Current Pharmaceutical Biotechnology - Volume 24, Issue 4, 2023

The sponge-microorganism partnership is one of the most successful symbiotic associations exploited from a biotechnological perspective. During the last thirty years, sponge-associated bacteria have been increasingly harnessed for bioactive molecules, notably antimicrobials and cytotoxic compounds. Unfortunately, there are gaps in sponge microbial biotechnology, with a multitude of applications being understudied or ignored. In this context, the current perspective aims to shed light on these underrated facets of sponge microbial biotechnology with a balance of existent reports and proposals for further research in the field. Our overview has showcased that the members of the sponge microbiome produce biomolecules whose usage can be valuable for several economically- relevant and demanding sectors. Outside the exhaustive search for antimicrobial secondary metabolites, sponge-associated microorganisms are gifted producers of antibiofilm, antivirulence and chronic diseases-attenuating substances highly envisaged by the pharmaceutical industry. Despite still at an infant stage of research, anti-ageing enzymes and pigments of special interest for the cosmetic and cosmeceutical sectors have also been reported from the sponge microbial symbionts. In a world urging for sustainability, sponge-associated microorganisms have been proven as fruitful resources for bioremediation, including recovery of heavy-metal contaminated areas, bioleaching processes, and as bioindicators of environmental pollution. In conclusion, we propose alternatives to better assess these neglected biotechnological applications of the sponge microbiome in the hope of sparking the interest of the scientific community toward their deserved exploitation.

Dengue fever is a disease with a high mortality rate around the world, which is an important issue for the health authorities of many countries. As a result of this, the search for new drugs that are effective to combat this disease has become necessary. Medicinal plants have been used since ancient times to treat a wide list of diseases, including dengue fever. In this mini-review, 12 medicinal plants with known pharmacological properties are presented, which have been used in studies to evaluate their antiviral activity in vitro tests. Among the chemical agents involved in the antiviral response, found in the alcoholic extracts of these plants, are flavonoids, terpenes and alkaloids, which within the mechanism of action in blocking viral replication are considered entry inhibitors, fusion inhibitors, translation inhibitors and protease inhibitors. The present work shows whether these plants possess antiviral activity and the chemical compounds involved in this response.

Plants have substantial potential for the development of various biopharmaceuticals. Plants provide a cost-effective and direct source for the production of biopharmaceuticals such as vaccines, antibodies, proteins, enzymes, and hormones. In most cases, purification is an important and expensive step in the production of these substances. The problem can be resolved when it is produced in plants and the whole plant can be consumed. Direct ingestion of plant materials may help in overcoming the purification step. Being produced in seeds, fruits and tubers, it helps in providing more immunization in developing countries at a cheaper rate. Moreover, it can be administered more efficiently than any other dosage forms. This review focuses on various immunization and therapeutic products that are produced in plants along with currently available formulations in each category.

A polymer is a macromolecule that has a significant number of repeating units. It is possible to modify the architecture of a polymer via grafting, bridging, mixing, or generating composites. There are several uses for using natural polymers in culinary and medicinal applications. Polymeric materials became appealing because of their low density and ability to incorporate properties of their constituent constituents. High-energy accelerated electrons from the plasma induce chemical bond breaking in the polymeric structure, resulting in the generation of macromolecule radicals and graft copolymerization. Polymer grafting has become an important aspect of the formulation development process. When polymer functional groups are changed, a wide variety of desirable and unwanted properties can be added or removed. It can be concluded from the findings of the literature survey that graft copolymers of polysaccharides have significant biomedical applications including drug delivery and tissue engineering applications.

Diabetes mellitus is a long-term chronicle disorder with a high prevalence rate worldwide. Continuous blood glucose and lifestyle monitoring enabled the control of blood glucose dynamics through machine learning applications using data created by various popular sensors. This survey aims to assess various classical time series, neural networks and state-of-the-art regression models based on a wide variety of machine learning techniques to predict blood glucose and hyper/hypoglycemia in Type 1 diabetic patients. The analysis covers blood glucose prediction modeling, regression, hyper/hypoglycemia alerts, diabetes diagnosis, monitoring, and management. However, the primary focus is on evaluating models for the prediction of Type 1 diabetes. A wide variety of machine learning algorithms have been explored to implement precision medicine by clinicians and provide patients with an early warning system. The automated pancreas may benefit from predictions and alerts of hyper and hypoglycemia.

