Hypoxia-inducible factor 1α regulates branching morphogenesis during kidney development

The kidneys are exposed to hypoxic conditions during development. Hypoxia-inducible factor (HIF), an important mediator of the response to hypoxia, is believed to have an important role in development. However, the relationship between HIF and branching morphogenesis has not been elucidated clearly.     

Biomarkers affected by impact velocity and maximum strain of cartilage during injury

Osteoarthritis is one of the most common, debilitating, musculoskeletal diseases; 12% associated with traumatic injury resulting in post-traumatic osteoarthritis (PTOA). Our objective was to develop a single impact model with cartilage “injury level” defined in terms of controlled combinations of strain rate to a maximum strain (both independent of cartilage load resistance) to study their sensitivity to articular cartilage cell viability and potential PTOA biomarkers. A servo-hydraulic test machine was used to measure canine humeral head cartilage explant thickness under repeatable pressure, then subject it (except sham and controls) to a single impact having controlled constant velocity V=1 or 100 mm/s (strain rate 1.82 or 182/s) to maximum strain ε=10%, 30%, or 50%. Thereafter, explants were cultured in media for twelve days, with media changed at day 1, 2, 3, 6, 9, 12. Explant thickness was measured at day 0 (pre-injury), 6 and 12 (post-injury). Cell viability, and tissue collagen and glycosaminoglycan (GAG) were analyzed immediately post-injury and day 12. Culture media were tested for biomarkers: GAG, collagen II, chondroitin sulfate-846, nitric oxide, and prostaglandin E₂ (PGE₂). Detrimental effects on cell viability, and release of GAG and PGE₂ to the media were primarily strain-dependent, (PGE₂ being more prolonged and sensitive at lower strains). The cartilage injury model appears to be useful (possibly superior) for investigating the relationship between impact severity of injury and the onset of PTOA, specifically for discovery of biomarkers to evaluate the risk of developing clinical PTOA, and to compare effective treatments for arthritis prevention.     

Rutin decreases lipopolysaccharide-induced acute lung injury via inhibition of oxidative stress and the MAPK–NF-κB pathway

Acute lung injury (ALI) is a serious disease with unacceptably high mortality and morbidity rates. Up to now, no effective therapeutic strategy for ALI has been established. Rutin, quercetin-3-rhamnosyl glucoside, expresses a wide range of biological activities and pharmacological effects, such as anti-inflammatory, antihypertensive, anticarcinogenic, vasoprotective, and cardioprotective activities. Pretreatment with rutin inhibited not only histopathological changes in lung tissues but also infiltration of polymorphonuclear granulocytes into bronchoalveolar lavage fluid in lipopolysaccharide (LPS)-induced ALI. In addition, LPS-induced inflammatory responses, including increased secretion of proinflammatory cytokines and lipid peroxidation, were inhibited by rutin in a concentration-dependent manner. Furthermore, rutin suppressed phosphorylation of NF-κB and MAPK and degradation of IκB, an NF-κB inhibitor. Decreased activities of antioxidative enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and heme oxygenase-1 caused by LPS were reversed by rutin. At the same time, we found that ALI amelioration by chelation of extracellular metal ions with rutin is more efficacious than with deferoxamine. These results indicate that the protective mechanism of rutin is through inhibition of MAPK–NF-κB activation and upregulation of antioxidative enzymes.     

Inter-session reliability and sex-related differences in hamstrings total reaction time,pre-motor time and motor time during eccentric isokinetic contractions in recreational athlete

The purposes were twofold: (a) to ascertain the inter-session reliability of hamstrings total reaction time, pre-motor time and motor time; and (b) to examine sex-related differences in the hamstrings reaction times profile. Twenty-four men and 24 women completed the study. Biceps femoris and semitendinosus total reaction time, pre-motor time and motor time measured during eccentric isokinetic contractions were recorded on three different occasions. Inter-session reliability was examined through typical percentage error (CV_TE), percentage change in the mean (CM) and intraclass correlations (ICC). For both biceps femoris and semitendinosus, total reaction time, pre-motor time and motor time measures demonstrated moderate inter-session reliability (CV_TE < 10%; CM < 3%; ICC > 0.7). The results also indicated that, although not statistically significant, women reported consistently longer hamstrings total reaction time (23.5 ms), pre-motor time (12.7 ms) and motor time (7.5 ms) values than men. Therefore, an observed change larger than 5%, 9% and 8% for total reaction time, pre-motor time and motor time respectively from baseline scores after performing a training program would indicate that a real change was likely. Furthermore, while not statistically significant, sex differences were noted in the hamstrings reaction time profile which may play a role in the greater incidence of ACL injuries in women.     

