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Biomolecules Jun 2024Zygotic genome activation (ZGA) is a pivotal event in mammalian embryogenesis, marking the transition from maternal to zygotic control of development. During the ZGA... (Review)
Review
Zygotic genome activation (ZGA) is a pivotal event in mammalian embryogenesis, marking the transition from maternal to zygotic control of development. During the ZGA process that is characterized by the intricate cascade of gene expression, who tipped the first domino in a meticulously arranged sequence is a subject of paramount interest. Recently, Dux, Obox and Nr5a2 were identified as pioneer transcription factors that reside at the top of transcriptional hierarchy. Through co-option of retrotransposon elements as hubs for transcriptional activation, these pioneer transcription factors rewire the gene regulatory network, thus initiating ZGA. In this review, we provide a snapshot of the mechanisms underlying the functions of these pioneer transcription factors. We propose that ZGA is the starting point where the embryo's own genome begins to influence development trajectory, therefore in-depth dissecting the functions of pioneer transcription factors during ZGA will form a cornerstone of our understanding for early embryonic development, which will pave the way for advancing our grasp of mammalian developmental biology and optimizing in vitro production (IVP) techniques.
Topics: Zygote; Animals; Transcription Factors; Humans; Genome; Gene Expression Regulation, Developmental; Embryonic Development; Retroelements; Transcriptional Activation; Homeodomain Proteins
PubMed: 38927123
DOI: 10.3390/biom14060720 -
Journal of Cardiothoracic Surgery Jun 2024For acute type A aortic dissection involving the aortic root with root diameter no more than 45 mm, there are various aortic root repair techniques. In this study, a...
BACKGROUND
For acute type A aortic dissection involving the aortic root with root diameter no more than 45 mm, there are various aortic root repair techniques. In this study, a novel surgical technique using a pericardial autograft for aortic root repair was introduced. We described its surgical steps in detail and compare its clinical outcomes with direct suture technique.
METHODS
Between July 2017 and August 2022, 95 patients with acute type A aortic dissection who underwent aortic root repair were enrolled, including aortic root repair using pericardial autograft (group A, n = 49) or direct suture (group B, n = 46). The patient's clinical data were retrospectively analyzed, and a 5-year follow-up was conducted.
RESULTS
The 30-day mortality, re-exploration for bleeding, postoperative new-onset renal failure requiring continuous renal replacement therapy, stroke, and paraplegia occurred in 3%, 4%, 11%, 5%, and 2% of the overall patients, respectively. There was no significant difference in the 30-day mortality and complication rate between the two groups. The 30-day mortality and re-exploration for bleeding marked the primary endpoint events. Logistic regression analysis indicated that there was a significant correlation between the primary endpoint events and surgical technique (odds ratio, 0.002; 95% confidence interval, 0-0.159; P = 0.026). The aortic valve insufficiency of the two groups were significantly improved after operation (group A, P < 0.001; group B, P < 0.001). During follow-up, there was no significant difference in short-term survival between the two groups after surgery (log-rank P = 0.75), and all patients were free from reoperation for aortic disease.
CONCLUSIONS
Patients who underwent aortic root repair using pericardial autograft tended to have reduced 30-day mortality and a lower risk of re-exploration for bleeding. Using pericardial autograft for aortic root repair is a safe and useful approach for patients with acute type A aortic dissection involving the aortic root.
Topics: Humans; Aortic Dissection; Male; Female; Retrospective Studies; Middle Aged; Pericardium; Treatment Outcome; Autografts; Aortic Aneurysm, Thoracic; Aged; Acute Disease; Postoperative Complications; Blood Vessel Prosthesis Implantation; Transplantation, Autologous; Follow-Up Studies
PubMed: 38926836
DOI: 10.1186/s13019-024-02909-2 -
Journal of Cardiothoracic Surgery Jun 2024At present, research comparing the short-term postoperative outcomes of anatomical resection in lung cancer under different ports of da Vinci robot-assisted surgery is... (Comparative Study)
Comparative Study
BACKGROUND
At present, research comparing the short-term postoperative outcomes of anatomical resection in lung cancer under different ports of da Vinci robot-assisted surgery is insufficient. This report aimed to compare the outcomes of three-port and four-port da Vinci robot-assisted thoracoscopic surgery for radical dissection of lung cancer.
METHODS
171 consecutive patients who presented to our hospital from January 2020 to October 2021 with non-small cell lung cancer and treated with da Vinci robot-assisted thoracoscopic surgery for radical resection of lung cancer were retrospectively collected and divided into the three-port group (n = 97) and the four-port group (n = 74). The general clinical data, perioperative data and life quality were individually compared between the two groups.
