Pattern recognition receptors as key players in adrenal gland dysfunction during sepsis

Background: Undergoing systemic inflammation, the innate immune system releases excessive proinflammatory mediators, which finally can lead to organ failure. Pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs) and NOD-like receptors (NLRs), form the interface between bacterial and viral toxins and innate immunity. During sepsis, patients with diagnosed adrenal gland insufficiency are at high risk of developing a multiorgan dysfunction syndrome, which dramatically increases the risk of mortality. To date, little is known about the mechanisms leading to adrenal dysfunction under septic conditions. Here, we investigated the sepsis-related activation of the PRRs, cell inflammation, and apoptosis within adrenal glands. Methods: Two sepsis models were performed: the polymicrobial sepsis model (caecal ligation and puncture (CLP)) and the LTA-induced intoxication model. All experiments received institutional approval by the Regierungspräsidium Darmstadt. CLP was performed as previously described [1], wherein one-third of the caecum was ligated and punctured with a 20-gauge needle. For LTA-induced systemic inflammation, TLR2 knockout (TLR2-/-) and WT mice were injected intraperitoneally with pure LTA (pLTA; 1 mg/kg) or PBS for 2 hours. To detect potential direct adrenal dysfunction, mice were additionally injected with adrenocorticotropic hormone (ACTH; 100 μg/kg) 1 hour after pLTA or PBS. Adrenals and plasma samples were taken. Gene expressions in the adrenals (rt-PCR), cytokine release (multiplex assay), and the apoptosis rate (TUNEL assay) within the adrenals were determined. Results: In both models, adrenals showed increased mRNA expression of TLR2 and TLR4, various NLRs, cytokines as well as inflammasome components, NADPH oxidase subunits, and nitric oxide synthases (data not shown). In WT mice, ACTH alone had no effect on inflammation, while pLTA or pLTA/ACTH administration showed increased levels of the cytokines IL-1β, IL-6, and TNFα. TLR2-/- mice indicated no response as expected (Figure 1, left). Interestingly, surviving CLP mice showed no inflammatory adrenal response, whereas nonsurvivors had elevated cytokine levels (Figure 1, right). Additionally, we identified a marked increase in apoptosis of both chromaffin and steroid-producing cells in adrenal glands obtained from mice with sepsis as compared with their controls (Figure 2). ... Conclusion: Taken together, sepsis-induced activation of the PRRs may contribute to adrenal impairment by enhancing tissue inflammation, oxidative stress and culminate in cellular apoptosis, while mortality seems to be associated with adrenal inflammation

Solution for managing preschools according to the education quality accreditation requirements in Ho Chi Minh City in Vietnam

This study addresses the management of preschools in Ho Chi Minh City, Vietnam, in alignment with education quality accreditation requirements. It evaluates the current state of preschool management, focusing on organization, facilities, teaching staff, and stakeholder engagement. Through a survey of 180 respondents, including retired and current education administrators, local administrators, parent representatives, and graduate students, the study identifies strengths, weaknesses, and influencing factors. Seven solutions are proposed: organizing awareness campaigns, developing management plans, training staff, enhancing child care quality, managing facilities, socializing education, and implementing inspection systems. These solutions aim to improve preschool management, ensure compliance with national standards, and foster holistic child development. The findings provide a foundation for policy recommendations to enhance early childhood education quality and support sustainable educational development in Ho Chi Minh City

The current state of preschool management in accordance with quality accreditation requirements in Ho Chi Minh City, Vietnam

This article examines the current state of preschool management in Ho Chi Minh City according to quality accreditation requirements. Early childhood education is the first level in the national education system and plays a crucial role in the holistic development of children. This study surveys various aspects of preschool management, including organization, management, facilities, teaching staff, and the relationship between schools, families, and communities, in meeting national education quality accreditation standards. The research uses a quantitative approach, with a survey conducted among 550 participants, including educational managers, teachers, staff, and parents. The survey results indicate that preschools have made significant progress in areas such as developing strategic plans, optimizing resources, and improving educational quality. However, challenges remain, including issues of transparency in sharing development plans, limited parental and community involvement, and inconsistencies in implementing the preschool education program across schools

The uncoordinated-5 homolog B receptor affects hepatic ischemia reperfusion injury

Recent evidence has demonstrated additional roles for the neuronal guidance protein receptor UNC5B outside the nervous system. Given the fact that ischemia reperfusion injury (IRI) of the liver is a common source of liver dysfunction and the role of UNC5B during an acute inflammatory response we investigated the role of UNC5B on acute hepatic IRI. We report here that UNC5B+/− mice display reduced hepatic IRI and neutrophil (PMN) infiltration compared to WT controls. This correlated with serum levels of lactate dehydrogenase (LDH), aspartate- (AST) and alanine- (ALT) aminotransferase, the presence of PMN within ischemic hepatic tissue, and serum levels of inflammatory cytokines. Moreover, injection of an anti-UNC5B antibody resulted in a significant reduction of hepatic IR injury. This was associated with reduced parameters of liver injury (LDH, ALT, AST) and accumulation of PMN within the injured hepatic tissue. In conclusion our studies demonstrate a significant role for UNC5B in the development of hepatic IRI and identified UNC5B as a potential drug target to prevent liver dysfunction in the future

