Spectrofluorimetric determination of the anti-Covid 19 agent,remdesivir, in vials and spiked human plasma

Following the sudden widespread of the novel coronavirus (COVID-19) which first appeared in Wuhan city. Remdesivir (REM) was the first medicine licensed by the US Food and Drug Administration (FDA) for COVID-19 infected hospitalized patients. Hence, there was an urgent demand for the optimization of efficient selective and sensitive methods to be developed for the determination of REM in pharmaceuticals as well as biological samples. A sensitive and simple green spectrofluorimetric method has been developed to determine REM in pharmaceutical formulation, in addition to, spiked human plasma. The technique involves measuring the native fluorescence of REM in distilled water at 410 nm followed by excitation at 241 nm, giving a linear relationship over the range 50.00–500.00 ng/mL, and then improving the sensitivity of REM through micellar formation using 2.00% w/v sodium dodecyl sulfate (SDS). A linear relationship has been obtained over the range 10.00–350.00 ng/mL having detection and quantitation limits of 2.34 and 7.10 ng/mL, respectively. Different analytical parameters have been carefully studied. A validation study has been conducted successfully in accordance with the FDA and the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines. The developed methods' greenness was assessed utilizing a greenness profile and analytical eco-scale standards. Both methods were discovered to be environmentally friendly and could be successfully used for the determination of the studied drugs in pharmaceutical formulation and human plasma with good accuracy and high precision. As a result, the developed spectrofluorimetric methods could be ideally suited for determination of REM in quality control and medicinal laboratories.     

Production and antioxidant activity of secondary metabolites in Hassawi rice (Oryza sativa L.) cell suspension under salicylic acid,yeast extract,and pectin elicitation

In Vitro Cellular & Developmental Biology - Plant - Plants that produce bioactive chemicals provide a viable in vitro method for producing key nutraceutical substances, especially in the...     

Magnetoelectric nanocomposite scaffold for high yield differentiation of mesenchymal stem cells to neural-like cells

While the differentiation factors have been widely used to differentiate mesenchymal stem cells (MSCs) into various cell types, they can cause harm at the same time. Therefore, it is beneficial to propose methods to differentiate MSCs without factors. Herein, magnetoelectric (ME) nanofibers were synthesized as the scaffold for the growth of MSCs and their differentiation into neural cells without factors. This nanocomposite takes the advantage of the synergies of the magnetostrictive filler, CoFe₂O ₄ nanoparticles (CFO), and piezoelectric polymer, polyvinylidene difluoride (PVDF). Graphene oxide nanosheets were decorated with CFO nanoparticles for a proper dispersion in the polymer through a hydrothermal process. After that, the piezoelectric PVDF polymer, which contained the magnetic nanoparticles, underwent the electrospun process to form ME nanofibers, the ME property of which has the potential to be used in areas such as tissue engineering, biosensors, and actuators.     

Curcumin attenuates proangiogenic and proinflammatory factors in human eutopic endometrial stromal cells through the NF-κB signaling pathway

Endometriosis is a chronic gynecological inflammatory disorder in which immune system dysregulation is thought to play a role in its initiation and progression. Due to altered sex steroid receptor concentrations and other signaling defects, eutopic endometriotic tissues have an attenuated response to progesterone. This progesterone-resistance contributes to lesion survival, proliferation, pain, and infertility. The current agency-approved hormonal therapies, including synthetic progestins, GnRH agonists, and danazol are often of limited efficacy and counterproductive to fertility and cause systemic side effects due to suppression of endogenous steroid hormone levels. In the current study, we examined the effects of curcumin (CUR, diferuloylmethane), which has long been used as an anti-inflammatory folk medicine in Asian countries for this condition. The basal levels of proinflammatory and proangiogenic chemokines and cytokines expression were higher in primary cultures of stromal cells derived from eutopic endometrium of endometriosis (EESC) subjects compared with normal endometrial stromal cells (NESC). The treatment of EESC and NESC with CUR significantly and dose-dependently reduced chemokine and cytokine secretion over the time course. Notably, CUR treatment significantly decreased phosphorylation of the IKKα/β, NF-κB, STAT3, and JNK signaling pathways under these experimental conditions. Taken together, our findings suggest that CUR has therapeutic potential to abrogate aberrant activation of chemokines and cytokines, and IKKα/β, NF-κB, STAT3, and JNK signaling pathways to reduce inflammation associated with endometriosis.     

