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The present study investigated the effect of arylsulfonyl indoline-benzamide (ASIB) on neovascular glaucoma in the mice model in vivo. In the mice model of glaucoma, ASIB treatment significantly (P

Exposure to lead (Pb) poses a threat to human bone health, including changes in bone mineral composition and the inhibition of skeletal growth and bone maturation. However, little is known about how Pb directly affects osteoblasts. In this work, we found that sub-toxic Pb concentrations suppressed bone nodule formation and inhibited differentiation in MC3T3-E1 subclone 14 cells, as shown by decreased expression levels of the differentiation markers alkaline phosphatase (ALP), type 1 collagen (COL1), osteocalcin (OC), and runt-related transcription factor 2 (RUNX2). Moreover, Pb inactivated the canonical Wnt pathway by regulating key components, such as Wnt3a, Dkk-1, pGSK3β, and β-catenin. Icaritin (ICT), a hydrolytic product of icariin from the genus Epimedium, attenuates the inhibitory effect of Pb on osteoblastic differentiation, as well as activate the canonical Wnt signal pathway. Taken together, the results suggest ICT as a potential bone protectant that may be used to prevent bone damage caused by Pb and can activate the canonical Wnt signal pathway.

The present study was aimed to investigate the protective effect of Pterocarpus marsupium bark extracts against cataract in streptozotocin-induced diabetic male albino rats. Aldose reductase is a key enzyme in the intracellular polyol pathway, which plays a major role in the development of diabetic cataract. Rats were divided into five groups as normal control, diabetic control, and diabetic control treated with different concentrations of Pterocarpus marsupium bark extracts. Presence of major constituents in Pterocarpus marsupium bark extract was performed by qualitative analysis. Body weight changes, blood glucose, blood insulin, and reduced glutathione (GSH) and aldose reductase mRNA and protein expression were determined. Rat body weight gain was noted following treatment with bark extracts. The blood glucose was reduced up to 36% following treatment with bark extracts. The blood insulin and tissue GSH contents were substantially increased more than 100% in diabetic rats following treatment with extracts. Aldose reductase activity was reduced up to 79.3% in diabetic rats following treatment with extracts. V(max), K(m), and K(i) of aldose reductase were reduced in the lens tissue homogenate compared to the diabetic control. Aldose reductase mRNA and protein expression were reduced more than 50% following treatment with extracts. Treatment with Pterocarpus marsupium bark was able to normalize these levels. Taking all these data together, it is concluded that the use of Pterocarpus marsupium bark extracts could be the potential therapeutic approach for the reduction of aldose reductase against diabetic cataract.

RHBDL2, a human homolog of the rhomboids, belongs to a unique class of serine intramembrane proteases; little is known about its function and regulation. Here, we show that RHBDL2 is produced as a proenzyme and that the processing of RHBDL2 is required for its cellular protease activity. The processing of RHBDL2 was shown by both Western blot and immunofluorescence analysis. We have demonstrated that a highly conserved Arg residue on loop 1 of RHBDL2 plays a critical role in the activation of the proenzyme. The activation of RHBDL2 is catalyzed by a protease that is sensitive to a class of sulfonamide compounds. Furthermore, endogenous RHBDL2 exists as the processed form and treatment of cells with a sulfonamide inhibitor led to an accumulation of the full length of RHBDL2. Therefore, this study has demonstrated that RHBDL2 activity is regulated by proenzyme activation, revealed a role for the conserved WR residues in loop 1 in RHBDL2 activity, and provided critical insights into the regulation and function of this human rhomboid protease.

It has been reported that phosphorylation of rabies virus N plays an important role in the process of viral transcription and replication. Rabies virus N is phosphorylated when expressed alone, indicating that cellular kinase phosphorylates rabies virus N. To identify what cellular kinase phosphorylates rabies virus N, the N was expressed in Escherichia coli and purified by metal affinity chromatography. The recombinant N was phosphorylated by BHK cellular extracts and by purified CK-II. In addition, the phosphorylation of the recombinant N in vitro can be blocked by a CK-II inhibitor, heparin. Furthermore, N phosphorylation in the virus-infected cells can be inhibited by a CK-II specific inhibitor, 5,6-dichloro-beta-D-ribofuranosyl benzimidazole. However, PKC did not phosphorylate the recombinant N in vitro; nor did staurosporine, a PKC and other kinase inhibitor, prevent rabies virus N from phosphorylation. Thus, our data demonstrate that cellular CK-II phosphorylates rabies virus N.

In the condition that the real valued function f : S → R is a arc connected function in arc connected set S ⊆ R n , this paper give the definition of generalized arc connected function. The class function is the promotion of convex function which satisfies identified local-global extremum property. Conversely, under certain conditions. the function meeting local-global extremum property must be one of those generalized functions. Also, the optimality sufficient condition of minx∈S f (x), s.t.g(x) ≤ 0 is obtained under generalized connected assumption.

Under the generalized weak convexity of (F, d , , ρ α ), we studied the results of several sorts of duality type about the problem of multi-objective fractional programming (MFP), extended this results to the generalized arcwise connected hypothesis, established the optimized problem of arcwise connected area (ACP) and the optimal sufficient condition of 0 ) ( . . ) ( min ≤ ∈ x g t s x f S x under constraint condition, and gave the duality model, and obtained the conclusions of

Rhomboid, a polytopic membrane serine protease, represents a unique class of proteases that cleave substrates within the transmembrane domain. Elucidating the mechanism of this extraordinary catalysis comes with inherent challenges related to membrane-associated peptide hydrolysis. Here we established a system that allows expression and isolation of YqgP, a rhomboid homologue from Bacillus subtilis, as a soluble protein. Intriguingly, soluble YqgP is able to specifically cleave a peptide substrate that contains the transmembrane domain of Spitz. Mutation of the catalytic dyad abolished protease activity, and substitution of another highly conserved residue, Asn241, with Ala or Asp significantly reduced the catalytic efficiency of YqgP. We have identified the cleavage site that resides in the middle of the transmembrane domain of Spitz. Replacement of two residues that contribute to the scissile bond by Ala did not eliminate cleavage, but rather led to additional or alternative cleavages. Moreover, we have demonstrated that soluble YqgP exists as oligomers that are required for catalytic activity. These results suggest that soluble oligomers of maltose binding protein-YqgP complexes form micellelike structures that are able to retain the active conformation of the protease for catalysis. Therefore, this work not only provides a unique system for elucidating the reaction mechanism of rhomboid but also will facilitate the characterization of other intramembrane proteases as well as non-protease membrane proteins.