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Muscle-Protective Effect of Carnosine against Dexamethasone-Induced Muscle Atrophy in C2C12 Myotube.Journal of Nutritional Science and... 2024This study investigated the protective effect of carnosine and its components (L-histidine and β-alanine [HA]) against dexamethasone (Dex)-induced muscle atrophy in...
This study investigated the protective effect of carnosine and its components (L-histidine and β-alanine [HA]) against dexamethasone (Dex)-induced muscle atrophy in C2C12 myotubes. Myotubes were treated with Dex (10 μM) to induce muscle atrophy manifested by decreased myotube diameter, low myosin heavy chain content, and increased expression of muscle atrophy-associated ubiquitin ligases (Atrogin-1, MuRF-1, and Cbl-b). Carnosine (20 mM) treatment significantly improved the myotube diameter and MyHC protein expression level in Dex-treated C2C12 myotubes. It also downregulated the expression of Atrogin-1, MuRF-1, and Cbl-b and suppressed the expression of forkhead box O3 (FoxO3a) mediated by Dex. Furthermore, reactive oxygen species production was increased by Dex but was ameliorated by carnosine treatment. However, HA (20 mM), the component of carnosine, treatment was found ineffective in preventing Dex-induced protein damage. Therefore, based on above results it can be suggested that carnosine could be a potential therapeutic agent to prevent Dex-induced muscle atrophy compared to its components HA.
Topics: Carnosine; Dexamethasone; Muscular Atrophy; Muscle Fibers, Skeletal; Animals; Mice; Muscle Proteins; Cell Line; Reactive Oxygen Species; SKP Cullin F-Box Protein Ligases; Ubiquitin-Protein Ligases; Forkhead Box Protein O3; Tripartite Motif Proteins; Myosin Heavy Chains
PubMed: 38945887
DOI: 10.3177/jnsv.70.219 -
Journal of Gastrointestinal and Liver... Jun 2024Mammoplasty, a common cosmetic procedure involving breast augmentation and reduction surgeries, has gained global popularity. Recently, attention has shifted towards...
BACKGROUND AND AIMS
Mammoplasty, a common cosmetic procedure involving breast augmentation and reduction surgeries, has gained global popularity. Recently, attention has shifted towards understanding the prevalence and significance of gastrointestinal (GI) symptoms following mammoplasty. This systematic review aims to consolidate existing literature to provide a comprehensive overview of the type and frequency of GI problems associated with various mammoplasty procedures.
METHODS
A systematic search of PubMed and Scopus databases was conducted until January 22, 2024, identifying observational and interventional studies examining GI symptoms post-mammoplasty. Inclusion criteria covered human studies, while exclusion criteria ensured specificity. Two independent investigators performed screening, and data extraction included study characteristics, surgical procedures, anesthesia methods, and interventions.
RESULTS
Nineteen studies, involving 2,487 subjects, were included in the review. Breast reconstruction emerged as the most studied procedure, followed by breast reduction, augmentation, mastectomy, and breast cancer surgery. Predominant GI symptoms included nausea and vomiting, with varying rates across mammoplasty types. Anesthesia modality influenced symptomatology, with general, local, and combined anesthesia associated with GI disturbances. Antiemetics, notably ondansetron and droperidol, showed variable efficacy. Non-pharmacological approaches, such as preoperative hypnosis, were explored for symptom management.
CONCLUSIONS
Our systematic review reveals insights into GI symptoms post-mammoplasty, emphasizing the common occurrence of symptoms such as nausea and vomiting, alongside less frequent manifestations such as constipation, dry mouth, retching, abdominal pain, and tightness. Variations in symptom prevalence were noted across diverse mammoplasty surgeries, anesthesia methods, and the use of antiemetics, underscoring the complex nature of post-mammoplasty GI disturbances.
