Biolmpacts
Volume:11 Issue: 3, May 2021

No nation is protected against the damages of COVID-19 and this disease seems to be changing the global collective consciousness, taking humans to the deepest conflict of "to be or not to be" - a "life or death" situation! The characteristic feature of the upcoming years in the expanded global collective consciousness seems to be “existential anxiety”, and human beings from various societies will deal with the existential issues more explicitly. Coping with existential anxiety could not be acquired merely by mental knowledge alone, and this ability must be acquired by going through mental growth and transcendence and find the ability to help people flourish themselves.

The coronavirus disease 2019 (COVID-19) is an emerged infectious disease characterized by a severe pneumonia leading to death in some cases. Currently, no licensed vaccines, drugs, or biologics have been confirmed to be absolutely effective in prophylaxis or treatment of this novel infection. Therefore, the treatment of this highly contagious disease remains a global concern and emergency. The viral interference is a competition phenomenon by which a primary virus infecting a cell prohibits the infection of the same cell by another (secondary) virus. The phenomenon has recently been indicated to be exploited for antiviral strategies. This strategy, particularly when there is no efficient drug against a viral infection, is of high importance. Some researchers have studied the application of the phenomenon among different viruses. In this paper, I discussed the possibility of the application of interference phenomenon in prophylaxis of the disease.

Histone modifying enzymes include several classes of enzymes that are responsible for various post-translational modifications of histones such as methylation and acetylation. They are important epigenetic factors, which may involve several diseases and so their assay, as well as screening of their inhibitors, are of great importance. Herein, a bioassay based on terbiumto-quantum dot (Tb-to-QD) time-resolved Förster resonance energy transfer (TR-FRET) was developed for monitoring the activity of G9a, the euchromatic histone-lysine N-methyltransferase 2. Overexpression of G9a has been reported in some cancers such as ovarian carcinoma, lung cancer, multiple myeloma and brain cancer. Thus, inhibition of this enzyme is important for therapeutic purposes.

In this assay, a biotinylated peptide was used as a G9a substrate in conjugation with streptavidin-coated ZnS/CdSe QD as FRET acceptor, and an anti-mark antibody labeled with Tb as a donor. Time-resolved fluorescence was used for measuring FRET ratios.

We examined three QDs, with emission wavelengths of 605, 655 and 705 nm, as FRET acceptors and investigated FRET efficiency between the Tb complex and each of them. Since the maximum FRET efficiency was obtained for Tb to QD705 (more than 50%), this pair was exploited for designing the enzyme assay. We showed that the method has excellent sensitivity and selectivity for the determination of G9a at concentrations as low as 20 pM. Furthermore, the designed assay was applied for screening of an enzyme inhibitor, S-(5’-Adenosyl)-L-homocysteine (SAH).

It was shown that Tb-to-QD FRET is an outstanding platform for developing a homogenous assay for the G9a enzyme and its inhibitors. The obtained results confirmed that this assay was quite sensitive and could be used in the field of inhibitor screening.

There have been thousands of neurochemical mechanism about blood glucose level regulation, but intrapancreatic taste buds and their roles in blood glucose level has not been described. We aimed to investigate if there are taste buds cored neural networks in the pancreas, and there is any relationship between blood glucose levels.

This examination was done on 32 chosen rats with their glucose levels. Animals are divided into owned blood glucose levels. If mean glucose levels were equal to 105±10 mg/dL accepted as euglycemic (G-I; n=14), 142±18 mg/dL values accepted as hyperglycemic (G-II; n=9) and 89±9 mg/dL accepted as hypoglycemic (G-III; n=9). After the experiment, animals were sacrificed under general anesthesia. Their pancreatic tissues were examined histological methods and numbers of newly described taste bud networks analyzed by Stereological methods. Results compared with Mann-Whitney U test P<0.005 considered as significant.

The mean normal blood glucose level (mg/dL) and taste bud network densities of per cm3 were: 105±10 mg/dL; 156±21 in G-I; 142±18 mg/dL and 95±14 in G-II and 89±9 mg/dL and 232±34 in G-III. P values as follows: P<0.001 of G-II/G-I; P<0.005 of G-III/G-I and P<0.0001 of G-III/G-II. We detected periarterial located taste buds like cell clusters and peripherally located ganglia connected with Langerhans cells via thin nerve fibers. There was an inverse relationship between the number of taste buds networks and blood glucose level.

Newly described intrapancreatic taste buds may have an important role in the regulation of blood glucose level.

The genus Morus is well known for its medicinal benefits from time immemorial. The present work reported the health-promoting properties of the biologically active molecules present in different species of the genus Morus.

Different solvent extracts of the three plant species of Morus were investigated initially for their antioxidant effects, followed by in vitro anticancer studies against MCF7 and 3T3 cell lines along with their bioactive isolates viz. cathafuran-B, moracin-M, and ursolic acid. Further, in silico docking studies were performed for the isolated compounds to predict their probable mode of interaction with P38Map Kinase.

The results indicated that all three species under study possessed remarkable antioxidant effects which are supported by a linear and positive correlation between different antioxidant activities. The in vitro cell antiproliferative test indicated that the cell survivability decreased with an increase in the concentration of extracts and compounds. Among the extracts, M. laevigata methanol extract showed 21.57, 6.27% of cell survival against MCF7 and 3T3 cell lines at 800 µg/ mL concentration while among the isolated compounds, ursolic acid showed 8.46, 17.58% of cell survival at 200 µg/mL concentration. Among the three compounds docked, ursolic acid showed greater binding affinity towards the target protein in terms of its binding energy (-9.97 kJ/mol) compared to Cathafuran B (-8.35 kJ/mol) and Moracin M (-6.91 kJ/mol).

