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Immunobiology Jun 2024The pro-tumorigenic or anti-tumorigenic role of tumor infiltrating mast cells (TIMs) in tumors depends not only on the type of cancer and the degree of tumor...
The pro-tumorigenic or anti-tumorigenic role of tumor infiltrating mast cells (TIMs) in tumors depends not only on the type of cancer and the degree of tumor progression, but also on their location in the tumor bulk. In our investigation, we employed immunohistochemistry to reveal that the mast cells (MCs) in the tumor stroma are positively correlated with metastasis of ovarian cancer (OC), but not in the tumor parenchyma. To delve deeper into the influence of different culture matrix stiffness on MCs' biological functions within the tumor parenchymal and stromal regions, we conducted a transcriptome analysis of the mouse MC line (P815) cultured in two-dimensional (2D) or three-dimensional (3D) culture system. Further research has found that the softer 3D extracellular matrix stiffness could improve the mitochondrial activity of MCs to promote proliferation by increasing the expression levels of mitochondrial activity-related genes, namely Pet100, atp5md, and Cox7a2. Furthermore, employing LASSO regression analysis, we identified that Pet100 and Cox7a2 were closely associated with the prognosis of OC patients. These two genes were subsequently employed to construct a risk score model, which revealed that the high-risk group model as one of the prognostic factors for OC patients. Additionally, the XCell algorithm analysis showed that the high-risk group displayed a broader spectrum of immune cell infiltrations. Our research revealed that TIMs in the tumor stroma could promote the metastasis of OC, and mitochondrial activity-related proteins Pet100/Cox7a2 can serve as biomarkers for prognostic evaluation of OC.
PubMed: 38944891
DOI: 10.1016/j.imbio.2024.152831 -
Mymensingh Medical Journal : MMJ Jul 2024Multiple myeloma (MM), mature B-cell lineage neoplasm, is characterized by abnormal clonal proliferation of plasma cells and presence of monoclonal protein (M protein)....
Multiple myeloma (MM), mature B-cell lineage neoplasm, is characterized by abnormal clonal proliferation of plasma cells and presence of monoclonal protein (M protein). The study was conducted to reveal presenting features, laboratory findings, Eastern Cooperative Oncology Group (ECOG) performance status and skeletal survey on patients with multiple myeloma. This descriptive, cross-sectional study was carried out in the Department of Haematology, Dhaka Medical College Hospital, Dhaka, Bangladesh from January 2019 to July 2020 with a sample size of 81. Data were collected in a case record form after obtaining informed verbal consent from patients and /or their legal guardians. Relevant ethical issues and data quality assurance were taken into consideration. Data were analyzed with SPSS, Version 25.0 with presentation in figures and tables with frequency, percentage, mean and standard deviation based on data nature. Statistical tests were carried out as appropriate with 5.0% level of significance for assessing statistical association. Mean age of the patients was 58.9±12.0 years. Male female ratio was 2:1. 35(43.2%) patients were smokers with only 2(2.5%) had family history of haematological malignancies. Bone pain (72.8%) was the most common presenting feature, while hypertension (59.1%), diabetes mellitus (29.5%), respiratory illness (11.3%) and cardiac disease (11.4%) were the common co-morbidities. Most common ECOG performance status was ECOG-1(48.1%). Mean haemoglobin (Hb) was 9.4±2.3gm/dl and mean erythrocyte sedimentation rate (ESR) was 89.5±42.1 mm in 1st hour. Mean serum creatinine level was 2.0±1.85 mg/dl and ≥2.0mg/dl in 42(34.2%). Among 50 documentation serum lactate dehydrogenase (LDH) was raised in 18(36.0%). Mean serum calcium level was 9.6±1.8mg/dl >11.0mg/dL in 10(14.5%) cases. Serum albumin <3.5gm/dl in 37(49.3%), β2-microglobulin >5.5mg/dl in 37(57.8%) cases, International staging system (ISS) stage III was in 59.4% and Bence Jones Protein (BJP) was present in 46.7% cases. Lytic lesions were present in 75.0%, In 38(74.5%) patients vertebrae were involved, while in 18(35.2%) ribs were involved, in 14(27.5%) patients skull was involved and in 3(5.9%) patients involved bones were femur, humerus, sternum and scapula. Mean plasma cells percentage was 62.1±24.9%. Immuno-Fixation Electrophoresis (IFE) revealed IgG (72.7%), IgA (18.2%), Free light chain (FLC) (9.1%). FLC ratio was ≥100 in 29.0% cases. Significant statistical association was observed between serum creatinine with Hb concentration (p<0.05), serum creatinine level with ISS staging (p<0.05) and serum calcium level (p<0/05), while insignificant association was revealed between BJP present status and serum creatinine level (p>0.05). Bone pain, fatigue, fever and neurological impairment were the common presenting features. Anaemia, renal impairment and skeletal lytic events were the prominent physical findings. ISS staging was statistically associated with serum creatinine level, while serum calcium level was associated with serum creatinine and lytic lesions.
