Protein kinase C

Induced oncoproteins degradation provides an attractive anti-cancer modality. Activation of anaphase-promoting complex (APC/CCDH1 ) prevents cell-cycle entry by targeting crucial mitotic proteins for degradation. Phosphorylation of its co-activator CDH1 modulates the E3 ligase activity, but little is known about its regulation after phosphorylation and how to effectively harness APC/CCDH1 activity to treat cancer. Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1)-catalyzed phosphorylation-dependent cis-trans prolyl isomerization drives tumor malignancy...

BACKGROUND: Vascular dementia (VaD) is a prevalent neurodegenerative disease characterized by cognitive impairment due to cerebrovascular factors, affecting a significant portion of the aging population and highlighting the critical need to understand specific targets and mechanisms for effective prevention and treatment strategies. We aimed to identify pathways and crucial genes involved in the progression of VaD through bioinformatics analysis and subsequently validate these findings...

This study aims to explore the pathogenesis of myocardial ischaemia reperfusion injury(MIRI) based on oxidative stress-mediated programmed cell death and the mechanism and targets of Chaihu Sanshen Capsules in treating MIRI via the protein kinase Cβ(PKCβⅡ)/NADPH oxidase 2(NOX2)/reactive oxygen species(ROS) signaling pathway. The rat model of MIRI was established by the ligation of the left anterior descending branch. Rats were randomized into 6 groups: sham group, model group, clinically equivalent-, high-dose Chaihu Sanshen Capsules groups, N-acetylcysteine group, and CGP53353 group...

Network pharmacology was employed to probe into the mechanism of Fushen Granules in treating peritoneal dialysis-rela-ted peritonitis(PDRP) in rats. The main active components of Fushen Granules were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and their targets were predicted. PDRP-related targets were retrieved from DisGeNET and other databases. The common targets shared by the drug and the disease were identified by the online tool, and protein-protein interaction(PPI) network of the common targets...

Based on the sarcoma receptor coactivator(Src)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway, the mechanism of action of bulleyaconitine A in the treatment of bone destruction of experimental rheumatoid arthritis(RA) was explored. Firstly, key targets of RA bone destruction were collected through GeneCards, PharmGKB, and OMIM databa-ses. Potential targets of bulleyaconitine A were collected using SwissTargetPrediction and PharmMapper databases. Next, intersection targets were obtained by the Venny 2...

The mechanism of total polyphenols of Cydonia oblonga Miller(TPCOM) against kidney cancer was elucidated through a combination of network pharmacology, bioinformatics, and experimental verification. The active polyphenolic compounds from C. oblonga were screened by network pharmacological techniques and kidney cancer-related targets were collected through the database. The differential gene expression analysis was performed on RNA sequencing data from tumor tissue and normal tissue of kidney cancer patients obtained from the Gene Expression Omnibus(GEO) database...

The chemical constituents of ethyl acetate from Hypericum himalaicum were isolated by silica gel column chromatography, gel column chromatography, and high-performance liquid chromatography. The structure of the isolated compounds was identified by modern spectral techniques(NMR, MS, IR, and UV), and the potential anti-inflammatory targets and action pathways were analyzed and predicted by network pharmacology and molecular docking methods.Ten compounds were isolated from H. himalaicum and identified as 5,9,11-trihydroxy-3,3-dimethyl-3H,8H-benzo[6,7][1,4]dioxepino[2,3-f]chromen-8-one(1), betulinic acid(2), demethyltorosaflavone C(3), kaempferol(4), quercetin(5), hyperwightin B(6), toxyloxanthone B(7), 1,7-dihydroxy-xanthone(8), emodin(9), and 1,7-dihydroxy-4-methoxy-xanthone(10)...

This study employed network pharmacology to investigate the effect of Guizhi Gancao Decoction(GGD) on myocardial ischemia-reperfusion injury(MI/RI) in rats and decipher the underlying mechanism. Firstly, the chemical components and targets of GGD against MI/RI were searched against the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), SwissTargetPrediction, and available articles. STRING and Cytoscape 3.7.2 were used to establish the protein-protein interaction(PPI) network for the common targets, and then Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses were carried out for the core targets...

Endoxifen, a protein kinase C inhibitor, has been approved for use in manic episodes in India. One of the symptom traits that it predominantly targets is impulsivity. Impulsivity can also be a symptom dimension of other mental health conditions, one of which is Borderline Personality Disorder (BPD). Management of BPD is challenging, with limited pharmacological options that are symptom-directed and psychotherapy sessions that are fraught with early dropouts and lack of compliance. Impulsive behaviors represent a major reason for seeking help in BPD, especially with regard to non-suicidal self-injury, substance abuse, high-risk sexual behavior, aggression, etc...

BACKGROUND/PURPOSE: Bacterial infection was the major etiology for pulpal/root canal infection. This study aimed to investigate the activation of toll-like receptor-3 (TLR) on cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2 ) and PGF2α production of human dental pulp cells (HDPCs) and associated signaling. MATERIALS AND METHODS: HDPCs were exposed to different concentrations of Poly (I:C) (a TLR3 activator). Cell viability was determined by 3- (4,5-Dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay and alkaline phosphatase (ALP) activity was evaluated by ALP staining...