RESULTS
All the 171 patients successfully underwent surgeries. Compared to the four-port group, the three-port group had comparable baseline characteristics in terms of age, sex, tumor location, tumor size, history of chronic disease, pathological type, and pathological staging. The three-port group also had shorter operation time, less intraoperative blood loss, lower chest tube drainage volume, shorter postoperative hospitalization stay durations, but showed no statistically significant difference (P > 0.05). Postoperative 24, 48 and 72 h visual analogue scale pain scores were lower in the three-port group (p < 0.001). No significant difference was observed between the two groups in the hospitalization costs (P = 0.664), number or stations of total lymph node dissected (p > 0.05) and postoperative respiratory complications (P > 0.05).
CONCLUSIONS
The three-port robot-assisted thoracoscopic surgery is safe and effective and took better outcomes than the four-port robot-assisted thoracoscopic surgery in non-small cell lung cancer.
Topics: Humans; Robotic Surgical Procedures; Male; Female; Lung Neoplasms; Retrospective Studies; Middle Aged; Aged; Carcinoma, Non-Small-Cell Lung; Thoracic Surgery, Video-Assisted; Pneumonectomy; Operative Time; Treatment Outcome
PubMed: 38926727
DOI: 10.1186/s13019-024-02920-7 -
Scientific Reports Jun 2024Japanese medaka (Oryzias latipes) has been used as a model organism in different research fields, including reproductive physiology. Sperm motility is the most important...
Japanese medaka (Oryzias latipes) has been used as a model organism in different research fields, including reproductive physiology. Sperm motility is the most important marker for male fertility in fish and, thus, reproduction success. However, because of small volume of ejaculate and short motility duration, it is still challenging to manage the sperm collection and analysis in small model fish. In the present study, we aimed to investigate sperm motility and to optimize sperm collection, short-term sperm storage, and cryopreservation in Japanese medaka (Oryzias latipes). Using two different approaches for sperm collection: testes dissection and abdominal massage, different housing conditions and activating the sperm with different activation solutions, we investigated immediate sperm motility. In the second part of this study, we used different osmolalities of immobilization solution, Hank's Balanced Salt Solution (HBSS) for sperm storage at 0, 2 and 3 h after sperm collection. Finally, the sperm were cryopreserved using methanol as cryoprotectant and HBSS as extender at two different osmolalities, and post-thaw sperm motility was investigated. The highest post-activating sperm motility was achieved in the groups activated by the extender at 300 mOsm/kg. The quality of sperm remained unaffected by co-housing with females or with males only. Furthermore, Hanks' Balanced Salt Solution (HBSS) with an osmolality of 600 mOsm/kg demonstrated its efficacy as a suitable extender for sperm storage, preserving motility and progressivity for 3 h. The highest post-thaw motility was around 35%. There were no significant differences between post-thaw motility in different groups. We also found that post-thaw incubation on ice can maintain the motility of the sperm for up to one hour after thawing.
Topics: Animals; Oryzias; Male; Sperm Motility; Cryopreservation; Spermatozoa; Semen Preservation; Female; Cryoprotective Agents
PubMed: 38926593
DOI: 10.1038/s41598-024-65376-8 -
Journal For Immunotherapy of Cancer Jun 2024Lung metastasis is the primary cause of breast cancer-related mortality. Neutrophil extracellular traps (NETs) are involved in the progression of breast cancer. However,...
BACKGROUND
Lung metastasis is the primary cause of breast cancer-related mortality. Neutrophil extracellular traps (NETs) are involved in the progression of breast cancer. However, the mechanism of NET formation is not fully understood. This study posits that tumor cell-released autophagosomes (TRAPs) play a crucial role in this process.
METHODS
TRAPs were isolated from breast cancer cell lines to analyze their impact on NET formation in both human and mouse neutrophils. The study used both in vitro and in vivo models, including Toll-like receptor 4 (TLR4/) mice and engineered breast cancer cell lines. Immunofluorescence, ELISA, Western blotting, RNA sequencing, and flow cytometry were employed to dissect the signaling pathways leading to NET production and to explore their immunosuppressive effects, particularly focusing on the impact of NETs on T-cell function. The therapeutic potential of targeting TRAP-induced NETs and their immunosuppressive functions was evaluated using DNase I and αPD-L1 antibodies. Clinical relevance was assessed by correlating circulating levels of TRAPs and NETs with lung metastasis in patients with breast cancer.
