Development of a Novel Design of Microfluidic Impedance Cytometry for Improved Sensitivity and Cell Identification.

A long-standing issue for microfluidic impedance cytometry devices is the accuracy in determining the size of cells during counting and measurements. In this paper, we introduce a novel design that produces a homogeneous electric field in the sensing region and demonstrates higher accuracy than traditional designs in cell counting and sizing, reducing the reliance on cell focusing and signal postprocessing. The concept is validated, and the increased accuracy of the device over traditional designs is demonstrated through the use of finite element simulations to generate suitable data sets for particle trajectories and model expected signal variations.

Nanoencapsulation of Hirudo medicinalis proteins in liposomes as a nanocarrier for inhibiting angiogenesis through targeting VEGFA in the Breast cancer cell line (MCF-7).

Introduction: Breast cancer is the most serious cause of women's death throughout the world. Using nanocarrier vehicles to the exact site of cancer upgrades the therapeutic efficiency of the drugs. Capsulation of active proteins in the vesicular liposomes' hydrophilic core is essential to develop a therapeutic protein carrier system. We aimed to encapsulate the medicinal leech saliva extract (LSE) and assess the inhibition of angiogenesis of breast cancer cells by targeting vascular endothelial growth factor A (VEGFA). Methods: In this research, enhanced formulation of liposomal protein was determined by zeta potential analysis, droplet size, drug release assay, and transmission electron microscopy (TEM). Furthermore, a cytotoxicity assay of liposomal LSE was performed to determine the cytotoxic activity of components. For assessing the expression of VEGFA, P53, and hypoxia-inducible factor subunit alpha (HIF1a) genes, Real-Time PCR was applied. Results: Nano liposome was chosen as an enhanced formulation due to its much smaller size (46.23 nm). Liposomal LSE had more practical actions on the MCF-7 cells. As noticed by DAPI staining, apoptosis was extensively greater in treated MCF-7 cells. Wound healing assay demonstrated that MCF-7 cells could not sustain growth at the presence of liposomal LSE and expression of the VEGFA gene was declined in treated cells. Downregulation of VEGFA was evaluated with western blotting technique. Conclusion: It can be concluded that our investigation of the tests confirmed the fact that nano liposomal LSE is a novel promising formulation for anticancer drugs and can significantly improve the penetration of protein drugs to cancer cells.

Time to Change Theory; Medical Leech from a Molecular Medicine Perspective Leech Salivary Proteins Playing a Potential Role in Medicine.

Followed by developing modern medicine, leeches did not have extensive use as before; however, in the late 19th century, they were still used in most countries all over the world. Thus far, leeches were utilized in treating various diseases like skin disorders, arthritis, and cancer. In Egypt, using leeches for treatment dates back to early 1500 BC. A medical leech's salivary glands involve over 100 bioactive proteins and the salivary gland secretion contains bacteriostatic, analgesic, and anticoagulation influences; with resolving activity, it causes microcirculation disorders elimination, restoring the hurt vascular permeability of organs and tissues, removing hypoxia, decreasing blood pressure and detoxifying the organism by antioxidant paths. The current work reviews the innovative treatment with medical leech, especially proteins in leech saliva extraction (LSE) with high potential in medicine. The virtue of salivary gland secretions which are proteinaceous enzymes, leech acts on various diseases such as venous congestion in reconstructive and plastic surgery, osteoarthritis, cardiovascular diseases caused by blood coagulation disorders, pain management, priapism, macroglossia, cancer complications, wounds and many other. To confirm the potential therapeutic impacts of leech treatment, more studies are required in more extensive areas with more exact methodologies.

PCSK9: A Key Target for the Treatment of Cardiovascular Disease (CVD).

Proprotein convertase subtilisin/kexin type 9 (PCSK9), as a vital modulator of low-density lipoprotein cholesterol (LDL-C) , is raised in hepatocytes and released into plasma where it binds to LDL receptors (LDLR), leading to their cleavage. PCSK9 adheres to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR which is confirmed by crystallography. LDLR expression is adjusted at the transcriptional level through sterol regulatory element binding protein 2 (SREBP-2) and at the post translational stages, specifically through PCSK9, and the inducible degrader of the LDLR PCSK9 inhibition is an appealing new method for reducing the concentration of LDL-C. In this review the role of PCSK9 in lipid homeostasis was elucidated, the effect of PCSK9 on atherosclerosis was highlighted, and contemporary therapeutic techniques that focused on PCSK9 were summarized. Several restoration methods to inhibit PCSK9 have been proposed which concentrate on both extracellular and intracellular PCSK9, and they include blockage of PCSK9 production by using gene silencing agents and blockage of it's binding to LDLR through antibodies and inhibition of PCSK9 autocatalytic processes by tiny molecule inhibitors.

