Research Advances

In a rat model of autosomal dominant polycystic kidney disease (ADPKD), treatment with an mTOR kinase inhibitor called PP242 decreased proliferation in cystic and non-cystic tubules, inhibited renal enlargement and cystogenesis, and significantly reduced the loss of kidney function. The findings are published in Nephrology Dialysis Transplantation. The mTOR pathway consists of mTOR complex 1 and mTOR complex 2 and is activated in PKD kidneys. mTOR kinase inhibitors target both mTOR complexes.

Researchers have successfully grown human skeletal muscle that contracts and responds to external stimuli such as electrical pulses, biochemical signals, and drugs. As described in an eLife article, the investigators started with a sample of human cells that had progressed beyond stem cells but had not yet become muscle.

A new type of test strip using microplasma-generated gold nanoparticles (AuNPs) has demonstrated potential for early detection of certain heart attacks. The strip tests for cardiac troponin I (cTn-I), a biomarker that is present in large amounts in patients experiencing myocardial infarction. The surfaces of these nanoparticles are able to attract more antibodies than AuNPs produced via other methods, which enhances the sensitivity of the test.

Short chain fatty acids (SCFAs), produced by intestinal microbiota via fermentation, have anti-inflammatory properties which researchers evaluated in an animal model of AKI induced by ischemia-reperfusion injury (IRI). Using 3 main SCFAs (acetate, propionate, and butyrate) the investigators found the therapy improved renal function, and was associated with apoptosis inhibition and cell proliferation. The SCFAs also inhibited histone deacetylase activity and modulated the inflammatory process.

Researchers have used a screening process to identify new compounds that may lead to the next generation of anesthetics. The team tested >350,000 compounds for their ability to bind a surrogate anesthetic binding protein target, apoferritin. Among these, 2600 compounds had strong interactions with apoferritin. A subset was chosen based on structural criteria to be tested for anesthetic activity, first on tadpoles and then on mice. Two compounds could potentially serve as anesthetics and will undergo additional testing.

Researchers have found that an increased response to sympathetic nerve activity and an inability to respond to nitric oxide, a factor important for blood vessel health, may promote kidney injury and cardiovascular disease in infants born with small kidneys. Children born with reduced congenital renal mass have an increased risk of hypertension and CKD in adulthood, but the mechanisms involved have been poorly understood. The Circulation study, which was conducted in sheep, provides new insights. 

Researchers have found that cone snails produce a venom containing a unique form of insulin that causes small fish on which the snails prey to go into hypoglycemic shock. The snail insulin could prove useful for studying how different forms of insulin control blood sugar and energy metabolism. It consists of 43 amino acid building blocks, fewer than any known insulin. The new findings are published in PNAS.

Researchers have found that targeting 2 nuclear receptors that play critical roles in the development of TH17 cells can prevent autoimmunity against pancreatic beta cells in a mouse model of type 1 diabetes. Blocking the receptors also reduced pro-inflammatory cytokine expression, reduced autoantibody production, and increased the frequency of CD4+Foxp3+ T regulatory cells.

The link between salt consumption and high blood pressure (BP) is well known, but not well understood. A new study found that high salt intake over a period of time can “reprogram” the brain, interfering with a natural safety mechanism that normally prevents blood pressure from rising.

Researchers have found that a modified form of the superabsorbent chemical used in disposable diapers can expand brain structures to 4.5 times their original size. When the team linked brain cell proteins to a mesh of sodium polyacrylate and then added water, the polyacrylate mesh swelled and expanded the size of protein complexes without disrupting their normal structural arrangement in the cell. By developing a labeling and treatment process, the researchers could accurately map expanded tissues.

A new xenotransplantation model could provide a platform for drug discovery and testing. The model uses an arterial flow regulator to enable low-pressure human fetal kidneys to be transplanted into high-pressure adult rats. The regulator consists of a volume-adjustable saline-filled cuff, and by incrementally withdrawing saline, blood flow entering the fetal kidney increased until full blood flow was restored 30 days posttransplantation.

A pilot study of 83 patients with uncontrolled hypertension who were assigned to implantation of an arteriovenous coupler device (inserted between the artery and vein in the upper thigh) plus current pharmaceutical treatment or to current treatment alone, average office systolic blood pressure after 6 months reduced by 26.9 mm Hg in the arteriovenous coupler group and by 3.7 mm Hg in the control group. Average systolic 24 hour ambulatory blood pressure reduced by 13.5 mm Hg in arteriovenous coupler recipients and by 0.5 mm Hg in controls.

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