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The pathogenesis of inflammatory bowel disease (IBD) is related to genetic susceptibility, enteric dysbiosis, and uncontrolled, chronic inflammatory responses that lead to colonic tissue damage and impaired intestinal absorption. As a consequence, patients with IBD are prone to nutrition deficits after each episode of disease resurgence. Nutritional supplementation, especially for protein components, is often implemented during the remission phase of IBD. Notably, ingested nutrients could affect the progression of IBD and the prognostic outcome of patients; therefore, they should be cautiously evaluated prior to being used for IBD intervention. Arginine (Arg) is a semi-essential amino acid required for protein synthesis and intimately associated with gut pathophysiology. To help optimize arginine-based nutritional intervention strategies, the present work summarizes that during the process of IBD, patients manifest colonic Arg deficiency and the turbulence of Arg metabolic pathways. The roles of Arg–nitric oxide (catalyzed by inducible nitric oxide synthase) and Arg–urea (catalyzed by arginases) pathways in IBD are debatable; the Arg–polyamine and Arg–creatine pathways are mainly protective. Overall, supplementation with Arg is a promising therapeutic strategy for IBD; however, the dosage of Arg may need to be carefully tailored for different individuals at different disease stages. Additionally, the combination of Arg supplementation with inhibitors of Arg metabolic pathways as well as other treatment options is worthy of further exploration.

Lymphangiogenesis occurs during renal fibrosis in patients with chronic kidney diseases and vascular endothelial growth factor (VEGF)-C is required for the formation of lymphatic vessels; however, the underlying mechanisms remain unclear. We demonstrate that macrophages can regulate unilateral ureteral obstruction (UUO)-induced renal lymphangiogenesis by expressing high levels of VEGF-C by C-C motif chemokine receptor 2 (CCR2)-mediated signaling. Mice deficient in Ccr2 manifested repressed lymphangiogenesis along with attenuated renal injury and fibrosis after UUO induction. The infiltrated macrophages after UUO induction generated a microenvironment in favor of lymphangiogenesis, which likely depended on Ccr2 expression. Mechanistic studies revealed that CCR2 is required for macrophages to activate phosphatidylinositol 3-kinase (PI3K)-AKT-mechanistic target of rapamycin (mTOR) signaling in response to its ligand monocyte chemoattractant protein 1 stimulation, whereas hypoxia-inducible factor (HIF)-1α is downstream of PI3K-AKT-mTOR signaling. HIF-1α directly bound to the VEGF-C promoter to drive its expression to enhance lymphangiogenesis. Collectively, we characterized a novel regulatory network in macrophages, in which CCR2 activates PI3K-AKT-mTOR signaling to mediate HIF-1α expression, which then drives VEGF-C expression to promote lymphangiogenesis.

The calix[4]arene-based podands which incorporates two terpyridinyl functional groups derived from the alkylation reactions of 4-(ω-chloroalkoxyphenyl)-2,2′:6′,2″-terpyridine in 1,3-alternate position at lower rim have been prepared in moderate yields. The structures of four pyridyl compounds were determined by X-ray single crystal diffraction method. The complexing properties of bis-terpyridinyl-calix[4]arenes for transition metal ions were investigated by fluorescence spectra. Bis-terpyridinyl-calix[4]arenes gave a more efficient fluorescent sensing ability to Zn2+.

Dendritic p-t-butylcalix[n]arene amide derivatives with terminal amino groups of the first and second generations were synthesized by using divergent methods from ammonolysis of ethyl calixarylacetate with 1,6-diaminohexane and Michael addition of methyl acrylate. Their structures were confirmed by IR, 1H NMR. The recognition properties of these amide derivatives for several kinds of metal ions were studied with UV-Vis spectroscopy. The results showed a great affinity for soft Ag+ and UO2 2+ ions and formed 1:2 or 1:3 stoichiometric complexes.

A 5/6 nephrectomized (Nx) rat model was employed to address the impact of telmisartan on CKD related renal injury and the underlying molecular mechanisms. It was noted that telmisartan provided protection for rats against 5/6 Nx induced lethality. Telmisartan treated 5/6 Nx rats manifested improved renal function as characterized by the higher GFR but lower urinary albumin, BUN and Scr as compared with that of control rats. Telmisartan treatment also significantly decreased systolic blood pressure and alleviated glomerulosclerosis and interstitial fibrosis. Mechanistic studies revealed that telmisartan possesses the capability to increase NO generation in the kidney. Further studies demonstrated that telmisartan promotes PPARγ expression, by which it specifically enhances nNOS expression in the kidneys after 5/6 Nx insult. Particularly, blockade of PPARγ signaling by GW9662 abolished the protective effect conferred by telmisartan, indicating that telmisartan induction of renal nNOS expression along with NO generation is dependent on PPARγ signaling. Together, our data support that telmisartan could be a promising drug for treatment of chronic kidney diseases in diverse clinical settings.