Long-term presence of angiotensin II type 1 receptor autoantibody reduces aldosterone production by triggering Ca<Superscript>2+</Superscript> overload in H295R cells

Preeclamptic women are reported to have inadequate plasma volume expansion coupled with a suppressed secretion of aldosterone; however, the specific mechanism of preeclampsia remains unclear. We demonstrated that the presence of long-term angiotensin II type 1 receptor autoantibody (AT1-AA) reduces aldosterone production by triggering a Ca²⁺ overload in H295R cells. AT1-AA was discovered in preeclamptic women and reported to activate AT₁R, and consequently elevate intracellular Ca²⁺. We found that AT1-AA significantly prolonged the time of intracellular Ca²⁺ elevation. Besides promoting aldosterone production as a second messenger, Ca²⁺ overload shows a cytotoxic effect. Our data reveals that long-term presence of AT1-AA triggered a Ca²⁺ overload and consequent impairment of aldosterone production, which could be prevented by a PKC inhibitor, Gö 6983, or a calcium channel inhibitor, nifedipine. These findings have clinical significance because AT₁R blockers are not recommended for treatment of preeclampsia due to their potential harm to the fetus. Our findings also emphasize a potential clinical benefit of immunoadsorption or neutralization of AT1-AA in preeclamptic women.     

The effect of dietary protein intake on immune status in pigs of different genotypes

Little is known about the immune status of different pig breeds and the role of dietary protein intake. The present study, performed on 96 barrows (48 pure-bred Bama mini-pigs (fatty genotype) and 48 Landrace pigs (lean genotype)) randomly assigned to two dietary treatment groups (low- or adequate protein diet), with twenty-four24 individuals per treatment), evaluated the levels of immunoglobulins and cytokines in serum, and intestinal and splenic innate immunity on the two breeds. Data showed significant interactions between breed and diet for adaptive and innate immunity. Throughout the experiment, Landrace pigs showed significantly higher intestinal immune responses than Bama mini-pigs, and an adequate provision of dietary protein improved the expression of specific antibodies in early growth phases. These finding have important implication for improving the immune status of Landrace pigs, which are a major source of protein for humans.

Abbreviations: BW: Body Weight; NRC diet: National Research Council diet; GB diet: Chinese conventional diet; CSFV: Classical Swine Fever Virus; IgG: Immunoglobulin G; IgM: Immunoglobulin M; SIgA: Secretory Immunoglobulin A.     

Effect of dietary copper source (inorganic vs. chelated) on immune response,mineral status,and fecal mineral excretion in nursery piglets

This experiment was conducted to determine the effect of dietary supplementation with copper sulfate and cupreous N-carbamylglutamate chelate (NCG-Cu) on the growth performance, serum biochemical profile, immune response, tissue mineral distributions, and fecal excretion of minerals in nursery piglets. Eighteen healthy nursery piglets were randomly assigned to 3 dietary treatments consisting of no copper in either form (control), 650?g/t copper sulfate (650?g/t Cu) or 320?g/t NCG-Cu (320?g/t NCG-Cu) for 35 days. Pigs fed the 320?g/t NCG-Cu diet showed a significantly (P?P?P?Abbreviations: NCG: N-carbamylglutamate chelate; ADG: average daily gain; ADFI: average daily feed intake; F/G: feed to gain ratio; ALB: albumin; GLU: blood glucose; CREA: creatinine; ALP: alkaline phosphatase; ALT: alanine aminotransferase; AST: aspartate amino transferase; GLB: globulin; TC: total cholesterol; TP: total protein; urea: Urea; D-BIL: direct-acting-bilirubin; T-BIL: total bilirubin; UA: urate; CK: creatine kinase; LDH: lactate dehydrogenase; IgG: immunoglobulin G; IgA: immunoglobulin A; IgM: immunoglobulin M; C₃: complement C₃; LD: longissimus dorsi; ICP-OES: inductively coupled plasma optical emission spectrometry; AA: amino acid; GIT: gastrointestinal; Cu-Met: Cu-methionine; CP: crude protein; NDF: neutral detergent fiber; ADF: acid detergent fiber.     

Role of class II P fimbriae and cytokine response in the pathogenesis of Escherichia coli kidney infection in diabetic mice

Background

The role of class II P fimbriae (P fimbriae II) in diabetic kidney infections is uncertain, although some genetic and epidemiological studies suggest a lower prevalence of P fimbriae II genes in Escherichia coli strains isolated from diabetic patients with complicated kidney infections.

