Quantifying Single Microvessel Permeability in Isolated Blood-perfused Rat Lung Preparation

The isolated blood-perfused lung preparation is widely used to visualize and define signaling in single microvessels. By coupling this preparation with real time imaging, it becomes feasible to determine permeability changes in individual pulmonary microvessels. Herein we describe steps to isolate rat lungs and perfuse them with autologous blood. Then, we outline steps to infuse fluorophores or agents via a microcatheter into a small lung region. Using these procedures described, we determined permeability increases in rat lung microvessels in response to infusions of bacterial lipopolysaccharide. The data revealed that lipopolysaccharide increased fluid leak across both venular and capillary microvessel segments. Thus, this method makes it possible to compare permeability responses among vascular segments and thus, define any heterogeneity in the response. While commonly used methods to define lung permeability require postprocessing of lung tissue samples, the use of real time imaging obviates this requirement as evident from the present method. Thus, the isolated lung preparation combined with real time imaging offers several advantages over traditional methods to determine lung microvascular permeability, yet is a straightforward method to develop and implement.     

Effect of natural exogenous antioxidants on aging and on neurodegenerative diseases

Abstract

Aging and neurodegenerative diseases share oxidative stress cell damage and depletion of endogenous antioxidants as mechanisms of injury, phenomena that are occurring at different rates in each process. Nevertheless, as the central nervous system (CNS) consists largely of lipids and has a poor catalase activity, a low amount of superoxide dismutase and is rich in iron, its cellular components are damaged easily by overproduction of free radicals in any of these physiological or pathological conditions. Thus, antioxidants are needed to prevent the formation and to oppose the free radicals damage to DNA, lipids, proteins, and other biomolecules. Due to endogenous antioxidant defenses are inadequate to prevent damage completely, different efforts have been undertaken in order to increase the use of natural antioxidants and to develop antioxidants that might ameliorate neural injury by oxidative stress. In this context, natural antioxidants like flavonoids (quercetin, curcumin, luteolin and catechins), magnolol and honokiol are showing to be the efficient inhibitors of the oxidative process and seem to be a better therapeutic option than the traditional ones (vitamins C and E, and β-carotene) in various models of aging and injury in vitro and in vivo conditions. Thus, the goal of the present review is to discuss the molecular basis, mechanisms of action, functions, and targets of flavonoids, magnolol, honokiol and traditional antioxidants with the aim of obtaining better results when they are prescribed on aging and neurodegenerative diseases.     

Three-dimensional model on thermal response of skin subject to laser heating

A three-dimensional (3D) multilayer model based on the skin physical structure is developed to investigate the transient thermal response of human skin subject to laser heating. The temperature distribution of the skin is modeled by the bioheat transfer equation, and the influence of laser heating is expressed as a source term where the strength of the source is a product of a Gaussian shaped incident irradiance, an exponentially shaped axial attenuation, and a time function. The water evaporation and diffusion is included in the model by adding two terms regarding the heat loss due to the evaporation and diffusion, where the rate of water evaporation is determined based on the theory of laminar boundary layer. Cryogen spray cooling (CSC) in laser therapy is studied, as well as its effect on the skin thermal response. The time-dependent equation is discretized using the finite difference method with the Crank–Nicholson scheme and the stability of the numerical method is analyzed. The large sparse linear system resulted from discretizing the governing partial differential equation is solved by a GMRES solver and the expected simulation results are obtained.     

Role of microRNA-26a in cartilage injury and chondrocyte proliferation and apoptosis in rheumatoid arthritis rats by regulating expression of CTGF

