Gastrulation is a key event in embryonic development when the germ layers are specified and the basic animal body plan is established. The complexities of primate gastrulation remain a mystery ...because of the difficulties in accessing primate embryos at this stage. Here, we report the establishment of an in vitro culture (IVC) system that supports the continuous development of cynomolgus monkey blastocysts beyond early gastrulation up to 20 days after fertilization. The IVC embryos highly recapitulated the key events of in vivo early postimplantation development, including segregation of the epiblast and hypoblast, formation of the amniotic and yolk sac cavities, appearance of the primordial germ cells, and establishment of the anterior-posterior axis. Single-cell RNA-sequencing analyses of the IVC embryos provide information about lineage specification during primate early postimplantation development. This system provides a platform with which to explore the characteristics and mechanisms of early postimplantation embryogenesis in primates with possible conservation of cell movements and lineages in human embryogenesis.
The prognosis of human papillomavirus (HPV)-infected head and neck squamous cell carcinoma (HNSCC) is often better than that of HPV
-
cancer, which is possibly caused by the differences in their ...immune microenvironments. The contribution of macrophage, as a principal innate immune cell, to this phenomenon is still unclear. In this study, a single-cell atlas of 4,388 high-quality macrophages from 18 HPV
-
and 8 HPV
+
HNSCC patients was constructed with single-cell RNA sequencing data. Eight macrophage subsets were identified from HNSCC, whereas their functional properties and developmental trajectory were delineated based on HPV status. Our results demonstrated that macrophages in HPV
+
HNSCC exhibit stronger phagocytic ability, although the infiltration rate of macrophages decreased. From the results, a unique macrophage subset with TCR and CD3-specific signatures was identified from HPV-related HNSCC. These TCR
+
macrophages potentially participate in the regulation of the TCR signaling pathway and phagocytosis. In conclusion, our results suggested that HPV could affect the infiltration rate, function, and differentiation of macrophages in HNSCC, whereas TCR
+
macrophages play a critical role in the HNSCC microenvironment. These results provide new insights into the immune microenvironment of HNSCC and offer a valuable resource for the understanding of the immune landscape of HPV-related HNSCC, which will in turn help the development of immunotherapy strategies for the disease.
Alzheimer's disease (AD) is an incurable neurodegenerative disease and many types of stem cells have been used in AD therapy with some favorable effects. In this study, we investigated the potential ...therapeutical effects of human dental pulp stem cells (hDPSCs) on AD cellular model which established by okadaic acid (OA)‐induced damage to human neuroblastoma cell line, SH‐SY5Y, in vitro for 24 h. After confirmed the AD cellular model, the cells were co‐culture with hDPSCs by transwell co‐culture system till 24 h for treatment. Then the cytomorphology of the hDPSCs‐treated cells were found to restore gradually with re‐elongation of retracted dendrites. Meanwhile, Cell Counting Kit‐8 assay and Hoechst 33258 staining showed that hDPSCs caused significant increase in the viability and decrease in apoptosis of the model cells, respectively. Observation of DiI labeling also exhibited the prolongation dendrites in hDPSCs‐treated cells which were obviously different from the retraction dendrites in AD model cells. Furthermore, specific staining of α‐tubulin and F‐actin demonstrated that the hDPSCs‐treated cells had the morphology of restored neurons, with elongated dendrites, densely arranged microfilaments, and thickened microtubular fibrils. In addition, results from western blotting revealed that phosphorylation at Ser 396 of Tau protein was significantly suppressed by adding of hDPSCs. These results indicate that hDPSCs may promote regeneration of damaged neuron cells in vitro model of AD and may serve as a useful cell source for treatment of AD.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
With the expansion of the aging population, age-associated sarcopenia (AAS) has become a severe clinical disease of the elderly and a key challenge for healthy aging. Regrettably, no approved ...therapies currently exist for treating AAS. In this study, clinical-grade human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were administrated to two classic mouse models (SAMP8 mice and D-galactose-induced aging mice), and their effects on skeletal muscle mass and function were investigated by behavioral tests, immunostaining, and western blotting. Core data results showed that hUC-MSCs significantly restored skeletal muscle strength and performance in both mouse models via mechanisms including raising the expression of crucial extracellular matrix proteins, activating satellite cells, enhancing autophagy, and impeding cellular aging. For the first time, the study comprehensively evaluates and demonstrates the preclinical efficacy of clinical-grade hUC-MSCs for AAS in two mouse models, which not only provides a novel model for AAS, but also highlights a promising strategy to improve and treat AAS and other age-associated muscle diseases. This study comprehensively evaluates the preclinical efficacy of clinical-grade hUC-MSCs in treating age-associated sarcopenia (AAS), and demonstrates that hUC-MSCs restore skeletal muscle strength and performance in two AAS mouse models via raising the expression of extracellular matrix proteins, activating satellite cells, enhancing autophagy, and impeding cellular aging, which highlights a promising strategy for AAS and other age-associated muscle diseases.