RESULTS
This study showed that TRAPs induced the formation of NETs in both human and mouse neutrophils by using the high mobility group box 1 and activating the TLR4-Myd88-ERK/p38 signaling axis. More importantly, PD-L1 carried by TRAP-induced NETs inhibited T-cell function in vitro and in vivo, thereby contributing to the formation of lung premetastatic niche (PMN) immunosuppression. In contrast, KD-4T1 breast tumors with decreased circulating TRAPs in vivo reduced the formation of NETs, which in turn attenuated the immunosuppressive effects in PMN and resulted in a reduction of breast cancer pulmonary metastasis in murine models. Moreover, treatment with αPD-L1 in combination with DNase I that degraded NETs restored T-cell function and significantly reduced tumor metastasis. TRAP levels in the peripheral blood positively correlated with NET levels and lung metastasis in patients with breast cancer.
CONCLUSIONS
Our results demonstrate a novel role of TRAPs in the formation of PD-L1-decorated NETs, which may provide a new strategy for early detection and treatment of pulmonary metastasis in patients with breast cancer.
Topics: Animals; Humans; Mice; Female; Breast Neoplasms; Lung Neoplasms; Extracellular Traps; B7-H1 Antigen; Autophagosomes; T-Lymphocytes; Cell Line, Tumor
PubMed: 38926151
DOI: 10.1136/jitc-2024-009082 -
Internal Medicine (Tokyo, Japan) Jun 2024Esophageal cell tumors are rare. Esophagogastroduodenoscopy performed on a 48-year-old woman revealed an elevated esophageal lesion and the presence of long-segment...
Esophageal cell tumors are rare. Esophagogastroduodenoscopy performed on a 48-year-old woman revealed an elevated esophageal lesion and the presence of long-segment Barrett's esophagus. Endoscopic ultrasonography showed a 15 mm homogeneous hypoechoic tumor extending from the lamina propria mucosa to the submucosa. Pathological examination of the biopsy tissue revealed a sheet-like cluster of histiocytoid cells with an abundant eosinophilic granular cytoplasm. Immunohistochemical examination revealed S-100 (+) and CD68 (+), thus suggesting the diagnosis of a granular cell tumor. The tumor was resected by endoscopic submucosal dissection. Pathologically, the background mucosa was Barrett's mucosa. This is the first reported case of an esophageal granular cell tumor in long-segment Barrett's esophagus.
PubMed: 38925966
DOI: 10.2169/internalmedicine.3933-24 -
Journal of Yeungnam Medical Science Jun 2024Myofascial pain syndrome (MPS) is a common musculoskeletal disorder characterized by muscle pain, tenderness, and trigger points. Ultrasonography has emerged as a key...
Myofascial pain syndrome (MPS) is a common musculoskeletal disorder characterized by muscle pain, tenderness, and trigger points. Ultrasonography has emerged as a key tool for diagnosing and treating MPS owing to its ability to provide precise, minimally invasive guidance. This review discusses the use of ultrasonography in various approaches to evaluate and manage MPS. Studies have shown that shear-wave sonoelastography can effectively assess muscle elasticity and offer insights into trapezius stiffness in patients with MPS. Ultrasound-guided interfascial hydrodissection, especially with visual feedback, has demonstrated effectiveness in treating trapezius MPS. Similarly, ultrasound-guided rhomboid interfascial plane blocks and perimysium dissection for posterior shoulder MPS have significantly reduced pain and improved quality of life. The combination of extracorporeal shockwave therapy with ultrasound-guided lidocaine injections has been particularly successful in reducing pain and stiffness in trapezius MPS. Research regarding various guided injections, including dry needling, interfascial plane blocks, and fascial hydrodissection, emphasizes the importance of ultrasonography for accuracy and safety. Additionally, ultrasound-guided delivery of local anesthetics and steroids to the quadratus lumborum muscle has shown lasting pain relief over a 6-month period. Overall, these findings highlight the pivotal role of ultrasonography in the assessment and treatment of MPS.
PubMed: 38925874
DOI: 10.12701/jyms.2024.00416 -
BMJ Open Jun 2024This study aimed to develop a patient-centred approach to the burden of acute type A aortic dissection (ATAAD) through modelling. The main objective was to identify...
OBJECTIVES
This study aimed to develop a patient-centred approach to the burden of acute type A aortic dissection (ATAAD) through modelling. The main objective was to identify potential improvements in managing this life-threatening cardiovascular condition and to provide evidence-based recommendations to optimise outcomes.
