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Fulltext AT1 receptor blockade alters nutritional and biometric development in obesity-resistant and obesity-prone rats submitted to a high fat diet

Smith PM, Hindmarch CC, Murphy D, Ferguson AV

Front Psychol, 2014;5:832.
PMID: 25120524 DOI: 10.3389/fpsyg.2014.00832

Obesity is a chronic metabolic condition with important public health implications associated with numerous co-morbidities including cardiovascular disease, insulin resistance, and hypertension. The renin angiotensin system (RAS), best known for its involvement in cardiovascular control and body fluid homeostasis has, more recently, been implicated in regulation of energy balance. Interference with the RAS (genetically or pharmacologically) has been shown to influence body weight gain. In this study we investigated the effects of systemic AT1 receptor blockade using losartan on ingestive behaviors and weight gain in diet induced obese (DIO) rats. Prior to losartan administration (30 mg/kg/day) body weight gain remained constant within the DIO animals (3.6 ± 0.3 g/day, n = 8), diet resistant (DR) animals (2.1 ± 0.6 g/day, n = 8) and in the age-matched chow fed control (CHOW) animals (2.8 ± 0.3 g/day, n = 8), Losartan administration abolished body weight gain in animals fed a high fat diet (DIO: -0.4 ± 0.7 g/day, n = 8; and DR: -0.8 ± 0.3 g/day, n = 8) while chow fed animals continued to gain weight (2.2 ± 0.3 g/day, n = 8) as they had previously to oral administration of losartan. This decrease in daily body weight gain was accompanied by a decrease in food intake in the HFD fed animals. Following the removal of losartan, both the DIO and DR animals again showed daily increases in body weight gain and food intake which were similar to control values. Our data demonstrate that oral losartan administration attenuates body weight gain in animals fed a HFD whether the animal is obese (DIO) or not DR while having no effect on body weight gain in age-matched chow fed animals suggesting a protective effect of losartan against body weight gain while on a HFD.

Matched MeSH terms: Homeostasis
Fulltext Increased Expression of Phosphorylated FADD in Anaplastic Large Cell and Other T-Cell Lymphomas

Patel S, Murphy D, Haralambieva E, Abdulla ZA, Wong KK, Chen H, et al.

Biomark Insights, 2014;9:77-84.
PMID: 25232277 DOI: 10.4137/BMI.S16553

FAS-associated protein with death domain (FADD) is a major adaptor protein involved in extrinsic apoptosis, embryogenesis, and lymphocyte homeostasis. Although abnormalities of the FADD/death receptor apoptotic pathways have been established in tumorigenesis, fewer studies have analyzed the expression and role of phosphorylated FADD (pFADD). Our identification of FADD as a lymphoma-associated autoantigen in T-cell lymphoma patients raises the possibility that pFADD, with its correlation with cell cycle, may possess role(s) in human T-cell lymphoma development. This immunohistochemical study investigated pFADD protein expression in a range of normal tissues and lymphomas, particularly T-cell lymphomas that require improved therapies. Whereas pFADD was expressed only in scattered normal T cells, it was detected at high levels in T-cell lymphomas (eg, 84% anaplastic large cell lymphoma and 65% peripheral T cell lymphomas, not otherwise specified). The increased expression of pFADD supports further study of its clinical relevance and role in lymphomagenesis, highlighting phosphorylation of FADD as a potential therapeutic target.

Matched MeSH terms: Homeostasis
The mechanisms of fibroblast-mediated compaction of collagen gels and the mechanical niche around individual fibroblasts

Feng Z, Wagatsuma Y, Kikuchi M, Kosawada T, Nakamura T, Sato D, et al.