A preliminary review of studies on adaptogens: comparison of their bioactivity in TCM with that of ginseng-like herbs used worldwide

Modern studies have shown that adaptogens can non-specifically enhance the resistance of human body under a wide range of external stress conditions with a multi-targeted and multi-channel network-like manner, especially by affect the immune-neuro-endocrine system and the hypothalamic–pituitary–adrenal axis. This review article draws the attention to the relationships of adaptogens, tonics from traditional Chinese medicine (TCM) and ginseng-like herbs worldwide, which all have similar plant sources and clinical applications. To clarify the sources and pharmacological mechanisms of these plant-originated adaptogens, which will provide useful information for the utilization of adaptogens to improve the human health. Meanwhile, the TCMs and the world-wide ginseng-like herbs from each region’s ethnopharmacology will be beneficial modernization and globalization.     

Mechanobiological oscillators control lymph flow

The ability of cells to sense and respond to physical forces has been recognized for decades, but researchers are only beginning to appreciate the fundamental importance of mechanical signals in biology. At the larger scale, there has been increased interest in the collective organization of cells and their ability to produce complex, “emergent” behaviors. Often, these complex behaviors result in tissue-level control mechanisms that manifest as biological oscillators, such as observed in fireflies, heartbeats, and circadian rhythms. In many cases, these complex, collective behaviors are controlled—at least in part—by physical forces imposed on the tissue or created by the cells. Here, we use mathematical simulations to show that two complementary mechanobiological oscillators are sufficient to control fluid transport in the lymphatic system: Ca²⁺-mediated contractions can be triggered by vessel stretch, whereas nitric oxide produced in response to the resulting fluid shear stress causes the lymphatic vessel to relax locally. Our model predicts that the Ca²⁺ and NO levels alternate spatiotemporally, establishing complementary feedback loops, and that the resulting phasic contractions drive lymph flow. We show that this mechanism is self-regulating and robust over a range of fluid pressure environments, allowing the lymphatic vessels to provide pumping when needed but remain open when flow can be driven by tissue pressure or gravity. Our simulations accurately reproduce the responses to pressure challenges and signaling pathway manipulations observed experimentally, providing an integrated conceptual framework for lymphatic function.Flow of fluid within the lymphatic system is central to many aspects of physiology, including fluid homeostasis and immune function, and poor lymphatic drainage results in significant morbidity in millions of patients each year (1). Although it is known that various mechanical and chemical perturbations can affect lymphatic pumping, there are still no pharmacological therapies for lymphatic pathologies. A fundamental understanding of how various signals coordinate lymphatic vessel function is a necessary first step toward development of treatments to restore fluid balance and enhance immunosurveillance.The lymphatic system consists of fluid-absorbing initial lymphatic vessels that converge to collecting lymphatic vessels, which transport lymph through lymph nodes and back to the blood circulation (2). The collecting lymphatic vessels actively transport fluid via contractions of their muscle-invested walls. Unidirectional flow is achieved by intraluminal valves that limit back flow. Unfortunately, lymphatic pumping is not always operational, and this can lead to lymphedema and immune dysfunction (3, 4).Much is known about the mechanisms responsible for the contractions of the vessel wall. As in blood vessels, the muscle cells that line lymphatic vessels respond to changes in Ca²⁺ concentration. Membrane depolarization results in an influx of Ca²⁺ to initiate the contractions, and this process can be modulated by neurotransmitters (5) or inflammatory mediators, which generally alter the frequency and amplitude of lymphatic pumping (4, 6). Many studies have also reported that physical distension, either by applying isometric stretch or by pressurizing the vessel can affect the phasic contractions (7–10). Interestingly, endothelial (11) and smooth muscle cells (12) have stretch-activated ion channels that can initiate Ca²⁺ mobilization in response to mechanical stresses. Thus, stretch may constitute an important trigger for the contraction phase of a pumping cycle.There are also complementary mechanisms for tempering the Ca²⁺-dependent contractions. The most notable is nitric oxide (NO), a vasodilator that acts at multiple points in the Ca²⁺-contraction pathway to modulate Ca²⁺ release and uptake, as well as the enzymes responsible for force production (13). Blocking or enhancing NO activity can dramatically affect pumping behavior (4, 14–17). Furthermore, lymphatic endothelial cells produce NO in response to fluid flow (16, 18, 19). Importantly, NO dynamics are faster than observed pumping frequencies, so flow-induced NO production is another potential mechanosignal involved in lymphatic regulation (20).