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Cureus May 2024Background Ulcerative colitis (UC) and Crohn's disease (CD) are classified as inflammatory bowel diseases (IBDs). However, they have different pathogeneses and treatment...
Background Ulcerative colitis (UC) and Crohn's disease (CD) are classified as inflammatory bowel diseases (IBDs). However, they have different pathogeneses and treatment strategies and need to be differentiated. Purpose To determine the feasibility of differentiating UC from CD in patients with first-time IBD based on simple abdominal computed tomography (CT) findings. Methods We conducted a retrospective study of patients diagnosed with IBD for the first time at our hospital between January and December 2021. Age, sex, white blood cell count, albumin concentration, C-reactive protein concentration, visceral fat area, subcutaneous fat area, and psoas major volume were extracted and used to differentiate the two groups. Results Forty-three patients were selected. Their mean age was 35.60 ± 17.19 years, and 32 were male, while 11 were female. The visceral fat cross-sectional area was 51.80 cm for UC and 21.10 cm for CD (p < 0.01). The subcutaneous fat cross-sectional area was 108.30 cm for UC and 66.30 cm for CD (p = 0.049). The total protein concentration was 6.15 g/L for UC and 6.60 g/L for CD (p = 0.012). Receiver operating characteristic curve analysis of the visceral and subcutaneous fat cross-sectional areas showed areas under the curve, 95% confidence intervals, sensitivities, and specificities of 0.750 and 0.675, 0.603-0.897 and 0.507-0.844, 0.810 and 1.00, and 0.591 and 0.409, respectively, at cutoffs of 26.53 and 36.6 cm. Conclusions The visceral and subcutaneous fat cross-sectional areas determined with simple abdominal CT can differentiate UC from CD in patients with first-time IBD.
PubMed: 38840987
DOI: 10.7759/cureus.59691 -
Orthopaedic Journal of Sports Medicine Jun 2024The effect of local corticosteroid (CS) injections on rotator cuff muscles remains poorly defined, despite the significance of muscle quality as a crucial prognostic...
Influence of Frequent Corticosteroid Local Injections on the Expression of Genes and Proteins Related to Fatty Infiltration, Muscle Atrophy, Inflammation, and Fibrosis in Patients With Chronic Rotator Cuff Tears: A Pilot Study.
BACKGROUND
The effect of local corticosteroid (CS) injections on rotator cuff muscles remains poorly defined, despite the significance of muscle quality as a crucial prognostic factor for patients with rotator cuff tears (RCTs).
PURPOSE
To compare alterations in gene and protein expression patterns in the rotator cuff muscles of patients with RCTs who received frequent joint CS injections with alterations in those without a history of CS injections.
STUDY DESIGN
Controlled laboratory study.
METHODS
A total of 24 rotator cuff muscle samples with medium-sized tears from 12 patients with a frequent joint CS injection history (steroid group; 7 men and 5 women who had received ≥5 injections with at least 1 within the previous 3 months; mean age, 63.0 ± 7.2 years) and 12 age- and sex-matched control patients without a history of CS injections (no-steroid group) were acquired. Alterations in the expression of genes and proteins associated with adipogenesis, myogenesis, inflammation, and muscle fibrosis were compared between the groups using quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. Statistical analysis included comparison of group means using the Mann-Whitney test, chi-square test, or Fisher exact test and logistic regression for multivariate analysis.
RESULTS
In the steroid group, the mRNA expression levels of adipogenic CCAAT/enhancer-binding protein alpha (C/EBPα; = .008) and muscle atrophy-related genes (atrogin; = .019) were significantly higher, and those of myogenic differentiation 1 (MyoD; = .035), inflammatory interleukin 6 (IL-6; = .035), and high mobility group box 1 ( = .003) were significantly lower compared with the no-steroid group. In addition, MyoD ( = .041) and IL-6 ( = .026) expression were decreased in the steroid versus no-steroid group. Immunohistochemistry revealed increased expression of C/EBPα and atrogin and decreased expression of MyoD and IL-6 in the steroid versus no-steroid group.
CONCLUSION
Patients with RCTs and a history of frequent CS injections exhibited an upregulation of adipogenic and muscle atrophy-related genes and proteins within the rotator cuff muscles and a downregulation in the expression of myogenic and inflammatory genes and proteins in the same muscles.
CLINICAL RELEVANCE
These altered gene and protein expressions by frequent local CS injections may cause poor outcomes in patients with RCTs.