Biomaterials, 2014 Sep;35(28):8078-91.
PMID: 24976242 DOI: 10.1016/j.biomaterials.2014.05.072

Fibroblast-mediated compaction of collagen gels attracts extensive attention in studies of wound healing, cellular fate processes, and regenerative medicine. However, the underlying mechanism and the cellular mechanical niche still remain obscure. This study examines the mechanical behaviour of collagen fibrils during the process of compaction from an alternative perspective on the primary mechanical interaction, providing a new viewpoint on the behaviour of populated fibroblasts. We classify the collagen fibrils into three types - bent, stretched, and adherent - and deduce the respective equations governing the mechanical behaviour of each type; in particular, from a putative principle based on the stationary state of the instantaneous Hamiltonian of the mechanotransduction system, we originally quantify the stretching force exerted on each stretched fibrils. Via careful verification of a structural elementary model based on this classification, we demonstrate a clear physical picture of the compaction process, quantitatively elucidate the panorama of the micro mechanical niche and reveal an intrinsic biphasic relationship between cellular traction force and matrix elasticity. Our results also infer the underlying mechanism of tensional homoeostasis and stress shielding of fibroblasts. With this study, and sequel investigations on the putative principle proposed herein, we anticipate a refocus of the research on cellular mechanobiology, in vitro and in vivo.

Matched MeSH terms: Homeostasis
Role of probiotics in modulating glucose homeostasis: evidence from animal and human studies

Firouzi S, Barakatun-Nisak MY, Ismail A, Majid HA, Nor Azmi K

Int J Food Sci Nutr, 2013 Sep;64(6):780-6.
PMID: 23484591 DOI: 10.3109/09637486.2013.775227

Evidences from several studies suggest that probiotics affect glucose homeostasis. This paper reviews the results of animal and human studies on the role of probiotics in modulating glucose homeostasis.

Matched MeSH terms: Homeostasis
Fulltext Temporal regulation of proteome profile in the fruit fly, Drosophila melanogaster

Subramanian P, Jayapalan JJ, Abdul-Rahman PS, Arumugam M, Hashim OH

PeerJ, 2016;4:e2080.
PMID: 27257555 DOI: 10.7717/peerj.2080

Background. Diurnal rhythms of protein synthesis controlled by the biological clock underlie the rhythmic physiology in the fruit fly, Drosophila melanogaster. In this study, we conducted a proteome-wide investigation of rhythmic protein accumulation in D. melanogaster. Materials and Methods. Total protein collected from fly samples harvested at 4 h intervals over the 24 h period were subjected to two-dimensional gel electrophoresis, trypsin digestion and MS/MS analysis. Protein spots/clusters were identified with MASCOT search engine and Swiss-Prot database. Expression of proteins was documented as percentage of volume contribution using the Image Master 2D Platinum software. Results. A total of 124 protein spots/clusters were identified using MS/MS analysis. Significant variation in the expression of 88 proteins over the 24-h period was observed. A relatively higher number of proteins was upregulated during the night compared to the daytime. The complexity of temporal regulation of the D. melanogaster proteome was further reflected from functional annotations of the differently expressed proteins, with those that were upregulated at night being restricted to the heat shock proteins and proteins involved in metabolism, muscle activity, protein synthesis/folding/degradation and apoptosis, whilst those that were overexpressed in the daytime were apparently involved in metabolism, muscle activity, ion-channel/cellular transport, protein synthesis/folding/degradation, redox homeostasis, development and transcription. Conclusion. Our data suggests that a wide range of proteins synthesized by the fruit fly, D. melanogaster, is under the regulation of the biological clock.

Matched MeSH terms: Homeostasis
Fulltext Embryo apoptosis identification: Oocyte grade or cleavage stage?

Bakri NM, Ibrahim SF, Osman NA, Hasan N, Jaffar FH, Rahman ZA, et al.

