80 research outputs found
Book Review: "Mystic Echoes: Stories Rooted in Sikh Spiritual Realms" (Book Author: Dr. Devinder Pal Singh; Book Reviewer: Prof. Hardev Singh Virk)
No full textDr. Devinder Pal (DP) Singh joined the Physics Department in 1983 as an Ad-hoc Lecturer to teach Physics and complete his doctorate degree in Physics (Acoustics). I found him as a dedicated teacher and researcher. Upon moving to Canada as an immigrant, he initiated a new venture, the “Center for Understanding Sikhism”. A similar organization, the “Institute for Understanding Sikhism,” was established in 1999 by Dr. D. S. Chahal in Montreal. I was perplexed as to why a hardcore physicist was meddling in Sikhism. My curiosity was satisfied after reviewing his book, “Science and Sikhism: Conflict or Coherence.” I started rating him as one of the greatest exponents of Sikhism (Sikhi) in the modern age.
The Foreword “A Sacred Mirror: Seeing Ourselves Through Sikh Narratives” is by Bhai Harbans Lal, Ph.D., D. Litt (Hons). Bhai Lal appreciates the technique used by D. P. Singh: “It brings the living essence of Gurbani into our day-to-day existence. These are not abstract theological exercises, nor are they simply nostalgic tales of rural life. Instead, they are powerful spiritual parables, immersive narratives that reveal how the universal truths embedded in Sikh teachings manifest in the hearts, struggles, and transformations of everyday people”.
The author introduces his UNIQUE work in the Preface “Bridging the Temporal and the Timeless” as follows: “The stories in Mystic Echoes: Stories Rooted in Sikh Spiritual Realms emerge from the convergence of profound spiritual reflection, lived experience, and the enduring resonance of Sikh philosophy. They are not merely works of fiction, but narrative expressions of spiritual truths rooted in the teachings of the Sikh Gurus”. Further, D. P. Singh explains the relevance and importance of chosen topics: “Each story in Mystic Echoes is an attempt to explore a specific spiritual theme from within the Sikh tradition: Naam (Divine Name), Hukam (Divine Order), Haumai (Ego), Maya (Worldly Illusion), Raza (Divine Will), Sunn (Primal Void), Sahaj (Equilibrium), Bhaau and Bhae (Devotional Love and Reverent Fear), Nadar (Grace), Wismad (Wondrous Bliss), Anhad Naad (Unstruck Melody), Chautha Pad (Fourth State), Dasam Duar (Tenth Gate), Panj Tat (Five classical elements), and Daya (Compassion) among others
Book Review: "Mystic Echoes: Stories Rooted in Sikh Spiritual Realms" (Book Author: Dr. Devinder Pal Singh; Book Reviewer: Prof. Hardev Singh Virk)
No full textDr. Devinder Pal (DP) Singh joined the Physics Department in 1983 as an Ad-hoc Lecturer to teach Physics and complete his doctorate degree in Physics (Acoustics). I found him as a dedicated teacher and researcher. Upon moving to Canada as an immigrant, he initiated a new venture, the “Center for Understanding Sikhism”. A similar organization, the “Institute for Understanding Sikhism,” was established in 1999 by Dr. D. S. Chahal in Montreal. I was perplexed as to why a hardcore physicist was meddling in Sikhism. My curiosity was satisfied after reviewing his book, “Science and Sikhism: Conflict or Coherence.” I started rating him as one of the greatest exponents of Sikhism (Sikhi) in the modern age.
The Foreword “A Sacred Mirror: Seeing Ourselves Through Sikh Narratives” is by Bhai Harbans Lal, Ph.D., D. Litt (Hons). Bhai Lal appreciates the technique used by D. P. Singh: “It brings the living essence of Gurbani into our day-to-day existence. These are not abstract theological exercises, nor are they simply nostalgic tales of rural life. Instead, they are powerful spiritual parables, immersive narratives that reveal how the universal truths embedded in Sikh teachings manifest in the hearts, struggles, and transformations of everyday people”.
