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The Impact of Minimal Sunlight Exposure on Bone Health: Insights From a Cohort Study in Erythropoietic Protoporphyria.
J Clin Endocrinol Metab
Louisa G Kluijver, Margreet A E M Wagenmakers, J H Paul Wilson +1 more
Erythropoietic protoporphyria (EPP) is a rare inherited metabolic disease, causing lifelong painful phototoxic reactions, minimal sunlight exposure, and vitamin D deficiency. Previous studies reported a high osteoporosis prevalence in EPP patients.
Contemporary insights into elamipretide's mitochondrial mechanism of action and therapeutic effects.
Biomed Pharmacother
Hani N Sabbah, Nathan N Alder, Genevieve C Sparagna +6 more
Mitochondria are cellular hubs integral for metabolism, signaling, and survival. Mitochondrial dysfunction is centrally involved in the aging process and an expansive array of disease states. Elamipretide is a novel mitochondria-targeting peptide that is under investigation for treating several disorders related to mitochondrial dysfunction. This review summarizes recent data that expand our understanding of the mechanism of action (MOA) of elamipretide. Elamipretide is a potential first-in-class therapeutic that targets the inner mitochondrial membrane. Despite initial descriptions of elamipretide's MOA involving reactive oxygen species scavenging, the last ten years have provided a significant expansion of how this peptide influences mitochondrial bioenergetics. The cardiolipin binding properties of elamipretide have been corroborated by different investigative teams with new findings about the consequences of elamipretide-cardiolipin interactions. In particular, new studies have shown elamipretide-mediated modulation of mitochondrial membrane electrostatic potentials and assembly of cardiolipin-dependent proteins that are centrally involved in mitochondrial physiology. These effects contribute to elamipretide's ability to improve mitochondrial function, structure, and bioenergetics. In animal studies, elamipretide-mediated amelioration of organ dysfunction has been observed in models of cardiac and skeletal muscle myopathies as well as ocular pathologies. A number of clinical trials with elamipretide have been recently completed, and a summary of the results focusing on Barth syndrome, primary mitochondrial myopathy, and age-related macular degeneration, is also provided herein. Elamipretide continues to show promise as a potential therapy for mitochondrial disorders. New basic science advances have improved understanding of elamipretide's MOA, enabling a better understanding of the molecular consequences of elamipretide-cardiolipin interactions.
A novel butyrylcholinesterase inhibitor induces antidepressant, pro-cognitive, and anti-anhedonic effects in Flinders Sensitive Line rats: The role of the ghrelin-dopamine cascade.
Biomed Pharmacother
Nadia Olivier, Brian H Harvey, Stanislav Gobec +4 more
Major depressive disorder (MDD) is often treatment resistant, particularly in addressing anhedonia and cognitive deficits. Novel pharmacological strategies are needed. While butyrylcholinesterase, ghrelin, and dopamine (DA) have been well studied in the context of stress and MDD, their interaction remains unclear.
Effect analysis of entecavir on serum hyaluronic acid, laminin and IV collagen in the treatment of hepatitis B E-antigen-positive chronic hepatitis B.
Afr Health Sci
Jiancheng Qian, Xiaoyong Sun, Yue Cheng
To observe and analyse the clinical effects of entecavir on serum hyaluronic acid (HA), laminin (LN), and type IV collagen (IVC) in patients with hepatitis B e-antigen (HBeAG)-positive chronic hepatitis B during clinical treatment.
Multifunctional cosmetic potential of extracellular vesicle‑like nanoparticles derived from the stem of Cannabis sativa in treating pigmentation disorders.
