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Stem Cell Reports May 2024Lung alveolar structure and function are maintained by subsets of alveolar type II stem cells (AT2s), but there is a need for characterization of these subsets and their...
Lung alveolar structure and function are maintained by subsets of alveolar type II stem cells (AT2s), but there is a need for characterization of these subsets and their associated niches. Here, we report a CD44 subpopulation of AT2s characterized by increased expression of genes that regulate immune signaling even during steady-state homeostasis. Disruption of one of these immune regulatory transcription factor STAT1 impaired the stem cell function of AT2s. CD44 cells were preferentially located near macro- blood vessels and a supportive niche constituted by LYVE1 endothelial cells, adventitial fibroblasts, and accumulated hyaluronan. In this microenvironment, CD44 AT2 cells were more responsive to transformation by KRAS than general AT2 cells. Moreover, after bacterial lung injury, there was a significant increase of CD44 AT2s and niche components distributed throughout the lung parenchyma. Taken together, CD44 AT2 cells and their perivascular niche regulate tissue homeostasis and tumor formation.
PubMed: 38759645
DOI: 10.1016/j.stemcr.2024.04.009 -
Medicine May 2024Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterized by widespread blood vessel clotting and bleeding. It can affect individuals of any age but is more... (Review)
Review
RATIONALE
Thrombotic thrombocytopenic purpura (TTP) is a syndrome characterized by widespread blood vessel clotting and bleeding. It can affect individuals of any age but is more commonly observed in females, particularly during pregnancy. Pregnancy combined with TTP is a critical and rapidly progressing condition that is often misdiagnosed as an obstetric disorder like severe preeclampsia or HELLP syndrome. To deepen the understanding of TTP during pregnancy with the help of a clinical case.
PATIENT CONCERNS
A 20-year-old patient, is pregnancy 1 birth 0, 32 weeks dated by her last menstrual period, presented chest tightness, and shortness of breath after physical activity for 3 days.
DIAGNOSES
TTP.
INTERVENTIONS
At present, there are no preventive measures. Timely diagnosis and treatment are useful. Plasma exchange and treat to the patient hinder autoantibodies, such as gamma globulin, methylprednisolone, rituximab, and cyclosporine were effective.
OUTCOMES
The patient exhibited stable vital signs, normal examination results, and experienced no complications. We continued to monitor her progress after she was discharged.
LESSONS SUBSECTIONS
The acute onset of TTP is often associated with pregnancy, as it is a triggering factor. Timely identification, accurate diagnosis, and a comprehensive treatment approach involving plasma exchange, immunosuppressants, and the termination of pregnancy can lead to remission and a favorable outlook for the majority of patients.
Topics: Humans; Female; Pregnancy; Purpura, Thrombotic Thrombocytopenic; Plasma Exchange; Young Adult; Pregnancy Complications, Hematologic
PubMed: 38758904
DOI: 10.1097/MD.0000000000038112 -
Cancer Research Communications May 2024Hemangiosarcoma and angiosarcoma are soft-tissue sarcomas of blood vessel-forming cells in dogs and humans, respectively. These vasoformative sarcomas are aggressive and...
Hemangiosarcoma and angiosarcoma are soft-tissue sarcomas of blood vessel-forming cells in dogs and humans, respectively. These vasoformative sarcomas are aggressive and highly metastatic, with disorganized, irregular blood-filled vascular spaces. Our objective was to define molecular programs which support the niche that enables progression of canine hemangiosarcoma and human angiosarcoma. Dog-in-mouse hemangiosarcoma xenografts recapitulated the vasoformative and highly angiogenic morphology and molecular characteristics of primary tumors. Blood vessels in the tumors were complex and disorganized, and they were lined by both donor and host cells. In a series of xenografts, we observed that the transplanted hemangiosarcoma cells created exuberant myeloid hyperplasia and gave rise to lymphoproliferative tumors of mouse origin. Our functional analyses indicate that hemangiosarcoma cells generate a microenvironment that supports expansion and differentiation of hematopoietic progenitor populations. Furthermore, gene expression profiling data revealed hemangiosarcoma cells expressed a repertoire of hematopoietic cytokines capable of regulating the surrounding stromal cells. We conclude that canine hemangiosarcomas, and possibly human angiosarcomas, maintain molecular properties that provide hematopoietic support and facilitate stromal reactions, suggesting their potential involvement in promoting the growth of hematopoietic tumors.
