Advances in Anti-Osteoporosis Polysaccharides Derived from Medicinal Herbs and Other Edible Substances

Osteoporosis is a common metabolic bone disease, and treatment is required for the pre-vention of low bone mass, deterioration of microstructural bone tissue, and fragility fractures. Osteoporosis therapy includes calcium, vitamin D, and drugs with antiresorptive or anabolic action on the bone. Therapy for osteoporosis does not include taking non-steroidal anti-inflammatory drugs (NSAID), but pain associated with osteoporotic fractures can be treated by taking non-steroidal anti-inflammatory drugs (NSAID). Recently, polysaccharides extracted from medicinal herbs and edible substances (PsMHES) have attracted attention on account of their safety and promising anti-osteoporosis effects, whereas a systematic review about their potential in anti-osteoporosis is vacant to date. Herein, we reviewed the recent progress of PsMHES with anti-osteoporosis activities, looking to introduce the advances in the various pharmacological mechanisms and targets involved in the anti-osteoporosis effects, extraction methods, main mechanism involved in Wnt/β-catenin pathways and pathways and RANKL (Receptor Activator for NFκB ligand or TNFSF25) pathways, and Structure-Activity elationships (SAR) analysis of PsMHES. Typical herbs like Achyranthes bidentate and Morinda officinalis used for the treatment of osteoporosis are introduced; their traditional uses in traditional Chinese medicine (TCM) are discussed in this paper as well. This review will help to the recognition of the value of PsMHES in anti-osteoporosis and provide guidance for the research and development of new anti-osteoporosis agents in clinic.

Four-Port MIMO Antenna System for 5G n79 Band RF Devices

In this article, a compact four-port MIMO antenna system resonating from 4.7–5.1 GHz on −6 dB criteria is discussed. The proposed antennas are arranged in a perpendicular manner providing diversity with good isolation characteristics. The proposed antenna was fabricated and designed on a commercially available low-cost FR-4 substrate with a relative permittivity of 4.4. The total size of the antenna is 40 × 40 mm2, and a minimum isolation of 25 dB was observed at most nearby resonating elements. The proposed antenna was fabricated and tested at an in-house facility, and the measured results agree well with the simulations. The MIMO antenna characteristics, such as the envelope correlation coefficient (ECC) among any two radiating elements, have been found to be less than 0.1, and the diversity gain (DG) value evaluated showed that the proposed antenna is well designed. Furthermore, the SAR analysis showed that the desired antenna system is safe for users, with a value of 0.94 W/Kg. The channel capacity (cc) was found to be 18.7 bps/Hz, approximately 2.7 times more than SISO systems. Through its robust and reliable performance and its peak gain of 2.8 dBi, the proposed compact antenna is a good candidate for future 5G devices.

A Sub-6 GHz MIMO Antenna Array for 5G Wireless Terminals

This paper presents a novel antenna with its array and MIMO configuration for the 5G sub-6 GHz applications. The proposed antenna element operates at the central frequency of 5.57 GHz dedicated for Sub-6 GHz 5G communication applications. The antenna element holds a circular-shaped radiating portion with an inner-circular slot, plus a rectangular slot at its right edge to make the proposed design resonate at the desired frequency band. The RT5880 substrate is used with a thickness of 0.787 mm, and the low-loss tangent of 0.0009. To achieve a desired gain of 12 dB, a four-element array configuration is adopted, which improved a bore side gain to 12.4 dB from 6.66 dB. Then, the two-port configuration is adopted such that the isolation achieved between them is more than −30 dB. The total efficiency of the proposed antenna array is observed to be more than 80% within the operating bandwidth. Moreover, the Specific Absorption Rate (SAR) analysis is also presented for the proposed MIMO configuration, obeying the standard value (i.e., <2 W/kg for any 10 g of tissue). The measured results are in good agreement with the simulated results. All the simulations of the proposed design are performed in the CST MWS software.

