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Frontiers in Genetics 2024Long QT syndrome (LQTS) is an autosomal dominant inherited cardiac condition characterized by a QT interval prolongation and risk of sudden death. There are 17 subtypes...
INTRODUCTION
Long QT syndrome (LQTS) is an autosomal dominant inherited cardiac condition characterized by a QT interval prolongation and risk of sudden death. There are 17 subtypes of this syndrome associated with genetic variants in 11 genes. The second most common is type 2, caused by a mutation in the gene, which is part of the potassium channel and influences the final repolarization of the ventricular action potential. This case report presents an Ecuadorian teen with congenital Long QT Syndrome type 2 (OMIM ID: 613688), from a family without cardiac diseases or sudden cardiac death backgrounds.
CASE PRESENTATION
A 14-year-old girl with syncope, normal echocardiogram, and an irregular electrocardiogram was diagnosed with LQTS. Moreover, by performing Next-Generation Sequencing, a pathogenic variant in the gene p.(Ala614Val) (ClinVar ID: VCV000029777.14) associated with LQTS type 2, and two variants of uncertain significance in the p.(Arg1654GlyfsTer23) (rs779447911), and p. (Arg34653Cys) (ClinVar ID: VCV001475968.4) genes were identified. Furthermore, ancestry analysis showed a mainly Native American proportion.
CONCLUSION
Based on the genomic results, the patient was identified to have a high-risk profile, and an implantable cardioverter defibrillator was selected as the best treatment option, highlighting the importance of including both the clinical and genomics aspects for an integral diagnosis.
PubMed: 38957812
DOI: 10.3389/fgene.2024.1395012 -
Frontiers in Genetics 2024Osteosarcoma (OS) is highly malignant and prone to local infiltration and distant metastasis. Due to the poor outcomes of OS patients, the study aimed to identify...
BACKGROUND
Osteosarcoma (OS) is highly malignant and prone to local infiltration and distant metastasis. Due to the poor outcomes of OS patients, the study aimed to identify differentially expressed genes (DEGs) in OS and explore their role in the carcinogenesis and progression of OS.
METHODS
RNA sequencing was performed to identify DEGs in OS. The functions of the DEGs in OS were investigated using bioinformatics analysis, and DEG expression was verified using RT-qPCR and Western blotting. The role of was evaluated using gene set enrichment analysis (GSEA) and then investigated using functional assays in OS cells.
RESULTS
In all, 8353 DEGs were screened. GO and KEGG enrichment analyses indicated these DEGs showed strong enrichment in the calcium signaling pathway and pathways in cancer. Moreover, the Kaplan-Meier survival analysis showed ten hub genes were related to the outcomes of OS patients. Both transcript and protein expression were significantly reduced in OS, and GSEA suggested that was associated with cell cycle, apoptosis and inflammation. -overexpressing OS cells exhibited suppressed proliferation, migration, invasion and enhanced apoptosis.
CONCLUSION
was found to be significantly downregulated in OS patients, which was associated with poor prognosis. Modulation of expression levels may be beneficial in OS treatment.
PubMed: 38957810
DOI: 10.3389/fgene.2024.1410145 -
Frontiers in Genetics 2024The C-X-C motif chemokine ligand 9 (CXCL9) plays a pivotal role in tumor immunity by recruiting and activating immune cells. However, the relationship between CXCL9...
The C-X-C motif chemokine ligand 9 (CXCL9) plays a pivotal role in tumor immunity by recruiting and activating immune cells. However, the relationship between CXCL9 expression and prognosis in triple-negative breast cancer (TNBC) is unclear. We investigated CXCL9 mRNA expression, clinicopathological features, and prognosis in TNBC patients. We also used computational image analysis to quantify and assess the distribution of CXCL9 protein in the tumor core (TC) and invasive margin (IM). CXCL9 mRNA expression was significantly higher in TNBC tumors compared to normal tissue ( < 0.001) and was associated with smaller tumors ( = 0.022) and earlier stages ( = 0.033). High CXCL9 mRNA expression was correlated with improved overall survival (OS) in three independent cohorts (all < 0.05). In a separate analysis, low CXCL9 protein expression was associated with increased lymph node metastasis ( = 0.018 and = 0.036). High CXCL9 protein expression in the TC, IM, or both was associated with prolonged OS (all < 0.001). High CXCL9 expression, at both the mRNA and protein levels, is associated with improved prognosis in TNBC patients. CXCL9 expression in the TC and/or IM may be an independent prognostic factor.