Saudi J Biol Sci, 2016 Jan;23(1):S50-5.
PMID: 26858565 DOI: 10.1016/j.sjbs.2015.10.023

Apoptosis is a programed cell death that is vital for tissue homeostasis. However, embryo apoptosis had been known to be related to embryo fragmentation which should be avoided in in vitro fertilization (IVF). The purpose of this study was to evaluate the relationship of embryo apoptosis with the grade of immature oocytes and cleavage stage of in vitro produced (IVP) cattle embryos. This study consisted of 345 oocytes collected through ovary slicing. Immature oocytes were graded as A, B and C. This grading was based on cumulus cell thickness and compactness. All oocytes then underwent an in vitro maturation (IVM) procedure. An IVF was done 24 h after IVM culture. Prior to staining, stage of cleaved embryos was determined and classified as either 2, 4, 8 or >8-cell embryo stage. Apoptosis status of cleaved IVP embryos was determined by using annexin V-FITC staining technique at 48 and 72 h post insemination (hpi). Apoptosis status for each embryo was classified as either early or late. The result showed that there was no significant difference (p > 0.05) of apoptosis status among grade A, B and C embryos. All grades of oocytes showed embryo apoptosis where 1.5% late apoptosis for grade A, 4.5% and 10.4% of early and late apoptosis for grade B and grade C. Early apoptosis was not seen in grade A embryo. We also noted no significant difference (p > 0.05) of apoptosis status between 2, 4, 8 and >8-cell embryo stage. Early apoptosis was also not seen in >8-cell stage. Even though there were no differences in apoptosis expression between the three classes, the cleavage rate of grade A oocytes was significantly higher (p

Matched MeSH terms: Homeostasis
Could hypertension possibly be adaptive?

Prakash ES, Fink GD

Clin Exp Pharmacol Physiol, 2010 Feb;37(2):e99-e106.
PMID: 19719749 DOI: 10.1111/j.1440-1681.2009.05284.x

1. We believe that the ultimate goal of cardiovascular regulatory mechanisms is not the regulation of arterial blood pressure (BP), but the maintenance of tissue blood flows commensurate with metabolic requirements. Thus, elevated BP can potentially contribute to optimizing tissue blood flows under select circumstances; for example, when there are primary defects in autoregulation of tissue blood flows. 2. The hypothesis that a primary defect in autoregulation of tissue blood flows may be responsible for the development of hypertension is presented. It is argued that, in this context, at least part of the rise in BP may be reflexly driven by a 'metaboreflex', a homeostatic mechanism acting to regulate tissue blood flows. 3. We argue that in the context of primary defects in autoregulation of tissue blood flows, the ability to generate and sustain a hypertensive phenotype increases the lifespan of species (i.e. if it were not for this adaptive hypertensive phenotype, death due to circulatory failure would occur much earlier). 4. Experimental and clinical evidence that indirectly supports the hypothesis is reviewed briefly and a means for testing this hypothesis is suggested.

Matched MeSH terms: Homeostasis
Fulltext Role of C-type natriuretic peptide signalling in maintaining cartilage and bone function

Peake NJ, Hobbs AJ, Pingguan-Murphy B, Salter DM, Berenbaum F, Chowdhury TT

Osteoarthritis Cartilage, 2014 Nov;22(11):1800-7.
PMID: 25086404 DOI: 10.1016/j.joca.2014.07.018

C-type natriuretic peptide (CNP) has been demonstrated in human and mouse models to play critical roles in cartilage homeostasis and endochondral bone formation. Indeed, targeted inactivation of the genes encoding CNP results in severe dwarfism and skeletal defects with a reduction in growth plate chondrocytes. Conversely, cartilage-specific overexpression of CNP was observed to rescue the phenotype of CNP deficient mice and significantly enhanced bone growth caused by growth plate expansion. In vitro studies reported that exogenous CNP influenced chondrocyte differentiation, proliferation and matrix synthesis with the response dependent on CNP concentration. The chondroprotective effects were shown to be mediated by natriuretic peptide receptor (Npr)2 and enhanced synthesis of cyclic guanosine-3',5'-monophosphate (cGMP) production. Recent studies also showed certain homeostatic effects of CNP are mediated by the clearance inactivation receptor, Npr3, highlighting several mechanisms in maintaining tissue homeostasis. However, the CNP signalling systems are complex and influenced by multiple factors that will lead to altered signalling and tissue dysfunction. This review will discuss the differential role of CNP signalling in regulating cartilage and bone homeostasis and how the pathways are influenced by age, inflammation or sex. Evidence indicates that enhanced CNP signalling may prevent growth retardation and protect cartilage in patients with inflammatory joint disease.

