A role for triglyceride lipase brummer in the regulation of sex differences in Drosophila fat storage and breakdown.

Triglycerides are the major form of stored fat in all animals. One important determinant of whole-body fat storage is whether an animal is male or female. Here, we use Drosophila, an established model for studies on triglyceride metabolism, to gain insight into the genes and physiological mechanisms that contribute to sex differences in fat storage. Our analysis of triglyceride storage and breakdown in both sexes identified a role for triglyceride lipase brummer (bmm) in the regulation of sex differences in triglyceride homeostasis. Normally, male flies have higher levels of bmm mRNA both under normal culture conditions and in response to starvation, a lipolytic stimulus. We find that loss of bmm largely eliminates the sex difference in triglyceride storage and abolishes the sex difference in triglyceride breakdown via strongly male-biased effects. Although we show that bmm function in the fat body affects whole-body triglyceride levels in both sexes, in males, we identify an additional role for bmm function in the somatic cells of the gonad and in neurons in the regulation of whole-body triglyceride homeostasis. Furthermore, we demonstrate that lipid droplets are normally present in both the somatic cells of the male gonad and in neurons, revealing a previously unrecognized role for bmm function, and possibly lipid droplets, in these cell types in the regulation of whole-body triglyceride homeostasis. Taken together, our data reveal a role for bmm function in the somatic cells of the gonad and in neurons in the regulation of male-female differences in fat storage and breakdown and identify bmm as a link between the regulation of triglyceride homeostasis and biological sex.

T cells participate in bone remodeling during the rapid palatal expansion.

Palatal expansion has been widely used for the treatment of transverse discrepancy or maxillae hypoplasia, but the biological mechanism of bone formation during this procedure is largely unknown. Osteoclasts, which could be regulated by T cells and other components of the immune system, play a crucial role in force-induced bone remodeling. However, whether T cells participate in the palatal expansion process remains to be determined. In this study, we conducted the tooth borne rapid palatal expansion model on the mouse, and detect whether the helper T cells (Th) and regulatory T cells (Treg) could affect osteoclasts and further bone formation. After bonding open spring palatal expanders for 3-day, 5-day, 7-day, and retention for 28-day, micro-computed tomography scanning, histologic, and immunofluorescence staining were conducted to evaluate how osteoclasts were regulated by T cells during the bone remodeling process. We revealed that the increased osteoclast number was downregulated at the end of the early stage of rapid palatal expansion. Type 1 helper T (Th1) cells and Type 17 helper T (Th17) cells increased initially and promoted osteoclastogenesis. Thereafter, the regulatory T (Treg) cells emerged and maintained a relatively high level at the late stage of the experiment to downregulate the osteoclast number by inhibiting Th1 and Th17 cells, which governed the new bone formation. In conclusion, orchestrated T cells are able to regulate osteoclasts at the early stage of rapid palatal expansion and further facilitate bone formation during retention. This study identifies that T cells participate in the palatal expansion procedure by regulating osteoclasts and implies the potential possibility for clinically modulating T cells to improve the palatal expansion efficacy.

TORCH screening used appropriately in China?─three years results from a teaching hospital in northwest China.

OBJECTIVES: TORCH infections caused by Toxoplasma gondii (TOX), rubella virus (RV), cytomegalovirus (CMV) and herpes simplex virus 1,2 (HSV-1,2) are associated with congenital anomalies. The study aimed to analyze the characteristics of TORCH screening in reproductive age women. METHODS: A total of 18,104 women (2015-2017) from a teaching hospital in Xi'an, China, were enrolled in the study. The characteristics of TORCH screening, i.e., the application of TORCH test, the seroprevalence, the impact of age, periods of gestation and woman with bad obstetric history (BOH) on the serological data were investigated. RESULTS: In the study, 319 women (1.76%) performed dynamic TORCH test. 51.66, 20.44 and 3.83% of the population did the test in the pre-gestation period, the first and third trimester, respectively. Quite a few pre-gestation women (29.74%) ignored screening of IgG antibodies. The overall IgG/IgM seropositvity of TOX, RV, CMV, HSV-1 and HSV-2 was 4.35%/0.35, 90%/0.63, 96.79%/0.97, 81.11%/0.14 and 6.1%/0.19%, respectively. The age-specific distributions and periods of gestation had no significant effect on the seroprevalence of TORCH agents, p>0.05. However, BOH was significantly associated with higher seropositvity of IgM (RV, CMV, HSV-1 and HSV-2) and IgG (CMV and HSV-1) antibodies, p < 0.05. CONCLUSION: In Xi'an region, more attentions should be paid to TOX, CMV, HSV-2 and the women with BOH for TORCH screening. Meanwhile, a greater emphasis needs to be placed on TORCH test used inappropriately in China.

Developing antifouling biointerfaces based on bioinspired zwitterionic dopamine through pH-modulated assembly.

