pkc signaling
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Author(s):  
Vaibhav Dubey

Bipolar disorder (BD) displays abnormalities in protein kinase C (PKC) signaling, and evidence suggests that inhibiting PKC may help treat mania. Endoxifen a potent inhibitor of the PKC signaling pathway, is effective in controlling acute bipolar mania, at doses of 8 mg OD, for a period of 3-weeks. Here we present the case of a patient with severe mania, increased alcohol consumption administered endoxifen 8 mg BID for a period of 3-months, to achieve a better response. High-dose, long-term treatment with endoxifen was efficacious in controlling manic symptoms, with no adverse effects. Additionally, the patient didn’t consume alcohol during the course of treatment. This case showed the long-term effectiveness and safety of high-dose endoxifen to control mania in a patient with BD.


Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 3894
Author(s):  
Juyong Kim ◽  
Sung-Chul Hong ◽  
Eun Ha Lee ◽  
Jae Wook Lee ◽  
Seung-Hoon Yang ◽  
...  

Whitening research is of particular interest in the cosmetics market. The main focus of whitening research is on melanogenesis inhibition through tyrosinase activity. The mechanism of melanogenesis is involved with tyrosinase activity and p-PKC signaling. In this study, we used Momordica cochinchinensis (Lour.) spreng, a tropical fruit found throughout Southeast Asia, to investigate the inhibitory effect of melanogenesis. M. cochinchinensis contains a high concentration of polyphenols, flavonoids, and unsaturated fatty acids, which might be related to antioxidant activity. This study aimed to determine whether M. cochinchinensis extracts inhibit melanin synthesis in melan-A cells by inhibiting tyrosinase activity and p-PKC signaling. M. cochinchinensis was divided into pulp and aril and extracted under various conditions, and it was confirmed that all pulp and aril extracts have high contents of both phenols and flavonoids. Melan-A cells were treated with PMA for three days to induce melanin synthesis. After PMA treatment, M. cochinchinensis extracts were added to cultured media in a dose-dependent manner. Melanin contents and MTS were used to determine the amount of melanin in live cells. M. cochinchinensis extracts were evaluated for their effects on tyrosinase activity and p-PKC signaling pathways by Western blotting. It was found that M. cochinchinensis extract treatment decreased the amount of melanin and suppressed p-PKC expression. Additionally, tyrosinase activity was reduced after M. cochinchinensis extract treatment in a dose-dependent manner. Therefore, it was concluded that M. cochinchinensis could be used in antimelanogenesis and functional cosmetic materials to improve whitening.


2021 ◽  
Vol 898 ◽  
pp. 173959
Author(s):  
Ziting Zhu ◽  
Yan He ◽  
Zhongrui Liu ◽  
Wenlong Zhang ◽  
Qiyun Kang ◽  
...  

2021 ◽  
Vol 11 (5) ◽  
pp. 903-911
Author(s):  
Lei Wang ◽  
Linjuan Liu ◽  
Sixin Sun ◽  
Li Xiao ◽  
Qinyi Jiang ◽  
...  

Objectives: This study was aimed to explore the effects of parathyroid hormone (PTH) on osteoporotic fracture healing in mice and the underlying mechanisms. Methods: Microarray analysis was conducted to analyze the gene expression level in MC3T3-E1 cells. Carboxyfluorescein succinimidyl ester (CFSE) staining and flow cytometry was adopted to analyze the proliferation and apopto-sis of MC3T3-E1 cells. qRT-PCR was used to analyze the mRNA expression level. Fluorescence resonance energy transfer (FRET) assay was conducted to detect PKC activity. The bone mineral density (BMD) and bone volume (BV)/total volume (TV) were determined via enzyme-linked immunosorbent assay (ELISA) and microscopic computed tomography (micro-CT). Results: ERK1/2 was abnormally expressed in MC3T3-E1 cells after GlylArg19hPTH (1-34) + KT5720 treatment. GlylArg19hPTH (1-34)+ KT5720 treatment promoted cell proliferation, inhibited cell apoptosis, and upregulatedthe expression of osteogenesis-related genes (ALP, OPN, Runx2 and OPG) in MC3T3-E1 cells, which were due to the activation of the non-PLC-dependent PKC signaling pathway and can be blocked by PKC inhibitor Go6983 or ERK1/2 inhibitor BVD-523. Moreover, the activity of PKC in MC3T3-E1 cells treated with GlylArg19hPTH (1-34) + KT5720 + Go6983 was alleviated by ERK1/2 inhibitor BVD-523. In vivo, specific activation of the non-PLC-dependent PKC signaling pathway increased the serum levels of APL and OPG in mice with osteoporotic fracture, which were reversed by PKC inhibitor Go6983 and ERK1/2 inhibitor BVD-523. Moreover, PKC inhibitor Go6983 and ERK1/2 inhibitor BVD-523 suppressed the elevation of BV/TV and BMD induced by specific activation of the non-PKC-dependent signaling pathway. Conclusions: Taken together, PTH stimulates osteoporotic fracture healing in mice through the non-PLC-dependent PKC signaling pathway in which ERK1/2 exerts a vital role.


2021 ◽  
Vol 169 ◽  
pp. 196-204
Author(s):  
Na Jin ◽  
Su-Yue Zhu ◽  
Xin-Yu Yang ◽  
Cheng Zhen ◽  
Yan Li ◽  
...  

2021 ◽  
Vol 77 ◽  
pp. 109819
Author(s):  
Avijit Dey ◽  
S.M. Anisul Islam ◽  
Rekha Patel ◽  
Mildred Acevedo-Duncan

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