Negative Modulation of B Cell Activation by Melanocortin 1 Receptor Signaling Protects against Membranous Nephropathy.

Significance Statement: Emerging evidence suggests that melanocortin neuropeptides-specifically adrenocorticotropic hormone-offer a novel, steroidogenic-independent therapeutic modality for membranous nephropathy (MN). The molecular mechanism underlying this beneficial effect, however, remains largely elusive. To investigate whether melanocortins modulate humoral immunity, the authors induced passive Heymann nephritis, a model of human MN, in wild-type and melanocortin 1 receptor (MC1R) knockout rats and treated them with melanocortin agents.

Hematopoietic-specific melanocortin 1 receptor signaling protects against nephrotoxic serum nephritis and mediates the beneficial effect of melanocortin therapy.

The melanocortin hormone system has emerged as a novel therapeutic target for treating refractory glomerular diseases. However, the role of hematopoietic melanocortin 1 receptor (MC1R) signaling remains unknown. Upon insult by rabbit nephrotoxic serum, MC1R null-mutant mice developed more severe crescentic glomerulonephritis than wild-type mice, marked by aggravated proteinuria, kidney dysfunction and histologic lesions.

Heme oxygenase-1 enhances autophagy by modulating the AMPK/mTORC1 signaling pathway as a renoprotective mechanism to mitigate lead-induced nephrotoxicity.

Lead (Pb), a highly poisonous heavy metal and an important occupational hazard, is currently a widespread environmental pollutant. The kidney is especially susceptible to the toxic effects of Pb because of its major role in Pb excretion. Heme oxygenase-1 (HO-1) is an inducible antioxidant enzyme that can mitigate cellular injury.

Melanocortin 5 receptor signaling pathway in health and disease.

Melanocortin hormone system plays a key role in maintaining the homeostasis of our body via their neuro-immune-endocrine activities and regulates a diverse array of physiological functions, including melanogenesis, inflammation, immunomodulation, adrenocortical steroidogenesis, hemodynamics, natriuresis, energy homeostasis, sexual function, and exocrine secretion. The pathobiologic actions of all melanocortins are conveyed by melanocortin receptors. As the last melanocortin receptor to be cloned and characterized, melanocortin receptor 5 (MC5R) is widely expressed in both central nervous system and a number of peripheral organ systems in man.

Reversal Effect of Oxypeucedanin on P-glycoprotein-mediated Drug Transport.

P-glycoprotein affects the transport of numerous drugs including chemotherapeutic drugs vincristine sulfate (VCR) and docetaxel (DTX), and is one of the main causes for multidrug resistance. Our previous studies have shown that oxypeucedanin (OPD) can enhance the intestinal transit of puerarin and VCR. However, the underlying mechanism is unclear.

Klotho Reduces Necroptosis by Targeting Oxidative Stress Involved in Renal Ischemic-Reperfusion Injury.

Background/aims: Klotho is a multifunctional protein expressed predominantly in kidney tubular epithelium. Here, we investigated the protective effects of Klotho on necroptosis in renal ischemic-reperfusion injury (IRI) and the role of oxidative stress in this process.

Methods: Mice were subjected to bilateral renal pedicle clamping.

[Effect investigation of coumarin constituents in Angelica dahurica on pharmacokinetics of docetaxel by LC-MS].

The study was aimed to establish a liquid chromatography-tandem mass spectrometric method for the determination of the docetaxel concentration in rat plasma, and study the effect of coumarin constituents (imperatorin, isoimperatorin and oxypeucedanin) in Angelica dahurica on pharmacokinetics of docetaxel.Plasma was precipitated with acetonitrile and determined by LC-MS method with Paclitaxel as an internal standard. The specificity, linearity, range, accuracy, precision and stability of the method were suitable for the determination of docetaxel in plasma.

Klotho ameliorates hydrogen peroxide-induced oxidative injury in TCMK-1 cells.

Purpose: Defects in Klotho gene expression in mice result in a vulnerability to oxidative injuries. We aimed to identify the expression of Klotho in a mouse tubular epithelial (TCMK-1) cell line, and also to investigate changes in Klotho expression induced by oxidative stress and the potential role of intra- and extracellular Klotho protein.

Methods: During exposure to hydrogen peroxide (HO), an overexpression of the Klotho gene was induced and exogenous Klotho protein was added in TCMK-1 cells.

[Correlation between four properties of traditional Chinese medicine and function of reversing multidrug resistance of tumor cells].

To study the correlation of four properties of traditional Chinese medicine and the function of reversing multidrug resistance (MDR) of tumor cells, with 580 herbs in Chinese Pharmacopoeia 2015 version as the research objects. CNKI, CBA, Wanfang, VIP, and PubMed were searched to screen the documents related to the reversal of MDR for collection, summarizing and analysis. The results of the research showed that a total of 114 species Chinese herbs had been reported to be associated with reversal of MDR in tumor cells.

Improvement of Transmembrane Transport Mechanism Study of Imperatorin on P-Glycoprotein-Mediated Drug Transport.

P-glycoprotein (P-gp) affects the transport of many drugs; including puerarin and vincristine. Our previous study demonstrated that imperatorin increased the intestinal absorption of puerarin and vincristine by inhibiting P-gp-mediated drug efflux. However; the underlying mechanism was not known.

Autophagy protects renal tubular cells against ischemia / reperfusion injury in a time-dependent manner.

Background/aims: Autophagy is a dynamic catabolic process that maintains cellular homeostasis. Whether it plays a role in promoting cell survival or cell death in the process of renal ischemia/reperfusion (I/R) remains controversial, partly because renal autophagy is usually examined at a certain time point. Therefore, monitoring of the whole time course of autophagy and apoptosis may help better understand the role of autophagy in renal I/R.