Mol Med Rep
Hyeon Jin Lee, Yun Hye Kim, Seo Jun Lee +5 more
While natural products and synthetic chemicals are used in functional cosmetics, their potential side effects remain a concern. This has driven the need for safer and more effective agents to treat skin disorders. This has driven the need safer and more effective agents to treat skin disorders. Therefore, the present study aimed to explore the functional properties of Cannabis sativa stem‑derived nanoparticles (CSS‑NPs) and evaluate their potential as a cosmetic ingredient. Using nanoparticle analysis, CSS‑NPs, with a mean diameter of ~120 nm exhibited notable resistance to external stress conditions, including pH fluctuation and enzymatic degradation by DNase, RNase and proteinase K. They also contained 48 distinct biochemical components. In vitro assays revealed that CSS‑NPs significantly downregulated the expression of genes and proteins associated with melanin synthesis in mouse B16F10 melanoma cells under α‑melanocyte stimulating hormone (α‑MSH)‑induced hyperpigmentation. These inhibitory effects were mediated by the activation of ERK and Akt signaling pathways. Furthermore, CSS‑NPs improved the viability of α‑MSH‑treated B16F10 cells; this was accompanied by the upregulation of antioxidant‑associated enzymes and a decrease in α‑MSH‑induced reactive oxygen species levels. Collectively, these findings suggested that CSS‑NPs carry out a key role in mitigating skin pigmentation and enhancing antioxidant defenses by modulating the ERK/Akt axis during excessive melanin synthesis. Thus, CSS‑NPs represent a promising multifunctional cosmetic ingredient with potential in treating pigmentation disorders and protecting skin cells.
Scrambled RGD Hexameric Peptide Hydrogel Supports Efficient Self-Assembly and Cell Activity.
Chemistry
Karrar Al Taief, Stephanie Nemec, Isis A Middleton +2 more
The amino acid sequence is crucial in controlling peptide-based hydrogel formation, whereby changing the position of a single amino acid can significantly alter the gel's properties. Herein, we report the gelation kinetics and cell viability of scrFmoc-GFFRDG (where we have scrambled the RGD-based gel hexapeptide; Fmoc-GFFRGD). The scrambled sequence showed improved gelation properties compared to the original Fmoc-GFFRGD sequence, with scrFmoc-GFFRDG forming a gel in under 10 min, significantly faster than the 2-h gelation time, and at a concentration eight times lower than the original Fmoc-GFFRGD sequence. We also examined the combination of the two gelators in a ratio of 1:1, final concentration of 0.4% (w/v). Interestingly, the stiffness of the hybrid hydrogel was ∼3 kPa, whereas individually, neither gelator at the same concentration exceeded 0.5 kPa. The cell-adhesion motif RGD improves the ability of the peptides to promote attachment of cells due to integrin recognition. However, when fibroblasts were cultured on the hydrogels, scrFmoc-GFFRDG yielded a higher level of α-SMA expression in cells than those cultured on Fmoc-GFFRGD, suggesting a microenvironment conducive to myofibroblast transitions. This study provides a new outlook on how a well-known scrambled peptide motif (RDG) can fine-tune hydrogel assembly and cell culture applications.
Modifiable risk factors and plasma proteomics in relation to complications of type 2 diabetes.
Nat Commun
Ruyi Li, Shufan Tian, Jun Liu +10 more
A comprehensive assessment of combined modifiable risk factors with common complications of type 2 diabetes (T2D) is lacking, and the potential role of proteomics remains unclear. Here, we examine the associations of cardiovascular health (CVH) score and degree of risk factor control with common diabetic complications using data from the UK Biobank (n = 14,102). Furthermore, we explore the mediation effects of plasma proteomics in a subset with proteomic data (n = 1287). Over median follow-ups of 12.4-13.4 years, higher CVH score and higher degree of risk factor control are associated with lower risks of 30 and 22 of 45 adverse outcomes among individuals with T2D, respectively. Mediation analyses reveal that mortality and multiple vascular diseases share common mediators, such as uromodulin and pro-adrenomedullin. These findings highlight the importance of risk factors modification in reducing disease burden among people with T2D and facilitate the understanding of mediation effects of plasma proteins underlying these associations.