Topics: Humans; Multiple Myeloma; Male; Female; Middle Aged; Cross-Sectional Studies; Tertiary Care Centers; Aged; Bangladesh; Adult
PubMed: 38944730
DOI: No ID Found -
Anatomia, Histologia, Embryologia Jul 2024The spleen is the largest secondary lymphoid organ with significant roles in pathogen clearance. It is involved in several avian diseases. The cattle egret is a wild...
The spleen is the largest secondary lymphoid organ with significant roles in pathogen clearance. It is involved in several avian diseases. The cattle egret is a wild insectivorous bird of agricultural and socioeconomic importance. Data related to microstructural features of cattle egret spleen are lacking. The present study investigated the gross anatomical, histological and immunohistochemical characteristics of the cattle egret spleen. Proliferation (PCNA and PHH3), apoptosis (cleaved caspase 3, C.CASP3) and T-cell (CD3 and CD8) markers were assessed. Grossly, the spleen appeared brownish red, oval-shaped and located at the oesophago-proventricular junction. Histologically, the spleen was surrounded by a thin capsule sending a number of trabeculae which contained branches of the splenic vessels. The white pulp consisted of the periarteriolar lymphoid sheath and periellipsoidal lymphatic sheath (PELS). The red pulp was formed of sinusoids and cords. The penicillar capillaries, which represent the terminal segments of the splenic arterial tree were highly branched, wrapped by prominent ellipsoids and directly connected to the splenic sinusoids, suggesting a closed type of circulation. Immunohistochemically, proliferating cell nuclear antigen (PCNA)-expressing cells were distributed with high counts throughout the splenic parenchyma, being highest within the splenic cords and PELS. Both PHH3- and C.CASP3-expressing cells revealed a similar pattern to that of PCNA, although with fewer counts. Large numbers of T cells were observed throughout the splenic parenchyma, mainly within the cords, as revealed by CD3 and CD8 immunoreaction. The present study provides a clear insight into the precise structure of the spleen in cattle egrets and thus improves our understanding about birds' immunity.
Topics: Animals; Spleen; Apoptosis; Cell Proliferation; Proliferating Cell Nuclear Antigen; T-Lymphocytes; Birds; Immunohistochemistry; CD3 Complex; Biomarkers; Caspase 3
PubMed: 38944689
DOI: 10.1111/ahe.13082 -
Journal of Extracellular Vesicles Jul 2024Extracellular vesicles (EVs) play a crucial role in triggering tumour-aggressive behaviours. However, the energetic process by which tumour cells produce EVs remains...
