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Maternal & Child Nutrition Apr 2022The Diabetes and Antenatal Milk Expressing (DAME) randomised controlled trial (RCT) was conducted in 2011-2015, at six sites in Melbourne, Australia to explore the... (Randomized Controlled Trial)
Randomized Controlled Trial
The Diabetes and Antenatal Milk Expressing (DAME) randomised controlled trial (RCT) was conducted in 2011-2015, at six sites in Melbourne, Australia to explore the effect of advising women with diabetes in pregnancy to express breast milk from 36 weeks gestation. Infants whose mothers were randomised to express in pregnancy were more likely to be exclusively breast milk fed during their hospital stay, and there was no evidence of harm. This paper explores women's views and experiences of antenatal expressing. In this two-arm RCT, 635 women with diabetes in pregnancy who were otherwise of low medical risk were randomised at 36-37 weeks gestation to usual care (not expressing, n = 316), or the intervention, where women were advised to hand express for 10 min twice daily until birth (n = 319). Semistructured face-to-face interviews were conducted with 10 women who expressed antenatally. They were asked about their experiences of antenatal expressing, including how they felt about the overall experience, the amount of breast milk they expressed, making time to express, and their experience of breastfeeding. Thematic analysis of the in-depth interviews identified six themes: (1) learning and adapting expressing, (2) feelings and sensations associated with expressing, (3) support, (4) dis/empowerment, (5) health, and (6) the value of breast milk. Women had both positive and negative experiences of antenatal expressing. If health professionals are advising antenatal expressing to women, it is important they understand the range of outcomes and experiences.
Topics: Breast Feeding; Diabetes Mellitus; Enkephalin, Methionine; Female; Humans; Infant; Milk, Human; Pregnancy; Prenatal Care; Qualitative Research
PubMed: 34939318
DOI: 10.1111/mcn.13307 -
Journal of Mass Spectrometry and... Nov 2021The worldwide prevalence of non-alcoholic fatty liver disease (NAFLD) has stimulated work to identify biomarkers and develop effective treatments. Metabolomics is an...
BACKGROUND
The worldwide prevalence of non-alcoholic fatty liver disease (NAFLD) has stimulated work to identify biomarkers and develop effective treatments. Metabolomics is an emerging tool that has been widely applied to discover biomarkers and simultaneously uncover pathological mechanisms. Here, we aim to optimize metabolomic acquisition with the goal of obtaining a systemic metabolic profile to unravel the potential link between dysregulated metabolism and NAFLD.
METHODS
We analyzed serum samples collected from healthy subjects (n = 8) and NAFLD patients (n = 8) via an integrative analytical workflow using two orthogonal separation modes with T3 and amide columns and two ionization polarity modes on a UPLC-ESI-Q/TOF. Data dependent acquisition was employed for data acquisition. Differentially expressed metabolites and lipids were identified by comparing the collected metabolic and lipidomic profiles between the healthy subjects and NAFLD patients.
RESULTS
The integrative LC-MS/MS analytical workflow employed here features an improved coverage of metabolites and lipids, which leads to the identification of 20 potential biomarkers of NAFLD, including lipids, acylcarnitines, and organic acids.
CONCLUSIONS
This pilot study has identified potential biomarkers for NAFLD and revealed corresponding dysregulated metabolic pathways related to NAFLD's occurrence and progression, establishing a molecular basis for NAFLD diagnosis and therapeutic intervention.
PubMed: 34939051
DOI: 10.1016/j.jmsacl.2021.10.001 -
Journal of Neuroscience Research Feb 2022Multiple sclerosis (MS) is a progressive disease of the central nervous system (CNS) that primarily affects women during the second or third decade of life. The...