The author introduces his UNIQUE work in the Preface “Bridging the Temporal and the Timeless” as follows: “The stories in Mystic Echoes: Stories Rooted in Sikh Spiritual Realms emerge from the convergence of profound spiritual reflection, lived experience, and the enduring resonance of Sikh philosophy. They are not merely works of fiction, but narrative expressions of spiritual truths rooted in the teachings of the Sikh Gurus”. Further, D. P. Singh explains the relevance and importance of chosen topics: “Each story in Mystic Echoes is an attempt to explore a specific spiritual theme from within the Sikh tradition: Naam (Divine Name), Hukam (Divine Order), Haumai (Ego), Maya (Worldly Illusion), Raza (Divine Will), Sunn (Primal Void), Sahaj (Equilibrium), Bhaau and Bhae (Devotional Love and Reverent Fear), Nadar (Grace), Wismad (Wondrous Bliss), Anhad Naad (Unstruck Melody), Chautha Pad (Fourth State), Dasam Duar (Tenth Gate), Panj Tat (Five classical elements), and Daya (Compassion) among others
COX-2 selective inhibitors as an adjunct to radiotherapy
No full textBackground
Radiotherapy is a common treatment modality for many solid state cancers including prostate cancer (PCa). Unfortunately, up to 50% of patients that undergo radiotherapy for localised PCa will develop biochemical failure. Acute and delayed toxicities and tumour resistance are two key factors limiting the effectiveness of many cancer treatments, including radiotherapy. Toxicity rates in PCa patients that accompany radiotherapy are high with 80% of men experiencing some degree of urinary frequency, 40% bowel frequency and chronic impotence is usual.
Furthermore, tumour radioresistance is driven by a number factors with tumour hypoxia playing a key role. In addition to hypoxia driving tumourigenesis the lack of oxygen reduces the ability of ionizing radiation to produce reactive oxygen species (ROS) necessary to produce DNA damage that results in tumour death. Hypoxia also increases the expression of a number of genes including cyclooxygenase (COX) -2. COX-2 is an inducible enzyme that is upregulated in inflammation and carcinomas, making it a suitable target for new cancer treatment options.
COX-2 expression has been shown to be upregulated in a number of cancers including PCa and found to be involved in proliferation, invasion, apoptosis, host immune response and angiogenesis. Past research has also demonstrated that the major product of COX-2, prostaglandins (PG), provide radioprotection to cancer cells. As well as the ability of COX-2 to directly impact radiosensitivity, it has the ability to influence other cellular products that impact survival and apoptosis. One product that has been linked to COX-2 is the tumour suppressor p53. The p53 protein protects against genomic instability and the development of cancer by inducing cell cycle arrest and apoptosis. COX-2 expression has been shown to be induced by p53 and in turn results in inhibition of p53 mediated apoptosis. To our knowledge no studies have investigated the use of COX-2 inhibitors, at clinically relevant doses, as an adjunct to radiotherapy. In addition, while the direct mechanisms of COX-2 mediated radiosensitivity have been well investigated, research into the indirect mechanisms and also the effect of COX-2 inhibitors as radiosensitising agents in hypoxia is lacking.
This study aims to demonstrate the ability of COX-2 inhibitors to improve treatment outcomes post-radiotherapy for PCa in human patients and also to investigate the mechanisms behind COX-2 inhibitor mediated radiosensitivity in normoxia and hypoxia.
Method
The ability of COX-2 to produce radiosensitisation in cancer cells was investigated in two ways in this research. Firstly, a retrospective human study investigated if the use of the COX-2 inhibitors meloxicam and celecoxib during radiotherapy improves treatment outcomes in PCa patients. Secondly, an in vitro model was developed that investigated the mechanisms behind COX-2 mediated radiosensitivity in human cancer cell lines.
The retrospective human study examined the patient database at Genesis Cancer Care to identify patients that received radiotherapy for primary treatment of localised PCa. Screening of the database then identified patients that had used meloxicam or celecoxib during radiotherapy treatment. Three treatment outcomes were measured; the percentage of patients that demonstrated biochemical relapse at 2 and 5 years post-treatment, the time to biochemical relapse and the prostate specific antigen (PSA) velocity of each group post-treatment.
