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Frontiers in Immunology 2021Treating premature infants with high oxygen is a routine intervention in the context of neonatal intensive care. Unfortunately, the increase in survival rates is...
Treating premature infants with high oxygen is a routine intervention in the context of neonatal intensive care. Unfortunately, the increase in survival rates is associated with various detrimental sequalae of hyperoxia exposure, most notably bronchopulmonary dysplasia (BPD), a disease of disrupted lung development. The effects of high oxygen exposure on other developing organs of the infant, as well as the possible impact such disrupted development may have on later life remain poorly understood. Using a neonatal mouse model to investigate the effects of hyperoxia on the immature immune system we observed a dramatic involution of the thymic medulla, and this lesion was associated with disrupted FoxP3 regulatory T cell generation and T cell autoreactivity. Significantly, administration of mesenchymal stromal cell-derived extracellular vesicles (MEx) restored thymic medullary architecture and physiological thymocyte profiles. Using single cell transcriptomics, we further demonstrated preferential impact of MEx treatment on the thymic medullary antigen presentation axis, as evidenced by enrichment of antigen presentation and antioxidative-stress related genes in dendritic cells (DCs) and medullary epithelial cells (mTECs). Our study demonstrates that MEx treatment represents a promising restorative therapeutic approach for oxygen-induced thymic injury, thus promoting normal development of both central tolerance and adaptive immunity.
Topics: Animals; Animals, Newborn; Extracellular Vesicles; Heterografts; Humans; Hyperoxia; Mesenchymal Stem Cells; Mice; T-Lymphocytes; Thymus Gland; Umbilical Cord
PubMed: 33936055
DOI: 10.3389/fimmu.2021.640595 -
European Review For Medical and... Oct 2014Epithelium-derived thymic stromal lymphopoietin (TSLP), is a key pro-allergic cytokine that has recently been linked to chronic airway diseases. Our aim is to determine...
OBJECTIVE
Epithelium-derived thymic stromal lymphopoietin (TSLP), is a key pro-allergic cytokine that has recently been linked to chronic airway diseases. Our aim is to determine cord blood TSLP levels in pregnancies with meconium stained amniotic fluid.
PATIENTS AND METHODS
A total of 44 pregnant women with meconium stained amniotic fluid and a total of 44 healthy pregnant women were enrolled in the study. Cord blood TSLP was measured with TSLP ELISA Kit.
RESULTS
We found no statistically significant differences between 2 groups in terms of age and parity. TSLP levels were found to be significantly higher in the cord blood of pregnant women with meconium stained amniotic fluid (104.3 ± 96.9 ng/ml) compared with the control group (63.2 ± 65.3 ng/ml) (p = 0.022).
CONCLUSIONS
It seems that TSLP is produced and released in response to meconium.
Topics: Adult; Amniotic Fluid; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Fetal Blood; Humans; Infant, Newborn; Meconium; Pregnancy; Staining and Labeling; Young Adult; Thymic Stromal Lymphopoietin
PubMed: 25392097
DOI: No ID Found -
Blood Advances Feb 2021Recipients of allogeneic hematopoietic cell transplantation (HCT) experience a substantial health care burden, with potentially differing patterns of long-term health...
Recipients of allogeneic hematopoietic cell transplantation (HCT) experience a substantial health care burden, with potentially differing patterns of long-term health care requirements using peripheral blood stem cells, bone marrow, and umbilical cord blood (UCB) grafts. We analyzed data from 1077 consecutive adult allogeneic HCT recipients who underwent transplant at the University of Minnesota between 2000 and 2016. To estimate health care burden over time, we compared the number of visits, laboratory studies, medications, and relative value units billed. Health care elements were analyzed both individually and together (ie, total health care elements used per patient days into a density composite score). UCB had the lowest density health care burden composite score from the time of transplant through year 5 (median score 64.0 vs 70.5 for peripheral blood stem cells and 88.0 for bone marrow; P < .01). In multivariate analysis of health care burden between years 1 and 5, recipients of either bone marrow (odds ratio [OR] 0.49 [95% confidence interval (CI) 0.29-0.84]) or peripheral blood stem cells (OR 0.49 [95% CI 0.36-0.67]) were half as likely to experience low health care burden compared with UCB. Adult recipients of UCB have a lower long-term health care burden compared with other graft sources, possibly reflecting a better quality of life.
