RESUMEN
To evaluate the safety and efficacy of L-glutamine in reducing vaso-occlusive crisis (VOC) and improving cerebral arterial blood flow in children with sickle cell disease (SCD). This is an interventional randomized controlled trial that recruited sixty SCD patients, aged 9.2 ± 3.7 years, who had at least two VOCs during the last 12 months and on a stable dose of hydroxyurea. They were randomly assigned in a 1:1 ratio to receive glutamine (0.3 gm/kg/dose/12h) orally for 24 weeks or the standard of care (SOC). All patients had VOCs in the last year > 3, those on glutamine had a higher number of VOCs and hospitalization for VOC in the last year. There was a decreasing trend in the number, severity, and hospitalization of VOC and a significantly lower cumulative number of VOCs and hospitalizations in the glutamine group than in SOC (p = 0.008, p < 0.001 respectively). Time-averaged mean maximum velocity for the glutamine group had a marginal increase in both middle cerebral arteries, all values remained normal within a normal range, and in both internal carotid arteries, values increased from abnormally low to normal ranges at week 24. Glutamine reduced the number of VOCs and severity and may have a potentially favorable impact on the cerebral arterial flow velocities.
Asunto(s)
Anemia de Células Falciformes , Glutamina , Humanos , Glutamina/uso terapéutico , Glutamina/administración & dosificación , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/complicaciones , Femenino , Masculino , Niño , Adolescente , Preescolar , Hidroxiurea/uso terapéutico , Hidroxiurea/efectos adversos , Circulación Cerebrovascular/efectos de los fármacos , Hospitalización , Resultado del TratamientoRESUMEN
Under optimal physiological conditions, muscle mass maintenance is ensured by dietary protein, which balances the amino acid loss during the post-absorption period and preserves the body's protein homeostasis. Conversely, in critical clinical conditions (acute, subacute or postacute), particularly those related to hypomobility or immobility, combined with malnutrition, and local/systemic inflammation, the loss of muscle mass and strength can be quantitatively significant. A decline of more than 1% in muscle mass and of more than 3% in muscle strength has been registered in subjects with aged 20-37 yr after just five days of bed rest, similarly to those observed during one year of age-related decline in individuals over the age of 50. Loss of muscle mass and strength can have a dramatic effect on subjects' functional capacities, on their systemic metabolic control and on the amino acid reserve function, all of which are fundamental for the maintenance of other organs' and tissues' cell processes. References available indicate that the average 1%-2% reduction per day of muscle mass in patients in the intensive care unit (ICU) could represent an independent predictor of hospital mortality and physical disability in the five years following hospitalization. After just a few days or weeks of administration, supplementation with EAAs and glutamine has shown significant effects in maintaining muscle size and strength, which are typically negatively affected by some acute/subacute or postacute critical conditions (muscle recovery after surgery, oncology patients, ICU treatments), especially in the elderly or in those with pre-existing degenerative diseases. In this review, we focused on the theoretical bases and the most relevant clinical studies of EAA and glutamine supplementation as a single compound, with the aim of clarifying whether their combined use in a blend (EAAs-glutamine) could be potentially synergistic to prevent disease-related muscle wasting and its impact on the duration and quality of patients' clinical course.
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Aminoácidos Esenciales , Suplementos Dietéticos , Glutamina , Músculo Esquelético , Atrofia Muscular , Humanos , Glutamina/administración & dosificación , Glutamina/uso terapéutico , Aminoácidos Esenciales/administración & dosificación , Aminoácidos Esenciales/uso terapéutico , Fuerza Muscular/efectos de los fármacos , Enfermedad Aguda , Enfermedad CríticaRESUMEN
BACKGROUND: After receiving radiation therapy, 60%-95% of patients with cancer develop radiodermatitis, which causes pain, wound infection, and poor quality of life. Glutamine is a popular nutritional supplement for patients with cancer. Several studies examined the usefulness of glutamine for reducing radiodermatitis. However, there is still no consolidated evidence for clinical use. METHODS: We searched PubMed, Embase, Cochrane Library, CINAHL PLUS, and the China Knowledge Resource Integrated Database for the relevant literature published up to March 2023, without language restrictions. Two reviewers screened, filtered, and appraised these articles independently, and their data were pooled using a random-effects model. RESULTS: Five randomized controlled trials (RCTs) with 218 participants were analyzed. The incidence of radiodermatitis in the glutamine group (89/110) was significantly lower than in the placebo group (99/108; risk ratio [RR], 0.90; 95% CI, 0.81-1.00; p = 0.05; I2 = 7%). The incidence of moderate to severe radiodermatitis was significantly lower in the glutamine group than in the placebo group (RR, 0.49; 95% CI, 0.32-0.76; p = 0.001; I2 = 52%). Moreover, subgroup analysis demonstrated heterogeneity (I2 = 52%) for moderate to severe radiodermatitis, the risk of which might be significantly reduced by a glutamine dose of 20-30 g/day (RR, 0.60; 95% CI, 0.41-0.87; I2 = 0%). CONCLUSION: The meta-analysis indicate that glutamine might lead to a lower incidence of radiodermatitis, and that a glutamine dose of 20-30 g/day might decrease the incidence of moderate to severe dermatitis. Thus, the serious impact of radiodermatitis on treatment follow-up makes the clinical use of glutamine even more important. PROSPERO number: CRD42021254394.