The Structural Determinants for α1-Adrenergic/Serotonin Receptors Activity among Phenylpiperazine-Hydantoin Derivatives

Several studies confirmed the reciprocal interactions between adrenergic and serotoninergic systems and the influence of these phenomena on the pathogenesis of anxiety. Hence, searching for chemical agents with a multifunctional pharmacodynamic profile may bring highly effective therapy for CNS disorders. This study presents a deep structural insight into the hydantoin-arylpiperazine group and their serotonin/α-adrenergic activity. The newly synthesized compounds were tested in the radioligand binding assay and the intrinsic activity was evaluated for the selected derivatives. The computer-aided SAR analysis enabled us to answer questions about the influence of particular structural fragments on selective vs. multifunctional activity. As a result of the performed investigations, there were two leading structures: (a) compound 12 with multifunctional adrenergic-serotonin activity, which is a promising candidate to be an effective anxiolytic agent; (b) compound 14 with high α1A/α1D affinity and selectivity towards α1B, which is recommended due to the elimination of probable cardiotoxic effect. The structural conclusions of this work provide significant support for future lead optimization in order to achieve the desired pharmacodynamic profile in searching for new CNS-modulating agents.

Lipophilic Salirasib analogs with enhanced antiproliferative activity against human solid tumor cell lines

Aim: We proposed to determine the antiproliferative activity of a series of synthetic salirasib analogs, presenting or not a 1,2,3-triazole linker, against five different cancer cell lines. Results: Bioassay, cheminformatic, and in silico ADME-Tox allowed the identification of new potent analogs. SAR analysis allowed the identification of structural and physicochemical features that benefit the antiproliferative activity. Conclusion: Isoprenyl R chains with three or more isoprene units, or long aliphatic R chains are the preferred ones within the active compounds. Likewise, we have identified three compounds with better activity profiles than salirasib against all the cell lines tested.

Inhibition of Aminoglycoside 6’-N-Acetyltransferase Type Ib [Aac(6′)-Ib]: Structure-Activity Relationship of Substituted Pyrrolidine Pentamine Derivatives as Inhibitors

The aminoglycoside 6&prime;-N-acetyltransferase type Ib [AAC(6&prime;)-Ib] is a common cause of resistance to amikacin and other aminoglycosides in Gram-negatives. Utilization of mixture-based combinatorial libraries and application of the positional scanning strategy identified an inhibitor of AAC(6&prime;)-Ib. This inhibitor&rsquo;s chemical structure consists of a pyrrolidine pentamine scaffold substituted at four locations (R1, R3, R4, and R5). The substituents are two S-phenyl (R1 and R4), an S-hydroxymethyl (R3), and a 3-phenylbutyl (R5) groups. Another location, R2, does not have a substitution, but it is named because its stereochemistry was modified in some compounds utilized in this study. Structure-activity relationship (SAR) analysis using derivatives with different functionalities, modified stereochemistry, and truncations were carried out by assessing the effect of the addition of each compound at 8 &micro;M to 16 &micro;g/ml amikacin-containing media and performing checkerboard assays varying the concentrations of the inhibitor analogs and the antibiotic. The results showed that: 1) the aromatic functionalities at R1 and R4 are essential, but the stereochemistry is essential only at R4, 2) the stereochemical conformation at R2 is critical, 3) the hydroxyl moiety at R3 as well as stereoconformation are required for full inhibitory activity, 4) the phenyl functionality at R5 is not essential and can be replaced by aliphatic groups, 5) the location of the phenyl group on the butyl carbon chain at R5 is not essential, 6) the length of the aliphatic chain at R5 is not critical, 7) all truncations of the scaffold resulted in inactive compounds. Molecular docking revealed that all compounds preferentially bind to the kanamycin C binding cavity, and binding affinity correlates with the experimental data for most of the compounds evaluated. The SAR results in this study will serve as the basis for the design of new analogs in an effort to improve their ability to induce phenotypic conversion to susceptibility in amikacin-resistant pathogens.