Topics: Adult; Cord Blood Stem Cell Transplantation; Delivery of Health Care; Hematopoietic Stem Cell Transplantation; Humans; Quality of Life; Transplantation, Homologous
PubMed: 33560398
DOI: 10.1182/bloodadvances.2020003369 -
Frontiers in Cellular Neuroscience 2020Cuprizone (CPZ)-feeding in mice induces atrophy of peripheral immune organs (thymus and spleen) and suppresses T-cell levels, thereby limiting its use as a model for...
Cuprizone (CPZ)-feeding in mice induces atrophy of peripheral immune organs (thymus and spleen) and suppresses T-cell levels, thereby limiting its use as a model for studying the effects of the immune system in demyelinating diseases such as Multiple Sclerosis (MS). To investigate whether castration () can protect the peripheral immune organs from CPZ-induced atrophy and enable T-cell recruitment into the central nervous system (CNS) following a breach of the blood-brain barrier (BBB), three related studies were carried out. In Study 1, prevented the dose-dependent reductions (0.1% < 0.2% CPZ) in thymic and splenic weight, size of the thymic medulla and splenic white pulp, and CD4 and CD8 (CD4/8) levels remained comparable to gonadally intact () control males. Importantly, 0.1% and 0.2% CPZ were equipotent at inducing central demyelination and glial activation. In Study 2, combining with 0.1% CPZ-feeding and BBB disruption with pertussis toxin (PT) enhanced CD8 T-cell recruitment into the CNS. The increased CD8 T-cell level observed in the parenchyma of the cerebrum, cerebellum, brainstem and spinal cord were confirmed by flow cytometry and western blot analyses of CNS tissue. In Study 3, PT+0.1% CPZ-feeding to female mice resulted in similar effects on the peripheral immune organs, CNS demyelination, and gliosis comparable to males, indicating that testosterone levels alone were not responsible for the immune response seen in Study 2. The combination of +0.1% CPZ-feeding+PT indicates that CPZ-induced demyelination can trigger an immune response when the peripheral immune system is spared and may provide a better model to study the initiating events in demyelinating conditions such as MS.
PubMed: 32210765
DOI: 10.3389/fncel.2020.00043 -
Journal of Family Medicine and Primary... Feb 2020Modern thyroid surgery has undergone a paradigm shift from subtotal thyroidectomy to an extended total thyroidectomy (TT) even for benign disorders. This entails removal...
CONTEXT
Modern thyroid surgery has undergone a paradigm shift from subtotal thyroidectomy to an extended total thyroidectomy (TT) even for benign disorders. This entails removal of all embryological remnants even in benign disorders.
AIMS
To study the prevalence of various embryological remnants of the thyroid and surgical utility and implications in preventing complications.
SETTINGS AND DESIGN
Retrospective study of total thyroidectomies done by a single endocrine surgeon by standardized technique.
METHODS AND MATERIAL
A detailed search of all embryological rests including Pyramidal tract (PT), Tubercle of Zuckerkandl (TZ), and Thyro-thymic thyroid rests (TTR) were done in 1118 patients undergoing TT over 6 years. The cases with and without TTR were divided as Group A and B, respectively. Their prevalence and impact on parathyroid preservation and other clinical parameters were analysed.
STATISTICAL ANALYSIS USED
Descriptive analyses.
RESULTS
Out of the 1118 TT cases, TTR was seen in 230 (20.57%) cases, TZ in 598 (53.48%), cases and PT in 641 (57.33%) cases. Among group-A ( = 230), 213 had unilateral and 17 had bilateral TTR with 51 (22.17%) having retrosternal extension. Compressive symptoms, presence of TZ and PT were also significantly higher in group A. On follow up the incidence of temporary hypoparathyroidism was significantly higher in group-A, where as permanent hypoparathyroidism, temporary and permanent vocal cord palsy were comparable between the two study groups.