Thymosin Beta-4 Modulates Cardiac Remodeling by Regulating ROCK1 Expression in Adult Mammals.
Int J Mol Sci
Klaudia Maar, Jeffrey E Thatcher, Egor Karpov +3 more
Although a myocardial infarction occurs roughly every minute in the U.S. alone, medical research has yet to unlock the key to fully enabling post-hypoxic myocardial regeneration. Thymosin beta-4 (TB4), a short, secreted peptide, was shown to possess a beneficial impact regarding myocardial cell survival, coronary re-growth and progenitor cell activation following myocardial infarction in adult mammals. It equally reduces scarring, however, the precise mechanisms through which the peptide assists this phenomenon have not been properly elucidated. Accordingly, the primary aim of our study was to identify novel molecular contributors responsible for the positive impact of TB4 during the remodeling processes of the infarcted heart. We performed miRNA profiling on adult mice hearts following permanent coronary ligation with or without systemic TB4 injection and searched for targets and novel mechanisms through which TB4 may mitigate pathological scarring in the heart. Our results revealed a significant increase in miR139-5p expression and identified ROCK1 as a potential target protein aligned. Real-time PCR, Western blot and immunostaining on adult mouse hearts and human cardiac cells revealed the peptide indirectly or directly modulates ROCK1 protein levels both in vivo and in vitro. We equally discovered TB4 may reverse or inhibit fibroblast/myofibroblast transformation and the potential downstream mechanisms by which TB4 alters cellular responses through ROCK1 are cell type specific. Given the beneficial effects of ROCK1 inhibition in various cardiac pathologies, we propose a potential utilization for TB4 as a ROCK1 inhibitor in the future.
Thymic Bmi-1 hampers γδT17 generation and its derived RORγt-IL-17A signaling to delay cardiac aging.
Proc Natl Acad Sci U S A
Qiuyi Wang, Yue Wang, Yujie Lin +13 more
New immunosenescence targets for preventing senescence-associated pathological cardiac hypertrophy (SA-PCH) need to be explored. In the present study, with physiologically aged human and mouse samples, the IL-17A level increased with physiological aging, heart failure (HF), and SA-PCH and was negatively correlated with thymic Bmi-1 expression. Bmi-1f/fLckCre+ mice and Bmi-1f/f littermates were generated to determine whether Bmi-1 delayed T cell aging by maintaining thymic T cell development to prevent SA-PCH. As a result, Bmi-1 promoted thymic T cell development by upregulating Notch signaling and prevented DN1 T cells from differentiating into γδT17 cells by downregulating γδT17 cell differentiation signaling. Bmi-1 upregulated Notch signaling by inhibiting p53-mediated Ikzf1 transcription at the -1,863 to -1,849 Ikzf1 promoter region. Bmi-1-RING1B promoted RORγt ubiquitination and degradation by proteasome to inhibit the production of IL-17A in γδT17 cells. Bmi-1 also downregulated Rorc transcribed by c-Maf by trimethylating H3K27 at the -1,511 to -1,497 Rorc promoter region. Subsequently, the number of peripheral γδT17 cells infiltrating the heart tissues was reduced, while alleviating IL-17A-dependent cardiac aging, hypertrophy, dysfunction, senescence-associated secretory phenotype (SASP), and macrophage-myofibroblast transition, ultimately improving SA-PCH. The RORγt inhibitor SR1001 and IL-17A neutralizing antibody ixekizumab prevented thymic RORγt-IL-17A-dependent SA-PCH. Furthermore, RORγt bound to Bmi-1 through ARG237 and to RING1B through GLU235, which could be used as a therapeutic strategy for SA-PCH to construct binding peptides promoting Bmi-1-RING1B binding to RORγt and degrading RORγt for inhibiting γδT17 cell differentiation and IL-17A production. Thus, thymic Bmi-1 prevented IL-17A-dependent SA-PCH by decreasing γδT17 cell numbers.