Matched MeSH terms: Homeostasis
Fulltext Comparative Evaluation of Dental Implant Failure among Healthy and Well-Controlled Diabetic Patients-A 3-Year Retrospective Study

Sghaireen MG, Alduraywish AA, Srivastava KC, Shrivastava D, Patil SR, Al Habib S, et al.

Int J Environ Res Public Health, 2020 07 21;17(14).
PMID: 32708165 DOI: 10.3390/ijerph17145253

Diabetes mellitus is known to compromise the various aspects of homeostasis, including the immune response and the composition of oral microflora. One of the oral manifestations of diabetes mellitus is tooth loss and the survival rate of dental implants chosen as a treatment modality for its rehabilitation is controversial. The current study aims to evaluate and compare the failure rate of dental implants between well-controlled diabetic and healthy patients. A retrospective study of case-control design was conceptualized with 121 well-controlled diabetic and 136 healthy individuals. Records of subjects who had undergone oral rehabilitation with dental implants between the periods of January 2013 to January 2016 were retrieved. Post-operative evaluation was carried out for all patients for about three years to assess the immediate and long-term success of the procedure. From a total of 742 dental implants, 377 were placed in well-controlled diabetic patients (case group) and 365 in healthy subjects (control group). A comparable (9.81%), but non-significant (p = 0.422) failure rate was found in the case group in comparison to the control group (9.04%). A non-significant (p = 0.392) raised number (4.98%) of failure cases were reported among females in comparison to males (4.44%). In respect to arch, the mandibular posterior region was reported as the highest failure cases (3.09%; p = 0.411), with 2.29% of cases reported in the mandibular anterior (p = 0.430) and maxillary posterior (p = 0.983) each. The maxillary anterior region was found to have the least number (1.75%; p = 0.999) of failure cases. More (4.98%; p = 0.361) cases were reported to fail during the functional loading stage in contrast to osseointegration (4.44%; p = 0.365). A well-controlled diabetic status does not impose any additional risk for individuals undergoing dental implant therapy.

Matched MeSH terms: Homeostasis
Fulltext Therapeutic roles of natural remedies in combating hereditary ataxia: A systematic review

Phang MWL, Lew SY, Chung I, Lim WK, Lim LW, Wong KH

Chin Med, 2021 Jan 28;16(1):15.
PMID: 33509239 DOI: 10.1186/s13020-020-00414-x

BACKGROUND: Hereditary ataxia (HA) represents a group of genetically heterogeneous neurodegenerative diseases caused by dysfunction of the cerebellum or disruption of the connection between the cerebellum and other areas of the central nervous system. Phenotypic manifestation of HA includes unsteadiness of stance and gait, dysarthria, nystagmus, dysmetria and complaints of clumsiness. There are no specific treatments for HA. Management strategies provide supportive treatment to reduce symptoms.
OBJECTIVES: This systematic review aimed to identify, evaluate and summarise the published literature on the therapeutic roles of natural remedies in the treatment of HA to provide evidence for clinical practice.
METHODS: A systematic literature search was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Web of Science, PubMed and Science Direct Scopus were thoroughly searched for relevant published articles from June 2007 to July 2020.
RESULTS: Ten pre-clinical and two clinical studies were eligible for inclusion in this systematic review. We identified the therapeutic roles of medicinal plants Brassica napus, Gardenia jasminoides, Gastrodia elata, Ginkgo biloba, Glycyrrhiza inflata, Paeonia lactiflora, Pueraria lobata and Rehmannia glutinosa; herbal formulations Shaoyao Gancao Tang and Zhengan Xifeng Tang; and medicinal mushroom Hericium erinaceus in the treatment of HA. In this review, we evaluated the mode of actions contributing to their therapeutic effects, including activation of the ubiquitin-proteasome system, activation of antioxidant pathways, maintenance of intracellular calcium homeostasis and regulation of chaperones. We also briefly highlighted the integral cellular signalling pathways responsible for orchestrating the mode of actions.
CONCLUSION: We reviewed the therapeutic roles of natural remedies in improving or halting the progression of HA, which warrant further study for applications into clinical practice.