CONCLUSIONS
Embryological remnants related to thyroid are not uncommonly encountered during total thyroidectomy. A thorough search and complete removal is crucial for the successful outcome of the procedure.
PubMed: 32318394
DOI: 10.4103/jfmpc.jfmpc_1141_19 -
Frontiers in Immunology 2020NBSGW mice are highly immunodeficient and carry a hypomorphic mutation in the gene, providing a host environment that supports robust human hematopoietic expansion... (Comparative Study)
Comparative Study
NBSGW mice are highly immunodeficient and carry a hypomorphic mutation in the gene, providing a host environment that supports robust human hematopoietic expansion without pre-conditioning. These mice thus provide a model to investigate human hematopoietic engraftment in the absence of conditioning-associated damage. We compared transplantation of human CD34 HSPCs purified from three different sources: umbilical cord blood, adult bone marrow, and adult G-CSF mobilized peripheral blood. HSPCs from mobilized peripheral blood were significantly more efficient (as a function of starting HSPC dose) than either cord blood or bone marrow HSPCs at generating high levels of human chimerism in the murine blood and bone marrow by 12 weeks post-transplantation. While T cells do not develop in this model due to thymic atrophy, all three HSPC sources generated a human compartment that included B lymphocytic, myeloid, and granulocytic lineages. However, the proportions of these lineages varied significantly according to HSPC source. Mobilized blood HSPCs produced a strikingly higher proportion of granulocyte lineage cells (~35% as compared to ~5%), whereas bone marrow HSPC output was dominated by B lymphocytic cells, and cord blood HSPC output was enriched for myeloid lineages. Following transplantation, all three HSPC sources showed a shift in the CD34 subset towards CD45RA progenitors along with a complete loss of the CD45RACD49f long-term HSC subpopulation, suggesting this model promotes mainly short-term HSC activity. Mice transplanted with cord blood HSPCs maintained a diversified human immune compartment for at least 36 weeks after the primary transplant, although mice given adult bone marrow HSPCs had lost diversity and contained only myeloid cells by this time point. Finally, to assess the impact of non-HSPCs on transplantation outcome, we also tested mice transplanted with total or T cell-depleted adult bone marrow mononuclear cells. Total bone marrow mononuclear cell transplants produced significantly lower human chimerism compared to purified HSPCs, and T-depletion rescued B cell levels but not other lineages. Together these results reveal marked differences in engraftment efficiency and lineage commitment according to HSPC source and suggest that T cells and other non-HSPC populations affect lineage output even in the absence of conditioning-associated inflammation.
Topics: Animals; Antigens, CD34; B-Lymphocytes; Cell Lineage; Cell Survival; Cells, Cultured; Cord Blood Stem Cell Transplantation; Female; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Immunocompromised Host; Integrin alpha6; Leukocyte Common Antigens; Male; Mice, Mutant Strains; Mutation; Peripheral Blood Stem Cell Transplantation; Phenotype; Proto-Oncogene Proteins c-kit; T-Lymphocytes; Time Factors; Transplantation Chimera
PubMed: 33193358
DOI: 10.3389/fimmu.2020.573406 -
Blood Jan 2002Umbilical cord blood has been increasingly used as a source of hematopoietic stem cells. A major area of concern for the use of cord blood transplantation is the delay... (Comparative Study)
Comparative Study
Umbilical cord blood has been increasingly used as a source of hematopoietic stem cells. A major area of concern for the use of cord blood transplantation is the delay in myeloid and lymphoid recovery. To directly compare myeloid and lymphoid recovery using an animal model of bone marrow and cord blood as sources of stem cells, hematopoietic engraftment and immune recovery were studied following infusion of T-cell-depleted adult bone marrow or full-term fetal blood cells, as a model of cord blood in a murine allogeneic transplantation model (C57BL/6 [H-2(b)] --> BALB/c [H-2(d)]). Allogeneic full-term fetal blood has poorer radioprotective capacity but greater long-term engraftment potential on a cell-to-cell basis compared with T-cell-depleted bone marrow. Allogeneic full-term fetal blood recipients had decreased absolute numbers of T, B, and dendritic cells compared with bone marrow recipients. Splenic T cells in allogeneic full-term fetal blood recipients proliferated poorly, were unable to generate cytotoxic effectors against third-party alloantigens in vitro, and failed to generate alloantigen-specific cytotoxic antibodies in vivo. In addition, reconstituting T cells in fetal blood recipients had decreased mouse T-cell receptor delta single-joint excision circles compared with bone marrow recipients. At a per-cell level, B cells from fetal blood recipients did not proliferate as well as those found in bone marrow recipients. These results suggest that full-term fetal blood can engraft allogeneic hosts across the major histocompatibility barrier with slower hematopoietic engraftment and impaired immune reconstitution.