A Metabolically Stable Apelin-13 Analog Acting as a Potent ITo Potassium Current Blocker with Potential Benefits for Brugada Syndrome.
Int J Mol Sci
Juan Antonio Contreras Vite, Alexandria Tiffinger, Léa Théroux +6 more
Apelin serves as the endogenous ligand for the APJ receptor and enhances cardiac contractility without significantly affecting potassium currents. However, its short in vivo half-life limits clinical application, prompting the development of metabolically stable APJ receptor agonists. This study employed the patch-clamp technique to investigate the effects of the C-terminally modified apelin-13-2Nal derivative (2Nal) on action potential dynamics, rapid sodium (INa), and transient potassium (ITO) currents in rat cardiomyocytes. We discovered that 2Nal prolongs ventricular action potential duration by selectively blocking ITo. Dose-response analysis indicated that 2Nal acts as a partial antagonist of ITO, achieving a maximum blockade of 47%, with an apparent EC50 of 0.3 nM, while not affecting INa. Our lab previously found that an imbalance between ITo and INa currents contributes to the development of cardiac arrhythmias in conditions like Brugada syndrome. Currently, few therapeutic options exist to safely address this imbalance, as sodium channel openers cannot restore it, and most ITo blockers are cardiotoxic. The selective blockade of ITo by 2Nal that we describe here helps restore the balance of electrical currents between ITo and INa. Our study presents a novel, safe partial antagonist of ITo that may help prevent arrhythmias associated with Brugada syndrome.
Vasoactive Intestinal Peptide (VIP) in COVID-19 Therapy-Shedding of ACE2 and TMPRSS2 via ADAM10.
Int J Mol Sci
Charlotte Gutzler, Kerstin Höhne, Daniele Bani +9 more
Patients infected with SARS-CoV-2 may develop mild respiratory symptoms but also Acute Respiratory Distress Syndrome (ARDS). Additionally, severe systemic inflammation contributes to morbidity and mortality. The SARS-CoV-2 virus enters the cell by binding to the angiotensin-converting enzyme 2 (ACE2) receptor, followed by cleavage by transmembrane serine protease 2 (TMPRSS2). Vasoactive intestinal peptide (VIP) is known for its immune-modulating effects by suppressing the release of pro-inflammatory cytokines and enhancing regulatory T-cells. Furthermore, it has been tested in SARS-CoV-2-related clinical trials. We set out to investigate its role in the setting of SARS-CoV-2 infection in vitro. Epithelial cells (CaCo-2) were stimulated with SARS-CoV-2 spike protein, treated with native VIP and analyzed to investigate the mRNA and surface expression of ACE2 and TMPRSS2, the enzyme activity of TMPRSS2 and the infection rate by a SARS-CoV-2 pseudovirus. VIP downregulated ACE2 and TMPRSS2 mRNA and surface expression. Beyond these direct effects, VIP mediates the shedding of surface-expressed ACE2 and TMPRSS2 via upregulation of a sheddase protease (ADAM10). Functionally, these dual mechanisms of VIP-mediated downregulation of proteins involved in SARS-CoV-2 cell entry resulted in a reduced infection rate by the SARS-CoV-2 pseudovirus. These data imply that VIP hampers viral entry mechanisms based on SARS-CoV-2 and the linkage to ADAM10 may stimulate research in other indications beyond SARS-CoV-2.
Cerebrolysin Induces Dendritic Tree Plastic Changes and BDNF Increase in the Amygdala of Male Rats with Maternal Deprivation.
