Double-hit

Salt stress significantly impacts the functions of the photosynthetic apparatus, with varying degrees of damage to its components. Photosystem II (PSII) is more sensitive to environmental stresses, including salinity, than photosystem I (PSI). This study investigated the effects of different salinity levels (0 to 200 mM NaCl) on the PSII complex in isolated thylakoid membranes from hydroponically grown pea ( Pisum sativum L.) and maize ( Zea mays L.) plants treated with NaCl for 5 days. The data revealed that salt stress inhibits the photochemical activity of PSII (H2 O → BQ), affecting the energy transfer between the pigment-protein complexes of PSII (as indicated by the fluorescence emission ratio F695 /F685 ), QA reoxidation, and the function of the oxygen-evolving complex (OEC)...

Objective: To investigate the prognostic value of the Second Revision of the International Staging System (R2-ISS) in patients with newly diagnosed multiple myeloma (NDMM) . Methods: The retrospective study was performed in 326 NDMM patients with immunomodulatory drugs and/or proteasome inhibitors as the first-line treatment attending the Department of Hematology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China, from December 2012 to March 2022. The Kaplan-Meier method was used for the survival analysis, with the Log-rank test comparing the between-group differences and Cox proportional risk regression modeling A multifactorial analysis was performed...

BACKGROUND: Autologous stem-cell transplantation (ASCT) remains a beneficial approach for patients with newly diagnosed multiple myeloma (NDMM) in the age of novel therapeutic agents. Nevertheless, limited real-world data is available to establish criteria for identifying high-risk ASCT patients. METHODS: We analyzed outcomes for 168 NDMM patients who underwent ASCT at our center from December 2015 to December 2022. We investigated the impact of the number of high-risk cytogenetics (HRCA), defined as t(4;14), t(14;16), 1q21 gain/amplification, and del(17p), as well as the post-ASCT minimal residual disease (MRD) status as prognostic indicators...

MYC-rearranged B-cell lymphoma (BCL) in the pediatric/young adult (YA) age group differs substantially in disease composition from adult cohorts. However, data regarding the partner genes, concurrent rearrangements, and ultimate diagnoses in these patients is scarce compared to that in adult cohorts. We aimed to characterize the spectrum of MYC-rearranged (MYC-R) mature, aggressive BCL in the pediatric/YA population. A retrospective study of morphologic, immunophenotypic, and fluorescence in situ hybridization (FISH) results of patients age ≤ 30 years with suspected Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBCL), and a MYC-R by FISH between 2013-2022 was performed...

Non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of lymphoproliferative disorders originating from B, T, or NK lymphocytes. They represent approximately 4-5% of new cancer cases and are classified according to the revised WHO system based on cell lineage, morphology, immunophenotype, and genetics. Diagnosis requires adequate biopsy material, though integrated approaches are used for leukemic presentations. Molecular profiling is improving classification and identifying prognostic markers. Indolent NHLs, such as follicular lymphoma and marginal zone lymphoma, typically pursue a non-aggressive clinical course with long survival...

The Orthopoxvirus genus, especially variola virus (VARV), monkeypox virus (MPXV), remains a significant public health threat worldwide. The development of therapeutic antibodies against orthopoxviruses is largely hampered by the high cost of antibody engineering and manufacturing processes. mRNA-encoded antibodies have emerged as a powerful and universal platform for rapid antibody production. Herein, by using the established lipid nanoparticle (LNP)-encapsulated mRNA platform, we constructed four mRNA combinations that encode monoclonal antibodies with broad neutralization activities against orthopoxviruses...

Careful microscopic observation of histopathological specimens, accumulation of large numbers of high-quality tissue specimens, and analysis of molecular pathology in relation to morphological features are considered to yield realistic data on the nature of multistage carcinogenesis. Since the morphological hallmark of cancer is disruption of the normal histological structure maintained through cell-cell adhesiveness and cellular polarity, attempts have been made to investigate abnormalities of the cadherin-catenin cell adhesion system in human cancer cells...

Mutations of the FBN1 gene lead to Marfan syndrome (MFS), which is an autosomal dominant connective tissue disorder featured by thoracic aortic aneurysm risk. There is currently no effective treatment for MFS. Here, we studied the role of mitochondrial dysfunction in the phenotypic transformation of human smooth muscle cells (SMCs) and whether a mitochondrial boosting strategy can be a potential treatment. We knocked down FBN1 in SMCs to create an MFS cell model and used rotenone to induce mitochondrial dysfunction...

Maternal obesity (MO) is a significant cause of increased cardiometabolic risk in offspring, who present endothelial dysfunction at birth. Alterations in physiologic and cellular redox status are strongly associated with altered gene regulation in arterial endothelium. However, specific mechanisms by which the pro-oxidant fetal environment in MO could modulate the vascular gene expression and function during the offspring's postnatal life are elusive. We tested if oxidative stress could reprogram the antioxidant-coding gene's response to a pro-oxidant challenge through an epigenetic transcriptional memory (ETM) mechanism...

It has been convincingly demonstrated in recent years that isolated acute brain injury (ABI) may cause severe dysfunction of peripheral extracranial organs and systems. Of all potential target organs and systems, the lung appears to be the most vulnerable to damage after ABI. The pathophysiology of the bidirectional brain-lung interactions is multifactorial and involves inflammatory cascades, immune suppression, and dysfunction of the autonomic system. Indeed, the systemic effects of inflammatory mediators in patients with ABI create a systemic inflammatory environment ("first hit") that makes extracranial organs vulnerable to secondary procedures that enhance inflammation, such as mechanical ventilation (MV), surgery, and infections ("second hit")...

