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Journal of Cachexia, Sarcopenia and... Jun 2024Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for...
BACKGROUND
Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for anabolic reactions. We hypothesize that a similar metabolic remodelling occurs during skeletal muscle hypertrophy.
METHODS
We used mass spectrometry in hypertrophying C2C12 myotubes in vitro and plantaris mouse muscle in vivo and assessed metabolomic changes and the incorporation of the [U-C]glucose tracer. We performed enzyme inhibition of the key serine synthesis pathway enzyme phosphoglycerate dehydrogenase (Phgdh) for further mechanistic analysis and conducted a systematic review to align any changes in metabolomics during muscle growth with published findings. Finally, the UK Biobank was used to link the findings to population level.
RESULTS
The metabolomics analysis in myotubes revealed insulin-like growth factor-1 (IGF-1)-induced altered metabolite concentrations in anabolic pathways such as pentose phosphate (ribose-5-phosphate/ribulose-5-phosphate: +40%; P = 0.01) and serine synthesis pathway (serine: -36.8%; P = 0.009). Like the hypertrophy stimulation with IGF-1 in myotubes in vitro, the concentration of the dipeptide l-carnosine was decreased by 26.6% (P = 0.001) during skeletal muscle growth in vivo. However, phosphorylated sugar (glucose-6-phosphate, fructose-6-phosphate or glucose-1-phosphate) decreased by 32.2% (P = 0.004) in the overloaded muscle in vivo while increasing in the IGF-1-stimulated myotubes in vitro. The systematic review revealed that 10 metabolites linked to muscle hypertrophy were directly associated with glycolysis and its interconnected anabolic pathways. We demonstrated that labelled carbon from [U-C]glucose is increasingly incorporated by ~13% (P = 0.001) into the non-essential amino acids in hypertrophying myotubes, which is accompanied by an increased depletion of media serine (P = 0.006). The inhibition of Phgdh suppressed muscle protein synthesis in growing myotubes by 58.1% (P < 0.001), highlighting the importance of the serine synthesis pathway for maintaining muscle size. Utilizing data from the UK Biobank (n = 450 243), we then discerned genetic variations linked to the serine synthesis pathway (PHGDH and PSPH) and to its downstream enzyme (SHMT1), revealing their association with appendicular lean mass in humans (P < 5.0e-8).
CONCLUSIONS
Understanding the mechanisms that regulate skeletal muscle mass will help in developing effective treatments for muscle weakness. Our results provide evidence for the metabolic rewiring of glycolytic intermediates into anabolic pathways during muscle growth, such as in serine synthesis.
Topics: Glucose; Muscle, Skeletal; Animals; Mice; Humans; Hypertrophy; Muscle Fibers, Skeletal; Insulin-Like Growth Factor I; Metabolomics
PubMed: 38742477
DOI: 10.1002/jcsm.13468 -
Clinical Chemistry and Laboratory... Nov 2023Monoclonal gammopathies (MG) are characterized by the proliferation of plasma cells that produce identical abnormal immunoglobulins (intact or some of their subunits)....
Recommendations for the study of monoclonal gammopathies in the clinical laboratory. A consensus of the Spanish Society of Laboratory Medicine and the Spanish Society of Hematology and Hemotherapy. Part I: Update on laboratory tests for the study of monoclonal gammopathies.
Monoclonal gammopathies (MG) are characterized by the proliferation of plasma cells that produce identical abnormal immunoglobulins (intact or some of their subunits). This abnormal immunoglobulin component is called monoclonal protein (M-protein), and is considered a biomarker of proliferative activity. The identification, characterization and measurement of M-protein is essential for the management of MG. We conducted a systematic review of the different tests and measurement methods used in the clinical laboratory for the study of M-protein in serum and urine, the biochemistry and hematology tests necessary for clinical evaluation, and studies in bone marrow, peripheral blood and other tissues. This review included literature published between 2009 and 2022. The paper discusses the main methodological characteristics and limitations, as well as the purpose and clinical value of the different tests used in the diagnosis, prognosis, monitoring and assessment of treatment response in MG. Included are methods for the study of M-protein, namely electrophoresis, measurement of immunoglobulin levels, serum free light chains, immunoglobulin heavy chain/light chain pairs, and mass spectrometry, and for the bone marrow examination, morphological analysis, cytogenetics, molecular techniques, and multiparameter flow cytometry.