The study generated interesting results in terms of health benefits of Morus species by documenting their antioxidant and anticancer activities, thereby validating the folk claims of therapeutic benefits of mulberry.

Triple-negative breast cancer (TNBC) is a lethal tumor with an advanced degree of metastasis and poor survivability as compared to other subtypes of breast cancer. TNBC which consists of 15% of all types of breast cancer is categorized by the absence of expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor-2 (HER2). This is the main reason for the failure of current hormonal receptorbased therapies against TNBCs, thus leading to poor patient outcomes. Therefore, there is a necessity to develop novel therapies targeting this devastating disease.

In this study, we have targeted TNBC by simultaneous activation of apoptosis through DNA damage via cytotoxic agent such as paclitaxel (PAC), inhibition of PARP activity via PARP inhibitor, olaparib (OLA) and inhibiting the activity of FOXM1 proto-oncogenic transcription factor by using RNA interference technology (FOXM1-siRNA) in nanoformulations. Experiments conducted in this investigation include cellular uptake, cytotoxicity and apoptosis study using MDA-MB-231 cells.

The present study validates that co-delivery of two drugs (PAC and OLA) along with FOXM1-siRNA by cationic NPs, enhances the therapeutic outcome leading to greater cytotoxicity in TNBC cells.

The current investigation focuses on designing a multifunctional drug delivery platform for concurrent delivery of either PAC or PARP inhibitor (olaparib) and FOXM1 siRNA in chitosan-coated poly(D, L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) with the ability to emerge as a front runner therapeutic for TNBC therapy.

Tissue regenerative medicine strategies, as a promising alternative has become of major interest to the reconstruction of critical size bone defects. This study evaluated the effects of the simultaneous application of polycaprolactone (PCL), amniotic fluid mesenchymal stem cells (AF-MSCs) and platelet-rich plasma (PRP) on the repair of rat cranial bone defects.

The AF-MSCs were isolated at the end of the second week of pregnancy in rats. PRP obtained from rat blood and the random PCL fibrous scaffolds were prepared using the electrospinning method. Circular full thickness (5 mm) bone defects were developed on both sides of the parietal bones (animal number=24) and the scaffolds containing AF-MSCs and PRP were implanted in the right lesions. Thereafter, after eight weeks the histological and immunohistochemistry studies were performed to evaluate the bone formation and collagen type I expression.

The spindle-shaped mesenchymal stem cells were isolated and the electron microscope images indicated the preparation of a random PCL scaffold. Immunohistochemical findings showed that collagen type I was expressed by AF-MSCs cultured on the scaffold. The results of hematoxylin and eosin (H&E) staining indicated the formation of blood vessels in the presence of PRP. Additionally, immunofluorescence findings suggested that PRP had a positive effect on collagen type I expression.

The simultaneous application of fibrous scaffold + AF-MSCs + PRP has positive effects on bone regeneration. This study showed that PRP can affect the formation of new blood vessels in the scaffold transplanted in the bone defect.

Acute kidney injury (AKI) induced by renal ischemia-reperfusion (I/R) injury is a pro-inflammatory process that activates tolllike receptors (TLRs). Stem cell therapy holds a great promise for kidney repair. Therefore, we investigated the immunomodulatory role of bone marrow stromal cells (BMSCs) on TLR2 and TLR4 expression in AKI in male Sprague-Dawley rats.

BMSCs were isolated from the bone marrow of male rats, cultured in DMEM, and characterized using appropriate markers before transplantation. Renal I/R was induced by 45 minutes bilateral ischemia followed by 24 hours of reperfusion. Rats received intraperitoneal injections of BMSCs (1.5 × 106 cells, i.p, per rat) immediately after termination of renal ischemia. Serum samples were collected pre-and post-stem cells injection for assessment of blood urea nitrogen (BUN) and creatinine (Cr) levels. The kidneys were harvested after 24 hours of reperfusion for structural and molecular analysis.

Renal I/R caused severe tissue injuries and increased the level of BUN (166.5 ± 12.9 vs. 18.25±1.75) and Cr (3.7±0.22 vs. 0.87±0.06) compared to the sham group. In addition, mRNA expression of TLR2 and TLR4 elevated in the renal I/R group. Administration of BMSCs improved the functional and structural state of the kidney induced by I/R and down-regulated TLR2 and TLR4 gene expression.

The results showed a highly significant renoprotection by BMSCs that indicates their therapeutic potential in I/R injures. These effects are most likely associated with the TLR2/4 signaling pathway via modulation of the inflammatory response cascades.

To be fully functional, pharmaceutical, and biomedical research centers need to be transformed to become innovative research and development (R&D) hubs. Such transformation, however, is a dynamic complex matter.

To establish an innovative R&D hub, a simple and concise manifesto is conceptualized for the nonlinear dynamic transformation towards an innovative research hub to reinforce the transition of the 2nd generation R&D centers.

Interdisciplinary research is the most demanded field of research to overcome various multi-sided health issues. To become an innovative R&D hub, pharmaceutical centers must function as a small-scale physical infrastructure to support the inter-communication of scientists and provide specific technological needs to promote the related innovation and entrepreneurship with advanced business plans and prototypes. Given that a success paradigm within an unorderly surrounding setting has already been condemned to fail, the orderly integration of nested systems and groups should be carefully implemented towards a shared vision with formal and tacit agreements among all parties, including academia, industry, and finance team.

To achieve a fully functional innovative R&D hub, a “know-how” approach with the systems thinking mindset within all the parties is of paramount necessity. The healthier the order of the whole working system is, the more effective will be the encompassed entitles and players. However, systems should have several checkpoints to enhance clarity and evade discrepancy and divergence. Since the medication is a highly trusted and needed public enterprise, the drug discovery and development paradigm should be practiced at the highest speed with maximum transparency and accountability.