This study is carried out to investigate the role of microRNA-26a (miR-26a) in cartilage injury and chondrocyte proliferation and apoptosis in rats with rheumatoid arthritis (RA) by regulating expression of CTGF. A rat model of RA induced by type II collagen was established. The rats were assigned into normal, RA, RA + mimics negative control (NC), and RA + miR-26a mimics groups, and the cells were classified into blank, mimics NC, and miR-26a mimics groups. The degree of secondary joint swelling and arthritis index, expression of miR-26a, pathological changes, proliferation and apoptosis of chondrocytes, and expression of CTGF, interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α, Bax, and Bcl-2 were also determined through a series of experiments. The targeting relationship between miR-26a and CTGF was verified. Initially, downregulated miR-26a was found in cartilage tissues and inflammatory articular chondrocytes of RA rats. In addition, CTGF was determined as a direct target gene of miR-26a, and upregulation of miR-26a inhibited CTGF expression in cartilage tissues of RA rats. Furthermore, upregulation of miR-26a reduced swelling and inflammation of joints, inhibited cartilage damage, apoptosis of chondrocytes, inflammatory injury, promotes proliferation, and inhibited apoptosis of inflammatory articular chondrocytes, which may be correlated with the targeting inhibition of CTGF expression. Collectively, the results demonstrate that upregulating the expression of miR-26a could attenuate cartilage injury, stimulate the proliferation, and inhibit apoptosis of chondrocytes in RA rats.     

Possible factors in the etiology of Alzheimer's disease

Inherited cases of Alzheimer's disease (AD) comprise only a very small proportion of the total. The remainder are of unknown etiopathogenesis, but they are very probably multifactorial in origin. This article describes studies on four possible factors: aluminum; viruses—in particular, herpes simplex type I virus (HSV1); defective DNA repair; and head trauma. Specific problems associated with aluminum, such as inadvertent contamination and its insolubility, have led to some controversy over its usage. Nonetheless, the effects of aluminum on animals and neuronal cells in culture have been studied intensively. Changes in protein structure and location in the cell are described, including the finding in this laboratory of a change in τ resembling that in AD neurofibrillary tangles, and also the lack of appreciable binding of aluminum to DNA. As for HSV1, there has previously been uncertainty about whether HSV1 DNA is present in human brain. Work in this laboratory using polymerase chain reaction has shown that HSV1 DNA is present in many normal aged brains and AD brains, but is absent in brains from younger people. Studies on DNA damage and repair in AD and normal cells are described, and finally, the possible involvement of head trauma is discussed.     

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.     

Tumor profiling using protein biomarker panels in malignant melanoma: application of tissue microarrays and beyond

In the past decade, analysis of the urinary proteome (urinary proteomics) has intensified in response to the need for novel biomarkers that support early diagnosis of kidney diseases. In particular, this also applies to acute kidney injury, which is a heterogeneous complex syndrome with a still-increasing incidence at the intensive care unit. Unfortunately, this major need remains largely unmet to date. The current report aims to explain why attempts to implement urinary proteomic-discovered acute kidney injury diagnostic candidates in the intensive care unit setting have not yet led to success. Subsequently, some key notes are provided that should enhance the chance of translating selected urinary proteomic candidates to valuable tools for the nephrologist and intensivist in the near future.     

The aetiology of myocardial injury after non-cardiac surgery

Recognition of myocardial injury after non-cardiac surgery is difficult, since strong analgesics (e.g. opioids) can mask anginal symptoms, and ECG abnormalities are subtle or transient. Thorough knowledge of the pathophysiological mechanisms is therefore essential. These mechanisms can be subdivided into four groups: type I myocardial infraction (MI), type II MI, non-ischaemic cardiac pathology, and non-cardiac pathology. The incidence of type I MI in patients with a clinical suspicion of perioperative acute coronary syndrome (ACS) is 45–57 %. This percentage is higher in patients with a high likelihood of MI such as patients with ST-elevation ACS. Of note, the generalisability of this statement is limited due to significant study limitations. Non-ischaemic cardiac pathology and non-cardiac pathology should not be overlooked as a cause of perioperative myocardial injury (PMI). Especially pulmonary embolism and dysrhythmias are a common phenomenon, and may convey important prognostic value. Implementation of routine postoperative troponin assessment and accessible use of minimally invasive imaging should be considered to provide adequate individualised therapy. Also, addition of preoperative imaging may improve the stratification of high-risk patients who may benefit from preoperative or perioperative interventions.