Curcumin is the main active constituent of the medicinal plant Curcuma longa L., used traditionally as a medicinal spice in several ancient civilizations. Different preclinical and clinical studies support the anti-inflammatory properties of curcumin in various inflammatory diseases. As inflammation has an essential role in the pathophysiology of many ocular diseases, curcumin has been suggested as a promising therapeutic agent with anti-inflammatory properties. Based on the extent of experimental and clinical evidence, curcumin can exert protective effects against the corneal, uveal, retinal, optic nerve, orbital, and lacrimal gland inflammatory disorders. Herein, the available literature on the beneficial effects of curcumin in inflammatory eye diseases is reviewed. The limitations and future directions of these investigations are also discussed.

Background: The bridge helix (BH) is a crucial region in bacterial RNA polymerase (RNAP) catalysis. It plays an essential role in the nucleotide addition cycle (NAC) by performing many modulated rearrangements and conformational changes. Any changes in the bridge helix conformational arrangements could perturb the NAC. Objective: Pseudouridimycin (PUM) was recently reported as a new RNAP inhibitor. However, the crucial role of the bridge helix in the inhibitory activity of PUM remains unclear, hence the aim of this study. Methods: The PUM interaction and the structural dynamics of bacterial Bridge Helix upon PUM binding were investigated using various dynamic analysis approaches. Results: Besides establishing the importance of the bridge helix residues in the binding of PUM, the findings of this study revealed that the adjacent binding of PUM induces a stabilized and structurally rigid bridge helix characterized by a reduction of individual residue flexibility, which could interfere with its role in the NAC. In addition, a hydrophobic structural rearrangement of the bridge helix is observed, evidenced by the burial and folding of residues into the hydrophobic core and a switch in the secondary structure of some regions of the bridge helix from the turn and bend to the alpha helix. The observed conformational disruption of the bridge helix upon binding of PUM also accounts for the reported inhibitory prowess and broad-spectrum activity as widely reported. Conclusion We believe findings from this study will further complement current drug discovery knowledge on disrupting bacterial RNAP machinery.

Background: Chia seed is an oil seed with multiple biological activities. Doxorubicin is effective chemotherapy for liver cancer. Resistance and adverse effects are doxorubicin limitations. Objective: This study aimed to investigate the effect of chia seeds oil (CSO) on the resistance of HepG2 cells to liposomal-doxorubicin (DOX). Methods: The objective were investigated through measuring cytotoxicity, doxorubicin-metabolizing enzyme Cytochrome P450 3A4 (CYP-3A4), multidrug resistance-associated protein (MRP1), and the expression of multiple tumor suppressor microRNAs. Results: The findings indicated that low concentration of CSO increased HepG2 cells' sensitivity to DOX, as concluded from its higher cytotoxicity. DOX-induced mRNAs of CYP-3A4 and MRP1 and their protein levels. CSO inhibited both in DOX-treated cells. CSO-induced tumor suppressor miRNAs. Doxorubicin inhibited miR-122 and let-7/b/e expression, while it led to overexpression of let- 7a. CSO/DOX upregulated let-7/b/e, miR-34a, and miR-122 (which inhibits MRP1) and downregulated let-7a, which may lead to increased apoptosis. Conclusion: CSO effectively re-sensitized HepG2 cells to liposomal-doxorubicin via inhibiting MRP1 and CYP-3A4, which may increase in vivo doxorubicin bioavailability and decrease its therapeutic dose to diminish its adverse effects.