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Neoplasias , Radiodermatitis , Humanos , Glutamina/uso terapéutico , Radiodermatitis/tratamiento farmacológico , Radiodermatitis/etiología , Radiodermatitis/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias/complicaciones , Neoplasias/radioterapia , Suplementos DietéticosRESUMEN
In arterial hypertension, the dysregulation of several metabolic pathways is closely associated with chronic immune imbalance and inflammation progression. With time, these disturbances lead to the development of progressive disease and end-organ involvement. However, the influence of cholecalciferol on metabolic pathways as a possible mechanism of its immunomodulatory activity in obesity-related hypertension is not known. In a phase 2, randomized, single-center, 24-week trial, we evaluated, as a secondary outcome, the serum metabolome of 36 age- and gender-matched adults with obesity-related hypertension and vitamin D deficiency, before and after supplementation with cholecalciferol therapy along with routine medication. The defined endpoint was the assessment of circulating metabolites using a nuclear magnetic resonance-based metabolomics approach. Univariate and multivariate analyses were used to evaluate the systemic metabolic alterations caused by cholecalciferol. In comparison with normotensive controls, hypertensive patients presented overall decreased expression of several amino acids (p < 0.05), including amino acids with ketogenic and glucogenic properties as well as aromatic amino acids. Following cholecalciferol supplementation, increases were observed in glutamine (p < 0.001) and histidine levels (p < 0.05), with several other amino acids remaining unaffected. Glucose (p < 0.05) and acetate (p < 0.05) decreased after 24 weeks in the group taking the supplement, and changes in the saturation of fatty acids (p < 0.05) were also observed, suggesting a role of liposoluble vitamin D in lipid metabolism. Long-term cholecalciferol supplementation in chronically obese and overweight hypertensives induced changes in the blood serum metabolome, which reflected systemic metabolism and may have fostered a new microenvironment for cell proliferation and biology. Of note, the increased availability of glutamine may be relevant for the proliferation of different T-cell subsets.
Asunto(s)
Hipertensión , Deficiencia de Vitamina D , Adulto , Humanos , Colecalciferol/farmacología , Colecalciferol/uso terapéutico , Glutamina/uso terapéutico , Glucosa/uso terapéutico , Vitamina D/uso terapéutico , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Suplementos Dietéticos , Deficiencia de Vitamina D/complicaciones , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Aminoácidos/metabolismo , Método Doble CiegoRESUMEN
Clinical pancreatic ductal adenocarcinoma (PDAC) treatment is severely limited by lack of effective KRAS suppression strategies. To address this dilemma, a reactive oxygen species (ROS)-responsive and PDAC-targeted nanodrug named Z/B-PLS was constructed to confront KRAS through dual-blockade of its downstream PI3K/AKT/mTOR and RAF/MEK/ERK for enhanced PDAC treatment. Specifically, photosensitizer zinc phthalocyanine (ZnPc) and PI3K/mTOR inhibitor BEZ235 (BEZ) were co-loaded into PLS which was constructed by click chemistry conjugating MEK inhibitor selumetinib (SEL) to low molecular weight heparin with ROS-responsive oxalate bond. The BEZ and SEL blocked PI3K/AKT/mTOR and RAF/MEK/ERK respectively to remodel glycolysis and non-canonical glutamine metabolism. ZnPc mediated photodynamic therapy (PDT) could enhance drug release through ROS generation, further facilitating KRAS downstream dual-blockade to create treatment-promoting drug delivery-therapeutic positive feedback. Benefiting from this broad metabolic modulation cascade, the metabolic symbiosis between normoxic and hypoxic tumor cells was also cut off simultaneously and effective tumor vascular normalization effects could be achieved. As a result, PDT was dramatically promoted through glycolysis-non-canonical glutamine dual-metabolism regulation, achieving complete elimination of tumors in vivo. Above all, this study achieved effective multidimensional metabolic modulation based on integrated smart nanodrug delivery, helping overcome the therapeutic challenges posed by KRAS mutations of PDAC.