Extracellular vesicles (EVs) play a crucial role in triggering tumour-aggressive behaviours. However, the energetic process by which tumour cells produce EVs remains poorly understood. Here, we demonstrate the involvement of β-hexosaminidase B (HEXB) in mediating EV release in response to oxidative stress, thereby promoting the development of hepatocellular carcinoma (HCC). Mechanistically, reactive oxygen species (ROS) stimulate the nuclear translocation of transcription factor EB (TFEB), leading to the upregulation of both HEXB and its antisense lncRNA HEXB-AS. HEXB-AS can bind HEXB to form a protein/RNA complex, which elevates the protein stability of HEXB. The stabilized HEXB interacts with lysosome-associated membrane glycoprotein 1 (LAMP1), disrupting lysosome-multivesicular body (MVB) fusion, which protects EVs from degradation. Knockdown of HEXB efficiently inhibits EV release and curbs HCC growth both in vitro and in vivo. Moreover, targeting HEXB by M-31850 significantly inhibits HCC growth, especially when combined with GW4869, an inhibitor of exosome release. Our results underscore the critical role of HEXB as a modulator that promotes EV release during HCC development.
Topics: Extracellular Vesicles; Carcinoma, Hepatocellular; Animals; Oxidative Stress; Humans; Liver Neoplasms; Mice; Up-Regulation; Cell Line, Tumor; Cell Proliferation; RNA, Long Noncoding; Reactive Oxygen Species; Gene Expression Regulation, Neoplastic; Male; Mice, Nude
PubMed: 38944674
DOI: 10.1002/jev2.12468 -
Cell and Tissue Banking Jun 2024An injury that affects the integrity of the skin, either inside or externally, is called a wound. Damaged tissue is repaired by a set of cellular and molecular...
An injury that affects the integrity of the skin, either inside or externally, is called a wound. Damaged tissue is repaired by a set of cellular and molecular mechanisms known as wound healing. Quercetin, a naturally occurring flavonoid, may hasten the healing of wounds. The study's objective was to investigate any potential impacts of quercetin on the wound-healing process. Human umbilical vein endothelial cells (HUVECs) were treated to varying dose ranges of quercetin (5-320 nM) for 24 and 48 h. Cultured cells were evaluated by using the MTT analysis, wound scratch assay and vascular tube formation. Furthermore the gene expression of VEGF and FGF were evaluated by qRT-PCR to determine the effects of quercetin on angiogenezis and wound repair. Positive effects of quercetin on cellular viability were demonstrated by the MTT experiment. In HUVECs quercetin promoted tube formation, migration, and proliferation while also averting wound breakage. Moreover, quercetin increased the expression of the FGF and VEGF genes, which aid in the healing of wounds in HUVECs. Quercetin may be bioactive molecule that successfully speeds up wound healing by regulating the vasculogenezis and healing cells.
PubMed: 38944663
DOI: 10.1007/s10561-024-10144-1 -
Nature Communications Jun 2024Children in malaria-endemic regions can experience repeated Plasmodium infections over short periods of time. Effects of re-infection on multiple co-existing CD4 T cell...
Children in malaria-endemic regions can experience repeated Plasmodium infections over short periods of time. Effects of re-infection on multiple co-existing CD4 T cell subsets remain unresolved. Here, we examine antigen-experienced CD4 T cells during re-infection in mice, using scRNA-seq/TCR-seq and spatial transcriptomics. TCR transgenic T cells initiate rapid Th1/Tr1 recall responses prior to proliferating, while GC Tfh counterparts are refractory, with T/Tfh-like cells exhibiting modest non-proliferative responses. Th1-recall is a partial facsimile of primary Th1-responses, with no upregulated effector-associated genes being unique to recall. Polyclonal, TCR-diverse, CD4 T cells exhibit similar recall dynamics, with individual clones giving rise to multiple effectors including highly proliferative Th1/Tr1 cells, as well as GC Tfh and Tfh-like cells lacking proliferative capacity. Thus, we show substantial diversity in recall responses mounted by multiple co-existing CD4 T cell subsets in the spleen, and present graphical user interfaces for studying gene expression dynamics and clonal relationships during re-infection.
Topics: Animals; Malaria; CD4-Positive T-Lymphocytes; Mice; Reinfection; Th1 Cells; Mice, Inbred C57BL; Spleen; Receptors, Antigen, T-Cell; Mice, Transgenic; Female; Immunologic Memory
PubMed: 38944658
DOI: 10.1038/s41467-024-49879-6 -
Nature Communications Jun 2024JNK signaling is a critical regulator of inflammation and regeneration, but how it is controlled in specific tissue contexts remains unclear. Here we show that, in the...