Stem cells have emerged as a potential therapy for a range of neural insults, but their application in Alzheimer's disease (AD) is still limited and the mechanisms underlying the cognitive benefits ...of stem cells remain to be elucidated. Here, the effects of clinical‐grade human umbilical cord‐derived mesenchymal stem cells (hUC‐MSCs) on the recovery of cognitive ability in SAMP8 mice, a senescence‐accelerated mouse model of AD is explored. A functional assay identifies that the core functional factor hepatocyte growth factor (HGF) secreted from hUC‐MSCs plays critical roles in hUC‐MSC‐modulated recovery of damaged neural cells by down‐regulating hyperphosphorylated tau, reversing spine loss, and promoting synaptic plasticity in an AD cell model. Mechanistically, structural and functional recovery, as well as cognitive enhancements elicited by exposure to hUC‐MSCs, are at least partially mediated by HGF in the AD hippocampus through the activation of the cMet‐AKT‐GSK3β signaling pathway. Taken together, these data strongly implicate HGF in mediating hUC‐MSC‐induced improvements in functional recovery in AD models.
This study explores the effects of clinical‐grade hUC‐MSCs on the recovery of cognitive ability of Alzheimer's disease (AD). All results uncover that HGF secreted from hUC‐MSCs, mediates the beneficial effects of hUC‐MSCs on functional recovery of damaged neural cells by downregulating hyperphosphorylated tau, improving neurofibrillary tangles, reversing spine loss, and promoting synaptic plasticity in AD hippocampus through the cMet‐AKT‐GSK3β signaling pathway.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Plasma S100A1 protein is a novel inflammatory biomarker associated with acute myocardial infarction and neurodegenerative disease's pathophysiological mechanisms. This study aimed to determine the ...levels of this protein in patients with acute ischemic stroke early in the disease progression and to investigate its role in the pathogenesis of acute ischemic stroke.
A total of 192 participants from hospital stroke centers were collected for the study. Clinically pertinent data were recorded. The volume of the cerebral infarction was calculated according to the Pullicino formula. Multivariate logistic regression analysis was used to select independent influences. ROC curve was used to analyze the diagnostic value of AIS and TIA. The correlation between S100A1, NF-
B p65, and IL-6 levels and cerebral infarction volume was detected by Pearson correlation analysis.
There were statistically significant differences in S100A1, NF-
B p65, and IL-6 among the AIS,TIA, and PE groups (S100A1, 230.96 ± 39.37
185.85 ± 43.24
181.47 ± 27.39,
< 0.001; NF-
B p65, 3.99 ± 0.65
3.58 ± 0.74
3.51 ± 0.99,
= 0.001; IL-6, 13.32 ± 1.57
11.61 ± 1.67
11.42 ± 2.34,
< 0.001). Multivariate logistic regression analysis showed that S100A1 might be an independent predictive factor for the diagnosis of disease (
< 0.001). The AUC of S100A1 for diagnosis of AIS was 0.818 (
< 0.001, 95% CI 0.749-0.887, cut off 181.03,
max 0.578,
95.0%,
62.7%). The AUC of S100A1 for diagnosis of TIA was 0.720 (
= 0.001, 95% CI 0.592-0.848, cut off 150.14,
max 0.442,
50.0%,
94.2%). There were statistically significant differences in S100A1, NF-
B p65, and IL-6 among the SCI,MCI, and LCI groups (S100A1, 223.98 ± 40.21
225.42 ± 30.92
254.25 ± 37.07,
= 0.001; NF-
B p65, 3.88 ± 0.66
3.85 ± 0.64
4.41 ± 0.45,
< 0.001; IL-6, 13.27 ± 1.65
12.77 ± 1.31
14.00 ± 1.40,
= 0.007). Plasma S100A1, NF-
B p65, and IL-6 were significantly different from cerebral infarction volume (S100A1,
= 0.259,
= 0.002; NF-
B p65,
= 0.316,
< 0.001; IL-6,
= 0.177,
= 0.036). There was a positive correlation between plasma S100A1 and IL-6 with statistical significance (R = 0.353,
< 0.001). There was no significant positive correlation between plasma S100A1 and NF-
B p65 (R < 0.3), but there was statistical significance (R = 0.290,
< 0.001). There was a positive correlation between IL-6 and NF-
B p65 with statistical significance (R = 0.313,
< 0.001).