The in vitro model used HeLa (cervical), PC3 (Prostate), MCF7 (breast) and MeWo (melanoma) cells to investigate, mechanistically, how structurally unrelated COX-2 inhibitors impact radiosensitivity in normoxia and hypoxia. This model utilised resazurin reduction to measure proliferation, siCOX-2 RNA to produce COX-2 knockdown cells and enzyme-linked immunosorbent assays (ELISAs) to measure p53 phosphorylation and prostaglandin E2 (PGE2) production.
Results
PSA velocity was found to be 0.197ng/mL/year (0.939) for the meloxicam group and 0.828 ng/mL/year (3.15) for the celecoxib group. The two treatment groups were found to have significantly lower (p<0.05) PSA velocities than the control group, 1.12 ng/mL/year (3.05). In addition, at the two year time point meloxicam was found to have no patients to have relapsed and the celecoxib and control groups had percentage relapse rates of 6.7% (n=4) and 8.6% (n=5). The percentage relapse at five years post-treatment was 18.9% (n=10), 18.3% (n=11) and 21.0% (n=31%) for the meloxicam, celecoxib and control groups respectively. Mean time to biochemical relapse was found to be 54.15 months (16.08) in the meloxicam group and 46.20 months (31.70) in the celecoxib group, in contrast the control group demonstrated a mean time to biochemical relapse of 35.53 months (20.21).
The in vitro model aimed to provide an insight to the mechanisms behind the results seen in the retrospective analysis. NS398 (10μM), a highly specific COX-2 inhibitor, selectively sensitised hypoxic HeLa (p<0.01) and MCF7 (p<0.05) cells to ioninsing radiation, however did not affect sensitisation in PC3 or MeWo cells. Celecoxib (20μM) and meloxicam (20μM) failed to produce radiosensitisation in any cell line in normoxia or hypoxia. Based on these findings further investigations were carried out in HeLa cells using NS398.
Investigations using COX-2 siRNA demonstrated that knockdown of the COX-2 enzyme did not produce radiosensitisation but resulted in the loss of radiosensitising ability of NS398. Furthermore, PGE2 release was significantly increased in response to hypoxia (p<0.05) and irradiation (p<0.001) and treatment with NS398 significantly (p<0.001) attenuated PGE2. Treatment with misoprostol, a prostaglandin analogue, significantly (p<0.01) increased cell survival in normoxic HeLa cells in response to ionising radiation, but had no effect on hypoxic HeLa cells.
The interaction between COX-2 and p53 was then explored. It was discovered that COX-2 knockdown HeLa cells had significantly (p<0.001) higher levels of p53 protein than wild-type HeLa cells. Furthermore, hypoxia was able to significantly (p<0.001) attenuate p53 phosphorylation at both 30 minutes and 4 hours post-irradiation and treatment of hypoxic HeLa cells with NS398 (10μM) resulted in a significant (p<0.01) increase in phosphorylated p53. The p53 inhibitor pifithrin-α did not effect the radiosensitivity of wild-type HeLa cells in either hypoxia or normoxia, however it significantly (p<0.01) increased cell survival in response to ionizing radiation in HeLa cells transfected with COX-2 siRNA.
Discussion
The findings from the retrospective analysis demonstrated that the use of the COX-2 inhibitors celecoxib and meloxicam may improve treatment outcomes in patients that receive radiation therapy for PCa. Importantly we were able to demonstrate that patients using these agents displayed a significantly lower PSA velocity than those who were not. Importantly, the PSA velocity was found to fall below the threshold of 0.35ng/mL, with PSA velocities that sit above this threshold having been found to have an approximate 5.3 to 10 fold increased risk of PCa. This retrospective analysis also found reduced biochemical relapse rates and reduced time to biochemical relapse in the celecoxib and meloxicam groups in comparison to the control.
The in vitro model was able to demonstrate the ability of COX-2 inhibitors to increase radiosensitivity, however this effect was not demonstrated by all COX-2 inhibitors or all cell lines. This finding suggested that this effect may be drug and cell line specific. Furthermore, COX-2 was found to be necessary for NS398 induced radiosensitivity but knockdown of COX-2 alone did not affect radiosensitivity. Based on these findings it was suggested that COX-2 inhibitor mediated radiosensitivity occurs through both direct and indirect COX-2 mechanisms. We also demonstrated the relationship between COX-2 and p53, with COX-2 knockdown cells demonstrating increased p53 expression. Furthermore, the inhibition of COX-2 by NS398 resulted in increased p53 phosphorylation.