PubMed: 38840789
DOI: 10.1177/23259671241252421 -
Frontiers in Molecular Neuroscience 2024Binge drinking in adolescence can disrupt myelination and cause brain structural changes that persist into adulthood. Alcohol consumption at a younger age increases the...
INTRODUCTION
Binge drinking in adolescence can disrupt myelination and cause brain structural changes that persist into adulthood. Alcohol consumption at a younger age increases the susceptibility of these changes. Animal models to understand ethanol's actions on myelin and white matter show that adolescent binge ethanol can alter the developmental trajectory of oligodendrocytes, myelin structure, and myelin fiber density. Oligodendrocyte differentiation is epigenetically regulated by H3K9 trimethylation (H3K9me3). Prior studies have shown that adolescent binge ethanol dysregulates H3K9 methylation and decreases H3K9-related gene expression in the PFC.
METHODS
Here, we assessed ethanol-induced changes to H3K9me3 occupancy at genomic loci in the developing adolescent PFC. We further assessed ethanol-induced changes at the transcription level with qPCR time course approaches in oligodendrocyte-enriched cells to assess changes in oligodendrocyte progenitor and oligodendrocytes specifically.
RESULTS
Adolescent binge ethanol altered H3K9me3 regulation of synaptic-related genes and genes specific for glutamate and potassium channels in a sex-specific manner. In PFC tissue, we found an early change in gene expression in transcription factors associated with oligodendrocyte differentiation that may lead to the later significant decrease in myelin-related gene expression. This effect appeared stronger in males.
CONCLUSION
Further exploration in oligodendrocyte cell enrichment time course and dose response studies could suggest lasting dysregulation of oligodendrocyte maturation at the transcriptional level. Overall, these studies suggest that binge ethanol may impede oligodendrocyte differentiation required for ongoing myelin development in the PFC by altering H3K9me3 occupancy at synaptic-related genes. We identify potential genes that may be contributing to adolescent binge ethanol-related myelin loss.
PubMed: 38840776
DOI: 10.3389/fnmol.2024.1389100 -
BMC Genomics Jun 2024Expansion of genomic resources for the Pacific white shrimp (Litopenaeus vannamei), such as the construction of dense genetic linkage maps, is crucial for the...
BACKGROUND
Expansion of genomic resources for the Pacific white shrimp (Litopenaeus vannamei), such as the construction of dense genetic linkage maps, is crucial for the application of genomic tools in order to improve economically relevant traits. Sexual dimorphism exists in Pacific white shrimp, and the mapping of the sex-determination region in this species may help in future reproductive applications. We have constructed male, female, and sex-averaged high-density genetic maps using a 50 K single-nucleotide polymorphism (SNP) array, followed by a genome-wide association study (GWAS) to identify genomic regions associated with sex in white shrimp.
RESULTS
The genetic map yielded 15,256 SNPs assigned to 44 linkage groups (LG). The lengths of the male, female, and sex-averaged maps were 5,741.36, 5,461.20 and 5,525.26 cM, respectively. LG18 was found to be the largest for both sexes, whereas LG44 was the shortest for males and LG31 for females. A sex-determining region was found in LG31 with 21 statistically significant SNPs. The most important SNP was previously identified as a sex-linked marker and was able to identify 99% of the males and 88% of the females. Although other significant markers had a lower ability to determine sex, putative genes were intercepted or close to them. The oplophorus-luciferin 2-monooxygenase, serine/arginine repetitive matrix protein and spermine oxidase genes were identified as candidates with possible participation in important processes of sexual differentiation in shrimp.
CONCLUSIONS
Our results provide novel genomic resources for shrimp, including a high-density linkage map and new insights into the sex-determining region in L. vannamei, which may be usefulfor future genetics and reproduction applications.
Topics: Animals; Penaeidae; Polymorphism, Single Nucleotide; Female; Male; Chromosome Mapping; Sex Determination Processes; Genetic Linkage; Genome-Wide Association Study
PubMed: 38840101
DOI: 10.1186/s12864-024-10431-x -
Nature Communications Jun 2024Most vertebrates develop distinct females and males, where sex is determined by repeatedly evolved environmental or genetic triggers. Undifferentiated sex chromosomes...