Asunto(s)
Carcinoma Ductal Pancreático , Nanopartículas , Neoplasias Pancreáticas , Humanos , Glutamina/farmacología , Glutamina/metabolismo , Glutamina/uso terapéutico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/uso terapéutico , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/uso terapéutico , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Neoplasias Pancreáticas/tratamiento farmacológico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/uso terapéutico , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Quinasas de Proteína Quinasa Activadas por Mitógenos/uso terapéutico , Glucólisis , Fototerapia , Línea Celular TumoralRESUMEN
Certain aggressive cancers, such as triple-negative breast cancer (TNBC), heavily bank on glutamine for their proliferation and survival. In this context, TNBC functions as a "glutamine trap," extracting circulating glutamine at a rate surpassing that of any other organ. Moreover, the overexpression of Alanine, Serine, Cysteine Transporter 2 (ASCT2), a key player in glutamine uptake, further underscores the significance of targeted therapy to enhance TNBC treatment. This led to the exploration of a novel approach involving hydrophobized Pluronic-based mixed micelles achieved through the use of docosahexaenoic acid and stapled with glutamine for displaying inherent ASCT2 targeting ability-a formulation termed LPT G-MM. LPT G-MM exhibited optimal characteristics, including a size of 163.66 ± 10.34 nm, a polydispersity index of 0.237 ± 0.083, and an enhanced drug loading capacity of approximately 15 %. Transmission electron microscopy validated the spherical shape of these micelles. In vitro release studies demonstrated drug release in a sustained manner without the risk of hemolysis. Importantly, LPT G-MM displayed heightened cellular uptake, increased cytotoxicity, a lower IC50 value, elevated reactive oxygen species, induced mitochondrial membrane depolarization, and a greater apoptosis index in TNBC cell lines compared to free LPT. The pharmacokinetic profile of LPT G-MM revealed a substantial rise in half-life (t1/2) by approximately 1.48-fold and an elevation in the area under the curve [AUC(0â∞)] by approximately 1.19-fold. Moreover, there was a significant reduction in the percentage of tumor volume by approximately 7.26-fold, along with decreased serum toxicity markers compared to free LPT. In summary, LPT G-MM demonstrated promising potential in boosting payload capacities and targeting specificity in the context of TNBC treatment.
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Micelas , Neoplasias de la Mama Triple Negativas , Humanos , Lapatinib/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Glutamina/uso terapéutico , Línea Celular Tumoral , ApoptosisRESUMEN
INTRODUCTION: Various nutrients play a physiological role in the healing process of pressure ulcers (PUs). Nutritional interventions include the administration of enteral nutritional supplements and formulas containing arginine, glutamine, and micronutrients. The aim of this systematic review is to evaluate the effectiveness of enteral nutritional supplements and formulas containing arginine and glutamine on wound-related outcomes. These include (1) time to healing, (2) changes in wound size, (3) local wound infection, (4) PU recurrence, and (5) PU-related pain. MATERIALS AND METHODS: This protocol was developed according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). A search will be conducted in the Cochrane Library, EMBASE, PubMed (MEDLINE), CINAHL (EBSCOhost interface) and Web of Science. In addition, a manual search will be conducted to identify relevant records. Except for systematic reviews, no restrictions will be placed on the study design, the population studied or the setting. Studies that do not address PUs, in vitro studies and studies that do not report wound-related outcomes will be excluded. Study selection, risk of bias assessment and data extraction will be performed independently by three researchers. Depending on the extent of heterogeneity of interventions, follow-up time and populations, results will be summarised either by meta-analysis or narrative synthesis. CONCLUSIONS: This is the first systematic review to identify, evaluate and summarise the current evidence for enteral arginine and glutamine supplementation on wound-related outcomes in PUs. The review will provide a solid basis for deriving valid and clinically relevant conclusions in this area.