DESIGN
We developed a predictive model along patient pathways to estimate the burden of ATAAD through the years of life lost (YLLs) metric. The model was created based on a systematic review of the literature and was parameterised using demographic data from the German healthcare environment. The model was designed to allow interactive simulation of different scenarios resulting from changes in key impact factors.
SETTING
The study was conducted using data from the German healthcare environment and results from the literature review.
PARTICIPANTS
The study included a comprehensive modelling of ATAAD cases in Germany but did not directly involve participants.
INTERVENTIONS
There were no specific interventions applied in this study based on the modelling design.
PRIMARY AND SECONDARY OUTCOME MEASURES
The single outcome measure was the estimation of YLL due to ATAAD in Germany.
RESULTS
Our model estimated 102 791 YLL per year for ATAAD in Germany, with 62 432 and 40 359 YLL for men and women, respectively. Modelling an improved care setting yielded 93 191 YLL or 9.3% less YLL compared with the current standard while a worst-case scenario resulted in 113 023 or 10.0% more YLL. The model is accessible at https://acuteaorticdissection.com/ to estimate custom scenarios.
CONCLUSIONS
Our study provides an evidence-based approach to estimating the burden of ATAAD and identifying potential improvements in the management of pathways. This approach can be used by healthcare decision-makers to inform policy changes aimed at optimising patient outcomes. By considering patient-centred approaches in any healthcare environment, the model has the potential to improve efficient care for patients suffering from ATAAD.
Topics: Humans; Aortic Dissection; Germany; Female; Male; Middle Aged; Aged; Aortic Aneurysm; Life Expectancy; Adult; Acute Disease; Aged, 80 and over; Cost of Illness
PubMed: 38925695
DOI: 10.1136/bmjopen-2023-078398 -
The Journal of Biological Chemistry Jun 2024The commitment of stem cells to differentiate into osteoblasts is a highly regulated and complex process that involves the coordination of extrinsic signals and...
The commitment of stem cells to differentiate into osteoblasts is a highly regulated and complex process that involves the coordination of extrinsic signals and intrinsic transcriptional machinery. While rodent osteoblastic differentiation has been extensively studied, research on human osteogenesis has been limited by cell sources and existing models. Here, we systematically dissect hPSC-derived osteoblasts to identify functional membrane proteins and their downstream transcriptional networks involved in human osteogenesis. Our results reveal an enrichment of type II transmembrane serine protease CORIN in humans but not rodent osteoblasts. Functional analyses demonstrated that CORIN depletion significantly impairs osteogenesis. Genome-wide ChIP enrichment and mechanistic studies show that p38 MAPK-mediated CEBPD upregulation is required for CORIN-modulated osteogenesis. Contrastingly, the type I transmembrane heparan sulfate proteoglycan SDC1 enriched in MSCs exerts a negative regulatory effect on osteogenesis through a similar mechanism. ChIP-seq, bulk and single-cell transcriptomes, and functional validations indicated that CEBPD plays a critical role in controlling osteogenesis. In summary, our findings uncover previously unrecognized CORIN-mediated CEBPD transcriptomic networks in driving human osteoblast lineage commitment.
PubMed: 38925326
DOI: 10.1016/j.jbc.2024.107494 -
Insects Jun 2024The arbovirus West Nile virus (WNV) is a danger to global health. Spread primarily by mosquitoes, WNV causes about 2000 cases per year in the United States. The natural...
The arbovirus West Nile virus (WNV) is a danger to global health. Spread primarily by mosquitoes, WNV causes about 2000 cases per year in the United States. The natural mosquito immune response controls viral replication so that the host survives but can still transmit the virus. Using the genetically malleable model, we previously dissected innate immune pathways used to control WNV infection. Specifically, we showed that insulin/IGF-1 signaling (IIS) activates a JAK/STAT-mediated immune response that reduces WNV. However, how factors that regulate IIS in insects control infection has not been identified. () encodes a peptide hormone that suppresses insulin secretion. Its mammalian ortholog, Neuromedin U (NMU), is a peptide that regulates the production and secretion of insulin from pancreatic beta cells. In this study, we used and human cell culture models to investigate the roles of these insulin regulators in immune signaling. We found that mutants, which have elevated insulin-like peptide expression, are less susceptible to WNV infection. Increased levels of insulin-like peptides in these flies result in upregulated JAK/STAT activity, leading to protection from infection. Treatment of human cells with the insulin regulator NMU results in increased WNV replication. Further investigation of methods to target Lst in mosquitoes or NMU in mammals can improve vector control methods and may lead to improved therapeutics for human and animal infection.
PubMed: 38921161
DOI: 10.3390/insects15060446