Topics: Humans; Mammaplasty; Female; Postoperative Nausea and Vomiting; Gastrointestinal Diseases; Adult; Prevalence
PubMed: 38944853
DOI: 10.15403/jgld-5598 -
Planta Medica Jun 2024Ginger (Zingiber officinale) has a rich history of traditional medicinal use and has attracted a global interest in its health benefits. This study aims to provide...
Ginger (Zingiber officinale) has a rich history of traditional medicinal use and has attracted a global interest in its health benefits. This study aims to provide insights into the clinical research landscape on ginger, focusing on its pharmacological effects and studied health-related outcomes. The study design involves systematic analysis of data from clinical trials available on ClinicalTrials.gov and discussion of findings in the context of the existing scientific knowledge. A comprehensive analysis of clinical trials registered on ClinicalTrials.gov related to ginger was first conducted, and the scientific background related to specific ginger clinical research avenues was further evaluated through PubMed searches. A variety of trial designs were identified, including treatment, prevention, and supportive care objectives. A total of 188 studies were identified on ClinicalTrials.gov, of which 89 met the inclusion criteria. Among the 89 trials, treatment objectives were predominant (47.2%), and dietary supplements (40.4%) and drugs (27%) were the most prevalent intervention types. These trials covered various health outcomes, such as antiemetic activity, analgesic function, effects on health-related quality of life, blood pressure variation, energy expenditure, and reduction of xerostomia. This study analysis provides a comprehensive overview of the clinical trials landscape on ginger, focusing on its broad spectrum of potential health benefits. While individual trials show promising results, a significant gap in the available data with a low reporting rate of final results is identified, underscoring the need for further research to establish conclusive evidence of ginger's therapeutic potentials.
PubMed: 38944033
DOI: 10.1055/a-2357-7064 -
Nature Communications Jun 2024Dexamethasone is the standard of care for critically ill patients with COVID-19, but the mechanisms by which it decreases mortality and its immunological effects in this...
Dexamethasone is the standard of care for critically ill patients with COVID-19, but the mechanisms by which it decreases mortality and its immunological effects in this setting are not understood. Here we perform bulk and single-cell RNA sequencing of samples from the lower respiratory tract and blood, and assess plasma cytokine profiling to study the effects of dexamethasone on both systemic and pulmonary immune cell compartments. In blood samples, dexamethasone is associated with decreased expression of genes associated with T cell activation, including TNFSFR4 and IL21R. We also identify decreased expression of several immune pathways, including major histocompatibility complex-II signaling, selectin P ligand signaling, and T cell recruitment by intercellular adhesion molecule and integrin activation, suggesting these are potential mechanisms of the therapeutic benefit of steroids in COVID-19. We identify additional compartment- and cell- specific differences in the effect of dexamethasone that are reproducible in publicly available datasets, including steroid-resistant interferon pathway expression in the respiratory tract, which may be additional therapeutic targets. In summary, we demonstrate compartment-specific effects of dexamethasone in critically ill COVID-19 patients, providing mechanistic insights with potential therapeutic relevance. Our results highlight the importance of studying compartmentalized inflammation in critically ill patients.
Topics: Dexamethasone; Humans; COVID-19 Drug Treatment; COVID-19; SARS-CoV-2; Lung; Cytokines; Critical Illness; Male; Single-Cell Analysis; Female; Middle Aged; T-Lymphocytes; Aged; Lymphocyte Activation
PubMed: 38942804
DOI: 10.1038/s41467-024-49756-2 -
Frontiers in Immunology 2024The primary treatment for acute relapses in multiple sclerosis (MS) is the intravenous administration of high-dose methylprednisolone (IVMP). However, the mechanisms...
BACKGROUND
The primary treatment for acute relapses in multiple sclerosis (MS) is the intravenous administration of high-dose methylprednisolone (IVMP). However, the mechanisms through which corticosteroid treatment impacts acute neuroinflammation in people with MS (pwMS) remain not fully understood. In particular, the changes induced by glucocorticoids (GCs) on cells of the innate immune system and the differences between patients with distinct immunotherapies have received little attention to date.