Asunto(s)
Arginina , Glutamina , Úlcera por Presión , Revisiones Sistemáticas como Asunto , Cicatrización de Heridas , Úlcera por Presión/tratamiento farmacológico , Arginina/uso terapéutico , Arginina/farmacología , Arginina/administración & dosificación , Glutamina/uso terapéutico , Glutamina/farmacología , Glutamina/administración & dosificación , Humanos , Cicatrización de Heridas/efectos de los fármacos , Cicatrización de Heridas/fisiologíaRESUMEN
BACKGROUND Hospital-acquired infections negatively impact the health of inpatients and are highly costly to treat. Oral care reduces the microorganism number in the mouth and lungs and is essential in preventing postoperative oral inflammation, lung infection, and other complications. This study was designed to determine the effects of oral care with glutamine on oral health, oral flora, and incidence of pneumonia in patients after neurosurgery. MATERIAL AND METHODS This was a parallel, double-blind, randomized trial. Patients admitted to the Neurosurgery Department of the hospital from July to October 2021 were selected. Three hundred patients who met the inclusion criteria were randomized into 3 groups. The control group (n=100) received oral care with routine oral nursing methods with saline, whereas the experimental group (n=100) received oral care with 5% glutamine. A compound chlorhexidine group (n=100) was set as a positive control. All patients, care providers, and investigators were blinded to the group assignment. The incidence of local debris, oral mucositis, halitosis, dryness, oral mucositis disorders, and oral flora types were collected and analyzed in all groups. RESULTS The incidence of local debris, oral mucositis, halitosis, dryness, and other oral mucositis disorders in the glutamine oral care group was significantly decreased, compared with that of the control group. Oral flora types in the glutamine and chlorhexidine groups were significantly reduced. CONCLUSIONS Oral care with 5% glutamine after neurosurgery is associated with a lower incidence of oral disorders and pneumonia, and a significant reduction in oral flora.
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Halitosis , Mucositis , Neurocirugia , Neumonía , Estomatitis , Humanos , Clorhexidina/farmacología , Salud Bucal , Glutamina/farmacología , Glutamina/uso terapéutico , Mucosa Bucal , Halitosis/complicaciones , Halitosis/tratamiento farmacológico , Estomatitis/tratamiento farmacológico , Mucositis/tratamiento farmacológico , Neumonía/prevención & control , Neumonía/complicacionesRESUMEN
INTRODUCTION: Sickle cell disease (SCD) is an inherited disorder characterised by polymerisation of deoxygenated haemoglobin S and microvascular obstruction. The cardinal feature is generalised pain referred to as vaso-occlusive crises (VOC), multi-organ damage and premature death. SCD is the most prevalent inherited life-threatening disorders in the world and over 85% of world's 400,000 annual births occur low-and-middle-income countries. Hydroxyurea remained the only approved disease modifying therapy (1998) until the FDA approved L-glutamine (2017), Crizanlizumab and Voxelotor (2019) and gene therapies (Exa-cel and Lovo-cel, 2023). AREAS COVERED: Clinical trials performed in the last 10 years (November 2013 - November 2023) were selected for the review. They were divided according to the mechanisms of drug action. The following pubmed central search terms [sickle cell disease] or [sickle cell anaemia] Hydroxycarbamide/ Hydroxyurea, L-Glutamine, Voxelotor, Crizanlizumab, Mitapivat, Etavopivat, gene therapy, haematopoietic stem cell transplantation, and combination therapy. EXPERT OPINION: We recommend future trials of combination therapies for specific complications such as VOCs, chronic pain and renal impairment as well as personalised medicine approach based on phenotype and patient characteristics. Following recent approval of gene therapy for SCD, the challenge is addressing the role of shared decision-making with families, global access and affordability.
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Anemia de Células Falciformes , Benzaldehídos , Dolor Crónico , Pirazinas , Pirazoles , Humanos , Hidroxiurea/uso terapéutico , Glutamina/uso terapéutico , Anemia de Células Falciformes/tratamiento farmacológico , Dolor Crónico/tratamiento farmacológico , Combinación de MedicamentosRESUMEN
BACKGROUND: The most frequently occurring painful and dose-limiting side effect of radiation therapy (RT) to the head and neck region is oral mucositis (OM). Several studies demonstrated that glutamine may reduce the severity and the duration of OM significantly during RT and chemo-radiotherapy in patients with head and neck cancer (HNC). MATERIALS AND METHODS: Between January 2021 and August 2022, a prospective single institutional case-control study compared the efficacy and safety of oral glutamine on radiation-induced mucositis in patients with HNC. Of 60 biopsy-proven patients with HNC, 30 patients in the study arm received oral glutamine suspension (10 g in 500 mL of water) orally once daily, 2 hours before RT, receiving definitive or adjuvant RT and chemo-radiotherapy, while as 30 patients in the control arm received placebo with the same dose and schedule (n = 30 in the study arm and n = 30 in the control arm). RESULTS AND ANALYSIS: A total of 27 (90%) in the glutamine arm and 28 (93.33%) patients in the control arm developed mucositis. Grade 3 mucositis (13.33%) and Grade 4 mucositis (6.66%), respectively, were significantly less ( P = .040 and P = .004) in the glutamine arm. The mean duration of grade 3 and grade 4 mucositis was significantly less in the glutamine arm (8.94 days in the study arm vs. 14.54 in the control arm; P = .0001). The mean time of onset of OM was significantly delayed in the glutamine arm in comparison to the control arm with P < .001. CONCLUSION: Glutamine delays the onset of OM and decreases the severity of OM in patients of HNC receiving RT with or without chemotherapy.