Most vertebrates develop distinct females and males, where sex is determined by repeatedly evolved environmental or genetic triggers. Undifferentiated sex chromosomes and large genomes have caused major knowledge gaps in amphibians. Only a single master sex-determining gene, the dmrt1-paralogue (dm-w) of female-heterogametic clawed frogs (Xenopus; ZW♀/ZZ♂), is known across >8740 species of amphibians. In this study, by combining chromosome-scale female and male genomes of a non-model amphibian, the European green toad, Bufo(tes) viridis, with ddRAD- and whole genome pool-sequencing, we reveal a candidate master locus, governing a male-heterogametic system (XX♀/XY♂). Targeted sequencing across multiple taxa uncovered structural X/Y-variation in the 5'-regulatory region of the gene bod1l, where a Y-specific non-coding RNA (ncRNA-Y), only expressed in males, suggests that this locus initiates sex-specific differentiation. Developmental transcriptomes and RNA in-situ hybridization show timely and spatially relevant sex-specific ncRNA-Y and bod1l-gene expression in primordial gonads. This coincided with differential H3K4me-methylation in pre-granulosa/pre-Sertoli cells, pointing to a specific mechanism of amphibian sex determination.
Topics: Animals; Male; Female; Sex Determination Processes; Y Chromosome; X Chromosome; Amphibians; Transcription Factors; RNA, Untranslated; Genome; Evolution, Molecular
PubMed: 38839766
DOI: 10.1038/s41467-024-49025-2 -
BMJ Open Jun 2024The relationship between Ki-67 expression and the prognosis of patients with oesophageal squamous cell carcinoma (ESCC) has been extensively studied. However, their... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The relationship between Ki-67 expression and the prognosis of patients with oesophageal squamous cell carcinoma (ESCC) has been extensively studied. However, their findings were inconsistent. Consequently, the present meta-analysis was performed to identify the precise value of Ki-67 in predicting the prognosis of ESCC.
DESIGN
The current meta-analysis was carried out in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
DATA SOURCES
Electronic databases of PubMed, Embase, Web of Science and Cochrane Library were systematically searched until 26 September 2023.
STATISTICAL METHODS
Pooled HRs and corresponding 95% CIs were calculated to estimate the role of Ki-67 in predicting overall survival (OS) and disease-free survival (DFS) in ESCC. Between-study heterogeneity was evaluated using Cochrane's Q test and I statistics. Specifically, significant heterogeneities were identified based on p<0.10 on the Q statistic test or I>50% so the random-effects model should be used; otherwise, the fixed-effects model should be used. The relationship between Ki-67 and clinicopathological characteristics of ESCC was evaluated by combining ORs with their corresponding 95% CIs.
RESULTS
11 articles with 1124 patients were included in the present meta-analysis. Based on our analysis, increased Ki-67 expression was markedly associated with poor OS (HR 1.62, 95% CI 1.15 to 2.28, p=0.006) and DFS (HR 1.72, 95% CI 1.22 to 2.43, p=0.002) in ESCC. Moreover, subgroup analysis revealed that Ki-67 upregulation significantly predicted OS and DFS when a Ki-67 threshold of >30% was used. Nonetheless, Ki-67 was not significantly associated with sex, T stage, N stage, TNM stage, tumour differentiation or tumour location.
CONCLUSIONS
In the present meta-analysis, high Ki-67 expression significantly predicted OS and DFS in patients with ESCC, especially when Ki-67>30% was used as the threshold. These results suggest that Ki-67 could serve as an effective and reliable prognostic indicator for ESCC.
Topics: Humans; Ki-67 Antigen; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Prognosis; Biomarkers, Tumor; Disease-Free Survival
PubMed: 38839387
DOI: 10.1136/bmjopen-2023-083637 -
Discover Oncology Jun 2024The role of mast cells in malignancies remains unclear, and there is no clear correlation between mast cells and tumor microvessels, tumor growth, or lung adenocarcinoma...
BACKGROUND
The role of mast cells in malignancies remains unclear, and there is no clear correlation between mast cells and tumor microvessels, tumor growth, or lung adenocarcinoma (LUAD) prognosis. This study aims to explore the association between mast cell density (MCD) and intratumoral microvessel density (MVD), clinicopathological parameters, and prognosis in LUAD, by evaluating mast cell infiltration characteristics and their prognostic significance.
METHODS
This retrospective investigation involved 238 patients with LUAD undergoing complete resection. Tumor and normal lung tissue sections outside the tumor were immunohistochemically stained for MCD in the intratumoral and outside regions, respectively. CD34 polyclonal antibody was used to measure intratumoral MVD.