Topics: Animals; B-Lymphocytes; Bone Marrow Cells; Bone Marrow Purging; Cell Count; Cell Division; Dendritic Cells; Fetal Blood; Gene Rearrangement, delta-Chain T-Cell Antigen Receptor; Graft Survival; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Immunity; Lymphocyte Count; Lymphocyte Subsets; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Models, Animal; Receptors, Antigen, T-Cell; Spleen; T-Lymphocytes; Thymus Gland; Transplantation, Homologous
PubMed: 11756193
DOI: 10.1182/blood.v99.1.364 -
JCO Global Oncology Mar 2021Treatment patterns and survival outcomes of patients with multiple myeloma (MM) in Kenya have not been adequately characterized. The objectives of this study were to...
PURPOSE
Treatment patterns and survival outcomes of patients with multiple myeloma (MM) in Kenya have not been adequately characterized. The objectives of this study were to describe the clinical, laboratory, and imaging findings at diagnosis, to describe the treatment offered, and to determine the survival outcomes of patients with MM over an 11-year period.
PATIENTS AND METHODS
A retrospective chart review was carried out for all patients who were diagnosed and treated for MM at Moi Teaching and Referral Hospital from 2009 to 2019. The Kaplan-Meier method was used to estimate survival. Factors affecting survival were identified using univariate and multivariate analyses.
RESULTS
A total of 221 patient charts were analyzed of which 124 belonged to male patients (56.1%). The median age at diagnosis was 61 years. Bone pain was the most common presenting complaint observed in 69.6% of 194 patients assessed. Out of 102 patients who received imaging studies, 60 (58.8%) had lytic lesions, 30 (29.4%) had fractures, whereas 30 (29.4%) had spinal cord compression. Anemia, renal failure, and hypercalcemia were observed in 87/187 (46.5%), 22/161 (13.7%), and 23/42 (54.8%) patients, respectively. Thalidomide and dexamethasone (65.2%); bortezomib, thalidomide, and dexamethasone (14.6%); and melphalan and prednisolone (11.9%) were the most prescribed initial chemotherapy regimens among 219 patients analyzed. Overall survival at 1 and 5 years was 70% and 21%, respectively; median overall survival was 29.0 months. In multivariate analysis, male sex (hazard ratio [HR] 1.9), baseline anemia (HR 1.8), and baseline renal failure (HR 3.2) were associated with significantly shorter survival.
CONCLUSION
Survival outcomes were poor despite increased use of multiagent-based chemotherapy regimens. Greater access to available diagnostics and treatments is required to achieve rational treatment and increased survival.
Topics: Antineoplastic Combined Chemotherapy Protocols; Hospitals; Humans; Kenya; Male; Multiple Myeloma; Referral and Consultation; Retrospective Studies
PubMed: 33729826
DOI: 10.1200/GO.20.00573 -
Oncology Letters Mar 2017The inhibitor of growth family, member 3 (ING3) protein may be capable of blocking the cell cycle via activating p53-transactivated promoters of p21 and Bcl2-associated...
