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Indian Journal of Orthopaedics Jul 2024Orthobiologic agents play a significant role in regenerative medicine. The quest for newer and more effective Orthobiologic agents is never-ending, leading to the... (Review)
Review
INTRODUCTION
Orthobiologic agents play a significant role in regenerative medicine. The quest for newer and more effective Orthobiologic agents is never-ending, leading to the evolution of more reformed products. GOLDIC (GOLD Induced cytokine) is a recently evolving Orthobiologic agent developed by conditioning autologous serum with gold particles. We aim to collate the available evidence on GOLDIC and provide a systematic literature review.
MATERIALS AND METHODS
Using Cochrane and PRISMA guidelines literature search was done for GOLDIC. After duplicate removal and exclusions, 62 articles were scrutinized, of which 8 articles qualified for full-text review. A risk-of-bias assessment of the included studies was done.
RESULTS
All articles showed standardized preparation methods of GOLDIC and uniformity in the number of doses administered, except one study. Reproducible results were noted like an increase in plasma gelsolin and improved KOOS, WOMAC, and VAS scores.
CONCLUSION
GOLDIC has the potential to be a significant Orthobiologic modality considering its standardized preparation techniques, method of administration, and uniformly reproducible outcome measures. However, further high-quality evidence is needed to analyze the clinical efficiency and safety profile of GOLDIC.
SYSTEMATIC REVIEW REGISTRATION
INPLASY202350027 [https://doi.org/10.37766/inplasy2023.5.0027].
PubMed: 38948367
DOI: 10.1007/s43465-024-01167-7 -
The effects of occupational disruption during COVID-19 lockdowns on health: a cross-sectional study.PeerJ 2024The disruption in daily activity performance during COVID-19 lockdowns is widely understood to have impacted health, but a better understanding of how restricted...
The disruption in daily activity performance during COVID-19 lockdowns is widely understood to have impacted health, but a better understanding of how restricted performance of specific activities are associated with health is needed. This cross-sectional study answers the following question: How were changes in the performance of 16 daily activities associated with health during COVID-19 lockdowns? A total of 116 participants completed an online survey rating their health before and during COVID-19 lockdowns and comparing their recollection of the performance of 16 activities before COVID-19 with their performance during lockdowns. Multiple stepwise linear regression analysis was used to estimate the relationship between self-reported changes in activities during lockdowns and concurrent (during-lockdown) health status, while controlling for pre-COVID-19 health status. Only changes in activities that were uniquely and significantly associated with lockdown health status were retained in the final model. Health before COVID-19 accounted for 3.7% ( = 0.039) of the variance in health during COVID-19 lockdowns. After controlling for health before COVID-19, five types of activity were significantly and uniquely predictive of health during lockdowns, together accounting for 48.3% of the variance. These activities and the variances they accounted for were rest and sleep (29.5%, < 0.001), play and recreational activities (8%, < 0.001), work (4.8%, = 0.002), personal hygiene (3.2%, = 0.01), and healthy eating (2.8%, = 0.013). The study suggests that these five types of activity should be prioritized in policy or interventions when participation in activity is constrained by lockdowns or comparable factors.
Topics: Humans; COVID-19; Cross-Sectional Studies; Male; Female; Health Status; Adult; Middle Aged; SARS-CoV-2; Quarantine; Communicable Disease Control; Surveys and Questionnaires
PubMed: 38948220
DOI: 10.7717/peerj.17594 -
Heliyon Jun 2024The GIMAP family genes play a key role in immune function. Increasing evidence suggests that GIMAP genes were implicated in the tumorigenesis of lung adenocarcinoma...
BACKGROUND
The GIMAP family genes play a key role in immune function. Increasing evidence suggests that GIMAP genes were implicated in the tumorigenesis of lung adenocarcinoma (LUAD). This study aimed to investigate the clinical significance of GIMAP family genes in LUAD.
METHODS
In this study, we explored the expression, mutation, prognostic value of GIMAP family genes and the correlation with immune microenvironment in LUAD. We further investigated the relationship between GIMAP family genes expression and immunotherapy response in GEO LUAD and melanoma cohorts.
