Intercellular Interactions of an Adipogenic CXCL12-Expressing Stromal Cell Subset in Murine Bone Marrow

Bone marrow houses a multifunctional stromal cell population expressing C-X-C motif chemokine ligand 12 (CXCL12), termed CXCL12-abundant reticular (CAR) cells, that regulates osteogenesis and adipogenesis. The quiescent pre-adipocyte-like subset of CXCL12⁺ stromal cells (“Adipo-CAR” cells) is localized to sinusoidal surfaces and particularly enriched for hematopoiesis-supporting cytokines. However, detailed characteristics of these CXCL12⁺ pre-adipocyte-like stromal cells and how they contribute to marrow adipogenesis remain largely unknown. Here we highlight CXCL12-dependent physical coupling with hematopoietic cells as a potential mechanism regulating the adipogenic potential of CXCL12⁺ stromal cells. Single-cell computational analyses of RNA velocity and cell signaling reveal that Adipo-CAR cells exuberantly communicate with hematopoietic cells through CXCL12-CXCR4 ligand-receptor interactions but do not interconvert with Osteo-CAR cells. Consistent with this computational prediction, a substantial fraction of Cxcl12-creER⁺ pre-adipocyte-like cells intertwines with hematopoietic cells in vivo and in single-cell preparation in a protease-sensitive manner. Deletion of CXCL12 in these cells using Col2a1-cre leads to a reduction of stromal-hematopoietic coupling and extensive marrow adipogenesis in adult bone marrow, which appears to involve direct conversion of CXCL12⁺ cells to lipid-laden marrow adipocytes without altering mesenchymal progenitor cell fates. Therefore, these findings suggest that CXCL12⁺ pre-adipocyte-like marrow stromal cells prevent their premature differentiation by maintaining physical coupling with hematopoietic cells in a CXCL12-dependent manner, highlighting a possible cell-non-autonomous mechanism that regulates marrow adipogenesis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Mamao Pomace Extract Alleviates Hypertension and Oxidative Stress in Nitric Oxide Deficient Rats

Reactive oxygen species (ROS)-induced oxidative stress plays a major role in pathogenesis of hypertension. Antidesma thwaitesianum (local name: Mamao) is a tropical plant distributed in the tropical/subtropical areas of the world, including Thailand. Mamao pomace (MP), a by-product generated from Mamao fruits, contains large amounts of antioxidant polyphenolic compounds. The aim of this study was to investigate the antihypertensive and antioxidative effects of MP using hypertensive rats. For this purpose, male Sprague-Dawley rats were given N^ω-nitro-l-arginine methyl ester (l-NAME), an inhibitor of endothelial nitric oxide synthase (eNOS), in drinking water (50 mg/kg) for three weeks. MP extract was orally administered daily at doses of 100 and 300 mg/kg. l-NAME administration induced marked increase in blood pressure, peripheral vascular resistance, and oxidative stress. MP treatment significantly prevented the increase in blood pressure, hindlimb blood flow and hindlimb vascular resistance of l-NAME treated hypertensive rats (p < 0.05). The antihypertensive effect of MP treatment was associated with suppression of superoxide production from carotid strips and also with an increase in eNOS protein expression and nitric oxide bioavailability. The present results provide evidence for the antihypertensive effect of MP and suggest that MP might be useful as a dietary supplement against hypertension.     

Curcumin Protects against Cadmium-Induced Vascular Dysfunction,Hypertension and Tissue Cadmium Accumulation in Mice

Curcumin from turmeric is commonly used worldwide as a spice and has been demonstrated to possess various biological activities. This study investigated the protective effect of curcumin on a mouse model of cadmium (Cd)—induced hypertension, vascular dysfunction and oxidative stress. Male ICR mice were exposed to Cd (100 mg/L) in drinking water for eight weeks. Curcumin (50 or 100 mg/kg) was intragastrically administered in mice every other day concurrently with Cd. Cd induced hypertension and impaired vascular responses to phenylephrine, acetylcholine and sodium nitroprusside. Curcumin reduced the toxic effects of Cd and protected vascular dysfunction by increasing vascular responsiveness and normalizing the blood pressure levels. The vascular protective effect of curcumin in Cd exposed mice is associated with up-regulation of endothelial nitric oxide synthase (eNOS) protein, restoration of glutathione redox ratio and alleviation of oxidative stress as indicated by decreasing superoxide production in the aortic tissues and reducing plasma malondialdehyde, plasma protein carbonyls, and urinary nitrate/nitrite levels. Curcumin also decreased Cd accumulation in the blood and various organs of Cd-intoxicated mice. These findings suggest that curcumin, due to its antioxidant and chelating properties, is a promising protective agent against hypertension and vascular dysfunction induced by Cd.     