METHODS
We conducted immunophenotyping using flow cytometry on peripheral blood mononuclear cells of pwMS who received IVMP treatment during a relapse. We compared the impact of an IVMP treatment on a broad variety of immune cell subsets within three groups: twelve patients who were treatment-naïve to disease modifying therapies (wDMT) to ten patients on platform therapies (PT) and eighteen patients on fingolimod therapy (FTY).
RESULTS
We observed pronounced interindividual short- and intermediate-term effects of IVMP on distinct immune cells subsets. In addition to the well-documented decrease in T-helper cells (Th cells), we detected significant alterations after the first IVMP infusion within the innate immune response among neutrophil, eosinophil and basophil granulocytes, monocytes and plasmacytoid dendritic cells (pDCs). When comparing patients wDMT to the PT and FTY cohorts, we found that IVMP had a similar impact on innate immune cells across all treatment groups. However, we did not observe a significant further decline in T lymphocyte counts during IVMP in patients with pre-existing lymphopenia under FTY treatment. Although T cell apoptosis is considered the main mechanism of action of GCs, patients with FTY still reported symptom improvement following IVMP treatment.
CONCLUSION
In addition to T cell suppression, our data suggests that further immunoregulatory mechanisms of GC, particularly on cells of the innate immune response, are of greater significance than previously understood. Due to the regulation of the adaptive immune cells by DMTs, the impact of GC on these cells varies depending on the underlying DMT. Additional studies involving larger cohorts and cerebrospinal fluid samples are necessary to gain a deeper understanding of the immune response to GC in pwMS with different DMTs during relapse to define and explain differences in clinical response profiles.
Topics: Humans; Female; Male; Adult; Middle Aged; Multiple Sclerosis; Fingolimod Hydrochloride; Immunity, Innate; Methylprednisolone; Immunophenotyping; Leukocytes, Mononuclear; Adrenal Cortex Hormones; Immunosuppressive Agents; Glucocorticoids
PubMed: 38938576
DOI: 10.3389/fimmu.2024.1404316 -
Nature Reviews. Disease Primers Jun 2024Multiple myeloma (MM) is a haematological lymphoid malignancy involving tumoural plasma cells and is usually characterized by the presence of a monoclonal immunoglobulin... (Review)
Review
Multiple myeloma (MM) is a haematological lymphoid malignancy involving tumoural plasma cells and is usually characterized by the presence of a monoclonal immunoglobulin protein. MM is the second most common haematological malignancy, with an increasing global incidence. It remains incurable because most patients relapse or become refractory to treatments. MM is a genetically complex disease with high heterogeneity that develops as a multistep process, involving acquisition of genetic alterations in the tumour cells and changes in the bone marrow microenvironment. Symptomatic MM is diagnosed using the International Myeloma Working Group criteria as a bone marrow infiltration of ≥10% clonal plasma cells, and the presence of at least one myeloma-defining event, either standard CRAB features (hypercalcaemia, renal failure, anaemia and/or lytic bone lesions) or biomarkers of imminent organ damage. Younger and fit patients are considered eligible for transplant. They receive an induction, followed by consolidation with high-dose melphalan and autologous haematopoietic cell transplantation, and maintenance therapy. In older adults (ineligible for transplant), the combination of daratumumab, lenalidomide and dexamethasone is the preferred option. If relapse occurs and requires further therapy, the choice of therapy will be based on previous treatment and response and now includes immunotherapies, such as bi-specific monoclonal antibodies and chimeric antigen receptor T cell therapy.
Topics: Multiple Myeloma; Humans; Dexamethasone; Lenalidomide; Antibodies, Monoclonal; Hematopoietic Stem Cell Transplantation; Melphalan; Thalidomide; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38937492
DOI: 10.1038/s41572-024-00529-7 -
BMJ Case Reports Jun 2024In this paper, we report the case of a boy in early childhood who presented with iron-deficiency anaemia, initially thought to be nutritional, who had a subsequent...