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Glutamina , Neoplasias de Cabeza y Cuello , Traumatismos por Radiación , Estomatitis , Centros de Atención Terciaria , Humanos , Glutamina/administración & dosificación , Glutamina/uso terapéutico , Femenino , Estudios de Casos y Controles , Masculino , Estudios Prospectivos , Persona de Mediana Edad , India , Traumatismos por Radiación/etiología , Traumatismos por Radiación/tratamiento farmacológico , Traumatismos por Radiación/patología , Traumatismos por Radiación/prevención & control , Estomatitis/etiología , Estomatitis/tratamiento farmacológico , Estomatitis/patología , Estomatitis/prevención & control , Neoplasias de Cabeza y Cuello/radioterapia , Adulto , Administración Oral , Anciano , Quimioradioterapia/efectos adversos , Quimioradioterapia/métodosRESUMEN
To evaluate the effect of glutamine supplement on patients with burns, we conducted a systematic review and meta-analysis via synthesizing up-to-date studies. Databases including PubMed, Cochrane Central Register, EMBASE, Google scholar, Wanfang data, and ClinicalTrials.gov were searched up to October 2023 to find randomized trials evaluating glutamine supplement on patients with burns. The main outcomes included hospital stay, in-hospital mortality, infection, and wound healing. Twenty-two trials that randomized a total of 2170 patients were included in this meta-analysis. Pooled the length of hospital stay was shortened by glutamine supplement (weighted mean differences [WMD] = -7.95, 95% confidence interval [CI] -10.53 to -5.36, I2 = 67.9%, 16 trials). Both pooled wound healing rates (WMD = 9.15, 95% CI 6.30 to 12.01, I2 = 82.7%, 6 studies) and wound healing times (WMD = -5.84, 95% CI -7.42 to -4.27, I2 = 45.7%, 7 studies) were improved by glutamine supplement. Moreover, glutamine supplement reduced wound infection (risk ratios [RR] = 0.38, 95% CI 0.21 to 0.69, I2 = 0%, 3 trials), but not nonwound infection (RR = 0.88, 95% CI 0.73 to 1.05, I2 = 39.6%, 9 trials). Neither in-hospital mortality (RR = 0.95, 95% CI 0.74 to 1.22, I2 = 36.0%, 8 trials) nor the length of intensive care unit stay (WMD = 1.85, 95% CI -7.24 to 10.93, I2 = 78.2%, 5 studies) was improved by glutamine supplement. Subgroup analysis showed positive effects were either influenced by or based on small-scale, single-center studies. Based on the current available data, we do not recommend the routine use of glutamine supplement for burn patients in hospital. Future large-scale randomized trials are still needed to give a conclusion about the effect of glutamine supplement on burn patients.
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Quemaduras , Suplementos Dietéticos , Glutamina , Tiempo de Internación , Cicatrización de Heridas , Humanos , Quemaduras/terapia , Quemaduras/mortalidad , Glutamina/uso terapéutico , Tiempo de Internación/estadística & datos numéricos , Cicatrización de Heridas/efectos de los fármacos , Mortalidad Hospitalaria , Infección de Heridas/prevención & controlRESUMEN
BACKGROUND: Solute carrier family 38 member 5 (SLC38A5), as an amino acid transporter, play a vital role in cellular biological processes. In this study, we analyzed the function of SLC38A5 and its potential mechanism in breast cancer (BC) progression. METHODS: The expression of SLC38A5 in cancer and adjacent-normal tissues was analyzed by qRT-PCR and Western blot, and its correlation with patient prognosis was analyzed. The immunohistochemical staining of cancer tissues and adjacent-normal tissues was performed on SLC38A5-positive specimens. BC mice were successfully applied to examine the role of SLC38A5 on tumor proliferation using the CCK-8 assay. In BC cells and mouse tumor tissues, SLC38A5 and PCNA expression were determined by Western blotting. RESULTS: The study found that SLC38A5 was highly expressed in BC patients and associated with a poor survival. SLC38A5 silencing inhibited BC cell viability and glutamine uptake. In addition, SLC38A5 overexpression promoted BC cell viability via the glutamine metabolism. SLC38A5 inhibited cisplatin chemosensitivity in BC cells. Importantly, SLC38A5 silencing inhibited tumor growth in vivo. CONCLUSION: Our findings suggest that SLC38A5 enhances BC cell viability by glutamine metabolism, inhibits the chemical sensitivity of cisplatin in BC cells, and promotes tumor growth, emphasizing the clinical relevance of SLC38A5 in BC management as a novel potential therapeutic target.