In vitro antioxidant and wound-healing activities of hydrolyzed collagen from defatted Asian sea bass skin as influenced by different enzyme types and hydrolysis processes

Hydrolyzed collagen (HC) from defatted Asian sea bass skin was prepared by different enzymatic hydrolysis processes. For one-enzyme hydrolysis, papain (0.3 unit per g dry matter, DM) at 40 °C for 90 min or Alcalase (0.2 or 0.3 unit per g DM) at 50 °C for 90 min were used. The two-enzyme hydrolysis was accomplished with papain at 0.3 unit per g DM (P0.3), followed by Alcalase hydrolysis at 0.2 or 0.3 units per g DM (A0.2 or A0.3, respectively). HC prepared using the P0.3 + A0.3 process showed higher peptide yield, recovery and imino acid content in addition to stronger ABTS, DPPH radical scavenging activities and ferric reducing antioxidant power than other hydrolysis processes. HC obtained from the P0.3 + A0.3 process (at 125–500 μg mL⁻¹) induced MRC-5 fibroblast proliferation and augmented migration and lamellipodia formation in the cells. Peptides with average molecular weight of 750 Da exhibited the highest ABTS radical scavenging activity while the 4652 Da fraction had the lowest. Thus, HC can be considered as a suitable ingredient to formulate functional products for skin nourishment and wound healing.

Hydrolyzed collagen (HC) from sea bass skin prepared using papain and Alcalase had antioxidant potency and could enhance MRC-5 cell proliferation and lamellipodia formation. HC can be used as a nutraceutical or functional food ingredient.     

Effects of working and residential location areas on air pollution related respiratory symptoms in policemen and their wives in Bangkok, Thailand

Factors, including air pollution, influencing the prevalence of respiratory symptoms were investigated in a cross-sectional study in policemen and their wives (530 couples) in Bangkok. Information on respiratory symptoms was obtained using the American Thoracic Society Division of Lung Diseases (ATS-DLD) questionnaire. Effects of working and residential locations were evaluated using a multiple logistic model adjusted for several potential confounding factors. In the policemen the increased risk of frequent cough or phlegm was related to smoking (OR=2.19, 95% CI: 1.47-3.26) and working in heavy traffic locations (OR=1.27, CI: 1.01-1.61), whereas in their wives it was related to their residential locations (OR=1.53, CI: 1.10-2.13).     

Electrolytic Generation of Oxygen Partially Explains Electrical Enhancement of Tobramycin Efficacy against Pseudomonas aeruginosa Biofilm

The role of electrolysis products, including protons, hydroxyl ions, reactive oxygen intermediates, oxygen, hydrogen, and heat, in mediating electrical enhancement of killing of Pseudomonas aeruginosa biofilms by tobramycin (the bioelectric effect) was investigated. The log reduction in biofilm viable cell numbers compared to the numbers for the untreated positive control effected by antibiotic increased from 2.88 in the absence of electric current to 5.58 in the presence of electric current. No enhancement of antibiotic efficacy was observed when the buffer composition was changed to simulate the reduced pH that prevails during electrolysis. Neither did stabilization of the pH during electrical treatment by increasing the buffer strength eliminate the bioelectric effect. The temperature increase measured in our experiments, less than 0.2°C, was far too small to account for the greatly enhanced antibiotic efficacy. The addition of sodium thiosulfate, an agent capable of rapidly neutralizing reactive oxygen intermediates, did not abolish electrical enhancement of killing. The bioelectric effect persisted when all of the ionic constituents of the medium except the two phosphate buffer components were omitted. This renders the possibility of electrochemical generation of an inhibitory ion, such as nitrite from nitrate, an unlikely explanation for electrical enhancement. The one plausible explanation for the bioelectric effect revealed by this study was the increased delivery of oxygen to the biofilm due to electrolysis. When gaseous oxygen was bubbled into the treatment chamber during exposure to tobramycin (without electric current), a 1.8-log enhancement of killing resulted. The enhancement of antibiotic killing by oxygen was not due simply to physical disturbances caused by sparging the gas because similar delivery of gaseous hydrogen caused no enhancement whatsoever.     

Production of dengue 2 envelope domain III in plant using TMV-based vector system

The envelope protein of dengue virus is the major protein involved in host cell receptor binding for viral entry and induction of immunity. A gene fragment encoding domain III of the dengue 2 envelope protein (D2EIII, amino acids 298-400) was successfully expressed in Nicotinana benthamiana plant using a tobacco mosaic virus (TMV)-based transient expression system. The N-terminal 5' untranslated region-omega sequence located upstream of D2EIII increased protein production in infected plant tissues. The recombinant protein was reactive with anti-D2EIII polyclonal and anti-His tag antibodies. The intramuscular immunization of mice with D2EIII induced the production of the anti-dengue virus antibody. The induced antibody demonstrated neutralizing activity against dengue type 2 virus. The result indicates that the TMV expression system produces the dengue virus antigen in plant, which possesses appropriate antigenicity and immunogenicity.     

Reduction of respiratory motion artifacts in transverse relaxation rate (R2) images of the liver.

An empirical motion artifact suppression technique has been developed to reduce the respiratory motion artifacts in axial single spin-echo magnetic resonance (MR) images of the liver post-acquisition. The correction scheme is based on the observation that the dominant motion artifacts within abdominal MR images are ghosts that follow the profile and signal intensity of high signal intensity boundaries, such as those for the subcutaneous fat along the anterior abdominal wall. The technique is applied to the reduction of respiratory motion artifacts in a spin echo image series of the liver of an iron-loaded patient and of a manganese chloride phantom subject to respiratory motion. Subsequent improvements to transverse relaxation rate (R2) image analysis are then demonstrated on the motion-corrected spin echo images, illustrating the utility of the technique for application in the R2 image-based measurement and mapping of liver iron concentration.