In this paper, we report the case of a boy in early childhood who presented with iron-deficiency anaemia, initially thought to be nutritional, who had a subsequent diagnosis of idiopathic pulmonary haemosiderosis (IPH). This is a slowly progressive and life-threatening disorder and is of paramount importance that this is identified early and treated appropriately. His first chest CT was not typical for IPH, and this appearance should be highlighted (small cystic changes alone initially). He also had focal disease, which allowed us to make the diagnosis using CT-guided biopsy. During his treatment, he experienced an uncommon side effect to a commonly prescribed medication (bradycardia with methylprednisolone). Since starting azathioprine as a steroid-sparing agent, he has been doing well.
Topics: Humans; Hemosiderosis; Male; Hemosiderosis, Pulmonary; Lung Diseases; Tomography, X-Ray Computed; Anemia, Iron-Deficiency; Azathioprine; Diagnosis, Differential; Methylprednisolone
PubMed: 38937263
DOI: 10.1136/bcr-2024-261171 -
In Vivo (Athens, Greece) 2024Anthracycline-based chemotherapies including doxorubicin monotherapy are recommended in major guidelines for patients with advanced or metastatic retroperitoneal sarcoma...
BACKGROUND/AIM
Anthracycline-based chemotherapies including doxorubicin monotherapy are recommended in major guidelines for patients with advanced or metastatic retroperitoneal sarcoma (RPS); however, few studies have reported the outcomes of doxorubicin monotherapy for these patients. We herein investigated the oncological efficacy and safety of doxorubicin monotherapy for patients with advanced or metastatic RPS in real-world clinical practice.
PATIENTS AND METHODS
Sixteen patients diagnosed with advanced or metastatic retroperitoneal sarcoma, receiving doxorubicin monotherapy as first-line treatment between February 2017 and March 2023 at our Institution were analyzed. Response rate, progression-free survival (PFS) periods, overall survival (OS) period, and adverse event (AE) profiles were retrospectively investigated.
RESULTS
The median age of patients was 69.5 years. Best responses to doxorubicin were as follows: complete response, 0 patients (0.0%); partial response, 3 (18.8%); stable disease, 9 (56.3%); and progressive disease, 4 (25.0%). The objective response rate and disease control rate were 18.8 and 75.0%, respectively. During the observation period (median, 22 months, range=2-53 months), median PFS and OS periods were 8.0 and 24.0 months, respectively. The following AEs Grade ≥3 occurred: neutropenia in 14 patients (87.5%), febrile neutropenia in 5 (31.3%), leukopenia in 2 (12.5%), thrombocytopenia in 1 (6.3%), and heart failure in 1 (6.3%). Grade ≥3 nausea and vomiting did not occur and there was no treatment-related death.
CONCLUSION
The oncological outcomes of doxorubicin monotherapy for RPS in real-world clinical practice were not inferior to those of the EORTC trial. The incidence of hematological AEs was higher; however, severe gastrointestinal AEs were prevented by prophylactic antiemetics and there were no treatment-related deaths. Collectively, doxorubicin monotherapy with appropriate prophylactic agents is a valid option for patients with advanced or metastatic RPS.
Topics: Humans; Female; Male; Aged; Doxorubicin; Middle Aged; Sarcoma; Retroperitoneal Neoplasms; Treatment Outcome; Aged, 80 and over; Neoplasm Metastasis; Adult; Retrospective Studies; Neoplasm Staging
PubMed: 38936944
DOI: 10.21873/invivo.13640 -
Journal of Perianesthesia Nursing :... Jun 2024Preoperative oral carbohydrate loading is a component of enhanced recovery after surgery protocols. The aim of this study is to investigate the effects of preoperative...