Matched MeSH terms: Homeostasis
The crosstalk of hedgehog, PI3K and Wnt pathways in diabetes

Benchoula K, Parhar IS, Wong EH

Arch Biochem Biophys, 2021 Feb 15;698:108743.
PMID: 33382998 DOI: 10.1016/j.abb.2020.108743

Hyperglycaemia causes pancreatic β-cells to release insulin that then attaches to a specific expression of receptor isoform and reverses high glucose concentrations. It is well known that insulin is capable of initiating insulin-receptor substrate (IRS)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) signaling pathways in target cells; such as liver, adipose tissues, and muscles. However, recent discoveries indicate that many other pathways, such as the Hedgehog (Hh) and growth factor-stimulating Wingless-related integration (Wnt) signaling pathways; are activated in hyperglycaemia as well. Although these two pathways are traditionally thought to have a decisive role in cellular growth and differentiation only, recent reports show that they are involved in regulating cellular homeostasis and energy balance. While insulin-activated IRS/PI3K/PKB pathway cascades are primarily known to reduce glucose production, it was recently discovered to increase the Hh signaling pathway's stability, thereby activating the PI3K/PKB/mammalian target of rapamycin complex 2 (mTORC2) signaling pathway. The Hh signaling pathway not only plays a role in lipid metabolism, insulin sensitivity, inflammatory response, diabetes-related complications, but crosstalks with the Wnt signaling pathway resulting in improved insulin sensitivity and decrease inflammatory response in diabetes.

Matched MeSH terms: Homeostasis
Fulltext Zinc transporter-3 [SLC30A3(rs11126936)]polymorphismis associated with major depressive disorderin Asian subjects

Lye, Munn-Sann, Aishah-Farhana Shahbudin, Tey, Yin-Yee, Tor, Yin-Sim, Ling, King-Hwa, Normala Ibrahim, et al.

Neuroscience Research Notes, 2019;2(3):20-28.
MyJurnal

Major depressive disorder (MDD) compromises the individual’s capacity for self-care and productivity. Single nucleotide polymorphisms (SNP) of a number of genes have been associated with MDD. The zinc transporter-3 protein, encoded by the ZnT3 (SLC30A3) gene, maintains zinc-glutamate homeostasis at the glutamatergic synapse, a disruption of which increases risk of MDD. We hypothesise that variation in SLC30A3 (rs11126936)SNP increases risk of MDD. We recruited 300 MDD cases and 300 controls, matched in theratio of 1:1 by age, gender and ethnicity. PCR-restriction fragment length polymorphism analysis was used in DNA genotyping, validated by sequencing 10%of samples. Deviation from the Hardy-Weinberg equilibrium was tested using the chi-square test. Conditional logistic regression was used to estimate adjusted odds ratios, controlling for age, gender, ethnicity, occupation and family monthly income.Genotypes G/G and G/T showed two times greater odds of developing MDD compared to variant genotype T/T (OR=1.983, 95% CI=1.031-3.815; p=0.040 and OR=2.232, 95% CI=1.100-4.533; p=0.026 respectively). Carriers of genotypes G/G and G/T of the SNP rs11126936 in SLC30A3are associated with increased risk of MDD.