RESULTS
Among the GIMAP family genes, the expression levels of GIMAP1, GIMAP2, GIMAP4, GIMAP5, GIMAP6, GIMAP7, and GIMAP8 were significantly lower in LUAD tumor tissues than normal tissues. Most GIMAP genes were closely related to age, tumor grade and T stage, but not significantly related to sex, N stage and M stage. In the overall population, patients with high expression of GIMAP family genes had a significant longer overall survival (OS). GO and KEGG enrichment analysis showed that GIMAP family genes were highly enriched in immune-related biological process. The expression of GIMAP family genes was positively correlated with immune cell infiltration and immune checkpoint molecules. Furthermore, high expression of GIMAP family genes were correlated with therapeutic response to immunotherapy in LUAD and melanoma patients.
CONCLUSION
In this study, we identified that GIMAP family genes were significantly associated with immune cell infiltration and immune checkpoint molecules. They potentially play a critical role in anti-tumor immunity and serve as immunotherapy biomarkers.
PubMed: 38948046
DOI: 10.1016/j.heliyon.2024.e33111 -
ACS Omega Jun 2024is the third most common infectious pathogen in AIDS patients and leads to the highest death rate in Guangxi, China. The lack of reliable biomarkers is one of the major...
is the third most common infectious pathogen in AIDS patients and leads to the highest death rate in Guangxi, China. The lack of reliable biomarkers is one of the major obstacles in current clinical diagnosis, which largely contributes to this high mortality. Here, we present a study that aimed at identifying diagnostic biomarker candidates through genome-wide prediction and functional annotation of secreted proteins. A total of 584 secreted proteins then emerged, including 382 classical and 202 nonclassical ones. Among them, there were 87 newly obtained functional annotations in this study. The annotated proteins were further evaluated by combining RNA profiling and a homology comparison. Three proteins were ultimately highlighted as biomarker candidates with robust expression and remarkable specificity. The predicted phosphoinositide phospholipase C and the galactomannoprotein were suggested to play an interactive immune game through metabolism of arachidonic acid. Therefore, they hold promise in developing new tools for clinical diagnosis of and also possibly serve as molecular targets for future therapy.
PubMed: 38947822
DOI: 10.1021/acsomega.4c00571 -
Health Care Science Jun 2024Occupational therapists can play a key role in early identification of delay at the population health level by providing education to public health employees on how to...
BACKGROUND
Occupational therapists can play a key role in early identification of delay at the population health level by providing education to public health employees on how to implement developmental monitoring with caregivers of children birth to age 5.
METHODS
A pretest posttest design was utilized to assess the online education and training that was provided to Department of Public Health employees ( = 339), including Head Start, Special Supplemental Nutrition Program for Women, Infants and Children, Home Visiting, and Early Intervention.
RESULTS
Analysis of pretest-posttest survey data showed significant results for all 12 key learning outcomes. Six out of 12 outcomes were found to have a large effect size ( > 0.8), 4 outcomes indicated a medium effect size ( > 0.5), and 2 outcomes had a small effect size ( > 0.2). Participants gained knowledge of the "Learn the Signs. Act Early." (LTSAE) developmental monitoring program, the difference between developmental monitoring and screening, the state's referral system and age-appropriate parental engagement activities through knowledge of child development.
CONCLUSIONS
Occupational therapists are child development specialists who can provide education on developmental monitoring and activities for parental engagement. The online course proved to be an effective platform to promote LTSAE within state agencies.
PubMed: 38947366
DOI: 10.1002/hcs2.95 -
Frontiers in Immunology 2024Monocytes play a critical role in tumor initiation and progression, with their impact on prostate adenocarcinoma (PRAD) not yet fully understood. This study aimed to...
BACKGROUND
Monocytes play a critical role in tumor initiation and progression, with their impact on prostate adenocarcinoma (PRAD) not yet fully understood. This study aimed to identify key monocyte-related genes and elucidate their mechanisms in PRAD.
METHOD
Utilizing the TCGA-PRAD dataset, immune cell infiltration levels were assessed using CIBERSORT, and their correlation with patient prognosis was analyzed. The WGCNA method pinpointed 14 crucial monocyte-related genes. A diagnostic model focused on monocytes was developed using a combination of machine learning algorithms, while a prognostic model was created using the LASSO algorithm, both of which were validated. Random forest and gradient boosting machine singled out CCNA2 as the most significant gene related to prognosis in monocytes, with its function further investigated through gene enrichment analysis. Mendelian randomization analysis of the association of HLA-DR high-expressing monocytes with PRAD. Molecular docking was employed to assess the binding affinity of CCNA2 with targeted drugs for PRAD, and experimental validation confirmed the expression and prognostic value of CCNA2 in PRAD.