Topics: Humans; Laboratories, Clinical; Consensus; Paraproteinemias; Immunoglobulin Light Chains; Hematology; Multiple Myeloma
PubMed: 37477188
DOI: 10.1515/cclm-2023-0326 -
International Wound Journal Aug 2023Excellent capability of exosome derived from human adipose-derived stem cell (ADSC) manifested in improving the quality of wound healing with SMD (STD Mean Difference).... (Meta-Analysis)
Meta-Analysis Review
Excellent capability of exosome derived from human adipose-derived stem cell (ADSC) manifested in improving the quality of wound healing with SMD (STD Mean Difference). However, it is still in the preclinical stage and its efficacy remains uncertain. Emphasised the need for a systematic review of preclinical studies to the validity of it in ameliorate wound healing quality which accelerate the clinical application translation. We performed a systematic literature review to identify all published controlled and intervention studies comparing exosome derived from human ADSC with placebo in animal models of wound closure during wound healing. PubMed, Embase and Cochrane were employed. Risk of bias assessed by the SYRCLE tool aimed at preclinical animal studies. Administration of exosome derived from human ADSC extremely improved wound closure compared with controls, which is primary outcome (SMD 1.423, 95% confidence interval (CI) 1.137-1.709 P < .001), the same effect as ADSC. The therapeutic effect is further enhanced by modified ADSC-EV. Other outcomes: density and the number of blood vessels: (SMD 1.593 95% CI 1.007-2.179 P < .001);Fibrosis-related protein expression was highly expressed in the early term of wound healing, decreased in shaping period, which automatically regulates wound collagen deposition. Scar size, number of fibroblast and epithelial cell migration and proliferation expressed were ranked as follows: modified adipose stem cell exosomes > adipose stem cell exosomes > controls. Exosome derived from human ADSC, especially after enrichment for specific non-coding RNA, is a promising approach to improve healing efficiency.
Topics: Animals; Humans; Adipose Tissue; Exosomes; Wound Healing; Diabetes Mellitus, Experimental; Stem Cells
PubMed: 37102269
DOI: 10.1111/iwj.14081 -
The Spine Journal : Official Journal of... Oct 2023Excessive production of epidural fibrosis in the nerve root can be a pain source after laminectomy. Pharmacotherapy is a minimally invasive treatment option to attenuate... (Review)
Review
BACKGROUND CONTEXT
Excessive production of epidural fibrosis in the nerve root can be a pain source after laminectomy. Pharmacotherapy is a minimally invasive treatment option to attenuate epidural fibrosis by suppressing proliferation and activation of fibroblasts, inflammation, and angiogenesis, and inducing apoptosis.
PURPOSE
We reviewed and tabulated pharmaceuticals with their respective signaling axes implicated in reducing epidural fibrosis. Additionally, we summarized current literature for the feasibility of novel biologics and microRNA to lessen epidural fibrosis.
STUDY DESIGN/SETTING
Systematic Review.
METHODS
According to the PRISMA guidelines, we systematically reviewed the literature in October 2022. The exclusion criteria included duplicates, nonrelevant articles, and insufficient detail of drug mechanism.
RESULTS
We obtained a total of 2,499 articles from PubMed and Embase databases. After screening the articles, 74 articles were finally selected for the systematic review and classified based on the functions of drugs and microRNAs which included inhibition of fibroblast proliferation and activation, pro-apoptosis, anti-inflammation, and antiangiogenesis. In addition, we summarized various pathways to prevent epidural fibrosis.