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Sistemas de Transporte de Aminoácidos Neutros , Neoplasias de la Mama , Humanos , Animales , Ratones , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Cisplatino/farmacología , Cisplatino/uso terapéutico , Glutamina/uso terapéutico , Línea Celular Tumoral , Proliferación Celular , Sistemas de Transporte de Aminoácidos Neutros/uso terapéuticoRESUMEN
This study aims to explore the roles of phenylacetyl glutamine (PAGln) on myocardial infarction (MI) pathogenesis. Here, using targeted metabolomics analysis, it was found that the plasma metabolite PAGln was upregulated in coronary artery disease (CAD) patients and MI mice and could be an independent risk factor for CAD. In vivo and in vitro functional experiments revealed that PAGln pretreatment enhanced MI-induced myocardial injury and cardiac fibrosis, as evident by the increased infarct size, cardiomyocyte death, and the upregulated expression of cardiac fibrosis markers (Col1a1 and α-SMA). Combined with RNA-sequencing analysis and G protein-coupled receptor (GPCR) inhibitor, we found that the GPCR signaling activation is essential for PAGln-mediated effects on cardiomyocyte death. Furthermore, drug affinity responsive target stability and cellular thermal shift assay demonstrated that PAGln could interact with ß1-adrenergic receptor (AR). Moreover, ß1-AR blocker treatment indeed extended the cardiac remodeling after PAGln-enhanced MI. These results suggest that PAGln might be a potential therapeutic target for extending the cardiac remodeling window in MI patients that signals via ß1-AR.
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Infarto del Miocardio , Miocitos Cardíacos , Humanos , Ratones , Animales , Miocitos Cardíacos/metabolismo , Glutamina/metabolismo , Glutamina/uso terapéutico , Remodelación Ventricular , Infarto del Miocardio/tratamiento farmacológico , Fibrosis , Receptores Adrenérgicos/metabolismo , Receptores Adrenérgicos/uso terapéutico , Miocardio/metabolismoRESUMEN
BACKGROUND: The efficacy of supplemental enteral glutamine (GLN) in critical illness patients remains uncertainty. OBJECTIVE: Based on a recently published large-scale randomized controlled trials (RCTs) as regards the use of enteral GLN, we updated a meta-analysis of RCTs for further investigating the effects of enteral GLN administration in critically ill patients. METHODS: We searched RCTs reporting the impact of supplemental enteral GLN about clinical outcomes in adult critical illness patients from EMBASE, PubMed, Clinical Trials.gov, Scopus and Web of Science and subsequently registered the protocol in the PROSPERO (CRD42023399770). RCTs of combined enteral-parenteral GLN or parenteral GLN only were excluded. Hospital mortality was designated as the primary outcome. We conducted subgroup analyses of primary outcome based on specific patient populations, dosages and therapy regimens, and further performed trial sequential analysis (TSA) for clinical outcomes. RESULTS: Eighteen RCTs involving 2552 adult critically ill patients were identified. There were no remarkable influences on hospital mortality regardless of different subgroups (OR, 1.05; 95% CI, 0.85-1.30; p = 0.67), intensive care unit (ICU) length of stay (LOS) (MD, -0.07; 95% CI, -1.12 - 0.98; p = 0.89) and infectious complications (OR, 0.90; 95% CI, 0.75-1.10; p = 0.31) with enteral GLN supplementation. Additionally, the results of hospital mortality were confirmed by TSA. However, enteral GLN therapy was related to a reduction of hospital LOS (MD, -2.85; 95% CI, -5.27 to -0.43; p = 0.02). CONCLUSIONS: In this meta-analysis, it seems that enteral GLN supplementation is unlikely ameliorate clinical outcomes in critical illness patients except for the reduction of hospital LOS. Our data do not support enteral GLN supplementation used routinely in critical illness patients.