Multiple sclerosis (MS) is a progressive disease of the central nervous system (CNS) that primarily affects women during the second or third decade of life. The mechanism is hypothesized to involve unregulated peripheral inflammation resulting in blood-brain barrier damage, and eventual axonal damage and demyelination. Based on this understanding, the animal model of MS, experimental autoimmune encephalomyelitis (EAE), often is utilized to study lymphocyte activation. Therapeutic paradigms of exogenous opioid growth factor (OGF) or low-dose naltrexone (LDN) treatment can modulate EAE, but little is reported regarding OGF or LDN effects on peripheral inflammation, microglia activation, and/or macrophage proliferation. Moreover, little is known about differential responses to LDN or OGF relative to the duration and timing of treatment. Utilizing a female mouse model of EAE, two treatment regimens were established to investigate differences between prophylactic treatment and traditional therapy initiated at the time of disease presentation. Prophylactic OGF or LDN treatment delayed the onset of behavior, suppressed neutrophil replication, and curtailed lymphocyte proliferation which ultimately improved behavioral outcome. Traditional therapy with OGF or LDN reversed behavioral deficits, restored OGF and IL-17 serum levels, and inhibited microglial activation within 8 days. Reduced serum OGF levels in untreated EAE mice correlated with increased microglia activation within lumbar spinal cords. Both treatment regimens of OGF or LDN reduced activated microglia, whereas only prophylactic treatment prevented CNS macrophage aggregation. These data demonstrate that the timing of LDN or OGF treatment initiation alters outcomes and can prevent or reverse behavioral deficits, cytokine activation, and spinal cord pathology.
Topics: Analgesics, Opioid; Animals; Encephalomyelitis, Autoimmune, Experimental; Enkephalin, Methionine; Female; Humans; Immunity; Mice; Mice, Inbred C57BL; Microglia; Spinal Cord
PubMed: 34821408
DOI: 10.1002/jnr.24983 -
International Immunopharmacology Oct 2021Methionine enkephalin (MENK) has an important role in both neuroendocrine and immune systems. MENK was known as an opioid growth factor (OGF) for its growth regulatory... (Review)
Review
Methionine enkephalin (MENK) has an important role in both neuroendocrine and immune systems. MENK was known as an opioid growth factor (OGF) for its growth regulatory characteristics. OGF interacts with the OGF receptor (OGFr) to inhibit DNA synthesis by upregulating p16 and/or p21, which delays the cell cycle transition from G0/G1 to S phase, and inhibits cell proliferation. In addition, OGF combines with OGFr in immune cells to exert its immunomodulatory activity and regulate immune function. OGF has been studied as an immunomodulator in a variety of autoimmune diseases, including multiple sclerosis, inflammatory bowel disease, diabetes and viral infections, and has been proven to relieve symptoms of certain diseases in animal and in vitro experiments. Also, OGF and OGFr have various anti-tumor molecular mechanisms. OGF can be used as the primary therapy alone or combined with other drugs to treat tumors. This article summarizes the research progress of OGF in immune-related diseases and cancer diseases.
Topics: Animals; Enkephalin, Methionine; Humans; Immune System Diseases; Narcotic Antagonists; Neoplasms
PubMed: 34426103
DOI: 10.1016/j.intimp.2021.107713 -
Molecular & Cellular Proteomics : MCP 2021Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has become a global health pandemic. COVID-19...
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has become a global health pandemic. COVID-19 severity ranges from an asymptomatic infection to a severe multiorgan disease. Although the inflammatory response has been implicated in the pathogenesis of COVID-19, the exact nature of dysregulation in signaling pathways has not yet been elucidated, underscoring the need for further molecular characterization of SARS-CoV-2 infection in humans. Here, we characterize the host response directly at the point of viral entry through analysis of nasopharyngeal swabs. Multiplexed high-resolution MS-based proteomic analysis of confirmed COVID-19 cases and negative controls identified 7582 proteins and revealed significant upregulation of interferon-mediated antiviral signaling in addition to multiple other proteins that are not encoded by interferon-stimulated genes or well characterized during viral infections. Downregulation of several proteasomal subunits, E3 ubiquitin ligases, and components of protein synthesis machinery was significant upon SARS-CoV-2 infection. Targeted proteomics to measure abundance levels of MX1, ISG15, STAT1, RIG-I, and CXCL10 detected proteomic signatures of interferon-mediated antiviral signaling that differentiated COVID-19-positive from COVID-19-negative cases. Phosphoproteomic analysis revealed increased phosphorylation of several proteins with known antiviral properties as well as several proteins involved in ciliary function (CEP131 and CFAP57) that have not previously been implicated in the context of coronavirus infections. In addition, decreased phosphorylation levels of AKT and PKC, which have been shown to play varying roles in different viral infections, were observed in infected individuals relative to controls. These data provide novel insights that add depth to our understanding of SARS-CoV-2 infection in the upper airway and establish a proteomic signature for this viral infection.