CONCLUSION
This study allows a comprehensive review of pharmacotherapies to prevent epidural fibrosis during laminectomy.
CLINICAL SIGNIFICANCE
We expect that our review would enable researchers and clinicians to better understand the mechanism of anti-fibrosis drugs for the clinical application of epidural fibrosis therapies.
Topics: Animals; Laminectomy; Fibrosis; Apoptosis; MicroRNAs; Models, Animal; Epidural Space
PubMed: 37187251
DOI: 10.1016/j.spinee.2023.05.007 -
Human Reproduction Update May 2024The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) and intrauterine adhesions (IUA), or endometrial atrophy (EA) and...
BACKGROUND
The establishment and maintenance of pregnancy depend on endometrial competence. Asherman syndrome (AS) and intrauterine adhesions (IUA), or endometrial atrophy (EA) and thin endometrium (TE), can either originate autonomously or arise as a result from conditions (i.e. endometritis or congenital hypoplasia), or medical interventions (e.g. surgeries, hormonal therapies, uterine curettage or radiotherapy). Affected patients may present an altered or inadequate endometrial lining that hinders embryo implantation and increases the risk of poor pregnancy outcomes and miscarriage. In humans, AS/IUA and EA/TE are mainly treated with surgeries or pharmacotherapy, however the reported efficacy of these therapeutic approaches remains unclear. Thus, novel regenerative techniques utilizing stem cells, growth factors, or tissue engineering have emerged to improve reproductive outcomes.
OBJECTIVE AND RATIONALE
This review comprehensively summarizes the methodologies and outcomes of emerging biotechnologies (cellular, acellular, and bioengineering approaches) to treat human endometrial pathologies. Regenerative therapies derived from human tissues or blood which were studied in preclinical models (in vitro and in vivo) and clinical trials are discussed.
SEARCH METHODS
A systematic search of full-text articles available in PubMed and Embase was conducted to identify original peer-reviewed studies published in English between January 2000 and September 2023. The search terms included: human, uterus, endometrium, Asherman syndrome, intrauterine adhesions, endometrial atrophy, thin endometrium, endometritis, congenital hypoplasia, curettage, radiotherapy, regenerative therapy, bioengineering, stem cells, vesicles, platelet-rich plasma, biomaterials, microfluidic, bioprinting, organoids, hydrogel, scaffold, sheet, miRNA, sildenafil, nitroglycerine, aspirin, growth hormone, progesterone, and estrogen. Preclinical and clinical studies on cellular, acellular, and bioengineering strategies to repair or regenerate the human endometrium were included. Additional studies were identified through manual searches.
OUTCOMES
From a total of 4366 records identified, 164 studies (3.8%) were included for systematic review. Due to heterogeneity in the study design and measured outcome parameters in both preclinical and clinical studies, the findings were evaluated qualitatively and quantitatively without meta-analysis. Groups using stem cell-based treatments for endometrial pathologies commonly employed mesenchymal stem cells (MSCs) derived from the human bone marrow or umbilical cord. Alternatively, acellular therapies based on platelet-rich plasma (PRP) or extracellular vesicles are gaining popularity. These are accompanied by the emergence of bioengineering strategies based on extracellular matrix (ECM)-derived hydrogels or synthetic biosimilars that sustain local delivery of cells and growth factors, reporting promising results. Combined therapies that target multiple aspects of tissue repair and regeneration remain in preclinical testing but have shown translational value. This review highlights the myriad of therapeutic material sources, administration methods, and carriers that have been tested.