PubMed: 38957805
DOI: 10.3389/fgene.2024.1421573 -
Frontiers in Veterinary Science 2024The effectiveness and safety of allogeneic mesenchymal stem/stromal cells (MSCs) can be affected by patient's immune recognition. Thus, MSC immunogenicity and their...
The effectiveness and safety of allogeneic mesenchymal stem/stromal cells (MSCs) can be affected by patient's immune recognition. Thus, MSC immunogenicity and their immunomodulatory properties are crucial aspects for therapy. Immune responses after allogeneic MSC administration have been reported in different species, including equine. Interactions of allogenic MSCs with the recipient's immune system can be influenced by factors like matching or mismatching for the major histocompatibility complex (MHC) between donor-recipient, and by the levels of MHC expression in MSCs. The latter can vary upon MSC inflammatory exposure or differentiation, such as chondrogenic induction, making both priming and differentiation interesting therapeutic strategies. This study investigated the systemic immune cellular response against allogeneic equine MSCs in these situations. Either MSCs in basal conditions (MSC-naïve), pro-inflammatory primed (MSC-primed) or chondrogenically differentiated (MSC-chondro) were repeatedly administered subcutaneously into autologous, MHC-matched or MHC-mismatched allogeneic equine recipients. At different time-points after each administration, lymphocytes were obtained from recipient horses and exposed to the same type of MSCs to assess the proliferative response of different T cell subsets (cytotoxic, helper, regulatory), B cells, and interferon gamma (IFNγ) secretion. Higher proliferative response of helper and cytotoxic T lymphocytes and IFNγ secretion was observed in response to all types of MHC-mismatched MSCs over MHC-matched ones. MSC-primed produced the highest immune response, followed by MSC-naïve, and MSC-chondro. However, MSC-primed activated Treg and had a mild effect on B cells, and the response after their second administration was similar to the first one. On the other hand, both MSC-chondro and MSC-naïve barely induced Treg response but promoted B lymphocyte activation, and proportionally induced a higher cell response after the second administration. In conclusion, both the type of MSC conditioning and the MHC compatibility influenced systemic immune recognition of equine MSCs after single and repeated administrations, but the response was different. Selecting MHC-matched donors would be particularly recommended for MSC-primed and repeated MSC-naïve administrations. While MHC-mismatching in MSC-chondro would be less critical, B cell response should not be ignored. Comprehensively investigating the immune response against equine allogeneic MSCs is crucial for advancing veterinary cell therapies.
PubMed: 38957800
DOI: 10.3389/fvets.2024.1391872 -
Journal of Orthopaedics Nov 2024Genu recurvatum deformity after treatment of leg-length discrepancy (LLD) with tension-band plating is a recognized, but poorly described phenomenon in medical...
AIMS AND OBJECTIVES
Genu recurvatum deformity after treatment of leg-length discrepancy (LLD) with tension-band plating is a recognized, but poorly described phenomenon in medical literature. The aim of this study was to evaluate clinical and radiological features of patients treated with tension-band plating for LLD assessing the development of a recurvatum deformity and its relationship to plate and screw disposition in a transversal plane, thus attempting to establish optimal plate positioning.
MATERIALS AND METHODS
Retrospective study of children with LLD treated with tension-band plating. Primary endpoints were clinical and radiological knee recurvatum and anterior and posterior physeal areas measured drawing a line spanning from the lateral to the medial tension-band plates in the transverse plane using volumetric magnetic resonance imaging (vMRI). These findings were compared between patients with and without knee recurvatum.
RESULTS
Twelve children (mean age 11.7 years) were included. Average follow-up was 2.6 years (1.5-5.0). Tension-band plating led to a significant reduction in LLD (mean, 15 mm). Six patients (50 %) developed clinical genu recurvatum (mean, 22°). According to vMRI, patients with genu recurvatum had a larger posterior to anterior physeal area ratio in both distal femur (1.6 versus 0.9, < 0.05) and proximal tibial physes (2.2 versus 1.0, < 0.05).