Complications of nonionizing radiofrequency on divided attention

Exposure to electromagnetic fields is considered as a potential hazard for biological systems. The objective of our investigation is the study of probable consequences of radiofrequency electromagnetic fields from Wi-Fi router devices on the short-term memory, and attention's levels. A population consisting of 312 female college students (14 to 17 years old) was elected by cluster random sampling. Teenagers were divided into two groups of control group (Wi-Fi nonusers; n = 138), and experiment group (Wi-Fi users; n = 174). Both groups have been examined using short-term memory tests; selective attention, and also divided attention tests. According to the results, there was no significant difference between using Wi-Fi router devices on levels of selective attentions and short-term memory of the sample students with the control group. However, analyses revealed that there is a significant correlation between the use of Wi-Fi routers and declining levels of divided attentions. Our investigation has demonstrated the adverse consequences of 2.4-2.48 GHz radiofrequency electromagnetic fields of Wi-Fi router devices on divided attention levels of female university students that should be mentioned as a technological risk factor and taken into account by healthcare organizations.     

Mitogen-activated protein kinase feedback phosphorylation regulates MEK1 complex formation and activation during cellular adhesion

Cell adhesion and spreading depend on activation of mitogen-activated kinase, which in turn is regulated both by growth factor and integrin signaling. Growth factors, such as epidermal growth factor, are capable of activating Ras and Raf, but integrin signaling is required to couple Raf to MEK and MEK to extracellular signal-regulated protein kinase (ERK). It was previously shown that Rac-p21-activated kinase (PAK) signaling regulated the physical association of MEK1 with ERK2 through phosphorylation sites in the proline-rich sequence (PRS) of MEK1. It was also shown that activation of MEK1 and ERK by integrins depends on PAK phosphorylation of S298 in the PRS. Here we report a novel MEK1-specific regulatory feedback mechanism that provides a means by which activated ERK can terminate continued PAK phosphorylation of MEK1. Activated ERK can phosphorylate T292 in the PRS, and this blocks the ability of PAK to phosphorylate S298 and of Rac-PAK signaling to enhance MEK1-ERK complex formation. Preventing ERK feedback phosphorylation on T292 during cellular adhesion prolonged phosphorylation of S298 by PAK and phosphorylation of S218 and S222, the MEK1 activating sites. We propose that activation of ERK during adhesion creates a feedback system in which ERK phosphorylates MEK1 on T292, and this in turn blocks additional S298 phosphorylation in response to integrin signaling.     

Unconventional interactions between water and heterocyclic nitrogens in protein structures

We report an unusual interaction in which a water molecule approaches the heterocyclic nitrogen of tryptophan and histidine along an axis that is roughly perpendicular to the aromatic plane of the side chain. The interaction is distinct from the well-known conventional aromatic hydrogen-bond, and it occurs at roughly the same frequency in protein structures. Calculations indicate that the water-indole interaction is favorable energetically, and we find several cases in which such contacts are conserved among structural orthologs. The indole-water interaction links side chains and peptide backbone in turn regions, connects the side chains in beta-sheets, and bridges secondary elements from different domains. We suggest that the water-indole interaction can be indirectly responsible for the quenching of tryptophan fluorescence that is observed in the folding of homeodomains and, possibly, many other proteins. We also observe a similar interaction between water and the imidazole nitrogens of the histidine side chain. Taken together, these observations suggest that the unconventional water-indole and water-imidazole interactions provide a small but favorable contribution to protein structures.     

Upper extremity limb salvage with microvascular reconstruction in patients with advanced sarcoma

Limb salvage is a viable alternative to amputation in many cases of advanced sarcoma. The authors examined their experience with microvascular reconstruction of upper extremity defects after sarcoma resection, focusing on oncologic and functional outcomes. A retrospective analysis yielded 17 patients who underwent 18 free flap procedures and met the inclusion criteria. Most patients (71 percent, n = 12) had recurrent sarcoma at presentation to the authors' institution. Malignant fibrous histiocytoma was the most common pathologic subtype (n = 6). High-grade tumors were present in 94 percent of patients (n = 16). The free flap survival rate was 100 percent. The rectus abdominis flap was the most common free flap used (39 percent; n = 7). Local recurrence occurred in nine flaps (50 percent), and five patients ultimately required amputations. Six patients (35 percent) had distant recurrence. The mean Enneking score for limb function was 73 percent of the maximum (21.9 of 30). The 5-year disease-specific survival rate was 61.3 percent. In select patients with advanced upper extremity sarcoma undergoing limb salvage, microvascular flap reconstruction can provide reliable, safe coverage with reasonable preservation of function.