Neurochem Res
Jhonathan Cárdenas-Bedoya, Blanca Miriam Torres-Mendoza, Nestor Ismael Martínez-Torres
Several psychopathologies may be triggered, among other factors, by stress or trauma in childhood. The maternal deprivation model (MD) replicates some of the core factors that may induce the onset of different psychopathologies like structural and plasticity defects. Among other brain regions, the amygdala is susceptible to stress and trauma and plays a key role in integrating social behavior. Several molecules, such as Cerebrolysin® (CBL), have been used to treat different symptoms by reversing the underlying neurobiological plasticity-related changes. In this study, maternal deprivation (MD) was conducted on 9-day-old male Sprague-Dawley rats (n = 28; 7 rats per group: Intact, Intact + CBL, MD, and MD + CBL). At 25 postnatal days (PND), CBL treatment was administered for 10 consecutive days, and social behavior was evaluated in a three-chamber social test at 35 PND. Moreover, Sholl analysis and immunohistochemistry were carried out for dendritic intersection and brain-derived neurotrophic factor (BDNF) presence in the amygdala, respectively. CBL treatment had an augmentative effect on intact animals in terms of social behavior and incidences, but no differences between MD and CBL-treated animals. Moreover, dendritic intersections and BDNF decreased after the MD protocol but increased by CBL treatment in MD animals. Our results show that CBL could be part of the treatment in case of a traumatic or stressful event in neurodevelopment, especially in the youth age. According to this preclinical study, CBL could help reverse symptoms of different psychopathologies caused by stress or trauma, with neurobiological changes underlying its effect.
Influence of Exogenous Neuropeptides on the Astrocyte Response Under Conditions of Continuous and Cyclic Hypoxia and Red Blood Cell Lysate.
Int J Mol Sci
Klaudyna Kojder, Magdalena Gąssowska-Dobrowolska, Wojciech Żwierełło +7 more
Acute brain injury includes different pathologies: stroke, traumatic injury, subarachnoidale haemorhhage. In the pathophysiology of acute brain injury, secondary injury with hyperactivation of glia plays a crucial role. Activated glial cells induce prolonged inflammation that impacts the recovery and further cognitive functions of patients. In our study, we have examined the neuroprotective impact of exogenous neuropeptides-Cerebrolysin on astrocytes under different conditions. In a model that simulates central nervous system damage associated with brain injury, stroke, and subarachnoid hemorrhage, the U87MG human brain cancer (glioblastoma astrocytoma like) cells were treated with Cerebrolysin and exposed to conditions of continuous and cyclic hypoxia and red blood cell lysate overload. The activity and expression of cyclooxygenases COX-1 and COX-2 and on cytokines (IL-8, IL-1β, IL-6, IL-10) and chemokines (CCL5/RANTES, CXCL9/MIG, CCL2/MCP-1, and CXCL10/IP-10) concentration were assessed. Cerebrolysin lowers IL-1β and IL-6 and increases IL-10 under all conditions. Cerebrolysin may exhibit a neuroimmunotrophic function, reducing inflammation under conditions that replicate traumatic brain injury and hemorrhagic insults to the central nervous system. By modulating both pro-inflammatory and anti-inflammatory cytokines, Cerebrolysin can help create a more balanced immune response conducive to tissue repair and reduced secondary damage. Its ability to lower harmful mediators like IL-1β and IL-6 while enhancing protective factors such as IL-10 suggests a promising therapeutic strategy in stroke, traumatic brain injury, and subarachnoid hemorrhage. Alongside other mechanisms such as neurotrophic factor enhancement and glial cell regulation, this cytokine modulation underscores the therapeutic potential of Cerebrolysin in a variety of central nervous system disorders.
Postprandial Responses to Animal Products with Distinct Fatty Acid and Amino Acid Composition Are Diet-Dependent.
Nutrients
Bjørg Egelandsdal, Anna Haug, Jens F Rehfeld +5 more
Though evidence is limited, animal products like pork sausages and cheese may affect satiety differently due to their distinct protein, fat, and calcium content. This study therefore compared their acute effects on breakfast using appetite-related markers.
Goldfish phoenixin: (I) structural characterization, tissue distribution, and novel function as a feedforward signal for feeding-induced food intake in fish model.
