Thermoresponsive Poly(N,N'-dimethylacrylamide)-Based Diblock Copolymer Worm Gels via RAFT Solution Polymerization: Synthesis, Characterization, and Cell Biology Applications.

RAFT solution polymerization is used to polymerize 2-hydroxypropyl methacrylate (HPMA). The resulting PHPMA precursor is then chain-extended using N,N'-dimethylacrylamide (DMAC) to produce a series of thermoresponsive PHPMA-PDMAC diblock copolymers. Such amphiphilic copolymers can be directly dispersed in ice-cold water and self-assembled at 20 °C to form spheres, worms, or vesicles depending on their copolymer composition. Construction of a pseudo-phase diagram is required to identify the pure worm phase, which corresponds to a rather narrow range of PDMAC DPs. Such worms form soft, free-standing gels in aqueous solution at around ambient temperature. Rheology studies confirm the thermoresponsive nature of such worms, which undergo a reversible worm-to-sphere on cooling below ambient temperature. This morphological transition leads to in situ degelation, and variable temperature 1H NMR studies indicate a higher degree of (partial) hydration for the weakly hydrophobic PHPMA chains at lower temperatures. The trithiocarbonate end-group located at the end of each PDMAC chain can be removed by treatment with excess hydrazine. The resulting terminal secondary thiol group can form disulfide bonds via coupling, which produces PHPMA-PDMAC-PHPMA triblock copolymer chains. Alternatively, this reactive thiol group can be used for conjugation reactions. A PHPMA141-PDMAC36 worm gel was used to store human mesenchymal stem cells (MSCs) for up to three weeks at 37 °C. MSCs retrieved from this gel subsequently underwent proliferation and maintained their ability to differentiate into osteoblastic cells.

Chronobiological Efficacy of Combined Therapy of Pelargonium Sidoides and Melatonin in Acute and Persistent Cases of COVID-19: A Hypothetical Approach.

Since the outbreak of the first SARS-CoV-2 epidemic in China, pharmacists have rapidly engaged and developed strategies for pharmaceutical care and supply. According to the guidelines of the International Pharmaceutical Federation (FIP), clinical pharmacists/hospital pharmacists, as members of care teams, play one of the most important roles in the pharmaceutical care of patients with COVID-19. During this pandemic, many immuno-enhancing adjuvant agents have become critical in addition to antivirals and vaccines in order to overcome the disease more easily. The liquid extract obtained from the Pelargonium sidoides plant is used for many indications such as colds, coughs, upper respiratory tract infections, sore throat, and acute bronchitis. The extract obtained from the roots of the plant has been observed to have antiviral and immunomodulatory activity. In addition to its anti-inflammatory and antioxidant effects, melatonin plays a role in suppressing the cytokine storm that can develop during COVID-19 infection. Knowing that the severity and duration of COVID-19 symptoms vary within 24 hours and/or in different time periods indicates that COVID-19 requires a chronotherapeutic approach. Our goal in the management of acute and long COVID is to synchronize the medication regimen with the patient's biological rhythm. This chapter provides a comprehensive review of the existing and emerging literature on the chronobiological use of Pelargonium sidoides and melatonin during acute and prolonged COVID-19 episodes.

Magnetic Targeting of 5-Fluorouracil-Loaded Liposome-Nanogels for In Vivo Breast Cancer Therapy and the Cytotoxic Effects on Liver and Kidney.

