Shenfu Injection(参附注射液) Suppresses Inflammation by Targeting Haptoglobin and Pentraxin 3 in Rats with Chronic Ischemic Heart Failure

Objective:To investigate the regulatory effects of Shenfu Injection(SFI,参附注射液) on hemodynamic parameters and serum proteins in rats with post-infarction chronic heart failure(CHF).Methods:Forty-five healthy Wistar rats were randomized into three groups:sham,heart failure(model) and SFI group.The CHF was induced by left coronary artery ligation.Seven days after the surgical operation,animals in the sham group and the model group received saline(6.2 mL/kg/d),while animals in the SFI group received SFI(6.2 mL/kg·d) intraperitoneally.Four weeks later,cardiac hemodynamic parameters were measured via the carotid route.The expression of serum proteins was analyzed by two-dimensional electrophoresis and matrixassisted laser desorption/ionization time-of-flight mass spectrometer(MALDI-TOF MS).Results:Recording of hemodynamic parameters showed that left ventricular systolic pressure(LVSP),maximum rate of left ventricular pressure(+dp/dt_(max)) rise,and maximum rate of left ventricular pressure(-dp/dt_(max)) decrease,while the left ventricular end diastolic pressure(LVEDP) rose in the model group compared to those in the sham group(P0.05).The results of the MALDI-TOF MS indicated that haptoglobin(HP),pentraxin 3(PTX3) and alpha-1-antitrypsin were up-regulated,while serum albumin and 40 S ribosomal protein were down-regulated in the model group(P0.05).Compared with the model group,LVSP,+dp/dt_(max)and-dp/dt_(max) were higher,while LVEDP was lower in the SFI group(P0.05).Expression levels of HP and PTX3 were lower than in the model group(P0.05).Conclusion:SFI could improve hemodynamic function and decrease inflammatory reactions in the pathophysiology of CHF.The serum proteins HP and PTX3 could be potential biomarkers for chronic ischemic heart failure,and they could also be the serum protein targets of SFI.     

Proteomics of Drosophila Compound Eyes: Early Studies,Now, and the Future—Light-Induced Protein Phosphorylation as an Example

Abstract:

In the past three decades, efforts to understand the molecular mechanisms underlying photoreceptor transduction of the fruit fly Drosophila melanogaster experienced drastic waves of technological development that involve multiple areas of scientific disciplines; the multidisciplinary approach includes a classical genetic manipulation in which random mutations are created and phenotypes are screened, a modern genetics maneuver in which a specific gene relevant to a hypothesis is molecularly cloned and manipulated, and, more recently, direct studies of proteins by proteomics technologies in combination with modern molecular biology and electrophysiology. This paper will review efforts that originated three decades ago in Professor William L. Pak's laboratory at Purdue University to study proteins involved in the Drosophila photoreceptor transduction process and show the power of such multidisciplinary approach that involves collaboration between molecular genetics, electrophysiology, and proteomics.     

Differential effects of estradiol and progesterone on human T cell activation in vitro

Estradiol (E2) and progesterone (P4) are steroid hormones important for the regulation of immune responses during pregnancy. Their increasing levels coincide with an improvement of T cell-mediated diseases such as multiple sclerosis (MS). Although immune-endocrine interactions are involved in this phenomenon, the relative contribution of hormones is not known. We here report a direct comparison of E2- and P4-mediated effects on human CD4⁺ T cells, key cells in immune regulation. T cells were stimulated to obtain different activation levels and exposed to a broad range of hormone concentrations. Activation level was assessed by CD69/CD25 expression by flow cytometry, and secreted proteins (n = 196) were measured in culture supernatants using proximity extension assay and electrochemiluminescence immunoassay. We found that in low activated cells, pregnancy-relevant E2 concentrations increased activation and the secretion of several immune- and inflammation-related proteins. P4, on the other hand, showed a biphasic pattern, where serum-related concentrations upregulated activation and protein secretion while placenta-relevant concentrations induced a prominent dampening irrespective of the initial activation level. Our results demonstrate the importance of P4 as a major hormone in the immune modulation of T cells during pregnancy and emphasize the need to further evaluate its potency in the treatment of diseases like MS.     

From high definition precision healthcare to precision public oral health: opportunities and challenges

In anticipation of a major transformation in healthcare, this review provides highlights that anticipate the near future for oral public health (and beyond). Personalized or precision healthcare reflects the expectation that advances in genomics, imaging, and other domains will extend our risk assessment, diagnostic, and prognostic capabilities, and enables more effective prevention and therapeutic options for all Americans. Meanwhile, the current healthcare system does not meet cost, access, or quality criteria for all Americans. It is now an imperative that the success of “smart,” quality, and cost-effective high definition precision healthcare requires a public health perspective for several reasons: a) to enhance generalizability, b) to assess methods of implementation, and c) to focus on both risk and prevention in large and small populations, thereby providing a balance between the generation of long-term knowledge and short-term health gains. Sensitivity and resolution, reasonable cost, access to all Americans, coordinated comprehensive care, and advances in whole genome sequencing (WGS) and big data analyses, coupled to other advances in biotechnology and digital/artificial intelligence/machine learning devices, and the behavioral, social, and environmental sciences, offer remarkable opportunities to improve the health and wellness of the American people [genotype + phenotype + environment + behavior = high definition healthcare]. The opportunity is to significantly improve the well-being and life expectancy of all people across the lifespan including the least-advantaged people in our society and potentially increase access, reduce the national costs, and improve health outcomes.     

How to diagnose amyloidosis

Amyloidosis is a rare but devastating condition caused by deposition of misfolded proteins as aggregates in the extracellular tissues of the body, leading to impairment of organ function. High clinical suspicion is required to facilitate early diagnosis. Correct identification of the causal amyloid protein is absolutely crucial for clinical management in order to avoid misdiagnosis and inappropriate, potentially harmful treatment, to assess prognosis, and to offer genetic counselling if relevant. This review summarises the current evidence on which the diagnosis and subtyping of amyloidosis is based, outlines the limitations of various diagnostic techniques, particularly in an Australian and New Zealand context, and discusses optimal strategies for the diagnostic approach to these patients. Recommendations are provided for when particularly to suspect amyloidosis, what investigations are required, as well as an approach to accurate subtyping of amyloidosis.