PubMed: 38757809
DOI: 10.1158/2767-9764.CRC-23-0441 -
The Kaohsiung Journal of Medical... May 2024Colorectal cancer (CRC) is notable for its high mortality and high metastatic characteristics. The shear force generated by bloodstream provides mechanical signals...
Colorectal cancer (CRC) is notable for its high mortality and high metastatic characteristics. The shear force generated by bloodstream provides mechanical signals regulating multiple responses of cells, including metastatic cancer cells, dispersing in blood vessels. We, therefore, studied the effect of shear flow on circulating CRC cells in the present study. The CRC cell line SW620 was subjected to shear flow of 12.5 dynes/cm for 1 and 2 h separately. Resulting elevated caspase-9 and -3 indicated that shear flow initiated the apoptosis of SW620. Enlarged cell size associated with a higher level of cyclin D1 was coincident with the flow cytometric results indicating that the cell cycle was arrested at the G phase. An elevated phosphor-eNOS increased the production of nitric oxide and led to reactive oxygen species-mediated oxidative stress. Shear flow also regulated epithelial-mesenchymal transition (EMT) by increasing E-cadherin and ZO-1 while decreasing Snail and Twist1. The migration and invasion of sheared SW620 were also substantially decreased. Further investigations showed that mitochondrial membrane potential was significantly decreased, whereas mitochondrial mass and ATP production were not changed. In addition to the shear flow of 12.5 dynes/cm, the expressions of EMT were compared at lower (6.25 dynes/cm) and at higher (25 dynes/cm) shear flow. The results showed that lower shear flow increased mesenchymal characteristics and higher shear flow increased epithelial characteristics. Shear flow reduces the malignancy of CRC in their metastatic dispersal that opens up new ways to improve cancer therapies by applying a mechanical shear flow device.
PubMed: 38757734
DOI: 10.1002/kjm2.12844 -
Ear, Nose, & Throat Journal May 2024Retiform hemangioendothelioma (RH) is a rare intermediate (locally aggressive) vascular tumor that mostly affects the dermis of the trunk and limbs, but has never been...
Retiform hemangioendothelioma (RH) is a rare intermediate (locally aggressive) vascular tumor that mostly affects the dermis of the trunk and limbs, but has never been reported in the inferior turbinate. A 10-year-old Chinese boy presented with recurrent epistaxis in his left nasal cavity and anemia for more than 2 years. Radiographic and electronic video laryngoscopic images showed an expansile mass in the left inferior turbinate. Endoscopic surgery and electrocautery were performed to resect the tumor beyond the macroscopic border. Histopathologically, the tissues were infiltrated by hyperplastic blood vessels arranged in a retiform pattern, and endothelial cells proliferate significantly in some areas. Immunohistochemistry showed a positive result for CD31, CD34, Fli-1, and ERG. No epistaxis, tumor recurrence, or metastasis was found on reexamination over 18 months after surgery.
PubMed: 38757668
DOI: 10.1177/01455613241253372 -
Annals of Clinical and Translational... May 2024Alzheimer's disease (AD) and cerebral small vessel disease (cSVD), the two most common causes of dementia, are characterized by white matter (WM) alterations diverging...
OBJECTIVE
Alzheimer's disease (AD) and cerebral small vessel disease (cSVD), the two most common causes of dementia, are characterized by white matter (WM) alterations diverging from the physiological changes occurring in healthy aging. Diffusion tensor imaging (DTI) is a valuable tool to quantify WM integrity non-invasively and identify the determinants of such alterations. Here, we investigated main effects and interactions of AD pathology, APOE-ε4, cSVD, and cardiovascular risk on spatial patterns of WM alterations in non-demented older adults.
METHODS
Within the prospective European Prevention of Alzheimer's Dementia study, we selected 606 participants (64.9 ± 7.2 years, 376 females) with baseline cerebrospinal fluid samples of amyloid β and p-Tau and MRI scans, including DTI scans. Longitudinal scans (mean follow-up time = 1.3 ± 0.5 years) were obtained in a subset (n = 223). WM integrity was assessed by extracting fractional anisotropy and mean diffusivity in relevant tracts. To identify the determinants of WM disruption, we performed a multimodel inference to identify the best linear mixed-effects model for each tract.
RESULTS
AD pathology, APOE-ε4, cSVD burden, and cardiovascular risk were all associated with WM integrity within several tracts. While limbic tracts were mainly impacted by AD pathology and APOE-ε4, commissural, associative, and projection tract integrity was more related to cSVD burden and cardiovascular risk. AD pathology and cSVD did not show any significant interaction effect.