Matched MeSH terms: Homeostasis
Comments on Point:Counterpoint: Sympathetic activity does/does not influence cerebral blood flow. When noradrenergic restraint of cerebral blood flow makes homeostatic sense

Prakash ES

J Appl Physiol (1985), 2008 10;105(4):1373.
PMID: 18938648 DOI: 10.1152/japplphysiol.zdg-8199.pcpcomm.2008
Matched MeSH terms: Homeostasis
Fulltext Bile Sensing: The Activation of Vibrio parahaemolyticus Virulence

Letchumanan V, Chan KG, Khan TM, Bukhari SI, Ab Mutalib NS, Goh BH, et al.

Front Microbiol, 2017;8:728.
PMID: 28484445 DOI: 10.3389/fmicb.2017.00728

Bacteria must develop resistance to various inhospitable conditions in order to survive in the human gastrointestinal tract. Bile, which is secreted by the liver, and plays an important role in food digestion also has antimicrobial properties and is able to disrupt cellular homeostasis. Paradoxically, although bile is one of the guts defenses, many studies have reported that bacteria such as Vibrio parahaemolyticus can sense bile and use its presence as an environmental cue to upregulate virulence genes during infection. This article aims to discuss how bile is detected by V. parahaemolyticus and its role in regulating type III secretion system 2 leading to human infection. This bile-bacteria interaction pathway gives us a clearer understanding of the biochemical and structural analysis of the bacterial receptors involved in mediating a response to bile salts which appear to be a significant environmental cue during initiation of an infection.

Matched MeSH terms: Homeostasis
Fulltext Purinergic P2Y receptors: Molecular diversity and implications for treatment of cardiovascular diseases

Nishimura A, Sunggip C, Oda S, Numaga-Tomita T, Tsuda M, Nishida M

Pharmacol Ther, 2017 Dec;180:113-128.
PMID: 28648830 DOI: 10.1016/j.pharmthera.2017.06.010

Purinergic signaling, mediated mainly by G protein-coupled P2Y receptors (P2YRs), is now attracting attention as a new therapeutic target for preventing or treating cardiovascular diseases. Observations using mice with genetically modified P2YRs and/or treated with a pharmacological P2YR inhibitor have helped us understand the physiological and pathological significance of P2YRs in the cardiovascular system. P2YR-mediated biological functions are predominantly activated by mononucleotides released from non-adrenergic, non-cholinergic nerve endings or non-secretory tissues in response to physical stress or cell injury, though recent studies have suggested the occurrence of ligand-independent P2YR function through receptor-receptor interactions (oligomerization) in several biological processes. In this review, we introduce the functions of P2YRs and possible dimerization with G protein-coupled receptors (GPCRs) in the cardiovascular system. We focus especially on the crosstalk between uridine nucleotide-responsive P2Y6R and angiotensin (Ang) II type1 receptor (AT1R) signaling, and introduce our recent finding that the P2Y6R antagonist MRS2578 interrupts heterodimerization between P2Y6R and AT1R, thereby reducing the risk of AT1R-stimulated hypertension in mice. These results strongly suggest that targeting P2Y6R oligomerization could be an effective new strategy to reduce the risk of cardiovascular diseases.

Matched MeSH terms: Homeostasis
Fulltext Molecular Signatures of Human Regulatory T Cells in Colorectal Cancer and Polyps

Johdi NA, Ait-Tahar K, Sagap I, Jamal R

Front Immunol, 2017;8:620.
PMID: 28611777 DOI: 10.3389/fimmu.2017.00620

Regulatory T cells (Tregs), a subset of CD4(+) or CD8(+) T cells, play a pivotal role in regulating immune homeostasis. An increase in Tregs was reported in many tumors to be associated with immune suppression and evasion in cancer patients. Despite the importance of Tregs, the molecular signatures that contributed to their pathophysiological relevance remain poorly understood and controversial. In this study, we explored the gene expression profiles in Tregs derived from patients with colorectal cancer [colorectal carcinoma (CRC), n = 15], colorectal polyps (P, n = 15), and in healthy volunteers (N, n = 15). Tregs were analyzed using CD4(+)CD25(+)CD127(low)FoxP3(+) antibody markers. Gene expression profiling analysis leads to the identification of 61 and 66 immune-related genes in Tregs derived from CRC and P patients, respectively, but not in N-derived Treg samples. Of these, 30 genes were differentially expressed both in CRC- and P-derived Tregs when compared to N-derived Tregs. Most of the identified genes were involved in cytokine/chemokine mediators of inflammation, chemokine receptor, lymphocyte activation, and T cell receptor (TCR) signaling pathways. This study highlights some of the molecular signatures that may affect Tregs' expansion and possible suppression of function in cancer development. Our findings may provide a better understanding of the immunomodulatory nature of Tregs and could, therefore, open up new avenues in immunotherapy.