The use of synthetic biomaterials as implantable devices typically is accompanied by considerable nonspecific adsorption of proteins, cells, and bacteria. These may eventually induce adverse pathogenic problems in clinical practice, such as thrombosis and biomaterial-associated infection. Thus, an effective surface coating for medical devices has been pursued to repel nonspecific adsorption from surfaces. In this study, we employ an adhesive dopamine molecule conjugated with zwitterionic sulfobetaine moiety (SB-DA), developed based on natural mussels, as a surface ligand for the modification of TiO2. The electrochemical study shows that the SB-DA exhibits fully reversible reduction-oxidation behavior at pH 3, but it is irreversible at pH 8. A contact angle goniometer and X-ray photoelectron spectroscopy were utilized to explore the surface hydration, chemical states, and bonding mechanism of SB-DA. The results indicate that the binding between hydroxyl groups of SB-DA and TiO2 converts from hydrogen bonds to bidentate binding upon the pH transition from pH 3 to 8. In order to examine the antifouling properties of SB-DA thin films, the modified substrates were brought into contact with bovine serum albumin and bacteria solutions. The fouling levels were monitored using a quartz crystal microbalance with dissipation sensor and fluorescence optical microscope. Tests showed that the sample prepared via the pH transition approach provides the best resistance to nonspecific adsorption due to the high coverage and stability of the SB-DA films. These findings support the mechanism of the pH-modulated assembly of SB-DA molecules, and for the first time we demonstrate the antifouling properties of the SB-DA to be comparable with traditional thiol-based zwitterionic self-assemblies. The success of modification with SB-DA opens an avenue for developing a biologically inspired surface chemistry and can have applications over a wide spectrum of bioapplications. The strategy of the pH transition can also be applied to other functional dopamine derivatives.

The Role, Function, and Mechanism of Long Intergenic Noncoding RNA1184 (linc01184) in Colorectal Cancer.

BACKGROUND: Long intergenic noncoding RNA1184 (linc01184) has been recently discovered; however, its role in human diseases is limited to date. The present study is aimed at investigating the expression pattern and mechanism of linc01184 in colorectal cancer (CRC) tumorigenesis. METHODS: The expression of linc01184 in CRC tissues and cell lines was compared with that in normal controls. The functions of linc01184 in CRC cells were identified by overexpression and small interfering RNA (siRNA) approaches in vitro. Meanwhile, the target gene prediction software, luciferase reporter, RNA pull-down, and western blotting assays were used to analyze the oncogenic mechanism. RESULTS: We found that linc01184 was obviously upregulated in CRC tissues and cells when compared to normal controls, and its upregulation had a positive association with the CRC progression. linc01184 knockdown significantly suppressed CRC cell proliferation and invasion and promoted apoptosis. Besides, linc01184 acted as a competitive endogenous RNA (ceRNA) by directly binding to microRNA-331 (miR-331), and its overexpression resulted in notable increases of human epidermal growth factor receptor 2 (HER2), phosphorylated Ser/Thr kinases (p-Akt), and extracellular regulated protein kinase 1/2 (p-ERK1/2) at posttranscriptional levels in CRC cells, which were antagonized by miR-331. CONCLUSIONS: The findings reveal for the first time that linc01184 is an enhancer for the proliferation and invasion of CRC by functioning as a ceRNA through the linc01184-miR-331-HER2-p-Akt/ERK1/2 pathway regulatory network.

The Delivery of Extracellular Vesicles Loaded in Biomaterial Scaffolds for Bone Regeneration.

Extracellular vesicles (EVs) are heterogeneous nanoparticles actively released by cells that comprise highly conserved and efficient systems of intercellular communication. In recent years, numerous studies have proven that EVs play an important role in the field of bone tissue engineering (BTE) due to several advantages, such as good biosafety, stability and efficient delivery. However, the application of EVs therapies in bone regeneration has not been widely used. One of the major challenges for the application of EVs is the lack of sufficient scaffolds to load and control the release of EVs. Thus, in this review, we describe the most advanced current strategies for delivering EVs with various biomaterials for the use in bone regeneration, the role of EVs in bone regeneration, the distribution of EVs mediated by biomaterials and common methods of promoting EVs delivery efficacy with a focus on biomaterial properties.

What Drives Innovation: The Canadian Touch on Liposomal Therapeutics.