Results from both the retrospective and in vitro studies provide evidence that further study into the role of COX-2 inhibitors as an adjunct treatment option in radiotherapy is warranted. Further studies, including large prospective human studies, are needed to confirm these findings. These large studies should collect tumour biopsies to allow for histological investigations. The research provides further evidence to the potential for COX-2 inhibitors to be used as an adjunct to radiotherapy in cancer.Thesis (Masters)Master of Medical Research (MMedRes)School of Medical ScienceGriffith HealthFull Tex
Protective Effects of Caffeine and Coffee Constituents in Inflammatory Models of Depression
No full textCaffeine is the most widely used compound that exerts a pharmacological effect on the central nervous system and is found most predominantly in coffee. It has been well established that coffee has a beneficial effect on numerous disease states including depression.
A number of prospective and cohort studies have shown the benefit of coffee in preventing episodes of depressive symptoms. Studies indicate that the amount of coffee consumed is important with studies showing that moderate intake of caffeinated coffee may be beneficial in decreasing the risk of developing symptoms of clinical depression. It has however been shown that high consumption of coffee increases the risk of depression and suicide. It appears that caffeine in combination with other constituents of coffee may be required to show the antidepressant activity. To date very few studies have been undertaken to evaluate components of coffee for their antidepressant effects and no studies have been undertaken assessing these compounds in combination with caffeine and their subsequent effects on symptoms of depression.
Over the last 50 years there have been countless proposed hypotheses of depression many of which are flawed including the well-accepted monoamine theory of depression. As a result of the shortcomings identified in this theory, numerous newer theories of depression have been proposed in recent times.Thesis (PhD Doctorate)Doctor of Philosophy (PhD)School of PharmacyGriffith HealthFull Tex
Investigation of the Effects of SIRT1 and SIRT2 Modulators in Neuroinflammatory Models of Depression
No full textDepression is regarded as a manifestation of mood disorder and a complex phenomenon. The etiology can be primary and/or secondary to organic diseases. Neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease and multiple sclerosis are often accompanied by the development of depression. A high prevalence of depression in populations with neurodegenerative diseases also indicates a close relationship between depression and neurodegeneration. There are several hypotheses of the pathogenesis of depression, including monoamine hypothesis, neurotrophic and the brain-derived neurotrophic factor (BDNF) hypothesis, HPA axis theory and circadian rhythm theory. There are apparently no infectious insults in the initiation of depression. However, depressed patients without apparent physical diseases showed an increased level of inflammatory markers. Evidence has indicated that neuroinflammation participates in the genesis and development of depression and interacts with other factors involved in depression. Excessive inflammatory cytokines can reduce the production of serotonin, fuel glutamate excitotoxicity, disturb neural plasticity, reduce the production of brain-derived neurotrophic factor and eventually prime the brain for neurodegeneration by facilitating inflammation and synaptic damage.
The target of current commercially available antidepressants is to increase levels of neurotransmitters including serotonin, noradrenaline and/or dopamine via different therapeutic mechanisms. However, the overall remission rate for the present medication options is under 30% according to the result of the National Institute of Mental Health (NIMH)-funded sequenced treatment alternatives to relieve depression (STAR*D) study. Additionally, they are frequently accompanied by undesirable side-effects and toxic effects in overdoses that limit their application. Therefore, there is an ongoing need to investigate the potential for novel medications that target neuroinflammation to address this underlying feature of depression.