Matched MeSH terms: Homeostasis
HAART induces cell death in a cervical cancer cell line, HCS-2: A Scanning Electron Microscopy study

Xulu KR, Hosie MJ

J Microsc Ultrastruct, 2016 06 17;5(1):39-48.
PMID: 30023236 DOI: 10.1016/j.jmau.2016.06.001

Apoptosis is a tightly programmed cell suicide which occurs in multiple physiologic and pathological conditions where it plays an important role in tissue development and homeostasis by eliminating unwanted and damaged cells. Appropriate apoptosis signalling is crucial in maintaining the fine balance between cell death and cell survival in cancer. In response to death stimuli the morphology of the cell undergoes unique changes. The aim of this study was to examine and compare the changes in the cell surface morphology using scanning electron microscopy in HCS-2 cells, following 24 hour treatment with components of highly active antiretroviral therapy (HAART) at their clinical plasma concentrations. The cells were fixed in 2.5% Glutaraldehyde and post-fixed in 1% osmium tetroxide. The cells were then dehydrated through a graded series of alcohol and treated with hexamethyl-disilazane, then coated with a double layer of carbon. The cells were viewed under a Zeiss Ultra FEG Scanning Electron Microscope and a one way ANOVA and Tukey Kramer Post Hoc test was conducted based on the scoring of surface morphology of the cells using JMP 11 statistical software. The drugs used in this study induced morphological features which are known to be characteristic of apoptotic cell death. The drug combinations (ATP and LPV/r) were seemingly more effective than individual treatments in inducing cell death because morphological features observed were more advanced than those observed in individual treatments. However, LPV/r was more potent than ATP. In conclusion, HAART showed anticancer properties by inducing cell death through apoptosis.

Matched MeSH terms: Homeostasis
Ghrelin stimulates growth hormone release from the pituitary via hypothalamic growth hormone-releasing hormone neurons in the cichlid, Oreochromis niloticus

Ogawa S, Liu X, Shepherd BS, Parhar IS

Cell Tissue Res, 2018 Nov;374(2):349-365.
PMID: 29934855 DOI: 10.1007/s00441-018-2870-6

Ghrelin, a gut-brain peptide hormone, is implicated in a multiplicity of biological functions, including energy homeostasis and reproduction. Neuronal systems that are involved in energy homeostasis as well as reproduction traverse the hypothalamus; however, the mechanism by which they control energy homeostasis is not fully understood. The present study analyzes the anatomical relationship of neurons expressing gonadotropin-releasing hormone (GnRH), neuropeptide Y (NPY) and growth hormone-releasing hormone (GHRH) in a cichlid, tilapia (Oreochromis niloticus). Additionally, we examine in vivo effects of ghrelin on these hypothalamic neurons and plasma growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels. Double-immunofluorescence showed neuronal fiber associations between GnRH, NPY and GHRH in the brain and pituitary. Intracerebroventricular injection of ghrelin had no effect on numbers, soma size, or optical density of GnRH and NPY neurons, whereas the number of GHRH neurons was significantly decreased in the animals injected with ghrelin when compared to controls, which may indicate administered ghrelin promoted GHRH release. Plasma GH and pituitary GH mRNA levels were significantly increased in the animals injected with ghrelin. These results suggest that central administration of ghrelin primarily act on hypothalamic GHRH neurons to stimulate GH release from the pituitary in the tilapia.