The inhibitor of growth family, member 3 (ING3) protein may be capable of blocking the cell cycle via activating p53-transactivated promoters of p21 and Bcl2-associated X protein, and may induce apoptosis via a Fas/caspase-8-dependent signaling pathway. In the present study, immunohistochemistry was performed in order to characterize the expression profile of ING3 protein in tissue microarrays containing mouse and human normal tissue, human hepatocellular (n=62), renal clear cell (n=62), pancreatic (n=62), esophageal squamous cell (n=45), cervical squamous cell (n=31), breast (n=144), gastric (n=196), colorectal (n=96), ovarian (n=208), endometrial (n=96) and lung carcinoma (n=192). In mouse tissue, ING3 protein was positively detected in the cytoplasm of cardiomyocytes, kidney and skeletal muscle cells, and was additionally detected in the cytoplasm and nucleus of bronchial and alveolar epithelium, gastric and intestinal gland, and mammary gland cells. In human tissues, ING3 protein was principally distributed in the cytoplasm, but was observed in the cytoplasm and nucleus of tongue, esophagus, stomach, intestine, lung, skin, appendix, bladder, cervix and breast cells. ING3 immunoreactivity was strongly detected in the stomach, skin and cervical tissues, whereas a weak signal was detected in the cerebellum, brain stem, thymus, liver, skeletal muscle, testis and prostate. In total, ING3-positive specimens were identified in 424 of 1,194 tested cancer entities (35.5%). In a number of cases, ING3 expression was observed to be restricted to the cytoplasm and nucleus, excluding the cytoplasmic distribution identified in breast and hepatocellular carcinoma. Among these cases, ING3 was more frequently expressed in breast and gynecological types of cancer, including ovarian (59.2%), endometrial (47.9%), breast (38.9%) and cervical (35.5%) cancer. ING3-positive cases were more rare in renal clear cell (17.7%), hepatocellular (16.1%) and esophageal carcinoma (17.8%). It is suggested that ING3 may be involved in the repair and regeneration of organs or tissues, and may be closely associated with gynecological carcinogenesis.
PubMed: 28454301
DOI: 10.3892/ol.2017.5632 -
Journal of Traditional Chinese Medicine... Oct 2023To investigate the efficacy of Zhenxin Anshen formula (, ZXAS) on atopic dermatitis (AD) by transient receptor potential vanilloid 1 (TRPV1) and transient receptor...
Zhenxin Anshen formula ameliorates atopic der-matitis-like skin dysfunction in mice and regulation of transient receptor potential vanilloid 1 and transient receptor potential ankyrin 1 in Neural pathways.
OBJECTIVE
To investigate the efficacy of Zhenxin Anshen formula (, ZXAS) on atopic dermatitis (AD) by transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) signalling pathway in mice and .
METHODS
AD-like lesions were induced by 1-chloro-2,4-dinitrobenzene (DNCB) to the shaved dorsal skin of BALB/c mice. BALB/c mice were divided into five groups: normal control, model control, cetirizine, low-, medium-, and high-dose of ZXAS. After ZXAS in-tervention, the skin lesions and blood samples were collected for hematoxylin and eosin-stained and measuring the concentrations of inflammatory cytokines. Immun-oglobulin E (IgE), interleukin (IL)-4, IL-5, IL-13, and thymic stromal lymphopoietin (TSLP) were de-tected by Enzyme-linked immunosorbent assay (ELISA). The spinal cords were collected for measuring the expression of gastrin-releasing peptide receptor (GRPR), TRPV1, and TRPA1 by using immunohistochemistry, western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR) analyses. In addition, 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, ELISA, and Western blotting were conducted for analysis of primary dorsal root ganglia (DRG) neurons .
RESULTS
ZXAS treatment improved DNCB-induced AD-like lesions through reducing dermatitis score, number of scratching and epidermal thickness, accompanied by the de-creased IgE and Th2 inflammatory cytokines. ZXAS also supressed the mRNA and protein expression of GRPR, TRPV1, and TRPA1 in the spinal cord. The medicated sera of ZXAS decreased capsaicin-induced Ca influx and downregulated the expression of TRPV1, TRPA1, and phospholipase C in DRG neurons.
CONCLUSIONS
The therapeutic effect of ZXAS on AD may be related to the regulation of TRPV1 and TRPA1 and inhibition of Ca2+ signals in neurons.
Topics: Animals; Mice; Ankyrins; Dinitrochlorobenzene; Antineoplastic Agents; Dermatitis, Atopic; Cytokines; Neural Pathways; Dinitrobenzenes; Immunoglobulin E
PubMed: 37679976
DOI: 10.19852/j.cnki.jtcm.20230802.003