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Enfermedad Crítica , Glutamina , Adulto , Humanos , Enfermedad Crítica/terapia , Glutamina/uso terapéutico , Mortalidad Hospitalaria , Unidades de Cuidados Intensivos , Tiempo de Internación , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND/IMPORTANCE: Dietary interventions, vitamins, and nutritional supplementation are playing an increasingly important role in the management of neuropathic pain. Current pharmacological treatments are poorly tolerated and ineffective in many cases. OBJECTIVE: This systematic review aims to study the efficacy of dietary interventions, vitamins, and nutritional supplementation in the management of chronic neuropathic pain in adults. EVIDENCE REVIEW: The review followed PRISMA guidelines and was registered with PROSPERO (#CRD42022300312). Ten databases and gray literature, including Embase.com, MEDLINE and Web of Science, were systematically searched using a combination of keywords and controlled vocabulary related to chronic neuropathic pain and oral non-pharmacological supplements. Studies on adult humans published between 2000 and 2021 were considered for inclusion. The Cochrane Handbook was used to assess risk of bias, and Grading of Recommendations Assessment, Development, and Evaluation was used to determine overall quality of evidence. FINDINGS: Forty studies were included in the final review, and results were categorized according to pain type including pain related to chemotherapy-induced peripheral neuropathy (CIPN, 22 studies, including 3 prospective cohorts), diabetic peripheral neuropathy (DPN, 13 studies, including 2 prospective), complex regional pain syndrome (CRPS-I, 3 studies, including 1 prospective), and other (2 studies, both RCT). The CIPN studies used various interventions including goshajinkigan (4 studies), vitamin E (5), vitamin B12 (3), glutamine (3), N-acetyl-cysteine (2), acetyl-l-carnitine (2), guilongtonluofang (1), ninjin'yoeito (1), alpha-lipoic acid (1), l-carnosine (1), magnesium and calcium (1), crocin (1), and antioxidants (1), with some studies involving multiple interventions. All CIPN studies involved varying cancers and/or chemotherapies, advising caution for generalizability of results. Interventions for DPN included alpha-lipoic acid (5 studies), vitamin B12 (3), acetyl-l-carnitine (3), vitamin E (1), vitamin D (2), and a low-fat plant-based diet (1). Vitamin C was studied to treat CRPS-I (3 studies, including 1 prospective). Magnesium (1) and St. John's wort (1) were studied for other or mixed neuropathologies. CONCLUSIONS: Based on the review, we cannot recommend any supplement use for the management of CIPN, although further research into N-acetyl-cysteine, l-carnosine, crocin, and magnesium is warranted. Acetyl-l-carnitine was found to be likely ineffective or harmful. Alpha-lipoic acid was not found effective. Studies with goshajinkigan, vitamin B12, vitamin E, and glutamine had conflicting results regarding efficacy, with one goshajinkigan study finding it harmful. Guilongtonluofang, ninjin'yoeito, and antioxidants showed various degrees of potential effectiveness. Regarding DPN, our review supports the use of alpha-lipoic acid, acetyl-l-carnitine, and vitamin D. The early use of vitamin C prophylaxis for the development of CRPS-I also seems promising. Further research is warranted to confirm these findings.
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Carnosina , Síndromes de Dolor Regional Complejo , Neuralgia , Ácido Tióctico , Humanos , Adulto , Acetilcarnitina/uso terapéutico , Magnesio/uso terapéutico , Ácido Tióctico/uso terapéutico , Carnosina/uso terapéutico , Glutamina/uso terapéutico , Cisteína/uso terapéutico , Estudios Prospectivos , Suplementos Dietéticos , Vitaminas/uso terapéutico , Neuralgia/tratamiento farmacológico , Vitamina E/uso terapéutico , Ácido Ascórbico/uso terapéutico , Dieta , Antioxidantes/uso terapéutico , Vitamina B 12 , Vitamina D/uso terapéuticoRESUMEN
Patients with ulcerative colitis (UC) are reported to have changes in body structure, with negative impact on the course of disease. This study explored the effects of a standardized nutritional supplement containing five bacterial strains of at least five billion bacteria (Bifidobacterium infantis, Bifidobacterium animalis, Lactobacillus bulgaricus, Lactobacillus helveticus, and Enterococcus faecium), L-glutamine, and biotin on the body composition and quality of life of patients with UC. Ninety-three patients over 18 years of age with a confirmed diagnosis of UC, for whom body composition could be accurately determined, were included in this observational follow-up randomized study. These patients were split into two groups: UC-P (44 patients with dietary counselling and supplement with probiotics) and UC-NP (49 patients with dietary counselling, without supplement). Body composition was assessed using the multifrequency bioelectrical impedance device, and the quality of life related to UC was evaluated by applying the short inflammatory bowel disease questionnaire (SIBDQ). The results showed that the average value of muscular mass (MM) and sarcopenic index (SMI) significantly increased (p = 0.043, respectively, p = 0.001) and a large fraction (p = 0.001) of patients had their SMI levels normalized in the UC-P group compared with UC-NP group. The extracellular water to total body water ratio (ECW/TBW) also had significantly different mean values (p = 0.022), favoring the UC-P group. By testing the differences between the average values of body composition parameters before and after treatment, we obtained significant results in body mass index (BMI) (p = 0.046), fat free mass (FFM) (p < 0.001), and ECW/TBW ratio (p = 0.048). The SIBDQ total score increased significantly (p < 0.001) in the UC-P group and was more strongly associated with changes in body parameters. Supplementation with probiotics associated with L-glutamine and biotin can improve body composition parameters, which in turn implies an increase in the overall quality of life of patients with UC.