Sirtuins are a unique class of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases that can affect multiple downstream targets by deacetylation activity. The sirtuin family consists of SIRT1-7 enzymes that differ in subcellular localization, enzymatic activities, physiological functions and pathological roles. Among these seven members, SIRT1 has been reported to exert neuroprotective effects in aging, oxidative stress, neuronal survival, neurogenesis and neuroinflammation. SIRT2 also participates in numerous aging-related cellular activities including DNA repair, oxidative stress and autophagy. Based on these important roles, the pharmacological effects of SIRT1 and SIRT2 modulators have been investigated in numerous neurodegeneration studies where different models were conducted, and contradictory results were generated. Therefore, this thesis proposed a systematic investigation of the effects of SIRT1 and SIRT2 modulators in neuroinflammation and neurodegeneration models of depression including in vitro and in vivo studies. The pharmacological agents assessed in this study include: SIRT1 activator resveratrol; selective SIRT1 inhibitor EX527; dual SIRT1/SIRT2 inhibitor sirtinol; SIRT2 inhibitor AGK2; and positive controls for depression and inflammation, fluoxetine and ibuprofen, respectively.
Microglia are the resident macrophages that are regarded as the prime components of the intrinsic immune system in CNS parenchyma. Therefore, microglia play a dominant role in neuroinflammation. Injury or other pathological insults can result in the activation of microglia which are able to release inflammatory mediators and chemokines such as TNF-α, IL-1β, PGE2 and reactive oxidative species. Thus the overall experimental design was to collect the supernatant from lipopolysaccharide (LPS)-stimulated microglia (HAPI cell line) and transfer it onto neuronal cells (SH-SY5Y cell line). Microglia were pre-treated with SIRT drugs to affect their biological performance under LPS stimulation and investigate the alteration of the subsequent outcome on neuronal cells.
To achieve this goal, methodology development was conducted to optimize the cell culture condition and differentiation method for SH-SY5Y cell line, which is key to achieve accurate results for this study. The glucose level in culture media needed to be correctly selected for the cell culture of SH-SY5Y cells in this supernatant transfer-based co-culture model. High glucose in culture media is considered a pre-diabetic condition for neurons. Data has shown that the cell viability of high-glucose cultured SH-SY5Y cells was reduced by treatment of HAPI cells-conditioned supernatant, which indicated the existence of low-glucose shock. Whereas, application of low-glucose media can effectively prevent SH-SY5Y cells from low-glucose shock after the treatment of the supernatant collected from HAPI cells. Moreover, the differentiation method for SH-SY5Y was also optimized. The combination induction treatment of retinoic acid and BDNF can successfully differentiate the SH-SY5Y cells morphologically and genetically. The RNA expression of neuronal gene marker synaptophysin (SYP) and enolase 2 (ENO2) have shown to significantly increase after combination treatment of retinoic acid and BDNF.
In the in vitro pharmacological study, the effects of these SIRT1 and SIRT2 drugs on the production of inflammatory mediators including PGE2, TNF-α, IL-1β and IL-10 on LPS (0.005 μg/L) -stimulated microglia were assessed. Resveratrol and sirtinol significantly reduced the TNF-α production in HAPI cells by up to 95% and 93% respectively. This result showed their potent inhibiting effects on TNF-α which can initiate cell death pathways by binding TNF receptors. Resveratrol, sirtinol, EX527 and AGK2 also significantly reduced PGE2 production by up to 97%, 100%, 65% and 69% respectively in microglia under LPS stimulation. These results are significant given that prostaglandins contribute to prolonged acute inflammatory responses.
The supernatant from LPS-stimulated HAPI cells was transferred to SH-SY5Y cells. All SIRT drugs pre-treated of HAPI cells were shown to significantly increase the survival of undifferentiated SH-SY5Y cells, following the transfer of the supernatant. Their inhibiting effects on the production of inflammatory mediators including TNF-α and PGE2 might contribute to this protection on SH-SY5Y cells. The SIRT1 activator resveratrol and dual SIRT1/SIRT2 inhibitor sirtinol demonstrated the most potent effect compared to others. Additionally, in undifferentiated cells, resveratrol was protective against apoptosis, as indicated by a reduction in Caspase 3/7 activity. However, in contrast, in differentiated SH-SY5Y cells, only sirtinol and AGK2 pre-treated supernatant were found to exert neuroprotective effects. Moreover, no increase in Caspase 3 activity was observed following treatment with supernatant indicating that protection against apoptosis is not the reason for increased cell survival.