Topics: COVID-19; Chromatography, Liquid; Epithelial Cells; Host-Pathogen Interactions; Humans; Interferons; Nasopharynx; Phosphoproteins; Proteasome Endopeptidase Complex; Protein Kinase C; Proteome; Proto-Oncogene Proteins c-akt; Receptors, Opioid; Signal Transduction; Tandem Mass Spectrometry; Ubiquitin
PubMed: 34400346
DOI: 10.1016/j.mcpro.2021.100134 -
Biochemical Pharmacology Oct 2021Diabetes is a multi-faceted disorder with increasing prevalence and rising healthcare costs. The burden of diabetes is increased because of associated complications... (Review)
Review
Diabetes is a multi-faceted disorder with increasing prevalence and rising healthcare costs. The burden of diabetes is increased because of associated complications affecting nearly all organs including the eye. The underlying pathophysiology for the onset of these ocular surface disorders is not well known. Enkephalins are endogenous opioids that originate in the brain and have numerous actions in the human body. Opioid growth factor (OGF), chemically termed [Met]-enkephalin, binds to a novel, nuclear-associated receptor and mediates cellular homeostasis. Serum OGF levels are elevated in diabetic individuals and rodent models of diabetes. Sustained blockade of the OGF receptor (OGFr) with opioid receptor antagonists, such as naltrexone (NTX), reverses many complications of diabetes in the animal model, including delayed cutaneous wound healing, dry eye, altered corneal surface sensitivity, and keratopathy. The increased enkephalin levels observed in diabetes suggest a relationship between endogenous opioid peptides and the pathophysiology of diabetes. It is common for diabetic patients to undergo insulin therapy to restore normal blood glucose levels. However, this restoration does not alter OGF serum levels nor ameliorate ocular surface complications in the animal model of diabetes. Moreover, sex differences in the prevalence of diabetes, response to insulin therapy, and abnormalities in the OGF-OGFr axis have been reported. This review highlights current knowledge on the dysregulation of the OGF-OGFr pathway and possible relationships of insulin and enkephalins to the development of ocular surface defects in diabetes. It proposes that this dysregulation is a fundamental mechanism for the pathobiology of diabetic complications.
Topics: Animals; Corneal Diseases; Diabetes Complications; Diabetes Mellitus; Dry Eye Syndromes; Enkephalins; Humans; Insulin; Naltrexone; Narcotic Antagonists; Receptors, Opioid
PubMed: 34324868
DOI: 10.1016/j.bcp.2021.114712 -
International Immunopharmacology Oct 2021This study examined the antitumor effect of methionine enkephalin (MENK) against lung cancer in vivo and in vitro and explored the underlying mechanisms. Changes in the...
This study examined the antitumor effect of methionine enkephalin (MENK) against lung cancer in vivo and in vitro and explored the underlying mechanisms. Changes in the immune status of the tumor microenvironment (TME) in response to MENK administration were examined in mice. MENK significantly inhibited the proliferation of lung cancer cells in vivo and in vitro by regulating the Wnt/β-catenin pathway and causing cell cycle arrest at the G0/G1 phase. Knockdown of opioid growth factor receptor abolished the effect of MENK on lung cancer cells. The immune status of the TME of mice differed between the MENK and control groups. MENK increased the infiltration of M1-type macrophages, natural killer cells, CD8+ T cells, CD4+ T cells, and dendritic cells into the TME, and decreased the proportion of myeloid inhibitory cells and M2-type macrophages. Immunohistochemical analysis of the expression of cytokines in the TME showed that MENK upregulated IL-15, IL-21, IFN-γ, and granzyme B and downregulated IL-10 and TGF-β1 in mice. Taken together, these finding indicate that MENK may be a potential agent for lung cancer treatment in the future, especially for overcoming immune escape and immune resistance.
Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Cytokines; Dendritic Cells; Enkephalin, Methionine; Female; Humans; Lung Neoplasms; Macrophages; Mice; Mice, Inbred C57BL; RNA, Small Interfering; T-Lymphocytes; Tumor Microenvironment; Wnt Signaling Pathway
PubMed: 34315116
DOI: 10.1016/j.intimp.2021.107999 -
International Immunopharmacology Oct 2021The antitumor effects of methionine enkephalin (MENK), also known as opioid growth factor (OGF), including its inhibitory effects on cutaneous squamous cell carcinoma...