Targeted therapy revolutionizes the treatment of non-small-cell lung cancer (NSCLC), harboring molecular change. Epidermal growth factor receptor (EGFR) mutations play a crucial role in the development of NSCLC, serving as a pivotal factor in its pathogenesis. We elucidated the mechanisms of resistance and potential therapeutic strategies in NSCLC resistant to the EGFR-tyrosine kinase inhibitor (EGFR-TKI). This is achieved by identifying rare missense variants through whole exome sequencing (WES). The goal is to enhance our understanding, identify biomarkers, and lay the groundwork for targeted interventions, thereby offering hope for an improved NSCLC treatment landscape...

Objective: Osteoarthritis (OA) is the most prominent chronic arthritic disease, affecting over 3 billion people globally. Synovial macrophages, as immune cells, play an essential role in cartilage damage in OA. Therefore, regulating macrophages is crucial for controlling the pathological changes in OA. Triggering receptor expressed on myeloid cells 2 (TREM2), as expressed on immune cell surfaces, such as macrophages and dendritic cells, has suppressed inflammation and regulated M2 macrophage polarization but demonstrated an unknown role in synovial macrophage polarization in OA...

Nonalcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease in the world. The problem of NAFLD had become increasingly prominent. However, its pathogenesis is still indistinct. As we all know, NAFLD begins with the accumulation of triglyceride (TG), leading to fatty degeneration, inflammation and other liver tissues damage. Notably, structure of nucleoporin 85 (NUP85) is related to lipid metabolism and inflammation of liver diseases. In this study, the results of researches indicated that NUP85 played a critical role in NAFLD...

AIMS: Hyperactivity of Ca2+ /calmodulin-dependent protein kinase II (CaMKII) has emerged as a central cause of pathologic remodelling in heart failure. It has been suggested that CaMKII-induced hyperphosphorylation of the ryanodine receptor 2 (RyR2) and consequently increased diastolic Ca2+ leak from the sarcoplasmic reticulum (SR) is a crucial mechanism by which increased CaMKII activity leads to contractile dysfunction. We aim to evaluate the relevance of CaMKII-dependent RyR2 phosphorylation for CaMKII-induced heart failure development in vivo...

Voltage-dependent anion channel 2 (VDAC2) is an important channel protein that plays a crucial role in the host response to viral infection. The receptor for activated C kinase 1 (RACK1) is also a key host factor involved in viral replication. Our previous research revealed that Bombyx mori VDAC2 (BmVDAC2) and B. mori RACK1 (BmRACK1) may interact with Bombyx mori nucleopolyhedrovirus (BmNPV), though the specific molecular mechanism remains unclear. In this study, the interaction between BmVDAC2 and BmRACK1 in the mitochondria was determined by various methods...

The JAK (Janus kinase)-STAT (Signal transducer and activator of transcription) is a well-known functional signaling pathway that plays a key role in several important biological activities such as apoptosis, cell proliferation, differentiation, and immunity. However, limited studies have explored the functions of STAT genes in invertebrates. In the present study, the gene sequences of two STAT genes from the Pacific oyster (Crassostrea gigas), termed CgSTAT-Like-1 (CgSTAT-L1) and CgSTAT-Like-2 (CgSTAT-L2), were obtained using polymerase chain reaction (PCR) amplification and cloning...

OBJECTIVES: Metformin protects against age-related muscle decline, termed sarcopenia. However, the effects on sarcopenia quality-of-life (SarQoL) are unknown. We investigated the effects of metformin on SarQoL and associated mechanisms in older adults. METHOD: This double-blind randomized, placebo-controlled trial included geriatric adult men, divided into non-sarcopenic controls (age = 72.2 ± 4.3 years, n = 52) and two groups of patients with sarcopenia randomized into placebo (age at baseline = 74...

ETHNOPHARMACOLOGICAL RELEVANCE: Trichosanthis pericarpium (TP; Gualoupi, pericarps of Trichosanthes kirilowii Maxim) has been used in traditional Chinese medicine (TCM) to reduce heat, resolve phlegm, promote Qi, and clear chest congestion. It is also an essential herbal ingredient in the "Gualou Xiebai" formula first recorded by Zhang Zhongjing (from the Eastern Han Dynasty) in the famous TCM classic "Jin-Guì-Yào-Lüe" for treating chest impediments. According to its traditional description, Gualou Xiebai is indicated for symptoms of chest impediments, which correspond to coronary heart diseases (CHD)...

BACKGROUND: Parkinson's disease is a progressive neurodegenerative disorder with multifactorial causes, among which genetic risk factors play a part. The RAB GTPases are regulators and substrates of LRRK2, and variants in the LRRK2 gene are important risk factors for Parkinson's disease. We aimed to explore genetic variability in RAB GTPases within cases of familial Parkinson's disease. METHODS: We did whole-exome sequencing in probands from families in Canada and Tunisia with Parkinson's disease without a genetic cause, who were recruited from the Centre for Applied Neurogenetics (Vancouver, BC, Canada), an international consortium that includes people with Parkinson's disease from 36 sites in 24 countries...

BACKGROUND: Triple-negative breast cancer (TNBC) subtyping by gene profiling has provided valuable clinical information. Here, we aimed to evaluate the relevance of TNBC subtyping using immunohistochemistry (IHC), which could be a more clinically practical approach, for prognostication and applications in patient management. METHODS: A total of 123 TNBC cases were classified using androgen receptor (AR), CD8, Forkhead box C1 protein (FOXC1), and doublecortin-like kinase 1 (DCLK1) into luminal androgen receptor (LAR), basal-like immunosuppressive (BLIS), mesenchymal-like (MES), and immunomodulatory (IM) subtypes...