In the animal study, the two most effective agents, SIRT1 activator resveratrol and dual SIRT1/2 inhibitor sirtinol, from the in vitro study were assessed in the acute phase of the LPS-induced depression mouse model and compared with fluoxetine. The behavioral parameters including locomotor activity and immobility time in the open field test, forced swim test and tail suspension test were significantly improved by resveratrol, sirtinol and fluoxetine in the acute sickness phase of the depression model.
In conclusion, this research has emphasized the necessity of increasing the understanding of the roles that neuroinflammation and neurodegeneration playing in the pathophysiology of depression and the importance of investigating SIRT drugs as a novel class of drugs targeting neuroinflammation. This research has shown the effectiveness of SIRT modulators in inhibiting neuroinflammation and subsequent neurodegeneration through in vitro and in vivo studies. Further studies, including combining SIRT modulators and current antidepressant medications are warranted.Thesis (PhD Doctorate)Doctor of Philosophy (PhD)School of Pharmacy and PharmacGriffith HealthFull Tex
Provision of pharmaceutical care in patients with limited English proficiency: preliminary findings
No full textObjective: Overcoming language and cultural barriers is becoming ever challenging for pharmacists as the patient population grows more ethnically diverse. To evaluate the current practices used by the pharmacists for communicating with patients with limited English proficiency (LEP) and to assess pharmacists’ knowledge of, attitude toward, and satisfaction with accessing available services for supporting LEPs patients within their current practice settings. Methods: Semi-structured interviews were conducted with five pharmacists employed in pharmacies representing multiple practice settings Queensland, Australia. Thematic analysis was primarily informed by the general inductive approach. NVivo software (QSR International Pty Ltd.) was used to manage the data. Findings: Three interlinked themes emerged from the analysis of interview data: (1) Barriers to the provision of pharmaceutical care, (2) Strategies employed in dealing with LEP patients, and (3) Lack of knowledge about existing services. Pharmacists recognized their lack of skills in communicating with LEP patients to have potential negative consequences for the patient and discussed these in terms of uncertainty around eliciting patient information and the patient’s understanding of their instructions and or advice. Current strategies were inconsistent and challenging for LEP patient care. While the use of informal interpreters was common, a significant degree of uncertainty surrounded their actual competency in conveying the core message. Conclusion: The present study highlights a significant gap in the provision of pharmaceutical care in patients with LEP. Strategies are needed to facilitate quality use of medicines among this patient group
Review of the anti-inflammatory effect of SIRT1 and SIRT2 modulators on neurodegenerative diseases
No full textNeurodegenerative disease refers to a range of chronic and progressive disorders that are characterized by dysfunction and loss of neurons. Neurodegeneration involves protein misfolding, oxidative injury, impaired mitochondrial function, neurotrophin deficiency and may also involve neuroinflammation. The sirtuin family of proteins plays a key role in this process suggesting that modulation of sirtuin can modify disease progression. This review examines experimental and clinical evidence relating to the potential role of SIRT1 and SIRT2, and their modulators in neurodegenerative diseases. Both neuroprotective effects and negative effects of SIRT1 activators, SIRT1 inhibitors and SIRT2 activators are discussed in a range of different disease models, including in vitro and in vivo Alzheimer's disease (AD), Parkinson's disease (PD), Huntingdon's disease (HD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS). This highlights the potential of SIRT1 and SIRT 2 modulators as potential therapeutic agents. However, there is a paucity of clinical trials related to the effects of selective SIRT1 modulators, selective SIRT2 modulators or dual SIRT1/2 modulators on neuroinflammation and subsequent neurodegeneration.Full Tex
Hydroxycinnamates alleviate chronic unpredictable mild stress‑induced depressive‑like behavior and neuroinflammation in mice