RESULT
Based on the identification of 14 monocyte-related genes by WGCNA, we developed a diagnostic model for PRAD using a combination of multiple machine learning algorithms. Additionally, we constructed a prognostic model using the LASSO algorithm, both of which demonstrated excellent predictive capabilities. Analysis with random forest and gradient boosting machine algorithms further supported the potential prognostic value of CCNA2 in PRAD. Gene enrichment analysis revealed the association of CCNA2 with the regulation of cell cycle and cellular senescence in PRAD. Mendelian randomization analysis confirmed that monocytes expressing high levels of HLA-DR may promote PRAD. Molecular docking results suggested a strong affinity of CCNA2 for drugs targeting PRAD. Furthermore, immunohistochemistry experiments validated the upregulation of CCNA2 expression in PRAD and its correlation with patient prognosis.
CONCLUSION
Our findings offer new insights into monocyte heterogeneity and its role in PRAD. Furthermore, CCNA2 holds potential as a novel targeted drug for PRAD.
Topics: Humans; Male; Prostatic Neoplasms; Monocytes; Prognosis; Immunotherapy; Biomarkers, Tumor; Machine Learning; Molecular Docking Simulation; Gene Expression Regulation, Neoplastic; Gene Expression Profiling; Computational Biology; Multiomics
PubMed: 38947325
DOI: 10.3389/fimmu.2024.1426474 -
Journal of Extracellular Biology Jun 2024Extracellular vesicles (EVs) are nanosized vesicles with a lipid bilayer that are secreted by cells and play a critical role in cell-to-cell communication. Despite the...
Extracellular vesicles (EVs) are nanosized vesicles with a lipid bilayer that are secreted by cells and play a critical role in cell-to-cell communication. Despite the promising reports regarding their diagnostic and therapeutic potential, the utilization of EVs in the clinical setting is limited due to insufficient information about their cargo and a lack of standardization in isolation and analysis methods. Considering protein cargos in EVs as key contributors to their therapeutic potency, we conducted a tandem mass tag (TMT) quantitative proteomics analysis of three subpopulations of mesenchymal stem cell (MSC)-derived EVs obtained through three different isolation techniques: ultracentrifugation (UC), high-speed centrifugation (HS), and ultracentrifugation on sucrose cushion (SU). Subsequently, we checked EV marker expression, size distribution, and morphological characterization, followed by bioinformatic analysis. The bioinformatic analysis of the proteome results revealed that these subpopulations exhibit distinct molecular and functional characteristics. The choice of isolation method impacts the proteome of isolated EVs by isolating different subpopulations of EVs. Specifically, EVs isolated through the high-speed centrifugation (HS) method exhibited a higher abundance of ribosomal and mitochondrial proteins. Functional apoptosis assays comparing isolated mitochondria with EVs isolated through different methods revealed that HS-EVs, but not other EVs, induced early apoptosis in cancer cells. On the other hand, EVs isolated using the sucrose cushion (SU) and ultracentrifugation (UC) methods demonstrated a higher abundance of proteins primarily involved in the immune response, cell-cell interactions and extracellular matrix interactions. Our analyses unveil notable disparities in proteins and associated biological functions among EV subpopulations, underscoring the importance of meticulously selecting isolation methods and resultant EV subpopulations based on the intended application.
PubMed: 38947171
DOI: 10.1002/jex2.159 -
Research Square Jun 2024Background The demethylating agent decitabine (DAC) effectively inhibits tumor growth and metastasis by targeting ESR1 methylation to restore estrogen receptor alpha...
Background The demethylating agent decitabine (DAC) effectively inhibits tumor growth and metastasis by targeting ESR1 methylation to restore estrogen receptor alpha (ERα) signaling and promoting cellular differentiation in models of human osteosarcoma (OSA). Whether this pathway can be targeted in canine OSA patients is unknown. Methods Canine OSA tumor samples were tested for ERα expression and ESR1 promoter methylation. Human (MG63.3) and canine (MC-KOS) OSA cell lines and murine xenografts were treated with DAC and , respectively. Samples were assessed using mRNA sequencing and tissue immunohistochemistry. Results ESR1 is methylated in a subset of canine OSA patient samples and the MC-KOS cell line. DAC treatment led to enhanced differentiation as demonstrated by increased ALPL expression, and suppressed tumor growth and . Metastatic progression was inhibited, particularly in the MG63.3 model, which expresses higher levels of DNA methyltransferases DNMT1 and 3B. DAC treatment induced significant alterations in immune response and cell cycle pathways. Conclusion DAC treatment activates ERα signaling, promotes bone differentiation, and inhibits tumor growth and metastasis in human and canine OSA. Additional DAC-altered pathways and species- or individual-specific differences in DNMT expression may also play a role in DAC treatment of OSA.