WIDER IMPLICATIONS
Therapies that promote endometrial proliferation, vascular development, and tissue repair may help restore endometrial function and, ultimately, fertility. Based on the existing evidence, cost, accessibility, and availability of the therapies, we propose the development of triple-hit regenerative strategies, potentially combining high-yield MSCs (e.g. from bone marrow or umbilical cord) with acellular treatments (PRP), possibly integrated in ECM hydrogels. Advances in biotechnologies together with insights from preclinical models will pave the way for developing personalized treatment regimens for patients with infertility-causing endometrial disorders such as AS/IUA, EA/TE, and endometritis.
REGISTRATION NUMBER
https://osf.io/th8yf/.
PubMed: 38796750
DOI: 10.1093/humupd/dmae013 -
Journal of Orthopaedic Surgery and... Aug 2023The onset of OA is affected by a variety of factors, which eventually lead to the loss of cartilage in the joints, the formation of osteophytes, the loss of normal knee... (Meta-Analysis)
Meta-Analysis
PURPOSE
The onset of OA is affected by a variety of factors, which eventually lead to the loss of cartilage in the joints, the formation of osteophytes, the loss of normal knee mobility, and pain and discomfort, which seriously affects the quality of life. HUC-MSCs can promote cartilage production and have been widely used in research in the past decade. This article systematically summarizes that it is well used in basic research and clinical studies to promote inflammatory chondrogenesis in the treatment of OA. Provide a theoretical basis for clinical treatment.
PATIENTS AND METHODS
This study collected CNKI, Wanfang, PubMed, and articles related to the treatment of OA with HUC-MSCs since their publication, excluding non-basic and clinical studies such as reviews and meta-analysis. A total of 31 basic experimental studies and 12 clinical studies were included. Systematically analyze the effects of HUC-MSCs on inhibiting inflammatory factors, promoting chondrocyte production, and current clinical treatment.
RESULTS
HUC-MSCs can reduce inflammatory factors such as MMP-13, ADAMTS-5, IL-1β, IL-1, IL-6, TNF-α, induced conversion from M1 to M2 in OA to protect cartilage damage and reduce OA inflammation. Synthesize ColII, SOX9, and aggrecan at the same time to promote cartilage synthesis.
CONCLUSION
HUC-MSCs not only have typical stem cell biological characteristics, but also have rich sources and convenient material extraction. Compared with stem cells from other sources, HUC-MSCs have stronger proliferation, differentiation, and immune regulation abilities. Furthermore, there are no ethical issues associated with their use.
SAFETY
Primarily attributed to pain, the majority of individuals experience recovery within 24 h following injection. HUC-MSCs possess the ability to alleviate pain, enhance knee joint function, and potentially postpone the need for surgical intervention in both non-surgical and other cases, making them highly deserving of clinical promotion and application.
Topics: Humans; Osteoarthritis, Knee; Chondrogenesis; Quality of Life; Knee Joint; Mesenchymal Stem Cells; Umbilical Cord
PubMed: 37644595
DOI: 10.1186/s13018-023-04131-7 -
Tissue Engineering. Part B, Reviews Aug 2023Surgical outcomes of pelvic organ prolapse (POP) surgery are poor, resulting in a 20% recurrence risk. Following the hypothesis that impaired wound healing is the main... (Meta-Analysis)
Meta-Analysis Review
Surgical outcomes of pelvic organ prolapse (POP) surgery are poor, resulting in a 20% recurrence risk. Following the hypothesis that impaired wound healing is the main determinant of recurrent POP, growth factors have the potential to promote wound healing and may improve surgical outcomes. In this study, we systematically reviewed the effect of growth factors on vaginal wound healing in both and animal studies. For each independent comparison, the standardized mean difference and 95% CI were calculated using the Hedges' g correction. Of the 3858 retrieved studies, seven studies were included, of which six were included in meta-analysis (three studies and four studies). , basic fibroblast growth factor (bFGF) promotes proliferation, differentiation, and collagen types I and III production. Epidermal growth factor stimulates proliferation and connective tissue growth factor promotes Tenascin-C expression. These effects, however, are less pronounced ; only bFGF slightly promotes collagen production. The review shows that growth factors, particularly bFGF, are able to promote vaginal wound healing . The uncertain findings suggest that preclinical models should be improved. The ultimate goal is to develop effective growth factor-supplemented therapies that improve surgical outcomes for POP.
