ABSTRACT
Stress and illness connection is complex and involves multiple physiological systems. Panax ginsengs, reputed for their broad-spectrum "cure-all" effect, are widely prescribed to treat stress and related illnesses. However, the identity of ginseng's "cure-all" medicinal compounds that relieve stress remains unresolved. Here, we identify ginsentides as the principal bioactives that coordinate multiple systems to restore homeostasis in response to stress. Ginsentides are disulfide-rich, cell-penetrating and proteolytic-stable microproteins. Using affinity-enrichment mass spectrometry target identification together with in vitro, ex vivo and in vivo validations, we show that highly purified or synthetic ginsentides promote vasorelaxation by producing nitric oxide through endothelial cells via intracellular PI3K/Akt signaling pathway, alleviate α1-adrenergic receptor overactivity by reversing phenylephrine-induced constriction of aorta, decrease monocyte adhesion to endothelial cells via CD166/ESAM/CD40 and inhibit P2Y12 receptors to reduce platelet aggregation. Orally administered ginsentides were effective in animal models to reduce ADP-induced platelet aggregation, to prevent collagen and adrenaline-induced pulmonary thrombosis as well as anti-stress behavior of tail suspension and forced swimming tests in mice. Together, these results strongly suggest that ginsentides are the principal panacea compounds of ginsengs because of their ability to target multiple extra- and intra-cellular proteins to reverse stress-induced damages.
ABSTRACT
Objective To study the renal toxicity of arsenic trioxide (As2O3) with therapeutic dose in acute promyelocytic leukemia (APL) in childhood. Methods Renal toxicity of 37 APL was monitored. The examinations of urinary routine, urinary microproteins[αt1-microglobulin (α1-MG), microalbumin (mAlb),β2-microglobulin (β2-MG), transferrin(TRF)] and renal function were performed. Results Five cases with leukocyturia, three cases with hematuria, six cases with proteinuria were observed before therapy. Ketonuria occurred in six cases associated with fever and less diet; overall abnormality disappeared in the first week. No significant changes of blood uric nitrigen(BUN), serum creatinine(Cr) and uric acid (UA) were founded in induction remission. Compared with tests before As2O3 infusion, obvious increase of uric α1-MG occurred in second week with arsenic trioxide, obvious increase of uric β2-MG in third week (P ＜0.01), slow recovery of uric α1-MG and β2-MG in fifth week. No significant changes of uric mAlb and TRF were seen in induction remission. Conclusion The renal toxicity of As2O3 was gentle in general therapeutic dose, renal tubercular damage could be seen. The important monitoring period were the second to fifth week in induction remission.Influence of As2O3 cumulant on renal function was not serious in the near future in childhood. The combined detection of urinary microproteins with dynamic variety could detect early renal damage with As2O3.
ABSTRACT
Objective To study the clinical significance of urinary mtcroprotems examination on early diagnosis of kidney damage of children with obesity. Method Urinary microproteins were tested in 40 obese children by enzyme - linked immunosorbent assay and 50 healthy children as controls. Results Urinary microprotem examination were abnormal in 8 obese children. Albumin in 5 cases increased, and transferrin(TRF) with retinol-binding protein in 1 case increased meanwhile. TRF in 3 cases increased. One case was abnormal by kidney biopsy.Conclusion Urinary microprotem examination was the sensitive index in early diagnosis of obesity-related glomerulopathy in children.