The role of toll-like receptors in the adrenal gland

Sepsis is caused by infection and often followed by an overwhelming inflammatory response. This can lead to shock, organ failure and even death. Each year approximately 60,000 people die in Germany due to sepsis. There is good evidence that sepsis is associated with failure of the hypothalamic-pituitary-adrenal-axis. In patients with sepsis, glucocorticoids (e.g. corticosterone, cortisol) released from adrenal glands play an essential role in preventing an excessive pro-inflammatory response. Adrenal insufficiency occurs in a large number of patients with septic shock and is associated with an increased mortality. In the innate immune system, Toll-like receptors (TLRs) play a crucial role in its onset by recognizing pathogenassociated molecules. It is well known that there are interactions between the immune and endocrine stress systems; glucocorticoids and TLRs regulate each other in a bi-directional way. Therefore, a coordinated response of the adrenal and immune system is of vital importance for survival during severe inflammation. This experimental study focuses on the role of TLR-2, TLR-4 and TLR-9 during adrenal stress. The results show that in mice, the absence of TLR-2 and TLR-4, but not TLR-9 leads to altered adrenal morphology, relating to size and cellular structure. However, this alteration does not appear to compromise the phenotype of TLR knock-out mice. Mice deficient of TLR-2, 4 and 9 are not able to respond adequately to inflammatory stress induced by their potential ligands lipopolysaccharide (LPS), lipoteichoic acid (LTA) or cytidine phosphate guanosine-oligodeoxynucleotides (CpG-ODN). This impaired adrenal stress response appears to be associated with a decrease in systemic and intra-adrenal cytokine expressions. Taken together, these results suggest that TLR-2, 4 and 9 are key players in the immuno-endocrine response during inflammation and SIRS. In conclusion, TLRs play a crucial role in the immune-adrenal crosstalk. This close functional relationship needs to be considered in the treatment of inflammatory diseases where an intact adrenal stress response is required. Furthermore, TLR polymorphisms could contribute to the underlying mechanisms of impaired adrenal stress response in patients with bacterial sepsisSepsis entsteht durch eine Infektion, der oft eine unkontrollierte Entzündungsreaktion folgt und die letztendlich in Schock, Organversagen oder Tod münden kann. Jedes Jahr sterben allein in Deutschland bis zu 60.000 Menschen an einer Sepsis. Vieles weist darauf hin, dass die Sepsis in Zusammenhang mit dem Versagen der Hypothalamus-Hypophysen-Nebennierenrinden-Achse steht. Es ist bekannt, dass bei septischen Patienten die von den Nebennieren freigesetzten Glukokortikoide (Kortisol, Kortikosteron) eine wesentliche Rolle während der Unterdrückung einer exzessiven proinflammatorischen Reaktion spielen. Die Nebenniereninsuffizienz tritt in großer Anzahl bei Patienten im septischen Schock auf und ist verantwortlich für die erhöhte Sterblichkeit der an Sepsis Erkrankten. Im Rahmen des angeborenen Immunsystems spielen die sogenannten Toll-like Rezeptoren (TLRs) eine bedeutende Rolle bei der Erkennung von pathogen-assoziierten Molekülen. Interaktionen zwischen dem Immunsystem und dem endokrinen Stresssystem sind bekannt. Demzufolge ist eine gut aufeinander abgestimmte Antwort des adrenalen Systems und des Immunsystems für das Überleben während einer schweren Entzündungsreaktion von besonderer Bedeutung. Die vorliegende Arbeit befasst sich mit der Rolle von TLR-2, TLR-4 und TLR-9 während adrenalem Stress. Die Ergebnisse zeigen, dass das Fehlen von TLR-2 oder TLR-4, aber nicht TLR-9 zur Änderung der Morphologie der Nebennieren, bezüglich ihrer Größe und zellulären Struktur, bei den Mäusen führt. Dennoch scheint diese Änderung den Phänotyp der TLR knock-out Mäuse nicht zu beeinträchtigen. Mäuse mit fehlendem TLR-2, 4 oder 9 sind unfähig, sich adäquat auf einen inflammatorischen Stress, der durch die entsprechenden Liganden Lipopolysaccharid (LPS, TLR-4), Lipoteichonsäure (LTA, TLR-2) oder Cytidin-Phosphat-Guanosin-Oligodeoxynucleotid (CpG-ODN, TLR-9) hervorgerufen wird, zu antworten. Diese verminderte adrenale Stressantwort scheint mit der Abschwächung der systemischen und auch der intra-adrenalen Zytokin-Expressionen einherzugehen. Zusammenfassend deuten diese Ergebnisse darauf hin, dass TLR-2, 4 und 9 Schlüsselrezeptoren in der immun-adrenalen Antwort bei Entzündung und SIRS sind. Das enge funktionale Verhältnis zwischen den beiden Systemen sollte im Rahmen der Behandlung von entzündlichen Krankheiten, bei denen eine intakte adrenale Stressantwort erforderlich ist, berücksichtigt werden. Darüber hinaus könnten TLR Polymorphismen zu den zugrunde liegenden Mechanismen der beeinträchtigten adrenalen Stressantwort bei Patienten mit bakterieller Sepsis beigetragen haben