INTERPRETATION
Our results suggest that AD pathology and cSVD exert independent and spatially different effects on WM microstructure, supporting the role of DTI in disease monitoring and suggesting independent targets for preventive medicine approaches.
PubMed: 38757392
DOI: 10.1002/acn3.52071 -
Frontiers in Pediatrics 2024This study aims to assess the comparative effectiveness of a conventional splitting needle or a peelable cannula vs. the modified Seldinger technique (MST) by utilizing...
OBJECTIVE
This study aims to assess the comparative effectiveness of a conventional splitting needle or a peelable cannula vs. the modified Seldinger technique (MST) by utilizing a dedicated micro-insertion kit across various clinically significant metrics, including insertion success, complications, and catheter-related infections.
METHODS
We conducted a retrospective observational cohort study using an anonymized data set spanning 3 years (2017-2019) in a large tertiary-level neonatal intensive care unit in Qatar.
RESULTS
A total of 1,445 peripherally inserted central catheter (PICC) insertion procedures were included in the analysis, of which 1,285 (89%) were successful. The primary indication for insertion was mainly determined by the planned therapy duration, with the saphenous vein being the most frequently selected blood vessel. The patients exposed to MST were generally younger (7 ± 15 days vs. 11 ± 26 days), but exhibited similar mean weights and gestational ages. Although not statistically significant, the MST demonstrated slightly higher overall and first-attempt insertion success rates compared to conventional methods (91 vs. 88%). However, patients undergoing conventional insertion techniques experienced a greater incidence of catheter-related complications ( < 0.001). There were 39 cases of catheter-related bloodstream infections (CLABSI) in the conventional group (3.45/1,000 catheter days) and eight cases in the MST group (1.06/1,000 catheter days), indicating a statistically significant difference ( < 0.001). Throughout the study period, there was a noticeable shift toward the utilization of the MST kit for PICC insertions.
CONCLUSION
The study underscores the viability of MST facilitated by an all-in-one micro kit for neonatal PICC insertion. Utilized by adept and trained inserters, this approach is associated with improved first-attempt success rates, decreased catheter-related complications, and fewer incidences of CLABSI. However, while these findings are promising, it is imperative to recognize potential confounding factors. Therefore, additional prospective multicenter studies are recommended to substantiate these results and ascertain the comprehensive benefits of employing the all-in-one kit.
PubMed: 38756973
DOI: 10.3389/fped.2024.1395395 -
Cell Transplantation 2024Subcutaneous islet transplantation is a promising treatment for severe diabetes; however, poor engraftment hinders its prevalence. We previously revealed that a gelatin...
Subcutaneous islet transplantation is a promising treatment for severe diabetes; however, poor engraftment hinders its prevalence. We previously revealed that a gelatin hydrogel nonwoven fabric (GHNF) markedly improved subcutaneous islet engraftment. We herein investigated whether the addition of adipose tissue-derived stem cells (ADSCs) to GHNF affected the outcome. A silicone spacer sandwiched between two GHNFs with (AG group) or without (GHNF group) ADSCs, or a silicone spacer alone (Silicone group) was implanted into the subcutaneous space of healthy mice at 6 weeks before transplantation, then diabetes was induced 7 days before transplantation. Syngeneic islets were transplanted into the pretreated space. Intraportal transplantation (IPO group) was also performed to compare the transplant efficiency. Blood glucose, intraperitoneal glucose tolerance, immunohistochemistry, and inflammatory mediators were evaluated. The results in the subcutaneous transplantation were compared using the Silicone group as a control. The results of the IPO group were also compared with those of the AG group. The AG group showed significantly better blood glucose changes than the Silicone and the IPO groups. The cure rate of AG group (72.7%) was the highest among the groups (GHNF; 40.0%, IPO; 40.0%, Silicone; 0%). The number of vWF-positive vessels in the subcutaneous space of the AG group was significantly higher than that in other groups before transplantation ( < 0.01). Lectin angiography also showed that the same results ( < 0.05). According to the results of the ADSCs tracing, ADSCs did not exist at the transplant site (6 weeks after implantation). The positive rates for laminin and collagen III constructed around the transplanted islets did not differ among groups. Inflammatory mediators were higher in the Silicone group, followed by the AG and GHNF groups. Pretreatment using bioabsorbable scaffolds combined with ADSCs enhanced neovascularization in subcutaneous space, and subcutaneous islet transplantation using GHNF with ADSCs was superior to intraportal islet transplantation.