Liposomes are considered one of the most successful drug delivery systems (DDS) given their established utility and success in the clinic. In the past 40⁻50 years, Canadian scientists have made ground-breaking discoveries, many of which were successfully translated to the clinic, leading to the formation of biotech companies, the creation of research tools, such as the Lipex Extruder and the NanoAssemblr™, as well as contributing significantly to the development of pharmaceutical products, such as Abelcet®, MyoCet®, Marqibo®, Vyxeos®, and Onpattro™, which are making positive impacts on patients' health. This review highlights the Canadian contribution to the development of these and other important liposomal technologies that have touched patients. In this review, we try to address the question of what drives innovation: Is it the individual, the teams, the funding, and/or an entrepreneurial spirit that leads to success? From this perspective, it is possible to define how innovation will translate to meaningful commercial ventures and products with impact in the future. We begin with a brief history followed by descriptions of drug delivery technologies influenced by Canadian researchers. We will discuss recent advances in liposomal technologies, including the Metaplex technology from the author's lab. The latter exemplifies how a nanotechnology platform can be designed based on multidisciplinary groups with expertise in coordination chemistry, nanomedicines, disease, and business to create new therapeutics that can effect better outcomes in patient populations. We conclude that the team is central to the effort; arguing if the team is entrepreneurial and well positioned, the funds needed will be found, but likely not solely in Canada.

Bio-inspired multifunctional catecholic assembly for photo-programmable biointerface.

This article reports a novel multifunctional mussel-inspired zwitterionic catecholic assembly to form a photoresponsive biointerface. The assembly is the combination of the antifouling sulfobetaine and photocleavable o-nitrophenyl moieties into a molecule, becoming sulfobetaine nitrodopamine (SB-nDA). We demonstrated the formation of a compact thin SB-nDA film on TiO2 by using the pH transition approach. The film thickness, surface wettability and elemental composition were characterized using ellipsometry, contact angle goniometer, atomic force microscopy and X-ray photoelectron spectroscopy, respectively. The SB-nDA thin films can effectively resist adhesion of both Gram-positive Staphylococcus epidermidis and Gram-negative Pseudomonas aeruginosa by more than 95% relative to bare TiO2. Quartz crystal microbalance with dissipation (QCM-D) sensor was employed for protein fouling tests, showing the comparable antifouling property of SB-nDA with thiol- or silane-based surface ligands. More importantly, the spatiotemporal control over the bioinertness by UV irradiation has been studied with bacterial and protein adsorption. Therefore, the catecholic chemistry can be used for programmable tailoring of interfacial properties, permitting potential application in light-guided targeting for nanomedicine.

Bioinspired Zwitterionic Surface Coatings with Robust Photostability and Fouling Resistance.

Great care has been paid to the biointerface between a bulk material and the biological environment, which plays a key role in the optimized performance of medical devices. In this work, we report a new superhydrophilic adsorbate, called L-cysteine betaine (Cys-b), having branched zwitterionic groups that give rise to surfaces and nanoparticles with enhanced chemical stability, biofouling resistance, and inertness to environmental changes. Cys-b was synthesized from the amphoteric sulfur-containing amino acid, L-cysteine (Cys), by quaternization of its amino group. Gold surfaces modified with Cys-b exhibited prominent repellence against the nonspecific adsorption of proteins, bacteria, and fibroblast cells. In addition, Cys-b existed in zwitterionic form over a wide pH range (i.e., pH 3.4 to 10.8), and showed excellent suppression in photoinduced oxidation on gold substrates. Furthermore, the modification of hollow Ag@Au nanoshells with Cys-b gave rise to nanoparticles with excellent colloidal stability and resistance to coordinative interaction with Cu(2+). Taken together, the unique features of Cys-b offer a new nanoscale coating for use in a wide spectrum of applications.

Natural zwitterionic organosulfurs as surface ligands for antifouling and responsive properties.

Natural sulfur-containing zwitterionic compounds, l-cysteine (Cys), l-methionine, and glutathionine (GSH), have been employed as surface ligands to prevent protein nonspecific adsorption on planar substrates. These organosulfur compounds form self-assembled monolayers (SAMs) on gold substrates by gold-sulfur interaction. The chemical elements of SAMs were confirmed using x-ray photoelectron spectroscopy. The surface wetting tests for SAMs show that films prepared from Cys and GSH exhibited super-hydrophilicity (contact angles of θ = ~5°) due to their high coverage and strong hydration via ionic solvation and formation of hydrogen bonding. Quartz crystal microbalance with dissipation sensor was used to quantitatively and qualitatively monitor the adsorption of bovine serum albumin (BSA) from buffer onto these SAMs. It was found that the GSH film enables the resistance of BSA adsorption to the best extent at a physiological pH. Moreover, the surface charges of modified substrates were modulated by varying the pH value to control BSA adsorption. The effect of electrostatic repulsion on the antifouling behavior becomes prominent at a pH where the protein and the surface carry same charges. Consolidating the BSA adsorption measurements at different pH values, the antifouling properties of GSH-modified Au should be attributed to prevention of entropy gain and enthalpy loss, making BSA adsorption energetically unfavorable. It is believed that the surface modification with natural organosulfur ligands holds great potential in improving the biocompatibility of medical devices and in offering intelligent biointerfaces in response to environmental stimuli.