The relationship of human resource management practices with employee's job satisfaction and turnover rate in Japanese agricultural businesses in Vietnam

岩手大学博士（農学）doctoral thesi

Ứng dụng công nghệ A/O kết hợp màng vi lọc để xử lý nước thải sinh hoạt ở Hà Nội

The study aims to investigate an appropriate wastewater treatment process to treat domestic wastewater in Hanoi City which contain low-strength for COD (120-200 mg/L) but high in nitrogen content (10-40 mg/L). A lab scale anoxic-oxic system with a hollow fiber-Membrane Separation Bioreactor was operated at a flow rate of 5-10 L/h over a period of 150 days. The reactor was operated at different sludge recirculation rates. The MBR maintained relatively constant transmembrane pressure. During 150 days of reactor operation, treated water quality have COD of around 20 mg/L, NH4-N of less than 1 mg/L, NO3-N of less than 5 mg/L. The system shows good and stable efficiency for organic matter and nitrogen removal without adding an external carbon source and coagulants. The results based on the study indicated that the proposed process configuration has potential to treat the low-strength wastewater in Hanoi. Mục tiêu của nghiên cứu là đềxuất được một công nghệhiệu quảvà phù hợp đểxửlý nước thải sinh họat ởcác đô thịcủaViệt nam, là loại nước thải được thu gom từhệthốngthoát nước chung có nồng độchất hữu cơ thấp (COD 120-200 mg/l) nhưng hàm lượng chất dinh dưỡng như Nitơ, Phốt pho khá cao (T-N:10-40 mg/L). Chúng tôi đã nghiên cứu và vận hành chạy thửmô hình xửlý sinh học yếm khí-kỵkhí (AO) kết hợp với màng vi lọc ởquy mô mô hình phòng thí nghiệm (công suất 5-10 L/h) ởcác chếđộcông suất bùn tuần hoàn khác nhau. Kết quảxửlý trong thời gian 5tháng vận hành mô hình cho thấy chất lượng nước thải sau xửlý có hàm lượng COD nhỏhơn 20 mg/L, NH4-N nhỏhơn 1 mg/L, NO3-N nhỏhơn 5 mg/L. Hiệu suất xửlý chất hữu cơ và chất dinh dưỡng rất ổn định và hệthống không phải sửdụng các nguồn bổsung chất hữu cơ hay các hóa chất trợlắng như các công nghệđang áp dụng. Kết quảcho thấy công nghệAO kết hợp màng vi lọc có khảnăng áp dụng thực tế,phù hợp với những nơi có quỹđất nhỏ, chất lượng nước sau xửlý rất cao có thểphục vụcho mục đích tái sửdụng.Mục tiêu của nghiên cứu là đề xuất được một công nghệ hiệu quả và phù hợp để xử lý nước thải sinh họat ở các đô thị của Việt nam, là loại nước thải được thu gom từ hệ thống thoát nước chung có nồng độ chất hữu cơ thấp (COD 120-200 mg/l) nhưng hàm lượng chất dinh dưỡng như Nitơ, Phốt pho khá cao (T-N: 10-40 mg/L). Chúng tôi đã nghiên cứu và vận hành chạy thử mô hình xử lý sinh học yếm khí - kỵ khí (AO) kết hợp với màng vi lọc ở quy mô mô hình phòng thí nghiệm (công suất 5-10 L/h) ở các chế độ công suất bùn tuần hoàn khác nhau. Kết quả xử lý trong thời gian 5 tháng vận hành mô hình cho thấy chất lượng nước thải sau xử lý có hàm lượng COD nhỏ hơn 20 mg/L, NH4-N nhỏ hơn 1 mg/L, NO3-N nhỏ hơn 5 mg/L. Hiệu suất xử lý chất hữu cơ và chất dinh dưỡng rất ổn định và hệ thống không phải sử dụng các nguồn bổ sung chất hữu cơ hay các hóa chất trợ lắng như các công nghệ đang áp dụng. Kết quả cho thấy công nghệ AO kết hợp màng vi lọc có khả năng áp dụng thực tế, phù hợp với những nơi có quỹ đất nhỏ, chất lượng nước sau xử lý rất cao có thể phục vụ cho mục đích tái sử dụng