The antitumor effects of methionine enkephalin (MENK), also known as opioid growth factor (OGF), including its inhibitory effects on cutaneous squamous cell carcinoma (CSCC), have been established. In this study, we determined the precise mechanism by which MENK suppresses CSCC cell growth. In particular, MENK induced G0/G1 cell cycle arrest and promoted apoptosis in CSCC cells via the Bcl-2/Bax/Caspase-3 signaling pathway. Moreover, MENK reduced immunosuppression by downregulating the number of myeloid-derived suppressor cells (MDSCs) and regulating the polarization of tumor-associated macrophages from M2 to M1 in vivo. Furthermore, JAK2/STAT3, an important tumor-promotion and immunosuppression signaling pathway that is involved in MDSC expansion in tumors and macrophage polarization, was inhibited. These findings highlight the potential of the JAK2/STAT3 signaling pathway as a therapeutic target and suggest the clinical application of MENK for CSCC.
Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; Carcinoma, Squamous Cell; Cell Cycle; Cell Line, Tumor; Cell Polarity; Cell Proliferation; Cytokines; Enkephalin, Methionine; Female; Humans; Immunosuppression Therapy; Janus Kinase 2; Macrophages; Mice, Inbred BALB C; Mice, Nude; Myeloid-Derived Suppressor Cells; RNA, Small Interfering; STAT3 Transcription Factor; Signal Transduction; Mice
PubMed: 34311187
DOI: 10.1016/j.intimp.2021.107996 -
Folia Histochemica Et Cytobiologica 2021A recent study has shown a close neuroanatomical relationship between the enkephalinergic (methionine-enkephalin) and tachykininergic (substance P) systems in the alpaca...
INTRODUCTION
A recent study has shown a close neuroanatomical relationship between the enkephalinergic (methionine-enkephalin) and tachykininergic (substance P) systems in the alpaca diencephalon. In this study, our aim is to show this relationship in the alpaca brainstem.
MATERIAL AND METHODS
Using an immunohistochemical technique, the distribution of immunoreactive (Ir) fibers and cell bodies containing substance P (SP) or methionine-enkephalin (MET) has been studied in the alpaca brainstem. Five adult males were used; brain tissue was fixed and processed by standard methods.
RESULTS
SP- and MET-Ir fibers showed a widespread and similar distribution in the mesencephalon, pons and medulla oblongata. The co-localization of fibers containing SP or MET was found in most of the nuclei/tracts of the alpaca brainstem. This close neuroanatomical relationship suggests multiple physiological interactions between both neuropeptides. The distribution of the cell bodies containing SP was very restricted (cell bodies were only observed in a few nuclei located in the mesencephalon and medulla oblongata), whereas MET-Ir perikarya showed a moderately widespread distribution in the mesencephalon, pons and medulla oblongata.
CONCLUSIONS
This study increases the knowledge on the neuroanatomical distribution/relationship of the tachykininergic (SP) and enkephalinergic (MET) systems in the alpaca central nervous system.
Topics: Animals; Brain Stem; Camelids, New World; Diencephalon; Enkephalin, Methionine; Male; Substance P
PubMed: 34309826
DOI: 10.5603/FHC.a2021.0016 -
International Immunopharmacology Sep 2021The aim of this study was to investigate how methionine enkephalin (MENK) regulates the biological behavior of lung cancer cells and to further explore its anti-lung...
The aim of this study was to investigate how methionine enkephalin (MENK) regulates the biological behavior of lung cancer cells and to further explore its anti-lung cancer mechanisms in vitro and in vivo. The results showed that MENK enhanced the expression of opioid receptor (OGFr) and induced apoptosis of lung cancer cells by activating the Bcl-1/Bax/caspase-3 signaling pathway in vitro and in vivo. However, the regulatory effects of MENK disappeared after blockade of the OGFr. This confirmed that a prerequisite for the anti-tumor action of MENK is binding to OGFr. Additionally, we observed that MENK treatment enhanced the immunogenicity of lung cancer by enhancing the exposure of calreticulin and high mobility group box 1, and increasing the expression of NKG2D ligands. Further studies showed that MENK treatment increased the expression of natural killer (NK) cell-related cytokines such as granzyme B and interferon-γ and NK cell activation. Thus, we concluded that MENK might inhibit the proliferation of lung cancer cells by activating the Bcl-2/Bax/caspase-3 signaling pathway and enhancing immunogenicity and NK cell-driven tumor immunity.
Topics: A549 Cells; Animals; Antineoplastic Agents; Caspase 3; Enkephalin, Methionine; Humans; Immunity, Cellular; Killer Cells, Natural; Lung Neoplasms; Mice; Mice, Inbred C57BL; NK Cell Lectin-Like Receptor Subfamily C; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; bcl-2-Associated X Protein
PubMed: 34116288
DOI: 10.1016/j.intimp.2021.107837