including cytokine release syndrome (CRS), immune cellassociated neurologic syndrome (ICANS), and difficulty in targeting solid tumors and delivering allogeneic cell therapy due to graft-versus-host disease (GvHD). Therefore, it is important to explore other cell sources for CAR engineering. Invariant natural killer T (iNKT) cells are a potential target, as they possess powerful antitumor ability and do not recognize mismatched major histocompatibility complexes (MHCs) and protein antigens, thus avoiding the risk of GvHD. CAR-engineered iNKT (CAR-iNKT) cell therapy offers a promising new approach to cancer immunotherapy by overcoming the drawbacks of CAR-T cell therapy while retaining potent antitumor capabilities. This review summarizes the current CAR-iNKT cell products, their functions and phenotypes, and their potential for off-the-shelf cancer immunotherapy.

Current Pharmaceutical Biotechnology. 2024;25(15):2001-2011
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Emerging Therapeutic Approaches Targeting Ferroptosis in Cancer: Focus on Immunotherapy and Nanotechnology

Yu Z., Mo Z., Qiu Y., Lu H., Zheng B., Liu L.

Abstract

:Ferroptosis is a newly discovered form of programmed cell death characterized by iron overload, ROS accumulation, and lipid peroxidation. It is distinguished by unique morphological, biochemical, and genetic features and stands apart from other known regulated cell death mechanisms. Studies have demonstrated a close association between ferroptosis and various cancers, including liver cancer, lung cancer, renal cell carcinoma, colorectal cancer, pancreatic cancer, and ovarian cancer. Inducing ferroptosis has shown promising results in inhibiting tumor growth and reversing tumor progression. However, the challenge lies in regulating ferroptosis in vivo due to the scarcity of potent compounds that can activate it. Integrating emerging biomedical discoveries and technological innovations with conventional therapies is imperative. Notably, considerable progress has been made in cancer treatment by leveraging immunotherapy and nanotechnology to trigger ferroptosis. This review explores the relationship between ferroptosis and emerging immunotherapies and nanotechnologies, along with their potential underlying mechanisms, offering valuable insights for developing novel cancer treatment strategies.

Current Pharmaceutical Biotechnology. 2024;25(15):2012-2021
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Iron(III) Monoglycerolate as a New Biocompatible Precursor in the Synthesis of Bioactive Nanocomposite Glycerohydrogels

Khonina T., Tishin D., Larionov L., Osipenko A., Dobrinskaya M., Bogdanova E., Karabanalov M., Bulatova M., Shadrina E., Chupakhin O.

Abstract

Background:Nanocomposite glycerohydrogels based on biocompatible elementcontaining glycerolates are of practicular interest for biomedical applications.

Objective:Using two biocompatible precursors, silicon and iron glycerolates, a new bioactive nanocomposite silicon‒iron glycerolates hydrogel was obtained by sol-gel method.

Methods:The composition and structural features of the hydrogel were studied using a complex of modern analytical techniques, including TEM, XRD, and AES. On the example of experimental animals hemostatic activity of the hydrogel was studied, as well as primary toxicological studies were carried out.

Results:The composition of dispersed phase and dispersion medium of silicon‒iron glycerolates hydrogel was determined. The structural features of hydrogel were revealed and its structure model was proposed. It was shown that silcon-iron glycerolates hydrogel is nontoxic, and exhibits pronounced hemostatic activity.

Conclusion:Silicon-iron glycerolates hydrogel is a potential hemostatic agent for topical application in medical and veterinary practice.

Current Pharmaceutical Biotechnology. 2024;25(15):2022-2031
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Deciphering Immune-related Gene Signatures in Diabetic Retinopathy: Insights from In silico Analysis and In vitro Experiment

Xia N., Zhao Q., Xu J., Cheng Z.

Abstract

Background:Diabetes retinopathy (DR) is one of the most common microvascular consequences of diabetes, and the economic burden is increasing. Our aim is to decipher the relevant mechanisms of immune-related gene features in DR and explore biomarkers targeting DR. Provide a basis for the treatment and prevention of DR.

Methods:The immune infiltration enrichment score of DR patients was evaluated from the single- cell RNA sequencing dataset, and the samples were divided into low immune subgroups and high immune subgroups based on this result. Through weighted gene correlation network analysis, differentially expressed genes (DEGs) between two subgroups were identified and crossed with genes with the strongest immune association, resulting in significant key genes. Then divide the DR individuals into two immune related differentially expressed gene (IDEG) clusters, A and B. Submit cross DEGs between two clusters through Gene Set Enrichment Analysis (GSEA) to further explore their functions. A protein-protein interaction (PPI) network of IDEG was established to further identify central genes associated with DR. Use the discovered central genes to predict the regulatory network involved in the pathogenesis of DR. Then, the role of the identified hub gene in the pathogenesis of DR was further studied through in vitro experiments.

Results:We found that the immune scores of DR and control groups were different, and 27 IDEGs were found in the DR subgroup. Compared with cluster A, the proportion of cytotoxic lymphocytes, B lineage, monocyte lineage, and fibroblasts in DR patients in cluster B is significantly enriched. GSEA indicates that these genes are associated with T cell activation, regulation of immune response processes, lymphocyte-mediated immunity, TNF signaling pathway, and other signaling pathways. The PPI network subsequently identified 10 hub genes in DR, including SIGLEC10, RGS10, PENK, FGD2, LILRA6, CIITA, EGR2, SIGLEC7, LILRB1, and CD300LB. The upstream regulatory network and lncRNA miRNA mRNA ceRNA network of these hub genes were ultimately constructed. The discovery and identification of these genes will provide biomarkers for targeted prediction and treatment of DR.

Conclusion:By integrating bioinformatics analysis and in vitro experiments, we have identified a set of central genes, indicating that these genes can serve as potential biomarkers for DR, which may be promising targets for future DR immunotherapy interventions.

Current Pharmaceutical Biotechnology. 2024;25(15):2032-2045
pages 2032-2045 views