Chromatinized Protein Kinase C-θ: Can It Escape the Clutches of NF-κB?

We recently provided the first description of a nuclear mechanism used by Protein Kinase C-theta (PKC-θ) to mediate T cell gene expression. In this mode, PKC-θ tethers to chromatin to form an active nuclear complex by interacting with proteins including RNA polymerase II, the histone kinase MSK-1, the demethylase LSD1, and the adaptor molecule 14-3-3ζ at regulatory regions of inducible immune response genes. Moreover, our genome-wide analysis identified many novel PKC-θ target genes and microRNAs implicated in T cell development, differentiation, apoptosis, and proliferation. We have expanded our ChIP-on-chip analysis and have now identified a transcription factor motif containing NF-κB binding sites that may facilitate recruitment of PKC-θ to chromatin at coding genes. Furthermore, NF-κB association with chromatin appears to be a prerequisite for the assembly of the PKC-θ active complex. In contrast, a distinct NF-κB-containing module appears to operate at PKC-θ targeted microRNA genes, and here NF-κB negatively regulates microRNA gene transcription. Our efforts are also focusing on distinguishing between the nuclear and cytoplasmic functions of PKCs to ascertain how these kinases may synergize their roles as both cytoplasmic signaling proteins and their functions on the chromatin template, together enabling rapid induction of eukaryotic genes. We have identified an alternative sequence within PKC-θ that appears to be important for nuclear translocation of this kinase. Understanding the molecular mechanisms used by signal transduction kinases to elicit specific and distinct transcriptional programs in T cells will enable scientists to refine current therapeutic strategies for autoimmune diseases and cancer

Inhibitory effects of Melicope ptelefolia extract on compound action potentials in frog sciatic nerves and its possible mechanism of action

Melicope ptelefolia is a medicinal plant from the Rutaceae, also known as ‘tenggek burung’ in Malaysia. Traditionally, natives ingest M. ptelefolia to treat a wide range of illnesses. This study aimed to investigate the effects of M. ptelefolia aqueous extract (MPAE) on compound action potentials (CAPs) in frog sciatic nerves and its mechanism involving the opioid receptors. The effects of MPAE on CAPs in frog sciatic nerves were examined using the AD Instrument Nerve Chamber. The frog sciatic nerves were dissected from the lumbar plexus to the knee of the frog and placed in Ringer’s solution. Three treatment groups with different dosages (1, 3 and 10 mg/mL) of MPAE, including negative (vehicle) and positive control group (3 mg/mL of morphine) were tested on the frog sciatic nerves by placing them in a nerve organ chamber. Following this, the involvement of opioid receptors in the effects of MPAE on CAPs was investigated by using naloxone hydrochloride as a non-selective opioid receptor antagonist. Our results showed that the peak amplitudes of CAPs were significantly (p<0.001) reduced when treated with MPAE (3 and 10 mg/mL) in frog sciatic nerves. The MPAE-induced CAPs inhibition was reversed when pre-treated with naloxone, suggesting the involvement of the opioidergic system. These results indicated the modulatory action of MPAE on nerve conduction, which may provide important leads in the development of new therapeutic drugs through the involvement of opioid receptors

Predicting late aortic complications after acute type A dissection surgery with volumetric measurements in a Singapore cohort

Introduction: This study was conducted to evaluate the efficacy of postoperative computed tomography (CT) measurements of aortic lumen volumes in predicting aortic-related complications following acute type A aortic dissection (ATAAD) repair. Methods: We conducted a single-institution retrospective aortic volumetric analysis of patients after ascending aorta replacement performed during 2001-2015. The volumetric measurements of total lumen (total-L), true lumen (TL), false lumen (FL), as well as the TL:FL ratio from the first and second postoperative computer angiograms were obtained. A generalised structural equation model was created to analyse the predictive utility of TL:FL ratio. Results: One hundred and twenty-five patients underwent surgical intervention, of whom 97 patients were eventually discharged and analysed for postoperative complications. A total of 19 patients were included in the final analysis. Patients with late postoperative aortic complications had a significantly higher FL volume and total-L volume on the first (FL volume P = 0.041, total-L volume P = 0.05) and second (FL volume P = 0.01, total-L volume P = 0.007) postoperative scans. The odds of having aortic complications were raised by 1% with a 1 cm3 increase in total-L volume and by 2% with a 1 cm3 increase in FL volume. The TL:FL ratio was significantly lower in patients who developed complications. Conclusion: Postoperative CT volumetric measurements in patients who developed complications are characterised by a significant increase in the FL volume and total-L volume from the first postoperative scans. Patients with disproportionately expanded FL presenting with TL:FL ratios less than 1 were associated with aortic complications. Hence, the TL:FL ratio may be a reliable and useful parameter to monitor postoperative disease progression and to evaluate the risk of late complications in ATAAD patients