In our previous paper, we demonstrated the ex vivo studies of non-toxic liposome-nanogel systems by which the long-term drug release could be provided from hybrid systems for the 5-fluorouracil (5-FU) drug molecule. The aim of this study was the in vivo magnetic targeting of 5-FU-loaded Fe3O4 nanoparticles including DPPC liposome-based PEGylated nanogels (5-FU loaded Fe3O4LPN) to breast cancer tissue and the investigation of the treatment and cytotoxic effects of that hybrid system to the liver and kidney in CD-1 mice using an external magnetic field. The effectiveness of the control, 5-FU group, Fe3O4LPN, and 5-FU-loaded Fe3O4LPN systems was evaluated using histopathology in terms of p53, ESR, PRG and C-erB-2, and qRT-PCR in terms of TYMS, ESR-1, RPG, and EGRF. Also, the cytotoxicity was analyzed by histopathological evaluation of kidney and liver tissues. Caspase-3 and caspase-9 evaluations were performed by qRT-PCR. The creatinine and ALT levels were also evaluated by comparing the blood samples of all groups. A total of 300-nm TEM-sized Fe3O4LNP hybrid system was successfully prepared. That system significantly decreased the TYMS and ESR1 levels after treatment process and increased the levels of p53 expression. The levels of caspase-3 mRNA did not change during the treatment, but the level of caspase-9 mRNA level was significantly decreased. The magnetically targeted liposome-based nanogel hybrid system is promising an effective therapy for the breast tumor with less liver and kidney damage. This Fe3O4LNP hybrid system could be useful for the similar small molecules.

Downregulation of SCARA5 may contribute to breast cancer via promoter hypermethylation.

Breast cancer is the most common malignant tumor in women worldwide. Breast tumors mostly exhibit aberrant gene expression and DNA hypermethylation patterns that predispose the disease. Understanding the genetic and epigenetic factors that contribute to breast cancer development is important to identify novel diagnostic and prognostic markers. SCARA5: Scavenger receptor class A, member 5; is a member of the scavenger receptor family located on chromosome 8p21 which is a frequently deleted region in human cancers. SCARA5 has been identified as a candidate tumor suppressor gene in various kinds of cancer. However, its role in breast cancer remains unclear. Therefore, in the present study SCARA5 expression levels in breast tumors and matched noncancerous tissue samples from 77 patients were analyzed by qRT-PCR and the expression levels were correlated with the methylation level of SCARA5 gene promoter. We found that SCARA5 expression was significantly decreased in tumors (92.2%) compared to non-cancerous tissue samples and this down-regulation was associated with hypermethylation of the promoter (p < 0.001). A significant correlation was also detected between SCARA5 expression and the histological grade of the breast tumors (p = 0.017). Taken together, our results indicate that SCARA5 may play an important role in tumorigenesis of breast cancer via promoter methylation.

Use of Sulfobetaine-Based Block Copolymer as Stabilizer in Silver Nanoparticle Production and Catalytic Activity Studies.

A zwitterionic sulfobetaine-based diblock copolymer was successfully synthesized and used in the preparation and stabilization of Ag nanoparticles (AgNPs). For the related block copolymer, a precursor AB type diblock copolymer was synthesized via atom transfer radical polymerization by using a MPEG-based ATRP macroinitiator and 2-(N-dimethylamino)ethyl methacrylate (DMA) comonomer. Tertiary amine residues of PDMA blocks in poly(ethylene glycol) methyl ether-b-poly[2-(N-diethylamino)ethyl methacrylate] (MPEG-b-PDMA) precursor was then converted to polybetaine structures by reacting with 1,3-propanesultone to obtain poly(ethylene glycol) methyl ether-b-poly[3-dimethyl(methacryloyloxyethyl) ammonium propane sulfonate] (MPEG-b-PßDMA) derivative. The resulting block copolymer was successfully used as stabilizer in the chemical and sonochemical synthesis of spherical AgNPs with a diameter in the range of 7.9-9.3 nm. The average diameter of AgNPs synthesized by sonochemical method was smaller than those synthesized by chemical method. The MPEG-b-PßDMA diblock copolymer was determined to be a good stabilizer for AgNPs. The AgNPs dispersion was stable for more than 5 months without any flocculation at room temperature. The catalytic activity of polymer-AgNP dispersion was also investigated in the reduction of p-nitrophenol to p-aminophenol and was found to be quite effective.