JNK signaling is a critical regulator of inflammation and regeneration, but how it is controlled in specific tissue contexts remains unclear. Here we show that, in the Drosophila intestine, the TNF-type ligand, Eiger (Egr), is expressed exclusively by intestinal stem cells (ISCs) and enteroblasts (EBs), where it is induced by stress and during aging. Egr preferentially activates JNK signaling in a paracrine fashion in differentiated enterocytes (ECs) via its receptor, Grindelwald (Grnd). N-glycosylation genes (Alg3, Alg9) restrain this activation, and stress-induced downregulation of Alg3 and Alg9 correlates with JNK activation, suggesting a regulatory switch. JNK activity in ECs induces expression of the intermembrane protease Rhomboid (Rho), driving secretion of EGFR ligands Keren (Krn) and Spitz (Spi), which in turn activate EGFR signaling in progenitor cells (ISCs and EBs) to stimulate their growth and division, as well as to produce more Egr. This study uncovers an N-glycosylation-controlled, paracrine JNK-EGFR-JNK feedforward loop that sustains ISC proliferation during stress-induced gut regeneration.
Topics: Animals; Drosophila Proteins; ErbB Receptors; Intestines; MAP Kinase Signaling System; Drosophila melanogaster; Enterocytes; Stem Cells; Intestinal Mucosa; Drosophila; Glycosylation; Receptors, Invertebrate Peptide; Cell Proliferation; JNK Mitogen-Activated Protein Kinases; Signal Transduction; Cell Communication; Cell Differentiation; Epidermal Growth Factor; Membrane Proteins
PubMed: 38944657
DOI: 10.1038/s41467-024-49786-w -
Communications Biology Jun 2024Macrolide antibiotics, pivotal in clinical therapeutics, are confronting resistance challenges mediated by enzymes like macrolide esterases, which are classified into...
Macrolide antibiotics, pivotal in clinical therapeutics, are confronting resistance challenges mediated by enzymes like macrolide esterases, which are classified into Ere-type and the less studied Est-type. In this study, we provide the biochemical confirmation of EstX, an Est-type macrolide esterase that initially identified as unknown protein in the 1980s. EstX is capable of hydrolyzing four 16-membered ring macrolides, encompassing both veterinary (tylosin, tidipirosin, and tilmicosin) and human-use (leucomycin A5) antibiotics. It uses typical catalytic triad (Asp233-His261-Ser102) from alpha/beta hydrolase superfamily for ester bond hydrolysis. Further genomic context analysis suggests that the dissemination of estX is likely facilitated by mobile genetic elements such as integrons and transposons. The global distribution study indicates that bacteria harboring the estX gene, predominantly pathogenic species like Escherichia coli, Salmonella enterica, and Klebsiella pneumoniae, are prevalent in 74 countries across 6 continents. Additionally, the emergence timeline of the estX gene suggests its proliferation may be linked to the overuse of macrolide antibiotics. The widespread prevalence and dissemination of Est-type macrolide esterase highlight an urgent need for enhanced monitoring and in-depth research, underlining its significance as an escalating public health issue.
Topics: Esterases; Anti-Bacterial Agents; Macrolides; Humans; Bacterial Proteins; Phylogeny; Hydrolases
PubMed: 38944651
DOI: 10.1038/s42003-024-06473-2 -
American Journal of Surgery Jun 2024There has been tremendous effort to improve quality following colorectal surgery, including the proliferation of minimally invasive techniques, enhanced recovery...
BACKGROUND
There has been tremendous effort to improve quality following colorectal surgery, including the proliferation of minimally invasive techniques, enhanced recovery protocols, and surgical site infection prevention bundles. While these programs have demonstrated improved postoperative outcomes at the institutional level, it is unclear whether similar benefits are present on a national scale.