CONCLUSION
The optimal position of the tension-band plates in distal femoral and proximal tibial physes should be in a point where a posterior to anterior physeal areas ratio is around 1.0, so as to achieve an even distribution of the physeal areas in the multidimensional physeal transverse plane. This point anatomically corresponds in the sagittal X-ray view to an imaginary line located just anterior to the posterior diaphyseal cortical bone on a true lateral radiograph for both femur and tibia.
PubMed: 38957798
DOI: 10.1016/j.jor.2024.06.004 -
Frontiers in Cellular and Infection... 2024Spontaneous preterm delivery is defined as the beginning of the birth process before the 37th week of pregnancy. The presence of microorganisms in the fetal membranes is...
BACKGROUND
Spontaneous preterm delivery is defined as the beginning of the birth process before the 37th week of pregnancy. The presence of microorganisms in the fetal membranes is accompanied by an increase in the production of prostaglandin, one of the important factors associated with the prevalence of preterm birth. The invasion of microorganisms leads to the production of protease, coagulase, and elastase, which directly stimulate the onset of childbirth. We investigated the role of genital infections in women with preterm birth.
METHODS
The present case-control study was conducted in the west of Iran on 100 women with spontaneous preterm delivery (following 24 weeks of gestation and before 36 weeks and 6 days) as the case group and 100 women with normal delivery as controls. A questionnaire was applied to collect the data. Polymerase chain reaction and pathological examination of the placenta were performed.
RESULTS
The average age in women with normal delivery (30.92 ± 5.10) in women with spontaneous preterm delivery (30.27 ± 4.93). The prevalence of , infections was zero in both groups. The highest prevalence of 19 (19%) in the case group and 15 (15%) in the control group. Also, Placental inflammation was zero in controls and 7(7%) in the patient group. There was a significant relationship between bacteria and spontaneous preterm delivery.
CONCLUSION
The results of our study showed that except for bacteria, there is no significant relationship between the above bacterial infections and spontaneous preterm birth. Moreover, despite the significant reduction in the prevalence of many sexually transmitted infections in this research, it is still suggested to increase the awareness of people, including pregnant women, about the ways it can be transmitted by gynecologists and health and treatment centers.
Topics: Humans; Female; Case-Control Studies; Adult; Pregnancy; Premature Birth; Iran; Reproductive Tract Infections; Prevalence; Pregnancy Complications, Infectious; Placenta; Young Adult; Gardnerella vaginalis; Bacterial Infections
PubMed: 38957796
DOI: 10.3389/fcimb.2024.1348472 -
IScience Jun 2024Osteophyte formation, a key indicator of osteoarthritis (OA) severity, remains poorly understood in its relation to gut microbiota and metabolites in knee osteoarthritis...
Osteophyte formation, a key indicator of osteoarthritis (OA) severity, remains poorly understood in its relation to gut microbiota and metabolites in knee osteoarthritis (KOA). We conducted 16S rDNA sequencing and untargeted metabolomics on fecal and serum samples from 20 healthy volunteers, 80 KOA patients in Guangdong, and 100 in Inner Mongolia, respectively. Through bioinformatics analysis, we identified 3 genera and 5 serum metabolites associated with KOA osteophyte formation. Blautia abundance negatively correlated with meat, cheese, and bean consumption. The 5 serum metabolites negatively correlated with dairy, beef, cheese, sugar, and salt intake, yet positively with age and oil consumption. Higher Blautia levels in the gut may contribute to KOA osteophyte formation, with serum metabolites LTB4 and PGD2 potentially serving as biomarkers. KOA patients in Inner Mongolia exhibited lower Blautia levels and reduced expression of 5 serum metabolites, possibly due to cheese consumption habits, resulting in less osteophyte formation.
PubMed: 38957790
DOI: 10.1016/j.isci.2024.110111 -
EJC Paediatric Oncology Jun 2024Despite intensive therapies, pediatric patients with relapsed or refractory solid tumors have poor outcomes and need novel treatments. Immune therapies offer an...