PubMed: 38946977
DOI: 10.21203/rs.3.rs-4451060/v1 -
World Journal of Gastroenterology Jun 2024Metabolic dysfunction-associated fatty liver disease (MAFLD) is a hepatic manifestation of the metabolic syndrome. It is one of the most common liver diseases worldwide... (Review)
Review
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a hepatic manifestation of the metabolic syndrome. It is one of the most common liver diseases worldwide and shows increasing prevalence rates in most countries. MAFLD is a progressive disease with the most severe cases presenting as advanced fibrosis or cirrhosis with an increased risk of hepatocellular carcinoma. Gut microbiota play a significant role in the pathogenesis and progression of MAFLD by disrupting the gut-liver axis. The mechanisms involved in maintaining gut-liver axis homeostasis are complex. One critical aspect involves preserving an appropriate intestinal barrier permeability and levels of intestinal lumen metabolites to ensure gut-liver axis functionality. An increase in intestinal barrier permeability induces metabolic endotoxemia that leads to steatohepatitis. Moreover, alterations in the absorption of various metabolites can affect liver metabolism and induce liver steatosis and fibrosis. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of drugs developed for the treatment of type 2 diabetes mellitus. They are also commonly used to combat obesity and have been proven to be effective in reversing hepatic steatosis. The mechanisms reported to be involved in this effect include an improved regulation of glycemia, reduced lipid synthesis, β-oxidation of free fatty acids, and induction of autophagy in hepatic cells. Recently, multiple peptide receptor agonists have been introduced and are expected to increase the effectiveness of the treatment. A modulation of gut microbiota has also been observed with the use of these drugs that may contribute to the amelioration of MAFLD. This review presents the current understanding of the role of the gut-liver axis in the development of MAFLD and use of members of the GLP-1 RA family as pleiotropic agents in the treatment of MAFLD.
Topics: Humans; Glucagon-Like Peptide-1 Receptor; Gastrointestinal Microbiome; Liver; Non-alcoholic Fatty Liver Disease; Animals; Metabolic Syndrome; Hypoglycemic Agents; Diabetes Mellitus, Type 2; Incretins; Intestinal Mucosa; Glucagon-Like Peptide-1 Receptor Agonists
PubMed: 38946874
DOI: 10.3748/wjg.v30.i23.2964 -
Disability and Rehabilitation Jun 2024To understand the expectations and demand for a movement-tracking videogame (Bootle Blast) for home-based, upper limb (UL) rehabilitation among Costa Rican children with...
PURPOSE
To understand the expectations and demand for a movement-tracking videogame (Bootle Blast) for home-based, upper limb (UL) rehabilitation among Costa Rican children with cerebral palsy (CP).
METHODS
Data were collected via telephone screening () and child-parent dyads Zoom interviews (). Descriptive statistics and data transformation were used to report on success criteria (i.e., recruitment rate, having an appropriate screen and space to play, setting a weekly play time goal (PTG) ≥45 min, identifying one UL therapy goal). The DEPICT model for collaborative qualitative analysis was used in the thematic analysis of interview data.
RESULTS
Fifteen dyads participated (1.6 ± 1 recruited/month). All had a flat-screen TV in a suitable location to play, were able to set a UL therapy goal, and established PTGs ranging from 45-120 min per week. Identified themes were: 1) Socio-cultural factors heighten demand, 2) Feelings of hope prevail for the intervention, and 3) Collaborative goal setting supports realistic expectations for Bootle Blast.
CONCLUSIONS
Dyads had positive and realistic expectations about implementing the proposed videogaming intervention. This study provides insights on tailoring a family-centered, therapy gaming intervention to improve access to motor rehabilitation for children with CP in rural/remote settings and low-middle income countries.
PubMed: 38946018
DOI: 10.1080/09638288.2024.2362952