Background: A diagnosis of pancreatic cancer is pretty grim. Saikosaponin-A (SSA) is a Chinese herbal extract with anticancer activity. However, the therapeutic effect of SSA on pancreatic cancer remains elusive. Aim: The study aims to evaluate the antitumor effects of SSA on pancreatic cancer cells in vitro and in vivo. Methods: After treatment with SSA, cell viability was measured using the CCK-8 assay, DAPI staining was performed to analyze the effect on nuclear morphology, propidium iodide (PI) staining was used to detect the cell cycle, and Annexin V/PI double staining was conducted to analyze apoptosis. Then, the expression of apoptosis-related proteins and EGFR/PI3K/Akt pathway-related proteins was determined using western blotting. The binding of SSA to EGFR was analyzed by performing molecular docking. The mouse pancreatic cancer model was established by subcutaneously injecting pancreatic cancer cells, and after 30 days of SSA gavage, the tumor volume was calculated. Tumor tissue sections were subjected to Ki67 immunohistochemical staining and HE staining. Results: SSA inhibited the proliferation of pancreatic cancer cells. As the concentration of SSA increased, the proportions of BxPC-3 and MIA PaCa-2 cells in the G0/G1 phase increased, the proportions of early and late apoptotic cells also increased, and the apoptosis rate gradually increased. Apoptosis inhibitor experiments indicated that SSA promoted the activation of caspase 3 to induce apoptosis in pancreatic cancer cells. In addition, SSA treatment significantly reduced the levels of phosphorylated EGFR, Akt, and PI3K in the two cell lines. Molecular docking results showed that SSA may have potential binding sites in EGFR. Results of the xenograft experiment confirmed the antitumor effects of SSA, as evidenced by the decreased tumor weight and downregulated expression of Ki67. Conclusion: The results revealed that SSA exerted inhibitory effects on pancreatic cancer cells. These effects may be related to the inactivation of the EGFR/PI3K/Akt signalling pathway.

Background: Multidrug-resistant tumor cells have special drug detoxification/inactivation mechanisms. The terminal amino groups of the polyamidoamine (PAMAM-NH2), which is cytotoxic to tumor sensitive cells, may have no cytotoxicity in tumor resistant cells with a mechanism different from tumor sensitive cells. Objective: This study aimed to investigate the cytotoxic effects of PAMAM-G4-NH2 on human multidrug- resistant breast cancer cells (MCF-7/ADR cells) and identify the possible molecular mechanisms. Methods: The cytotoxicity of PAMAM-G4-NH2 (10-1000 μg/mL) against MCF-7 and MCF-7/ADR cells was detected. Then, MCF-7 and MCF-7/ADR cells were treated with PAMAM-G4-NH2 (10, 100 and 1000 μg/mL), and apoptosis, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP), activities of caspase-3, -8 and -9 and cell cycle distribution were determined. Results: Within 48 h, the cell viabilities in MCF-7/ADR cells after treatment with PAMAM-G4-NH2 were significantly higher than that in MCF-7 cells in the concentration range of 200-500 μg/mL (P < 0.05). Viabilities of MCF-7/ADR cells treated with PAMAM-G4-OH and PAMAM-G4-COOH for 48 and 72 h were much higher than that of MCF-7/ADR cells treated with PAMAM-G4-NH2. Treated with high concentration (1000 μg/mL) of PAMAM-G4-NH2 for 24 h, the apoptosis ratio, ROS levels, as well as caspase-3 and -9 activities in MCF-7 and MCF-7/ADR cells increased, while MMP decreased, and the cells were arrested in the G0/G1 phase. Conclusion: PAMAM-G4-NH2 induced concentration-dependent cytotoxicity in MCF-7/ADR cells via G0/G1 arrest, and acted through h the mitochondria-dependent apoptotic pathway, which was similar to those in tumor sensitive cell, MCF-7 cells. The results suggest that PAMAM-G4-NH2, instead of PAMAM-G4-OH and PAMAM-G4-COOH, can be used as a carrier for drug delivery, concomitantly, it can also induce apoptosis in multidrug-resistant cancer cells in combination with the loaded drug through multiple apoptotic pathways.