No full textThe polyphenolic compounds ferulic acid (FA) and p‑coumaric acid (PCA) have been extensively studied for their free radical scavenging and anti‑inflammatory properties. Both compounds are present in food and beverages commonly consumed globally. Our molecular modeling, in‑vitro, and in‑vivo studies suggest that the compounds may be neuroprotective by modulating the nucleotide‑binding domain, leucine‑rich‑containing family, pyrin domain‑containing‑3 (NLRP3) inflammasome pathway. The current study explored the dose‑dependent neuroprotective potential of FA and PCA in a chronic unpredictable mild stress (CUMS) mouse model. Male Swiss albino mice were divided into nine groups consisting of control (CON), CUMS, FA10 (10 mg/kg FA), FA40 (40 mg/kg FA), FA160 (160 mg/kg FA), PCA10 (10 mg/kg PCA), PCA40 (40 mg/kg PCA), PCA160 (160 mg/kg PCA), and FLX (10 mg/kg fluoxetine). All animals, except the CON group, received random mild stressors for 21 days, and from day 22‑42, the treatments were administered alongside the stressors. Behavioral assessments were performed on day 42, followed by sample collection. Brain homogenates from CUMS‑exposed animals expressed elevated levels of the pro‑inflammatory cytokines interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑alpha (TNF‑α), and oxidative stress markers. Treatment with FA and PCA effectively reduced cytokine release and oxidative stress, alleviating the depressive‑like behavior.Full Tex
Inhibition of NLRP3-inflammasome mediated IL-1β release by phenylpropanoic acid derivatives: in-silico and in-vitro approach
No full textNLRP3 inflammasome activation and subsequent release of IL-1β are being explored as a causal pathology for inflammatory and autoimmune disorders. Modulation of this pathway by the compounds from natural sources may provide a better targeted approach with improved therapeutic outcome. The study was carried out to test the ability of phenylpropanoic acid derivatives to inhibit the NLRP3 inflammasome pathway and IL-1β release. The main purpose of the study was to test the active derivatives with respect to the possible molecular interactions in-silico, effect on mRNA expression of molecular markers and, effect on released cytokine. Autodock along with SwissADME was used to carry out the in-silico studies including the prediction studies as well as molecular docking studies. The effect of test compounds on mRNA expression of important proteins was evaluated against U87MG cells using RT-qPCR. The changes in released cytokine levels was evaluated using ELISA. The tested phenylpropanoic acid derivatives had a comparable molecular docking profile to that of selected standards. The prediction studies indicated that these compounds have suitable properties to be a drug candidate. mRNA expression studies showed that the derivatives can downregulate the proteins responsible for inflammasome activation and same was reflected in ELISA when the concentration of released cytokine was evaluated. Based on the above results, phenylpropanoic acid derivatives have potential to be developed as specific NLRP3-inflammasome inhibitors.No Full Tex
Elisabeth Meru – A Prolific Author and a Devoted Sikh Proponent
No full textElisabeth Meru, born in Hamburg, is a poetess by heart, a storyteller by nature, a forwarding merchant / financial accountant by training, and a Sikh by choice. She is currently settled in Munich, Germany. During the past three decades, she has authored numerous short stories, articles, and poetic compositions for various newspapers, journals, and radio broadcasts. With over a dozen books, both in English and German languages, to her credit to date, she is a prolific author who specializes in writing on Sikh history, tradition, and culture. Her 24-year-long spiritual quest brought her to the Gurdwara in Munich, wherein she heard Gurbani Kirtan for the first time. Therein she felt as if she had reached home. After continuous devotion and dedication to Sikhi for about seven years, she converted to Sikhism. Due to her love for Sikhi, Punjabi and Punjabiat, she learned Gurmukhi. Her first book in German, “Aus dem Herzen des Sikhismus - Guru Nanak Dev Ji - In deinem stillen Rosengarten” was published in 2009. The English version of the book "From the Heart of Sikhism - Guru Nanak Dev Ji - In your quiet rose garden" was published in 2010. These books describe the legends about the ten Gurus, their wisdom and teachings, and her poems, fables and a fairytale in German style. Elisabeth’s second set of books “Sikhism - Wellspring of Love” (in English) and “Sikhismus - Quell der Liebe” (in German), were published in 2010. This book contains her poems and stories about Sikhism. The stories are rooted in the spirit of fairy tales. Her next book, in German, “Sikhs und Sikhismus: Religion, Riten und der Goldene Tempel ” was published in 2011. In Feb. 2012,she with her team published the German edition of “Guru Granth Sahib Ji Essenz und Sikh Terminologie von A - Z.” It is a must-book for German-speaking Sikhs and all those who want a quick overview of basic terms in Sikhism. Another of her book, in German, “Sikhs ... der Bart ist ab,” was published in 2017
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