S100A1 might have a better diagnostic efficacy for AIS and TIA. S100A1 was associated with infarct volume in AIS, and its level reflected the severity of acute cerebral infarction to a certain extent. There was a correlation between S100A1 and IL-6 and NF-
B p65, and it was reasonable to speculate that this protein might mediate the inflammatory response through the NF-
B pathway during the pathophysiology of AIS.
Molecular assays on nasopharyngeal swabs act as a confirmatory test in coronavirus disease (COVID-19) diagnosis. However, the technical requirements of nasopharyngeal sampling and molecular assays ...limit the testing capabilities. Recent studies suggest the use of saliva for the COVID-19 diagnostic test. In this study, 44 patients diagnosed with COVID-19 in The Third People’s Hospital of Shenzhen were enrolled. Saliva and serum specimens were obtained at different time points and the immunoglobulins against SARS-CoV-2 were measured. The results showed that saliva IgA presented a higher COI value than IgG and IgM. In matched saliva and serum samples, all saliva samples presented lower IgG levels than serum samples, and only one saliva sample presented a higher IgM level. The conversion rates of saliva IgA and the detection of viral nucleic acids were analyzed in the first and second weeks after hospitalization. The positive rates increased when combining saliva IgA and viral nucleic acid detection. In conclusion, our results provide evidence that saliva IgA could serve as a useful index for the early diagnosis of COVID-19.
The fundamental physical features such as the mechanical properties and microstructures of the uterus need to be considered when building in vitro culture platforms to mimic the uterus for embryo ...implantation and further development but have long been neglected. Here, a uterus‐inspired niche (UN) constructed by grafting collagen gels onto polydimethylsiloxane based on a systematic investigation of a series of parameters (varying concentrations and thicknesses of collagen gel) is established to intrinsically specify and simulate the mechanics and microstructures of the mouse uterus. This brand‐new and unique system is robust in supporting embryo invasion, as evidenced by the special interaction between the embryos and the UN system and successfully promoting E3.5 embryo development into the early organogenesis stage. This platform serves as a powerful tool for developmental biology and tissue engineering.
A uterus‐inspired niche drives blastocyst development to early organogenesis. The uterine horn's modulus and the endometrium microstructure is mimicked to construct a uterus‐inspired niche to support the embryo development to the early organogenesis stage in vitro and to study the invasion of the embryo into collagen fibers for in‐depth studies of embryonic implantation in the future.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Dattani et al.1 developed a method for inducing hypoblast-like cells from human naive pluripotent stem cells. They elucidated the requirement for FGF signaling in human hypoblast specialization at a ...specific time window, which was previously controversial.
Dattani et al. developed a method for inducing hypoblast-like cells from human naive pluripotent stem cells. They elucidated the requirement for FGF signaling in human hypoblast specialization at a specific time window, which was previously controversial.
The basic body plan of the mammalian embryo is established through gastrulation, a pivotal early postimplantation event during which the three major germ layers (endoderm, ectoderm, and mesoderm) are ...specified with cellular and spatial diversity. Despite its basic and clinical importance, human embryo development from peri-implantation to gastrulation remains shrouded in mystery. Recent advances in the elongated in vitro culture of rodent and non‐primate embryos and the construction of embryo-like structures have helped to improve understanding of the mechanisms of human early embryonic development. Here, we review the recent advances and possible future directions in the development of in vitro models to better understand human embryogenesis from peri-implantation to gastrulation.
In vitro culture of mammalian embryos, especially primate embryos, greatly enriches our knowledge of the dynamic characteristics of human early embryo development.Culturing non-human primate embryos beyond the gastrulation stage is one of the best strategies to understand human gastrulation.Reconstructions of stem cell–based embryo models provide insight to decipher the mechanisms underlying human embryogenesis.Advancements in single-cell multiomic studies and imaging techniques contribute to clarifying the cell lineage trajectory and unveiling the underpinning molecular mechanisms of human embryogenesis and gastrulation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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