Asunto(s)
Colitis Ulcerosa , Enfermedades Inflamatorias del Intestino , Probióticos , Humanos , Adolescente , Adulto , Colitis Ulcerosa/tratamiento farmacológico , Biotina/uso terapéutico , Glutamina/uso terapéutico , Calidad de Vida , Probióticos/uso terapéutico , Suplementos Dietéticos , Composición Corporal , Enfermedades Inflamatorias del Intestino/complicacionesRESUMEN
Glutamine synthetase (GS) is an enzyme that converts ammonia and glutamate to glutamine using adenosine triphosphate. GS is expressed in the brain, kidney, and liver tissues under normal physiological conditions. GS is involved in abnormal lipid metabolism of the liver by catalyzing de novo synthesis of glutamine, thereby inducing liver inflammation. Metabolic dysfunction-associated steatotic liver diseases (MASLD), such as Metabolic Associated Fatty Liver Disease and Metabolic Associated Steato Hepatitis, are considered risk factors for HCC. GS may also be involved in the development and progression of hepatocellular carcinoma (HCC) through other signaling pathways, including the rapamycin (mTOR) and Wnt/ß-catenin signaling pathways. Furthermore, the correct combination of HSP70, GPC3, and GS can improve the accuracy and precision of HCC diagnosis. However, the prognostic value of GS in different HCC populations remains controversial. The expression of GS affects the sensitivity of HCC cells to radiotherapy and chemotherapy. In addition, immunotherapy has been approved for the treatment of advanced HCC. This article delves into the development and application of GS in HCC, laying a theoretical foundation for the subsequent exploration of GS as a potential target for treating HCC.
Asunto(s)
Carcinoma Hepatocelular , Glutamato-Amoníaco Ligasa , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Glutamato-Amoníaco Ligasa/metabolismo , Glutamina/metabolismo , Glutamina/uso terapéutico , Glipicanos/metabolismo , Glipicanos/uso terapéutico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Vía de Señalización WntRESUMEN
BACKGROUND: The use of immune nutrients in the treatment of severe pancreatitis remains controversial. No study has yet compared the effects of different immune nutrients on patients with severe acute pancreatitis. This study aimed to compare the effects of different immune nutrients in treating severe acute pancreatitis through a network meta-analysis. METHODS: PubMed, Embase, Cochrane Library, Web of Science, and Scopus were used to search randomized controlled trials from the inception to July 2023. Information was collected from patients with severe acute pancreatitis and their intervention methods, which included the administration of glutamine, omega-3 polyunsaturated fatty acids, arginine, and nucleotides. The evaluated outcomes included mortality, infection, the length of the hospital stay (LOH), the length of intensive care unit stay (LOI), and C-reactive protein (CRP). Risk ratio (95% confidence interval [CI]) and mean difference (MD) (95% CI) were calculated using a network meta-analysis random-effects model. The ranking between interventions was calculated using the surface under the cumulative ranking curve. The Cochrane Risk of Bias tool 2 was used to assess the risk of bias. The sources of heterogeneity were assessed using sensitivity analysis and network meta-regression. The credibility of the evidence was assessed using grading of recommendations assessment, development, and evaluation. RESULTS: Nineteen studies with 1035 patients were included in this network meta-analysis. Parenteral glutamine was more effective in reducing mortality, infection, LOH, and LOI, as well as in the downregulation of CRP compared to the control. Risk ratio (95%CI) or MD (95%CI) were 0.38 (0.16, 0.90), 0.35 (0.14, 0.90), -3.32 (-4.90, -1.75), -2.53 (-4.46, -0.61), and -17.78 (-28.77, -6.78), respectively. Parenteral omega-3 polyunsaturated fatty acids was more effective in reducing LOH and LOI, as well as in the downregulation of CRP. MD (95%CI) were -6.77 (-11.40, -2.14), -5.19 (-7.80, -2.57), and -26.20 (-39.71, -12.68), respectively. Immune nutrients in the other groups did not exert any effect compared to the control regarding all the outcomes. Parenteral glutamine ranked best in reducing infections. Parenteral omega-3 polyunsaturated fatty acids ranked best in reducing mortality, LOH, and LOI, as well as in the downregulation of CRP. CONCLUSION: Some immune nutrients were beneficial for patients with severe acute pancreatitis. Parenteral administration could be better than enteral administration.