The effect of DMEM and DMEM:F12 culture media on the growth of SH-SY5Y cells

The human neuroblastoma cell line, SH-SY5Y cells, is commonly used as an in vitro model for neuroscience and neurobiology research. SH-SY5Y cells were established during the 1970’s from the parental metastatic bone tumor, SK-N-SH cell line. The utilization of SH-SY5Y cells in neurobiology research is due to their resemblance to the human primary neuronal cells with several limitations, considering the cells are derived from malignant tumor cells. Since SH-SY5Y cells are widely cultured for research, several different culture media have been used to optimize the growth of the cells, including Eagle's Minimum Essential Medium (EMEM), Dulbecco’s modified Eagle’s medium (DMEM) and other recently developed culture media. The ability of SH-SY5Y cells to reach confluency in culture flasks ranges from 5 days to 15 days, depending on the culture media. Hence, the optimization of the culture media is crucial to achieve the fastest growth rate for the cells. The objective of the study is to evaluate the culture media for the proliferation of SH-SY5Y cells. We compared the growth rate of SH-SY5Y cells cultured in Dulbecco’s modified Eagle’s medium (DMEM) supplemented with 15% heat-inactivated fetal bovine serum (hiFBS), Dulbecco’s modified Eagle’s medium: Nutrientmixture F-12 (DMEM:F12) + supplemented with 15% hiFBS and DMEM:F12 supplemented with 10% hiFBS. In DMEM:F12 supplemented with 15% hiFBS, cells grew up to 6.67E+05 cells. In DMEM:F12 supplemented with 10%hiFBS, cells grew up to 5.28E+05 cells. In DMEM supplemented with 15% hiFBS, the cells grew up to 4.76E+05 cells. There was a significant difference between culture media DMEM:F12 supplemented with 15% hiFBS as compared to DMEM:F12 supplemented with 10%hiFBS and DMEM supplemented with 15% hiFBS (p0.05)

Zerumbone alleviates chronic constriction injury-induced allodynia and hyperalgesia through serotonin 5-HT receptors

Zerumbone, a bioactive sesquiterpene isolated from Zingiber zerumbet (Smith), has shown to exert antiallodynic and antihyperalgesic effects in neuropathic pain mice model in our recent study. The mechanism through which zerumbone alleviates neuropathic pain has yet to be elucidated. Thus, this study aimed to determine whether the serotonergic system, part of the descending pain modulation pathway, contributes to the antineuropathic effect of zerumbone. Participation of the serotonergic system in zerumbone-induced antiallodynia and antihyperalgesia was assessed using Dynamic Plantar Aesthesiometer von Frey test and Hargreaves plantar test respectively in chronic-constriction injury mice model. Administration of ρ-chlorophenylalanine (PCPA, 100 mg/kg, i.p.) for four consecutive days to deplete serotonin (5-HT) prior to zerumbone administration blocked the antiallodynic and antihyperalgesic effects of zerumbone. Further investigation with 5-HT receptor antagonists methiothepin (5-HT 1/6/7 receptor antagonist, 0.1 mg/kg), WAY-100635 (5-HT 1A receptor antagonist, 1 mg/kg), isamoltane (5-HT 1B receptor antagonist, 2.5 mg/kg), ketanserin (5-HT 2A receptor antagonist, 0.3 mg/kg) and ondansetron (5-HT 3 receptor antagonist, 0.5 mg/kg) managed to significantly attenuate antiallodynic and antihyperalgesic effects of zerumbone (10 mg/kg). These findings demonstrate that zerumbone alleviates mechanical allodynia and thermal hyperalgesia through the descending serotonergic system via 5-HT receptors 1A, 1B, 2A, 3, 6 and 7 in chronic constriction injury neuropathic pain mice