Functional lung imaging with synchrotron radiation: Methods and preclinical applications

Many lung disease processes are characterized by structural and functional heterogeneity that is not directly appreciable with traditional physiological measurements. Experimental methods and lung function modeling to study regional lung function are crucial for better understanding of disease mechanisms and for targeting treatment. Synchrotron radiation offers useful properties to this end: coherence, utilized in phase-contrast imaging, and high flux and a wide energy spectrum which allow the selection of very narrow energy bands of radiation, thus allowing imaging at very specific energies. K-edge subtraction imaging (KES) has thus been developed at synchrotrons for both human and small animal imaging. The unique properties of synchrotron radiation extend X-ray computed tomography (CT) capabilities to quantitatively assess lung morphology, and also to map regional lung ventilation, perfusion, inflammation and biomechanical properties, with microscopic spatial resolution. Four-dimensional imaging, allows the investigation of the dynamics of regional lung functional parameters simultaneously with structural deformation of the lung as a function of time. This review summarizes synchrotron radiation imaging methods and overviews examples of its application in the study of disease mechanisms in preclinical animal models, as well as the potential for clinical translation both through the knowledge gained using these techniques and transfer of imaging technology to laboratory X-ray sources.     

Neuronal calcium signaling via store-operated channels in health and disease

Store-operated calcium entry (SOCE) is the flow of calcium ions (Ca²⁺) into cells in response to the depletion of intracellular Ca²⁺ stores that reside predominantly in the endoplasmic reticulum (ER). The role of SOCE has been relatively well understood for non-excitable cells. It is mediated mostly by the ER Ca²⁺ sensor STIM1 and plasma membrane Ca²⁺ channel Orai1 and serves to sustain Ca²⁺ signaling and refill ER Ca²⁺ stores. In contrast, because of the complexity of Ca²⁺ influx mechanisms that are present in excitable cells, our knowledge about the function of neuronal SOCE (nSOCE) is still nascent. This review summarizes the available data on the molecular components of nSOCE and their relevance to neuronal signaling. We also present evidence of disturbances of nSOCE in neurodegenerative diseases (namely Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease) and traumatic brain injury. The emerging important role of nSOCE in neuronal physiology and pathology makes it a possible clinical target.     

Injury Delays Stem Cell Apoptosis after Radiation in Planarians

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Expression of manganese superoxide dismutase is not altered in transgenic mice with elevated level of copper-zinc superoxide dismutase

In evaluating the relative expression of copper-zinc and manganese superoxide dismutase (CuZnSOD and MnSOD) in vivo in states like Down syndrome in which one dismutase is present at increased levels, we measured activities of both enzymes, in tissues of control and transgenic mice constitutively expressing increased levels of CuZnSOD, during exposure to normal and elevated oxygen tensions. Using SOD gel electrophoresis assay, CuZnSOD and MnSOD activities of brain, lung, heart, kidney, and liver from mice exposed to either normal (21%) or elevated (>99% oxygen, 630 torr) oxygen tensions for 120 h were compared. Whereas CuZnSOD activity was elevated in tissues of transgenic relative to control mice under both normoxic or hyperoxic conditions, MnSOD activities in organs of transgenic mice were remarkably similar to those of controls under both conditions. To confirm the accuracy of this method in quantitating MnSOD relative to CuZnSOD expression, two other methods were utilized. In lung, which is the organ exposed to the highest oxygen tension during ambient hyperoxia, a sensitive, specific ELISA for MnSOD was used. Again, MnSOD protein was not different in transgenic relative to control mice during exposure to air or hyperoxia. In addition, lung MnSOD protein was not changed significantly by exposure to hyperoxia in either group. In kidney, a mitochondrion-rich organ, SOD assay, before and after inactivation of CuZnSOD with diethyldithiocarbamate, was used. MnSOD activity was not different in organs from air-exposed transgenic relative to control mice. The data indicated that expression of MnSOD in vivo was not affected by overexpression of the CuZnSOD and, therefore, the two enzymes are probably regulated independently.     

The significance of combined detection of CysC,urinary mAlb and β2-MG in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome

ObjectiveTo elaborate the significance of combined detection of cystatin C, urinary micro-albumin (mAlb) and β₂-microglobulin (β₂-MG) in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome.MethodsA total of 120 patients with pregnancy-induced hypertension syndrome who were admitted to this hospital for treatment between November 2015 and October 2018 were enrolled as subjects, and divided into the control group (without complication of renal injury, n = 76) and the observation group (with complication of renal injury, n = 44) according to the complications of early renal injury. Furthermore, 60 patients who participated in the antenatal care in this hospital were enrolled as the normal subjects (normal group). Automatic biochemistry analyzer was utilized to measure CysC, urinary mAlb and β₂-MG in serum to evaluate the specificity, sensitivity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of single or combined measurements of these indexes in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome.ResultsIn the observation group, the levels of CysC, urinary mAlb and β₂-MG were higher than those in the control group, while the levels in the normal group were the lowest (P < 0.05). Combined measurement of CysC, urinary mAlb and β₂-MG showed a higher accuracy (90.0%) in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome than the single measurements, and the difference had statistical significance (P < 0.05). Besides, the sensitivity, specificity, PPV and NPV of the combined measurements were 94.59%, 87.30%, 81.40% and 94.49%, slightly higher than the single measurements, with no statistical significance in differences (P > 0.05).ConclusionCysC, urinary mAlb and β₂-MG can reflect the renal injury effectively, and the combined measurements shows potent accuracy in diagnosis of the early renal injury in pregnancy-induced hypertension syndrome, thereby providing the scientific evidence for early diagnosis and stipulation of rational therapeutic regimen and improving the pregnancy outcome.