Purification of hyaluronidase as an anticancer agent inhibiting CD44.

Hyaluronidase (Hyal) can be employed to accomplish a diversity of complications related to hyaluronic acid (HA). Hyal contains some classes of catalysts that cleave HA. This enzyme is detected in several human tissues as well as in animal venoms, pathogenic organisms and cancers. Destructive cancer cells regularly increase the CD44 receptor existing in a cell membrane. This receptor acts as an exact receptor for HA, and HA is recognized to motivate the migration, spread, attack and metastasis of cancer cells. Nearly all of the methods used to purify Hyal are highly costly and not proper for industrial applications. This survey aims to review different methods of Hyal purification, which acts as an anticancer agent by degrading HA in tissues and thus inhibiting the CD44-HA interaction. Hyal can be successfully employed in the management of cancer, which is associated with HA-CD44. This review has described different methods for Hyal purification to prepare an origin to develop a novel purification technique for this highly appreciated protein. Using multiple columns is not applicable for the purification of Hyal and thus cannot be used at the industrial level. It is better to use affinity chromatography of anti-Hyal for Hyal with one-step purification.

Deep-subwavelength control of acoustic waves in an ultra-compact metasurface lens.

Space-coiling acoustic metasurfaces have been largely exploited and shown their outstanding wave manipulation capacity. However, they are complex in realization and cannot directly manipulate acoustic near-fields by controlling the effective path length. Here, we propose a comprehensive paradigm for acoustic metasurfaces to extend the wave manipulations to both far- and near-fields and markedly reduce the implementation complexity with a simple structure, which consists of an array of deep-subwavelength-spaced slits perforated in a thin plate. A semi-analytical approach for such a design is established using a microscopic coupled-wave model, which reveals that the acoustic diffractive pattern at every slit exit is the sum of the initial transmission and the secondary scatterings of the coupled fields from other slits. For proof-of-concept, we examine two metasurface lenses for sound focusing within and beyond the diffraction limit. This work provides a feasible strategy for creating ultra-compact acoustic components with versatile potentials.

Effectiveness of topical gel of medical leech (Hirudo medicinalis) saliva extract on patients with knee osteoarthritis: A randomized clinical trial.

Leech saliva extract (LSE) in the liposome-based gel was used as a supplementary treatment to relief the signs and symptoms of osteoarthritis (OA). The saliva of medical leech was extracted and nano liposomes were used to formulate the supplement to enhance skin absorption. A clinical trial was designed to evaluate the therapeutic effects of LSE liposomal gel. Lenquesne and VAS questionnaires were used as indexes of this supplement therapy efficacy for 30 days. Questionnaires analysis showed that after one-month administration of LSE liposomal gel, patients' pain was relieved approximately up to 50%; also, due to reduction in joint inflammation and stiffness, the range of motion was increased and the patients' quality of life was enhanced (p < 0.001). LSE nano scaled liposomal gel as an innovative supplement therapy in OA patients, makes desirable therapeutic approach, which seems to make a significant impact on patient's quality of life and self-care capability.

Controlled folding of graphene: GraFold printing.

We have used elastomeric stamps with periodically varying adhesive properties to introduce structure and print folded graphene films. The structure of the induced folds is investigated with scanning probe techniques, high-resolution electron-microscopy, and tip-enhanced Raman spectroscopy. Furthermore, a finite element model is developed to show the fold formation process. Terahertz spectroscopy reveals induced anisotropy of carrier mobility along, and perpendicular to, the graphene folds. Graphene fold printing is a new technique which allows for significant modification of the properties of 2D materials without damaging or chemically modifying them.

Combining cell sheet technology and electrospun scaffolding for engineered tubular, aligned, and contractile blood vessels.

Herein we combine cell sheet technology and electrospun scaffolding to rapidly generate circumferentially aligned tubular constructs of human aortic smooth muscles cells with contractile gene expression for use as tissue engineered blood vessel media. Smooth muscle cells cultured on micropatterned and N-isopropylacrylamide-grafted (pNIPAm) polydimethylsiloxane (PDMS), a small portion of which was covered by aligned electrospun scaffolding, resulted in a single sheet of unidirectionally aligned cells. Upon cooling to room temperature, the scaffold, its adherent cells, and the remaining cell sheet detached and were collected on a mandrel to generating tubular constructs with circumferentially aligned smooth muscle cells which possess contractile gene expression and a single layer of electrospun scaffold as an analogue to a small diameter blood vessel's internal elastic lamina (IEL). This method improves cell sheet handling, results in rapid circumferential alignment of smooth muscle cells which immediately express contractile genes, and introduction of an analogue to small diameter blood vessel IEL.