Front Endocrinol (Lausanne)
Xiangfeng Qin, Cheng Ye, Ying Wai Chan +1 more
Phoenixin (PNX) is a novel peptide with diverse functions mediated by the orphan receptor GPR173. It also plays a role in appetite control, but the effect is not consistent across species and the mechanisms involved are still unclear. Using goldfish as a model, the mechanisms underlying feeding regulation by PNX were examined. In our study, two isoforms of PNX, PNXa and PNXb, and one form of GPR173 were cloned in goldfish and found to be highly conserved compared to their counterparts in other species based on sequence alignment, phylogenetic analysis, and in silico protein modeling. Using RT-PCR, PNXa/b and GPR173 were confirmed to be ubiquitously expressed at the tissue level. In goldfish, transcript expression of PNXa/b and GPR173 in the liver and brain areas including the telencephalon, hypothalamus, and optic tectum, were elevated by food intake but suppressed by fasting. Intraperitoneal (IP) and intracerebroventricular (ICV) injections of PNX20a and PNX20b, the mature peptides for PNXa and PNXb respectively, were both effective in increasing foraging behavior, surface motility, and food intake. Furthermore, the expression of orexigenic factors (neuropeptide Y (NPY), agouti-related peptide, orexin, and apelin) was elevated with parallel drops in anorexigenic signals (cholecystokinin, pro-opiomelanocortin, corticotropin-releasing hormone, and melanin-concentrating hormone) in the telencephalon, hypothalamus, and/or optic tectum. In the same brain areas, receptor expression for anorexigenic factors (leptin and adiponectin) was attenuated with concurrent rises in receptor levels for orexigenic signals (NPY and ghrelin). In our study, after IP injection of PNX20a/b, downregulation of leptin, adiponectin, and other feeding inhibitors expressed in the liver was also noted. Our findings reveal that PNX20a/b can serve as an orexigenic factor in goldfish. PNX signals (both central and peripheral) can be induced by food intake and act within the brain to trigger foraging and food consumption via differential modulation of appetite-regulating factors and their receptors in different brain areas. The feeding responses observed may also involve a hepatic component with PNX repression of feeding inhibitors expressed in the liver. The PNX signals induced by feeding may form a feedforward loop to maintain/prolong food intake during a meal prior to the onset of satiation response in our fish model.
Pharmacological treatment for metabolic dysfunction-associated steatotic liver disease and related disorders: Current and emerging therapeutic options.
Pharmacol Rev
Xiang Zhang, Harry Cheuk-Hay Lau, Jun Yu
Metabolic dysfunction-associated steatotic liver disease (MASLD; formerly known as nonalcoholic fatty liver disease) is a chronic liver disease affecting over a billion individuals worldwide. MASLD can gradually develop into more severe liver pathologies, including metabolic dysfunction-associated steatohepatitis (MASH), cirrhosis, and liver malignancy. Notably, although being a global health problem, there are very limited therapeutic options against MASLD and its related diseases. While a thyroid hormone receptor agonist (resmetirom) is recently approved for MASH treatment, other efforts to control these diseases remain unsatisfactory. Given the projected rise in MASLD and MASH incidence, it is urgent to develop novel and effective therapeutic strategies against these prevalent liver diseases. In this article, the pathogenic mechanisms of MASLD and MASH, including insulin resistance, dysregulated nuclear receptor signaling, and genetic risk factors (eg, patatin-like phospholipase domain-containing 3 and hydroxysteroid 17-β dehydrogenase-13), are introduced. Various therapeutic interventions against MASH are then explored, including approved medication (resmetirom), drugs that are currently in clinical trials (eg, glucagon-like peptide 1 receptor agonist, fibroblast growth factor 21 analog, and PPAR agonist), and those failed in previous trials (eg, obeticholic acid and stearoyl-CoA desaturase 1 antagonist). Moreover, given that the role of gut microbes in MASLD is increasingly acknowledged, alterations in the gut microbiota and microbial mechanisms in MASLD development are elucidated. Therapeutic approaches that target the gut microbiota (eg, dietary intervention and probiotics) against MASLD and related diseases are further explored. With better understanding of the multifaceted pathogenic mechanisms, the development of innovative therapeutics that target the root causes of MASLD and MASH is greatly facilitated. The possibility of alleviating MASH and achieving better patient outcomes is within reach. SIGNIFICANCE STATEMENT: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide, and it can progress to more severe pathologies, including steatohepatitis, cirrhosis, and liver cancer. Better understanding of the pathogenic mechanisms of these diseases has facilitated the development of innovative therapeutic strategies. Moreover, increasing evidence has illustrated the crucial role of gut microbiota in the pathogenesis of MASLD and related diseases. It may be clinically feasible to target gut microbes to alleviate MASLD in the future.