PURPOSE
Preoperative oral carbohydrate loading is a component of enhanced recovery after surgery protocols. The aim of this study is to investigate the effects of preoperative oral carbohydrate loading on postoperative clinical outcomes in spinal surgery patients.
DESIGN
This is a prospective case-control study.
METHODS
This study was conducted with patients who underwent spinal surgery from October 1, 2020 to October 1, 2021 in a neurosurgery clinic of an education and research hospital. The intervention group (n = 46) ingested 800 mL oral carbohydrate drinks at least 8 hours before surgery. The postoperative clinical outcomes were nausea, vomiting, antiemetic and analgesic drug medication, inflammation, and bleeding. The first flatus and defecation time, oral intake time, mobilization time, and length of stay in hospital were assessed postoperatively. Adverse events were monitored up to 24 hours postoperatively. The control group (n = 46) underwent routine fasting protocols.
FINDINGS
Lower rates of vomiting and bleeding during and after surgery and earlier defecation time and first mobilization time were determined in the intervention group, and the difference compared with the control group was statistically significant.
CONCLUSIONS
Preoperative oral carbohydrate loading is a nonpharmacological intervention that has a positive effect on postoperative clinical outcomes in patients who underwent spinal surgery and should be included in the enhanced recovery after surgery protocol.
PubMed: 38935011
DOI: 10.1016/j.jopan.2024.03.002 -
Frontiers in Pharmacology 2024Chemotherapy-induced nausea and vomiting (CINV) is one of the most frequent and critical side effects due to chemotherapeutics. In China, Xiao-Ban-Xia-Tang (XBXT) has...
BACKGROUND
Chemotherapy-induced nausea and vomiting (CINV) is one of the most frequent and critical side effects due to chemotherapeutics. In China, Xiao-Ban-Xia-Tang (XBXT) has already been applied extensively to prevent and treat CINV. However, there is limited testimony on the effectiveness and safety of this purpose, and there was no correlative systematic review. The aim of this review was to systematically evaluate the effectiveness and safety of XBXT in preventing and treating CINV.
METHODS
The systematic search was conducted in eight databases to acquire randomized controlled trials (RCTs) that appraised the effect of XBXT in treating CINV. The vomiting and nausea relief efficiency, eating efficiency, quality of life, and adverse reactions were explored for efficacy assessment. Bias risk was rated by manipulating the Cochrane risk of bias tool 2.0 (RoB 2). The retrieved investigations were analyzed by utilizing ReviewManager 5.4 and Stata 17.0. The quality of evidence was evaluated adopting the GRADE tool.
RESULTS
A total of 16 clinical RCTs of XBXT in the treatment of CINV were incorporated into the investigation, with a total of 1246 participants. The meta-analysis showed that compared with conventional antiemetic drugs, XBXT and antiemetics improved the vomiting relief efficiency (RR 1.35, 95% confidence interval: 1.25-1.46, < 0.00001), nausea relief efficiency (N = 367, RR 1.23, 95% CI: 1.09-1.38, < 0.00001), and quality of life (RR = 1.37, 95% CI: 1.14-1.65, = 0.0009) and reduced the adverse events (N = 370, RR 0.53, 95% CI: 0.29-0.96, = 0.04). XBXT and DARAs raised eating efficiency compared with DARAs (N = 208, RR 1.30, 95% CI: 1.07-1.57, = 0.007). The data existed as statistically significant, and the publication bias was identified as relatively low from the funnel plot and trim and fill analysis. In addition, sensitivity analysis demonstrated robust outcomes. The quality of evidence for each outcome ranged from moderate to high.
CONCLUSION
There is some encouraging evidence that XBXT and antiemetics had better therapeutic effects and safety in treating CINV than antiemetic drugs alone. The quality assessment and low publication bias indicated that the overall criterion was scientific. Better research is required to verify the evidence designed with large-scale RCTs and rigorous methods.
UNLABELLED
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=281046.
PubMed: 38933673
DOI: 10.3389/fphar.2024.1393597