Topics: Animals; Female; Wound Healing; Collagen
PubMed: 37051705
DOI: 10.1089/ten.TEB.2022.0225 -
Clinical & Translational Oncology :... Feb 2024Glioblastoma (GBM) constitutes the most common primary brain tumor in adults. The challenges in GBM therapeutics have shed light on zebrafish used as a promising animal... (Review)
Review
Glioblastoma (GBM) constitutes the most common primary brain tumor in adults. The challenges in GBM therapeutics have shed light on zebrafish used as a promising animal model for preclinical GBM xenograft studies without a standardized methodology. This systematic review aims to summarize the advances in zebrafish GBM xenografting, compare research protocols to pinpoint advantages and underlying limitations, and designate the predominant xenografting parameters. Based on the PRISMA checklist, we systematically searched PubMed, Scopus, and ZFIN using the keywords "glioblastoma," "xenotransplantation," and "zebrafish" for papers published from 2005 to 2022, available in English. 46 articles meeting the review criteria were examined for the zebrafish strain, cancer cell line, cell labeling technique, injected cell number, time and site of injection, and maintenance temperature. Our review designated that AB wild-type zebrafish, Casper transparent mutants, transgenic Tg(fli1:EGFP), or crossbreeding of these predominate among the zebrafish strains. Orthotopic transplantation is more commonly employed. A number of 50-100 cells injected at 48 h post-fertilization in high density and low infusion volume is considered as an effective xenografting approach. U87 cells are used for GBM angiogenesis studies, U251 for GBM proliferation studies, and patient-derived xenograft (PDX) to achieve clinical relevance. Gradual acclimatization to 32-33 °C can partly address the temperature differential between the zebrafish and the GBM cells. Zebrafish xenograft models constitute valuable tools for preclinical studies with clinical relevance regarding PDX. The GBM xenografting research requires modification based on the objective of each research team. Automation and further optimization of the protocol parameters could scale up the anticancer drug trials.
Topics: Animals; Humans; Glioblastoma; Transplantation, Heterologous; Zebrafish; Heterografts; Brain Neoplasms; Cell Line, Tumor; Xenograft Model Antitumor Assays; Disease Models, Animal
PubMed: 37400666
DOI: 10.1007/s12094-023-03258-7 -
Nutrition Reviews Mar 2024Resveratrol (RV) is a natural compound found in grapes, wine, berries, and peanuts and has potential health benefits-namely, neurogenesis improvement. Neurogenesis,...
CONTEXT
Resveratrol (RV) is a natural compound found in grapes, wine, berries, and peanuts and has potential health benefits-namely, neurogenesis improvement. Neurogenesis, which is the process through which new neurons or nerve cells are generated in the brain, occurs in the subventricular zone and hippocampus and is influenced by various factors. RV has been shown to increase neural stem cell proliferation and survival, improving cognitive function in hippocampus-dependent tasks. Thus, to provide a convergent and unbiased conclusion of the available evidence on the correlation between the RV and neurogenesis, a systematic review needs to be undertaken meticulously and with appropriate attention.
OBJECTIVE
This study aimed to systematically review any potential connection between the RV and neurogenesis in animal models.
DATA SOURCES AND EXTRACTION
Based on the particular selection criteria, 8 original animal studies that investigated the relationship between RV and neurogenesis were included. Studies written in English and published in peer-reviewed journals with no restrictions on the starting date of publication on August 17, 2023, were searched in the Google Scholar and PubMed databases. Furthermore, data were extracted and analyzed independently by 2 researchers and then reviewed by a third researcher, and discrepancies were resolved by consensus. This project followed PRISMA reporting standards.