The neuroprotective role of Humanin in Alzheimer's disease: The molecular effects.
Eur J Pharmacol
Saad Misfer Alqahtani, Hayder M Al-Kuraishy, Ali I Al-Gareeb +6 more
Humanin (HN) is an endogenous micropeptide also known as a mitochondria-derived peptide. It has a neuroprotective effect against Alzheimer's disease (AD) and other neurodegenerative diseases by improving hippocampal acetylcholine and attenuating the development of oxidative stress and associated neurotoxicity. HN protects the neuron from the toxic effects of amyloid beta (Aβ). HN is regarded as a biomarker of mitochondrial stress. Interestingly, aging reduces brain expression of HN, leading to cognitive impairment and elevating the risk of neurodegeneration, including AD. However, in old subjects and AD patients, circulating HN levels increase as a compensatory mechanism to reduce neurodegeneration and mitochondrial dysfunction in AD. Conversely, other studies demonstrated a reduction in circulating HN levels in AD. These findings indicated controversial points regarding the precise mechanistic role of HN in AD. Therefore, the aim of this review was to discuss the exact role of HN in AD neuropathology and also to discuss the molecular mechanisms of HN in AD.
Intraoperative Diagnosis and Management of Arginine Vasopressin Disorder During Pituitary Tumor Resection via Transsphenoidal Endoscopic Navigation.
Cureus
Delayne M Coleman, Emily Kim, Krupa Patel +2 more
Arginine vasopressin (AVP) disorders (previously called diabetes insipidus) lead to excessive urination due to reduced antidiuretic hormone (ADH) secretion or kidney resistance to ADH. This results in decreased water reabsorption, causing dehydration and electrolyte imbalances. Diagnosing these disorders during general anesthesia is challenging, but close monitoring of electrolytes and urine output, especially during high-risk surgeries such as intracranial procedures, is crucial. A 64-year-old woman with a history of asthma presented with severe bifrontal headaches and left-eye medial gaze palsy. Imaging showed a large sellar mass extending into the sphenoid sinus, requiring a transsphenoidal resection. An hour and 30 minutes into surgery, the patient developed acute polyuria (1 L urine), hyperosmolality (Na: 149 mmol/L), and colorless urine with low specific gravity (1.003), indicating an arginine vasopressin disorder. Desmopressin (DDAVP) was administered, improving urine specific gravity to 1.013, and a D5W infusion corrected a 2.5 L fluid deficit. Severe hypokalemia (K: 2.6 mmol/L) and hyperglycemia (glucose: 230 mg/dL) were also treated, with electrolyte and glucose levels stabilizing postoperatively. On postoperative day (POD) 2, the patient experienced polyuria up to 23 L and excessive thirst, requiring additional desmopressin on POD 3. She was discharged on POD 9. Arginine vasopressin disorders, especially vasopressin deficiency (central diabetes insipidus), commonly result from neurohypophyseal damage during cranial surgery. Prompt diagnosis and treatment with desmopressin and fluids can effectively manage fluid and electrolyte imbalances, preventing severe complications such as hypernatremia and neurological deficits. This case highlights the importance of intraoperative urine and laboratory monitoring to ensure timely recognition and management.
