Research Advances

Researchers estimate that worldwide, 184,000 deaths per year are attributable to consumption of sugar-sweetened beverages (SSBs): 133,000 from diabetes, 45,000 from cardiovascular disease, and 6450 from cancers. Five percent of such deaths occurred in low-income, 70.9% in middle-income, and 24.1% in high-income countries. Proportional mortality due to SSB consumption ranged from <1% in Japanese >65 years old to 30% in Mexicans <45 years old, and 8.5 million disability-adjusted life years were related to SSB intake.

Researchers are working to refine 3-D human tissue chips and to combine them into an integrated system. Fifteen NIH institutes and centers are involved in coordinating the effort, which is called the Tissue Chip for Drug Screening program. One collaborative effort will share resources and expertise for the heart, blood vessel, and liver tissue chips.

A new study shows that bortezomib, a proteasome inhibitor that is already approved by the FDA for treatment of multiple myeloma, reduces HLA antibodies in patients with CKD to a greater extent than traditional methods employing intravenous immunoglobulin. A 51.5% reduction in immunodominant antibodies was observed at 28 days with bortezomib treatment (1.3 mg/m2) and reductions increased with higher bortezomib dosing densities. Nineteen out of 44 treated patients (43.2%) were transplanted with low acute rejection rates (18.8%) and donor-specific antibody formation (12.5%).

New research suggests very small changes in blood pH levels may affect renal calcium reabsorption and parathyroid hormone (PTH) secretion. In both human embryonic kidney cells and bovine parathyroid cells, decreasing the extracellular pH from 7.4 to 7.2 rapidly inhibited intracellular calcium mobilization through the calcium-sensing receptor, whereas raising extracellular pH to 7.6 increased responsiveness to extracellular calcium. Also, pH elevation suppressed PTH secretion from human parathyroid cells, while acidosis increased PTH secretion.

New research sheds light on why most rhinovirus strains, which cause the common cold, replicate better at the cooler temperatures found in the nasal cavity than at lung temperature. Investigators found that airway epithelial cells supporting rhinovirus replication initiate a more robust antiviral defense response at warmer temperatures. Airway cells with genetic deficiencies in interferon receptor signaling supported much higher levels of viral replication at 37°C.

By analyzing epigenetic markers, or chemical tags, at more than 7 million sites in the DNA of the fat cells in mice, researchers found clear differences between normal and obese mice—and they found a similar pattern in human cells. Some of the epigenetic changes associated with obesity affect genes already known to raise diabetes risk. Others affect genes that had not been conclusively linked to the disease, but that have roles in metabolism. Some of the genes regulate insulin action on sugar uptake, making them potential targets for treating type 2 diabetes.

People with CKD often have an overactivation of the sympathetic nervous system, which contributes to increased risks for cardiovascular events. However, tetrahydrobiopterin may be able to dial back this process. In a randomized study of 36 patients with CKD, the drug had positive effects on the sympathetic nervous system and some measures of arterial stiffness.

New methods that extract drugs from soil bacteria have yielded a powerful new antibiotic, called teixobactin, that can cure severe gram-positive bacterial infections in mice with no adverse effects. Teixobactin inhibits cell wall synthesis by binding to a precursor of peptidoglycan and a precursor of cell wall teichoic acid. During their studies, investigators found no signs of any mutants of Staphylococcus aureus or Mycobacterium tuberculosis that became resistant to teixobactin.

Interactions of diet, genetics, and ethnicity may affect magnesium-mediated diabetes risk, according to a new study. After identifying 17 magnesium-related ion channel genes, investigators examined whether variations in the genes were associated with type 2 diabetes risk in 7287 African-American and 3285 Hispanic-American postmenopausal women. Several variants stood out in the Journal of Nutrition study.

Through experiments conducted in mice and lab-grown heart cells, researchers found that brain-derived neurotrophic factor (BDNF), a nerve growth factor known to act as a natural antidepressant and to enhance learning and memory, helps sustain the ability of heart muscle cells to contract and relax properly. Compared with cardiac cells from mice with normal hearts, cells from mice with failing hearts had a sub-performing version of BDNF’s receptor, a molecule called TrkB.

New research shows that retroviruses, which constitute about 5% of our DNA, help regulate which genes in the brain’s neurons are expressed, and when. When investigators analyzed neural stem cells, they discovered that these cells use a particular molecular mechanism to control the activation processes of retroviruses.

New research reveals how amlexanox, an anti-inflammatory drug, reverses obesity, diabetes, and fatty liver disease. Investigators found that amlexanox exerts its effects through subcutaneous fat cells by increasing the level of a second messenger molecule called cAMP. In turn, cAMP increases the rate by which cells metabolize fat so that the animal loses weight. Amlexanox also coaxes fat cells to release the hormone interleukin-6, which then travels in the circulation to the liver, where it reduces glucose production and thereby lowers overall blood sugar levels.

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