Topics: Animals; Islets of Langerhans Transplantation; Adipose Tissue; Gelatin; Mice; Hydrogels; Male; Diabetes Mellitus, Experimental; Stem Cells; Islets of Langerhans; Blood Glucose; Mice, Inbred C57BL
PubMed: 38756050
DOI: 10.1177/09636897241251621 -
Fluids and Barriers of the CNS May 2024Most subarachnoid hemorrhage (SAH) patients have no obvious hematoma lesions but exhibit blood-brain barrier dysfunction and vasogenic brain edema. However, there is a...
BACKGROUND
Most subarachnoid hemorrhage (SAH) patients have no obvious hematoma lesions but exhibit blood-brain barrier dysfunction and vasogenic brain edema. However, there is a few days between blood‒brain barrier dysfunction and vasogenic brain edema. The present study sought to investigate whether this phenomenon is caused by endothelial injury induced by the acute astrocytic barrier, also known as the glial limitans.
METHODS
Bioinformatics analyses of human endothelial cells and astrocytes under hypoxia were performed based on the GEO database. Wild-type, EGLN3 and PKM2 conditional knock-in mice were used to confirm glial limitan formation after SAH. Then, the effect of endothelial EGLN3-PKM2 signaling on temporal and spatial changes in glial limitans was evaluated in both in vivo and in vitro models of SAH.
RESULTS
The data indicate that in the acute phase after SAH, astrocytes can form a temporary protective barrier, the glia limitans, around blood vessels that helps maintain barrier function and improve neurological prognosis. Molecular docking studies have shown that endothelial cells and astrocytes can promote glial limitans-based protection against early brain injury through EGLN3/PKM2 signaling and further activation of the PKC/ERK/MAPK signaling pathway in astrocytes after SAH.
CONCLUSION
Improving the ability to maintain glial limitans may be a new therapeutic strategy for improving the prognosis of SAH patients.
Topics: Animals; Astrocytes; Humans; Subarachnoid Hemorrhage; Mice; Signal Transduction; Blood-Brain Barrier; Endothelial Cells; Mice, Inbred C57BL; Male; Pyruvate Kinase; Carrier Proteins; Brain Edema; Mice, Transgenic; Membrane Proteins
PubMed: 38755642
DOI: 10.1186/s12987-024-00550-8 -
Respiratory Research May 2024Mitogen-activated protein kinase (MAPK)signaling-mediated smoking-associated pulmonary vascular remodeling (PVR) plays an important role in the pathogenesis of group 3...
BACKGROUND
Mitogen-activated protein kinase (MAPK)signaling-mediated smoking-associated pulmonary vascular remodeling (PVR) plays an important role in the pathogenesis of group 3 pulmonary hypertension (PH). And G protein pathway suppressor 2 (GPS2) could suppress G-protein signaling such as Ras and MAPK, but its role in cigarette smoking -induced PVR (CS-PVR) is unclear.
METHODS
An in vivo model of smoke-exposed rats was constructed to assess the role of GPS2 in smoking-induced PH and PVR. In vitro, the effects of GPS2 overexpression and silencing on the function of human pulmonary arterial smooth cells (HPASMCs) and the underlying mechanisms were explored.
RESULTS
GPS2 expression was downregulated in rat pulmonary arteries (PAs) and HPASMCs after CS exposure. More importantly, CS-exposed rats with GPS2 overexpression had lower right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), and wall thickness (WT%) than those without. And enhanced proliferation and migration of HPASMCs induced by cigarette smoking extract (CSE) can be evidently inhibited by overexpressed GPS2. Besides, GPS2siRNA significantly enhanced the proliferation, and migration of HPASMCs as well as activated Ras and Raf/ERK signaling, while these effects were inhibited by zoledronic acid (ZOL). In addition, GPS2 promoter methylation level in rat PAs and HPASMCs was increased after CS exposure, and 5-aza-2-deoxycytidine (5-aza) inhibited CSE-induced GPS2 hypermethylation and downregulation in vitro.
CONCLUSIONS
GPS2 overexpression could improve the CS-PVR, suggesting that GPS2 might serve as a novel therapeutic target for PH-COPD in the future.
Topics: Animals; Vascular Remodeling; Rats; Male; Rats, Sprague-Dawley; Humans; Cigarette Smoking; MAP Kinase Signaling System; Cells, Cultured; ras Proteins; Pulmonary Artery; raf Kinases; Hypertension, Pulmonary; Extracellular Signal-Regulated MAP Kinases
PubMed: 38755610
DOI: 10.1186/s12931-024-02831-0