Anserine, Balenine, and Ergothioneine: Impact of Histidine-Containing Compounds on Exercise Performance-A Narrative Review.
Nutrients
Maciej Jędrejko, Katarzyna Kała, Bożena Muszyńska
Histidine is an amino acid which plays a critical role in protein synthesis, muscle buffering during anaerobic exercise, and antioxidation. It also acts as a precursor to carnosine, a dipeptide that enhances physical performance by being present in fast-contracting muscle fibers and contributing to buffering capacity. Recent studies have examined other histidine-containing compounds, such as anserine, balenine, and ergothioneine, to assess their potential benefits for physical activity. This narrative review focuses on the literature about the effects of dietary supplementation with these histidine-containing compounds on exercise capacity in animals and humans. The findings indicate that anserine may improve physical performance and reduce fatigue, particularly in quick, repetitive activities. Although balenine has been less extensively studied, it has shown promise in enhancing muscle regeneration and antioxidative defense in animal models. Ergothioneine, a sulfur-containing histidine derivative, displayed antioxidant and anti-inflammatory properties in both animal and human studies, suggesting its potential role in reducing exercise-induced oxidative stress and aiding recovery. The diversity of the presented studies and their limitations do not provide an opportunity to confirm the ergogenic properties of the histidine-containing compounds studied. Nevertheless, supplementation with anserine and ergothioneine shows promise for enhancing physical performance and recovery, though further research is required to better understand their mechanisms and optimize their use in sports and exercise.
GHSR gene knockout alleviates the liver pathological response in Echinococcus granulosus infection by reducing parasite survival.
Vet Res
Jiang Zhu, Tanfang Zhou, Guangfeng Chen +6 more
Cystic echinococcosis (CE) is a parasitic disease caused by the larval stage of Echinococcus granulosus, and the immunosuppressive microenvironment exacerbates disease progression. Ghrelin, a peptide hormone, plays a role in modulating immune inflammation and may influence the progression of E. granulosus infection through its receptor, GHSR (growth hormone secretagogue receptor). However, whether GHSR downregulation can inhibit E. granulosus infection remains unclear. In this study, we extracted liver tissues from E. granulosus-infected mice and those treated with the GHSR antagonist [D-Lys3]-GHRP-6. Proteomic analysis revealed 341 differentially expressed proteins, of which 185 were upregulated and 156 were downregulated. Metabolomic sequencing revealed 101 differentially expressed metabolites, including 62 upregulated and 39 downregulated metabolites. KEGG pathway enrichment analysis of both proteomic and metabolomic data revealed seven key signalling pathways, 11 key proteins, and 26 key metabolites that interact through metabolic and organic system networks. Next, we examined the disease progression of E. granulosus infection in GHSR-knockout mice. Compared with the E. granulosus (Eg) group, the GHSR-KO group presented a significant reduction in the number of liver infection foci. The serum and liver ghrelin levels were significantly greater in the E. granulosus group than in the control group, along with increased secretion of proinflammatory cytokines (IL-2 and IFN-γ) and decreased secretion of anti-inflammatory cytokines (IL-4 and IL-10). In contrast, the GHSR-KO group presented significantly lower ghrelin levels in both the serum and liver, with reduced proinflammatory cytokine secretion and increased anti-inflammatory cytokine secretion, similar to those of the control group. Furthermore, ghrelin and inflammation-related factors, including MyD88, NF-κB p65, iNOS, and Arg-1, exhibited coordinated expression changes in liver lesions and surrounding areas. These findings suggest that GHSR gene knockout can ameliorate the progression of liver E. granulosus infection and associated liver inflammation.