DATA ANALYSIS
In the studies analyzed in this review, there is a definite correlation between RV and neurogenesis, meaning that RV intake, irrespective of the mechanisms thereof, can boost neurogenesis in both the subventricular zone and hippocampus.
CONCLUSION
This finding, albeit with some limitations, provides a plausible indication of RV's beneficial function in neurogenesis. Indeed, RV intake may result in neurogenesis benefits-namely, cognitive function, mood regulation, stress resilience, and neuroprotection, potentially preventing cognitive decline.
PubMed: 38511504
DOI: 10.1093/nutrit/nuae025 -
Systematic Reviews Apr 2024Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Immunosuppressive therapy (IST) is the first choice for severe aplastic anemia (SAA) patients with hematopoietic stem cell transplantation (HSCT) limitation, and the main factor limiting its efficacy is too few residual hematopoietic stem/progenitor cells (HSPC). Eltrombopag (EPAG), as a small molecule thrombopoietin receptor agonist, can stimulate the proliferation of residual HSPC and restore the bone marrow hematopoietic function of patients. In recent years, many studies have observed the efficacy and safety of IST combined with EPAG in the treatment of SAA, but the results are still controversial. The aim of this study is to systematically evaluate the efficacy and safety of IST combined with or without EPGA in the treatment of SAA.
METHODS
We conducted a systematic review of all relevant literature published up to January 19, 2024. Pooled odds ratio (OR) was calculated to compare the rates, along with 95% confidence intervals (CI) and p value to assess whether the results were statistically significant by Review Manager 5.4.1. The p values for the interactions between each subgroup were calculated by Stata 15.1. The Newcastle-Ottawa Scale and the Cochrane bias risk assessment tools were respectively used to evaluate the quality of the literature with cohort studies and randomized controlled trials. The Review Manager 5.4.1 and Stata 15.1 were used to assess bias risk and perform the meta-analysis.
RESULTS
A total of 16 studies involving 2148 patients were included. The IST combined with the EPAG group had higher overall response rate (ORR) than the IST group at 3 months (pooled OR = 2.10, 95% CI 1.58-2.79, p < 0.00001) and 6 months (pooled OR = 2.13, 95% CI 1.60-2.83, p < 0.00001), but the difference between the two groups became statistically insignificant at 12 months (pooled OR = 1.13, 95% CI 0.75-1.72, p = 0.55). The results of complete response rate (CRR) (pooled OR at 3 months = 2.73, 95% CI 1.83-4.09, p < 0.00001, 6 months = 2.76, 95% CI 2.08-3.67, p < 0.00001 and 12 months = 1.38, 95% CI 0.85-2.23, p = 0.19) were similar to ORR. Compared with the IST group, the IST combined with the EPAG group had better overall survival rate (OSR) (pooled OR = 1.70, 95% CI 1.15-2.51, p = 0.008), but there were no statistically significant differences in event-free survival rate (EFSR) (pooled OR = 1.40, 95% CI 0.93-2.13, p = 0.11), clonal evolution rate (pooled OR = 0.68, 95% CI 0.46-1.00, p = 0.05) and other adverse events between the two groups. The results of subgroup analysis showed that different ages were a source of heterogeneity, but different study types and different follow-up times were not. Moreover, all p-values for the interactions were greater than 0.05, suggesting that the treatment effect was not influenced by subgroup characteristics.
CONCLUSION
EPAG added to IST enables patients to achieve earlier and faster hematologic responses with a higher rate of complete response. Although it had no effect on overall EFSR, it improved OSR and did not increase the incidence of clonal evolution and other adverse events.
Topics: Humans; Immunosuppressive Agents; Anemia, Aplastic; Immunosuppression Therapy; Benzoates; Pathologic Complete Response; Treatment Outcome; Hydrazines; Pyrazoles
PubMed: 38576005
DOI: 10.1186/s13643-024-02515-2