METHODS
American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) Targeted Colectomy data from 2012 to 2020 were used to identify patients undergoing minimally invasive surgery (MIS) or open partial colectomy (CPT 44140, 44204) or low anterior resection (CPT 44145, 44207). Chronological cohorts as well as annual trends in 30-day postoperative outcomes including surgical site infection, venous thromboembolism, and length of stay were assessed using both univariable and multivariable regression analyses.
RESULTS
261,301 patients, 135,876 (52 %) female, with a median age of 62 (IQR 53-72) were included. Across all years, MIS partial colectomy was the most common procedure (37 %), followed by MIS low anterior resection (27 %), open partial colectomy (24 %), and open low anterior resection (12 %). MIS increased from 59 % in 2012-2014 to 66 % in 2018-2020 (p < 0.001). During this same period, postoperative length of stay decreased from a median of 5 days (IQR 4-7) in 2012-2014 to 4 days (IQR 3-6) in 2018-2020 (p < 0.001). Superficial surgical site infections decreased from 5.5 % in 2012-2014 to 2.9 % in 2018-2020 (p < 0.001). Deep surgical site infections similarly decreased from 1.1 % to 0.4 % between these periods (p < 0.001). Pulmonary embolism also decreased from 0.6 % to 0.5 % between periods (p = 0.02). 30-day mortality was unchanged at 1.7 % between 2012-2014 and 2018-2020 (p = 0.40). After adjustment for ACS NSQIP estimated probability of morbidity and mortality, undergoing a colectomy in 2020 compared to 2012 was associated with a 14 % decrease in postoperative length of stay (p < 0.001).
CONCLUSIONS
Between 2012 and 2020, significant improvements in postoperative outcomes after colectomy were observed in the United States. These results support the positive impact that the widespread adoption of quality improvement initiatives is having on colorectal patient care nationally.
PubMed: 38944622
DOI: 10.1016/j.amjsurg.2024.115808 -
Cancer Genomics & Proteomics 2024Metastatic prostate cancer (mPCa) results in high morbidity and mortality. Visceral metastases in particular are associated with a shortened survival. Our aim was to...
BACKGROUND/AIM
Metastatic prostate cancer (mPCa) results in high morbidity and mortality. Visceral metastases in particular are associated with a shortened survival. Our aim was to unravel the molecular mechanisms that underly pulmonary spread in mPCa.
MATERIALS AND METHODS
We performed a comprehensive transcriptomic analysis of PCa lung metastases, followed by functional validation of candidate genes. Digital gene expression analysis utilizing the NanoString technology was performed on mRNA extracted from formalin-fixed, paraffin-embedded (FFPE) tissue from PCa lung metastases. The gene expression data from primary PCa and PCa lung metastases were compared, and several publicly available bioinformatic analysis tools were used to annotate and validate the data.
RESULTS
In PCa lung metastases, 234 genes were considerably up-regulated, and 78 genes were significantly down-regulated when compared to primary PCa. Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) was identified as suitable candidate gene for further functional validation. CEACAM6 as a cell adhesion molecule has been implicated in promoting metastatic disease in several solid tumors, such as colorectal or gastric cancer. We showed that siRNA knockdown of CEACAM6 in PC-3 and LNCaP cells resulted in decreased cell viability and migration as well as enhanced apoptosis. Comprehensive transcriptomic analyses identified several genes of interest that might promote metastatic spread to the lung.
CONCLUSION
Functional validation revealed that CEACAM6 might play an important role in fostering metastatic spread to the lung of PCa patients via enhancing proliferation, migration and suppressing apoptosis in PC-3 and LNCaP cells. CEACAM6 might pose an attractive therapeutic target to prevent metastatic disease.
Topics: Humans; Male; Apoptosis; Cell Adhesion Molecules; Cell Proliferation; Cell Movement; Lung Neoplasms; Antigens, CD; Prostatic Neoplasms; GPI-Linked Proteins; Gene Expression Regulation, Neoplastic; Cell Line, Tumor
PubMed: 38944419
DOI: 10.21873/cgp.20459