RESULTS
Intratumoral regions of LUAD had a higher MCD (P < 0.001) than normal lung tissue. In the intratumoral region, MCD and CD34-MVD were positively correlated (r = 0.411, P < 0.001). Intratumoral MCD correlated with sex, smoking history, tumor differentiation, pathological subtype, and tumor size. Female sex (P = 0.012), no smoking history (P = 0.002), acinar predominant type (P = 0.012), and tumor size ≤ 3 cm (P = 0.009) were associated with a higher MCD, whereas poorly differentiated (P = 0.039) and solid/micropapillary predominant types (P = 0.001) were associated with a lower MCD. Higher intratumoral MCD exhibited a marginally improved overall survival, and individuals with higher MCD infiltration ratios (intratumoral MCD/outside the MCD) had higher disease-free and overall survival rates (log-rank P < 0.001). A high MCD infiltration ratio was associated with decreased risk of tumor progression and death following complete resection.
CONCLUSION
The tumor microenvironment controls mast cell infiltration in LUAD, and patients with increased intratumoral mast cell infiltration have better prognosis.
PubMed: 38834833
DOI: 10.1007/s12672-024-01062-5 -
Cancer Immunology, Immunotherapy : CII Jun 2024There is an ongoing debate as to whether sex could be associated with immune checkpoint inhibitor (ICI) benefit. Existing literature data reveal contradictory results,... (Observational Study)
Observational Study
BACKGROUND
There is an ongoing debate as to whether sex could be associated with immune checkpoint inhibitor (ICI) benefit. Existing literature data reveal contradictory results, and data on first-line immune combinations are lacking.
METHOD
This was a real-world, multicenter, international, observational study to determine the sex effects on the clinical outcomes in metastatic renal cell carcinoma (mRCC) patients treated with immuno-oncology combinations as first-line therapy.
RESULTS
A total of 1827 mRCC patients from 71 cancer centers in 21 countries were included. The median OS was 38.7 months (95% CI 32.7-44.2) in the overall study population: 40.0 months (95% CI 32.7-51.6) in males and 38.7 months (95% CI 26.4-41.0) in females (p = 0.202). The median OS was higher in males vs. females in patients aged 18-49y (36.9 months, 95% CI 29.0-51.6, vs. 24.8 months, 95% CI 16.8-40.4, p = 0.426, with + 19% of 2y-OS rate, 72% vs. 53%, p = 0.006), in the clear cell histology subgroup (44.2 months, 95% CI 35.8-55.7, vs. 38.7 months, 95% CI 26.0-41.0, p = 0.047), and in patients with sarcomatoid differentiation (34.4 months, 95% CI 26.4-59.0, vs. 15.3 months, 95% CI 8.9-41.0, p < 0.001). Sex female was an independent negative prognostic factor in the sarcomatoid population (HR 1.72, 95% CI 1.15 - 2.57, p = 0.008).
CONCLUSIONS
Although the female's innate and adaptive immunity has been observed to be more active than the male's, women in the subgroup of clear cell histology, sarcomatoid differentiation, and those under 50 years of age showed shorter OS than males.
Topics: Humans; Carcinoma, Renal Cell; Female; Male; Middle Aged; Kidney Neoplasms; Adult; Aged; Young Adult; Adolescent; Sex Factors; Immune Checkpoint Inhibitors; Prognosis; Immunotherapy; Antineoplastic Combined Chemotherapy Protocols; Survival Rate; Aged, 80 and over
PubMed: 38832989
DOI: 10.1007/s00262-024-03719-0 -
BMC Veterinary Research Jun 2024Neutering dogs is a widespread method and is carried out for various behavioural and husbandry reasons. This study's main objective is to investigate the behavioural...