High-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements are known for their aggressive clinical course and so are the ones with MYC and BCL2 protein overexpression. The optimal therapy for these lymphomas remains to be elucidated. A retrospective analysis of all diffuse large B-cell lymphomas and high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements diagnosed between 2017 and 2021 at the Institute of Oncology Ljubljana, Slovenia, has been performed. Only patients with double-expressor lymphoma (DEL), double-hit lymphoma (DHL), or triple-hit lymphoma (THL) were included...

Plasmablastic transformation of follicular lymphoma is very rare and has been reported in only 5 cases till date. We report a case of simultaneous identification of extranodal, soft tissue plasmablastic lymphoma in the ankle and bone marrow involvement by follicular lymphoma. This unusual case presentation is a challenge for the treating physician with the patient becoming resistant to chemotherapy and succumbing to the disease within a few months of diagnosis. These cases are known to have an aggressive clinical course with very poor prognosis and survival rate of less than 6 months...

BACKGROUND: Proinflammatory cytokines powerfully induce the rate-limiting enzyme indoleamine 2, 3-dioxygenase-1 (IDO-1) in dendritic cells (DCs) and monocytes, it converts tryptophan (Trp) into L-kynurenine (KYN), along the kynurenine pathway (KP). This mechanism represents a crucial innate immunity regulator that can modulate T cells. This work explores the role of IDO1 in lymphocyte proliferation within a specific pro-inflammatory milieu. METHODS: PBMCs were isolated from buffy coats taken from healthy blood donors and exposed to a pro-inflammatory milieu triggered by a double-hit stimulus: lipopolysaccharide (LPS) plus anti-CD3/CD28...

Neurodevelopmental disorders (NDs) are neuropsychiatric conditions affecting central nervous system development, characterized by cognitive and behavioural alterations. Inflammation has been recently linked to NDs. Animal models are essential for understanding their pathophysiology and identifying therapeutic targets. Double-hit models can reproduce neurodevelopmental and neuroinflammatory impairments. Sixty-seven newborn rats were assigned to four groups: Control, Maternal deprivation (MD, 24-h-deprivation), Isolation (Iso, 5 weeks), and Maternal deprivation ​+ ​Isolation (MD ​+ ​Iso, also known as double-hit)...

BACKGROUND: Early life stress is a major risk factor for later development of psychiatric disorders, including post-traumatic stress disorder (PTSD). An intricate relationship exists between various neurotransmitters (such as glutamate, norepinephrine or serotonin), calcium/calmodulin-dependent protein kinase II (CaMKII), as an important regulator of glutamatergic synaptic function, and PTSD. Here, we developed a double-hit model to investigate the interaction of maternal deprivation (MD) as an early life stress model and single prolonged stress (SPS) as a PTSD model at the behavioral and molecular levels...

Purpose: We constructed biomimetic nanoparticles with biocompatible, tumor-targeting, laser-responsive properties for ferroptosis-induced colorectal cancer chemo-photothermal therapy, with the aim to realize double-hit ferroptosis treatment for colorectal cancer. Methods: The nanoparticles were prepared by first loading the chemotherapy drug bufotalin (CS-5) with Prussian blue (PB), then combining a hybridized erythrocyte-tumor membrane (M) with PB@CS-5 to produce PB@CS-5@M. The chemo-photothermal therapy efficiency of PB@CS-5@M was tested by in vitro and in vivo experiments...

There is limited experimental evidence on the biochemical consequences of aluminium (Al) and cadmium (Cd) co-exposures during pregnancy and postnatal life.This study investigated the impacts of perinatal Al chloride (AlCl3 ) and Cd chloride (CdCl2 ) co-exposures on neuroendocrine functions in mice offspring during postnatal life. The study comprised of four pregnant experimental groups. Group 1 received AlCl3 (10 mg/kg), group 2 were administered CdCl2 (1.5 mg/kg), while group 3 received both AlCl3 (10 mg/kg) and CdCl2 (1...

MYC translocation occurs in 8-14% of diffuse large B-cell lymphoma (DLBCL), and may concur with BCL2 and/or BCL6 translocation, known as double-hit (DH) or triple-hit (TH). DLBCL-MYC/BCL2-DH/TH are largely germinal centre B-cell like subtype, but show variable clinical outcome, with IG::MYC fusion significantly associated with inferior survival. While DLBCL-MYC/BCL6-DH are variable in their cell-of-origin subtypes and clinical outcome. Intriguingly, only 40-50% of DLBCL with MYC translocation show high MYC protein expression (>70%)...

BACKGROUND: Economic stress can serve as a "second-hit" for those who already accumulated a history of adverse life experiences. How one recovers from a setback is a core feature of resilience but is seldom captured in animal studies. METHODS: We challenged mice in a novel two-hit stress model by first exposing animals to chronic social defeat stress and then testing adaptations to increasing reward-scarcity on a neuroeconomic task. Mice were tested across months on the Restaurant Row task during which mice foraged daily for their primary source of food while on a limited time-budget in a closed-economy system...

BACKGROUND: There is paucity of data regarding outcomes of children, adolescents and young adults (CAYA) patients with non-Hodgkin lymphoma (NHL) undergoing autologous stem cell transplantation (ASCT). METHODS: Patients aged 0-39 years undergoing first ASCT for NHL at MD Anderson Cancer Center between 2000 and 2020 were analyzed. RESULTS: Two hundred twenty-one patients were included in the analysis, 129 (58%) were male and the median age was 32 (range 6-39) years...