An insight into the paradigms of osteoporosis: From genetics to biomechanics.

Considered as one of the major epidemics of the 21st century, osteoporosis affects approximately 200 million people globally, with significant worldwide impact on rates of morbidity and mortality and massive socioeconomic burdens. Mainly characterized by decreased bone mineral density (BMD) and increased risk of bone fragility/deterioration, this devastating silent epidemic typically has no symptoms until a fracture occurs. The multifactorial disease, osteoporosis is instigated by complex interactions between genetic, metabolic and environmental factors, with severe impact on the biomechanics of the musculoskeletal system. This article provides a review of the epidemiology, genetic and biomechanical aspects of primary osteoporosis. The review begins with a summary of the epidemiology and global prevalence of osteoporosis. Sections 1 and 2 discuss the genetic associations and molecular signaling pathways involved in normal and pathological osteogenesis while Section 3 explores the biomechanics of osteoporosis and its quantitative damaging effects on critical bone mechanical properties, and associated bone remodeling. Overall, this review summarizes the recent findings about osteoporosis and emphasizes the importance of an integrative holistic approach in investigating osteoporosis towards providing better informed, more effective preventive and treatment modalities. Importantly, this work also explores the limited available literature on the various aspects of osteoporosis in the United Arab Emirates (UAE), Gulf Cooperation Council (GCC), and Middle East despite its alarming prevalence in the region, and highlights the need for further research and studies taking into consideration the importance of the vitamin D receptor (VDR) gene influencing the development of osteoporosis.

Ultrasound-mediated drug delivery by gas bubbles generated from a chemical reaction.

Highly echogenic and ultrasound-responsive microbubbles such as nitrogen and perfluorocarbons have been exploited as ultrasound-mediated drug carriers. Here, we propose an innovative method for drug delivery using microbubbles generated from a chemical reaction. In a novel drug delivery system, luminol encapsulated in folate-conjugated bovine serum albumin nanoparticles (Fol-BSAN) can generate nitrogen gas (N2) by chemical reaction when it reacts with hydrogen peroxide (H2O2), one of reactive oxygen species (ROS). ROS plays an important role in the initiation and progression of cancer and elevated ROS have been observed in cancer cells both in vitro and in vivo. High-intensity focussed ultrasound (HIFU) is used to burst the N2 microbubbles, causing site-specific delivery of anticancer drugs such as methotrexate. In this research, the drug delivery system was optimised by using water-soluble luminol and Mobil Composition of Matter-41 (MCM-41), a mesoporous material, so that the delivery system was sensitive to micromolar concentrations of H2O2. HIFU increased the drug release from Fol-BSAN by 52.9 ± 2.9% in 10 minutes. The cytotoxicity of methotrexate was enhanced when methotrexate is delivered to MDA-MB-231, a metastatic human breast cancer cell line, using Fol-BSAN with HIFU. We anticipate numerous applications of chemically generated microbubbles for ultrasound-mediated drug delivery.

Intermolecular interactions between cucurbit[7]uril and pilocarpine.

The interactions between cucurbit[7]uril (CB7) macrocycles and pilocarpine (PIL) were investigated in aqueous solution by using (1)H NMR and circular dichroism (CD) spectroscopic techniques. The characterizations of the freeze-drying solid complex were conducted by electrospray ionization mass spectroscopy (ESI-MS), Fourier transform-infrared spectroscopy (FT-IR), thermogravimetry, and differential scanning calorimetry (DSC) techniques. The DSC and thermogravimetry confirmed the production of a thermally stable solid complex. The NMR, CD and ESI-MS measurements confirmed asymmetric induction during the complexation reaction, in which the γ-lactone ring of PIL (not the imidazole nucleus) has been fully encapsulated within the cavity of CB7. The stability of the drug has significantly enhanced as evidenced by the high-performance liquid chromatographic (HPLC) method. The results are discussed in the context of utilizing non-conventional supramolecular host-guest approaches to enhance the chemical stability in aqueous media of hydrophilic PIL drugs as model compounds. The non-classical stereospecific interactions between CB7 and PIL drugs are also highlighted.

Genotoxicity of structurally related copper and zinc containing Schiff base complexes.

The utilization of Schiff bases in the industrial and pharmaceutical fields has led to an increase in their syntheses and evaluation of their biological activities. In this study, we described the synthesis and genotoxicity of two Schiff bases that share common platform in their construction, namely, naphthalene, and are complexed to either Cu(II) or Zn(II). The genotoxicity of these complexes was evaluated in cultured lymphocytes using sister chromatid exchanges (SCEs) and chromosomal aberrations (CAs), and in rats using the urine 8-OH-2-deoxyguanosine (8-OH-dG) assay. The results showed that the examined complexes are genotoxic, but with different degrees. The order of genotoxicity of the complexes at 10 µg/mL was: Cu(L3)(NCS)(H2O) > Zn(L3)(NCS)(H2O) > Cu(L2)(NCS) > Zn(L2)(NCS), where L2 and L3 are the conjugate bases of N-(8-quinolyl)napthaldimine and N-(anilinyl)napthaldimine, respectively. However, at the 1-µg/mL concentration, only the Cu(L3)(NCS)(H2O) complex induced significant CAs, whereas at the 0.1-µg/mL concentration, only Cu(L3)(NCS)(H2O) and Zn(L2)(NCS) complexes induced significant SCEs, compared to controls. In the urine 8-OH-dG assay, all complexes at 10 mg/100 g body weight (b.w.) were found to cause DNA damage with the following order: Cu(L3)(NCS)(H2O) > Zn(L2)(NCS) > Zn(L3)(NCS)(H2O) > Cu(L2)(NCS), whereas no significant DNA damage was observed in animals exposed to 1 and 0.1 mg/100 g b.w. (p > 0.05). In conclusion, the two examined Schiff base complexes are found to induce DNA damage, but with different degrees.