Neutering dogs is a widespread method and is carried out for various behavioural and husbandry reasons. This study's main objective is to investigate the behavioural correlations between neutering and the breed of male dogs. In order to possibly find breed-dependent differences in the behaviour of intact and castrated dogs, a differentiation between two clades - the "Huskies"(chow chow, shar pei, akita/shiba inu, alaskan malamute, siberian/alaskan husky) and the "Bulldogs" (german boxer, english/french bulldog, old english mastiff, boston terrier, english bull terrier, staffordshire bull terrier, american staffordshire terrier), based on Parker et al. [1], was made.Using an online questionnaire,, 31 neutered and 37 intact male dogs from the clade "Huskies" and 30 neutered and 38 intact male dogs from the clade "Bulldogs", participated in the study (N = 136).The survey included detailed questions on the dogs' personality and any associated issues as well as a behavioural anamnesis. Further questions relating to four of the "big five" personality dimensions based on the "Budapest questionnaire" by Turcsán et al. from 2011 [2] were also added.The results show, that neutered males from both breed clades more frequently displayed aggression toward humans than intact males (multinomial logistic regression, p = 0.002). When it came to aggression towards other dogs, it was the "Huskies" that differed significantly from the "Bulldogs"(multinomial logistic regression, p = 0.04) with being more aggressive. There were also significant differences in stress-related behaviour depending on castration status and breed (multinomial logistic regression, p < 0.001; Cramer's V = 0.33) and only the castration status had an impact on the significance (multinomial logistic regression, p < 0.001). The analysis also revealed significance for stress-indicating behaviour with dependence on neutering status (multinomial logistic regression, p < 0.001) and showed that stress as well as uncertainty are significantly more common in neutered dogs depending on breed and neutering status (multinomial logistic regression, p < 0.001; Cramer's V = 0.42), in that only neutered "Bulldogs" were stressed, but more "Huskies" overall.According to the Budapest questionnaire data, the "Bulldog" clade had considerably greater extraversion scores overall (ordinal regression, p < 0.001) than the "Huskies".Our findings highlight the risks and potential negative effects of neutering. Gonadectomy in no way substitutes for the dog receiving the necessary socialization, training, or bonding. Although in some circumstances it might have a favourable impact on the dog's behaviour, it should not be seen as a panacea for unwanted behaviour. Given that not all behaviours are influenced by sex hormones, every castration decision must be weighed up individually.
Topics: Animals; Dogs; Male; Behavior, Animal; Orchiectomy; Surveys and Questionnaires; Aggression
PubMed: 38831350
DOI: 10.1186/s12917-024-04097-6 -
Cell Death & Disease Jun 2024Obesity exacerbates tissue degeneration and compromises the integrity and reparative potential of mesenchymal stem/stromal cells (MSCs), but the underlying mechanisms...
Obesity exacerbates tissue degeneration and compromises the integrity and reparative potential of mesenchymal stem/stromal cells (MSCs), but the underlying mechanisms have not been sufficiently elucidated. Mitochondria modulate the viability, plasticity, proliferative capacity, and differentiation potential of MSCs. We hypothesized that alterations in the 5-hydroxymethylcytosine (5hmC) profile of mitochondria-related genes may mediate obesity-driven dysfunction of human adipose-derived MSCs. MSCs were harvested from abdominal subcutaneous fat of obese and age/sex-matched non-obese subjects (n = 5 each). The 5hmC profile and expression of nuclear-encoded mitochondrial genes were examined by hydroxymethylated DNA immunoprecipitation sequencing (h MeDIP-seq) and mRNA-seq, respectively. MSC mitochondrial structure (electron microscopy) and function, metabolomics, proliferation, and neurogenic differentiation were evaluated in vitro, before and after epigenetic modulation. hMeDIP-seq identified 99 peaks of hyper-hydroxymethylation and 150 peaks of hypo-hydroxymethylation in nuclear-encoded mitochondrial genes from Obese- versus Non-obese-MSCs. Integrated hMeDIP-seq/mRNA-seq analysis identified a select group of overlapping (altered levels of both 5hmC and mRNA) nuclear-encoded mitochondrial genes involved in ATP production, redox activity, cell proliferation, migration, fatty acid metabolism, and neuronal development. Furthermore, Obese-MSCs exhibited decreased mitochondrial matrix density, membrane potential, and levels of fatty acid metabolites, increased superoxide production, and impaired neuronal differentiation, which improved with epigenetic modulation. Obesity elicits epigenetic changes in mitochondria-related genes in human adipose-derived MSCs, accompanied by structural and functional changes in their mitochondria and impaired fatty acid metabolism and neurogenic differentiation capacity. These observations may assist in developing novel therapies to preserve the potential of MSCs for tissue repair and regeneration in obese individuals.
Topics: Humans; Mesenchymal Stem Cells; Obesity; Mitochondria; Epigenesis, Genetic; Adipose Tissue; Cell Differentiation; Female; Male; 5-Methylcytosine; Adult; Middle Aged; Cell Proliferation
PubMed: 38824145
DOI: 10.1038/s41419-024-06774-8