Matched MeSH terms: Homeostasis
Fulltext Patched-1 and smoothened, a hedgehog receptor and signal transducer are highly expressed in diffuse large B-cell lymphoma

Siti Nur Lina Azman, Huzlinda Hussin, Salmiah Md Said, Zanariah Alias, Maizaton Atmadini Abdullah

Malaysian Journal of Medicine and Health Sciences, 2017;13(2):1-6.
MyJurnal

Introduction: The Hedgehog (Hh) signalling pathway is a developmental signalling pathway involved in normal mammalian developmental and homeostasis of adult renewable tissues. In most adult tissues, this pathway remains silent and previous studies have shown that constitutive activation of Hedgehog signalling pathway leads to various types of malignancies including medulloblastomas, basal cell carcinoma, gastrointestinal, breast and prostate cancer. The purpose of this study was to investigate the immunohistochemical expression of Hedgehog pathway proteins in Diffuse Large B-cell Lymphoma and determine their association with overall survival (OS). Methods: Positive control using normal tonsils were included in each batch of immunohistochemical staining procedure. Results: PTCH1 proteins were highly expressed in DLBCL and showed strong staining intensity in 107 (100%) cases and SMO proteins were expressed in 105 (98.1%) cases. PTCH1 proteins were localised in the nucleus of tumour cells, whereas SMO proteins were mainly localised in the cytoplasm of tumour cells. Positive expression of PTCH1 and SMO proteins and overall survival of DLBCL patients were correlated with age, gender, race and tumour location. There was no significant correlation between the expression of these two proteins with any of the parameters. PTCH1 expression showed significant association with SMO expression (P=0.03). Conclusions: Our findings suggest that high expression of both PTCH1 and SMO may be important in the pathogenesis of DLBCL. However, additional mechanisms that may contribute to the activation of HH signalling in DLBCL needs to be further explored.

Matched MeSH terms: Homeostasis
Fulltext Cytotoxic effects of Benzodioxane, Naphthalene diimide, Porphyrin and Acetamol derivatives on HeLa cells

Jeyamogan S, Khan NA, Anwar A, Shah MR, Siddiqui R

SAGE Open Med, 2018;6:2050312118781962.
PMID: 30034805 DOI: 10.1177/2050312118781962

Objectives: To synthesize novel compounds belonging to Benzodioxane, Naphthalene diimide, Aminophenol derivatives and Porphyrin classes and test their potential anticancer properties.
Methods: Several compounds were synthesized and their molecular identity was confirmed using nuclear magnetic resonance. Potential anticancer properties were determined using cytopathogenicity assays and growth inhibition assays using cervical cancer cells (HeLa). Cells were incubated with different concentrations of compounds belonging to Benzodioxane, Naphthalene diimide, Aminophenol derivatives and Porphyrins and effects were determined. HeLa cells cytopathogenicity was determined by measuring lactate dehydrogenase release using cytotoxicity detection assay. Growth inhibition assays were performed by incubating 50% semi-confluent HeLa cells with Benzodioxane, Naphthalene diimide, Aminophenol derivatives and Porphyrin compounds and HeLa cell proliferation was observed. Growth inhibition and host cell death were compared in the presence and absence of drugs.
Results: Cytopathogenicity assays showed that the selected compounds were cytotoxic against HeLa cells, killing up to 90% of cells. Growth inhibition assays exhibited 100% growth inhibition. These effects are likely via oxidative stress, production of reactive oxygen species, changes in cytosolic and intracellular calcium/adenine nucleotide homeostasis, inhibition of ribonucleotide reductase/cyclooxygenase and/or glutathione depletion.
Conclusions: Benzodioxane, Naphthalene diimide, Aminophenol derivatives and Porphyrins exhibited potent anticancer properties. These findings are promising and should pave the way in the rationale development of anticancer drugs. Using different cancer cell lines, future studies will determine their potential as anti-tumour agents as well as their precise molecular mode of action.

Matched MeSH terms: Homeostasis

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