Why i trust my father? : in the eyes of malaysian adolescents

This study aims to investigate how much both son and daughter trust their father and what are the underlying reasons they trust their father. The results revealed five main reasons why Malaysian adolescents trust their father. Those reasons are related to the role of father, father-child relationship, father’s characteristics, father’s nurturing nature and father’s attitude and behavior. A total of 1022 students (males = 241, females = 781) from one of public university in Sabah, Malaysia participated in the study. The participants completed open-ended questionnaires developed by Kim (2008), asking how much the adolescents trust their father, and the reasons why they trust their father. The data was analysed by using the indigenous psychology method proposed by [1] Findings of this study revealed the pattern of trust towards father for both Malaysian male and female adolescents. The results contributed new information about Malaysian adolescents’ trust towards their father form the indigenous context. The implications of finding will be discussed

A fatal case of oral intoxication by mustard gas

Opisan je slučaj peroralne intosikacije iperitom u namjeri samoubojstva i iznesen obdukcioni nalaz. Ukratko su izneseni neki toksikološki pogledi na otrovanje iperifom, te klinički simptomi i patomorfološke promjene kod intoksikacije ovim otrovom.A case is presented of a man aged 27 who swallowed 50 g of mustard gas (dichlor-diethylsulphide) in order to commit suicide. Although immediately treated at the Internal Clinic of the Medical Faculty, he died 8 hours and 20 minutes after taking the poison. A postmortem examination carried out 19 hours after death, as well as histological findings showed congestion and oedema of the brain, fragmentation of cardiac muscle, oedema of mucous membranes of the upper part of gastrointestinal tract, oedema of larynx and epiglotis, oedema of the liver, and congestion of the spleen, adrenal glands, and kidneys. A microscopic examination of the lung tissue revealed hemorrhages probably due to the irritative effect of the poison

Boesenbergia rotunda ethanolic extract inhibits compound action potentials via opioid receptors

Boesenbergia rotunda, traditionally used to relieve stomach, abdomen, joint, muscle, and rheumatic pain was also reported for its antinociceptive effect on a mouse model. However, the possible pain relief effect of Boesenbergia rotunda ethanolic extract (BREE) via the inhibition to the neural pain pathway remains to be elucidated. This study investigated the inhibitory effect of BREE on compound action potentials (CAPs) and the possible involvement of the opioid receptors. The changes in the CAPs amplitudes of the frog’s sciatic nerves were evaluated following the exposure to three different dosages of BREE (1, 3 and 10 mg/ml and morphine (3 mg/ml). In another set of experiment, the nerves were pretreated with a non-selective opioid receptor antagonist, naloxone (0.1 mg/ml), before exposing the nerve to BREE (1 mg/ml) to investigate the involvement of opioid receptors in the CAPs inhibitory mechanism. The outcome showed a reduction in the CAPs amplitudes when treated with BREE (1, 3 and 10 mg/ml) whereby the effect was reversible. The CAPs inhibition by BREE was absent when the opioid receptors were blocked. Taken together, these findings suggest that BREE-induced CAPs amplitude reduction involves the activation of opioid receptors

36th Malaysian Society of Pharmacology and Physiology Annual Scientific Meeting 2023

The 36th Malaysian Society of Pharmacology and Physiology (MSPP) Annual Scientific Meeting was hosted in collaboration with the Faculty of Medicine and Health Sciences, Universiti Putra Malaysia from the 7th to 8th of August 2023 at Bangi Resort Hotel in Bangi, Malaysia. The event focused on the theme "Pharmacology & Physiology Post-Millenial Era: Challenges & Opportunities". This platform is one of the suitable avenues to facilitate the exchange of scientific endeavors and enhance networking among scientists, academicians, clinicians, and postgraduate students involved in the fields of pharmacology and physiology, as well as multidisciplinary areas such as drug discovery, omics approaches, stem cells, and regenerative medicine. The primary objective of the special issue is to revitalize recent advances and breakthroughs in pharmacology and physiology to enhance opportunities and vanquish challenges in the post-millenial era, especially in the wake of the COVID-19 pandemic. In light of this, the special issue compiles the conference proceeding, to provide opportunities for knowledge integration of research and innovations