Despite intensive therapies, pediatric patients with relapsed or refractory solid tumors have poor outcomes and need novel treatments. Immune therapies offer an alternative to conventional treatment options but require the identification of differentially expressed antigens to direct antitumor activity to sites of disease. B7-H3 (CD276) is an immune regulatory protein that is expressed in a range of malignancies and has limited expression in normal tissues. B7-H3 is highly expressed in pediatric solid tumors including osteosarcoma, rhabdomyosarcoma, Ewing sarcoma, Wilms tumor, neuroblastoma, and many rare tumors. In this article we review B7-H3-targeted chimeric antigen receptor (B7-H3-CAR) T cell therapies for pediatric solid tumors, reporting preclinical development strategies and outlining the landscape of active pediatric clinical trials. We identify challenges to the success of CAR T cell therapy for solid tumors including localizing to and penetrating solid tumor sites, evading the hostile tumor microenvironment, supporting T cell expansion and persistence, and avoiding intrinsic tumor resistance. We highlight strategies to overcome these challenges and enhance the effect of B7-H3-CAR T cells, including advanced CAR T cell design and incorporation of combination therapies.
PubMed: 38957786
DOI: 10.1016/j.ejcped.2024.100160 -
Toxicology Research Aug 2024Improving the quality of life in elderly patients and finding new treatment options for neurological diseases such as Alzheimer's has become one of the priorities in the...
Improving the quality of life in elderly patients and finding new treatment options for neurological diseases such as Alzheimer's has become one of the priorities in the scientific world. In recent years, the beneficial effects and therapeutic properties of natural foods on neurological health have become a very remarkable issue. Walnut oil (WO) is a promising nutraceutical, with many phytochemicals and polyunsaturated fatty acids and is thought to be promising in the treatment of many neurological diseases and cognitive deficits, such as Alzheimer's disease (AD). Polyphenolic compounds found in WO enhance intraneuronal signaling and neurogenesis and improve the sequestration of insoluble toxic protein aggregates. The objective of this study was to investigate the potential protective and therapeutic effects of WO in a model of AD induced by retinoic acid (RA) and brain-derived neurotrophic factor (BDNF). In order to achieve this, the experimental groups were formed as follows: Control group, WO group, Alzheimer's disease (AD) group, AD + WO applied group (AD + WO). WO supplementation almost significantly reduced oxidative stress in the ad model, providing 2-fold protection against protein oxidation. Additionally, WO showed a significant reduction in tau protein levels (2-fold), increased acetylcholine (ACh) levels (12%), and decreased acetylcholine esterase (AChE) activity (~50%). Since it has been known for centuries that WO does show any adverse effects on human health and has neuroprotective properties, it may be used in the treatment of AD as an additional nutraceutical to drug treatments.
PubMed: 38957781
DOI: 10.1093/toxres/tfae097 -
Case Reports in Neurological Medicine 2024Focal muscle vibration (FMV) is increasingly being recognized as a rehabilitative therapy for enhancing motor function in central nervous system (CNS) diseases,...
Focal muscle vibration (FMV) is increasingly being recognized as a rehabilitative therapy for enhancing motor function in central nervous system (CNS) diseases, particularly in patients with fine motor control deficits stemming from CNS damage. Brain lesions from these diseases disrupt the motor networks, necessitating novel rehabilitation strategies. By applying vibrations to muscles, FMV stimulates sensory fibers to induce cortical activity and kinesthetic illusions. While initial studies have highlighted FMV's role in reducing spasticity, recent evidence points to its potential in treating motor paralysis. However, prior research has been limited by the lack of acute-phase studies and a focus on patients with minimal muscle contraction capability. This report aimed to explore FMV's efficacy on upper limb motor function in patients with flaccid motor paralysis immediately after acute CNS diseases. We report the case of a septuagenarian male with a brain abscess in the right parietal lobe, leading to flaccid motor paralysis. Rehabilitation included 28 sessions of occupational and physical therapy that incorporated FMV. Significant improvements were observed in upper extremity function, with moderate to very large effect sizes, while lower limb function showed lesser improvement without adverse effects. This case suggests the utility of FMV in enhancing upper-limb motor function after acute CNS injuries, potentially serving as a supplementary therapy for spontaneous recovery. This report contributes to emerging evidence on FMV's benefits in acute flaccid motor paralysis, expanding the documented therapeutic scope.
PubMed: 38957779
DOI: 10.1155/2024/2469074