Prophylactic and therapeutic effects of EsV3 on atherosclerotic lesions in ApoE mice.

Background: Atherosclerosis (AS) is a major contributor to vascular disorders and represents a significant risk to human health. Currently, first-line pharmacotherapies are associated with substantial side effects, and the development of atherosclerosis is closely linked to dietary factors. This study evaluated the effects of a dietary supplement, EsV3, on AS in apolipoprotein E (ApoE) model mice.

Early effects of LT3 + LT4 combination therapy on quality of life in hypothyroid patients: a randomized, double-blind, parallel-group comparison trial.

Background: This study aimed to evaluate the impact of combined levothyroxine (LT4) and triiodothyronine (LT3) therapy on quality of life in patients with primary hypothyroidism.

Methods: In a randomized, double-blind, parallel-group trial, 151 Iranian patients diagnosed with primary hypothyroidism between 2020 and 2021 were enrolled. One group received LT4 alone (n = 80), while the other received LT4 and LT3 (n = 71) for a minimum of six months.

Rationale and design of the multicenter, national, randomized, open labeled phase III trial: allogeneic stem cell transplantation as a potential curative treatment for patients with relapsed or progressed multiple myeloma (AlloRelapseMM Study).

Background: Even though major improvements have been made in the treatment of myeloma, the majority of patients eventually relapse or progress. Patients with multiple myeloma who relapse after initial high-dose chemotherapy with autologous stem cells have a median progression free survival up to 2-3 years, depending on risk factors such as previous remission duration. In recent years, growing evidence has suggested that allogeneic stem cell transplantation could be a promising treatment option for patients with relapsed or progressed multiple myeloma.

Rescue RM/CS-AKI by blocking strategy with one-dose anti-myoglobin RabMAb.

Rhabdomyolysis or Crush syndrome-related AKI (RM/CS-AKI) has high mortality, and there is no effective early on-site treatment method. The critical pathogenic factor of RM/CS-AKI is the excessive free myoglobin (Mb) in blood circulation. Here, based on the concept of creating a "mobile barrier", we develop an anti-Mb rabbit monoclonal antibody (RabMAb) with high specificity, affinity, stability, and broad species reactivity.

Development and validation of a prognostic nomogram for predicting of patients with acute sedative-hypnotic overdose admitted to the intensive care unit.

To develop and evaluate a predictive model for intensive care unit (ICU) admission among patients with acute sedative-hypnotic overdose. We conducted a retrospective analysis of patients admitted to the emergency department of West China Hospital, Sichuan University, between October 11, 2009, and December 31, 2023. Patients were divided into ICU and non-ICU groups based on admission criteria including the need for blood purification therapy, organ support therapy (ventilatory support, vasoactive drugs, renal replacement therapy, artificial liver), or post-cardiopulmonary resuscitation.

Isovitexin targets SIRT3 to prevent steroid-induced osteonecrosis of the femoral head by modulating mitophagy-mediated ferroptosis.

The death of osteoblasts induced by glucocorticoid (GC)-mediated oxidative stress plays a crucial role in the development of steroid-induced osteonecrosis of the femoral head (SIONFH). Improving bone formation driven by osteoblasts has shown promising outcomes in the prognosis of SIONFH. Isovitexin has demonstrated antioxidant properties, but its therapeutic effects on GC-induced oxidative stress and SIONFH remain unexplored.

Induction of IMPDH-Based Cytoophidia by a Probable IMP-Dependent ARL13B-IMPDH Interaction.

Inosine Monophosphate Dehydrogenase (IMPDH) catalyzes rate-limiting step of the reaction converting inosine monophosphate (IMP) to guanine nucleotides. IMPDH is up-regulated in the healthy proliferating cells and also in tumor cells to meet their elevated demand for guanine nucleotides. An exclusive regulatory mechanism for this enzyme is filamentation, through which IMPDH can resist allosteric inhibition by the end product, GTP.

Effect of 8-Oxo-1,-Ethenoadenine Derivatives on the Activity of RNA Polymerases from SARS-CoV-2 and .

Bacterial and viral RNA polymerases are promising targets for the development of new transcription inhibitors. One of the potential blockers of RNA synthesis is 7,8-dihydro-8-oxo-1,-ethenoadenine (oxo-εA), a synthetic compound that combines two adenine modifications: 8-oxoadenine and 1,-ethenoadenine. In this study, we synthesized oxo-εA triphosphate (oxo-εATP) and showed that it could be incorporated by the RNA-dependent RNA polymerase of SARS-CoV-2 into synthesized RNA opposite template residues A and G in the presence of Mn ions.

Combination of Carbonic Anhydrase Isoform IX Inhibitors and Gefitinib Suppresses on the Invasive Potential of Non-Small Cell Lung Cancer Cells.

Human carbonic anhydrase IX (CAIX) plays a key role in maintaining pH homeostasis of malignant neoplasms, thus creating a favorable microenvironment for the growth, invasion, and metastasis of tumor cells. Recent studies have established that inhibition of CAIX expressed on the surface of tumor cells significantly increases the efficacy of classical chemotherapeutic agents and makes it possible to suppress the resistance of tumor cells to chemotherapy, as well as to increase their sensitivity to drugs (in particular, to reduce the required dose of cytostatic agents). In this work, we studied the ability of new CAIX inhibitors based on substituted 1,2,4-oxadiazole-containing primary aromatic sulfonamides, to potentiate the cytostatic effect of gefitinib (selective inhibitor of epidermal growth factor receptor tyrosine kinase domain) under hypoxic conditions.

Auxin Triggers AHR Pathway Activation in the Auxin-Inducible Degron System in Mammalian Cells.

The auxin-inducible degron (AID) system is widely used to study function of various proteins. The plant hormone auxin is used as an inducer in this system, which easily penetrates into the cells and causes proteasomal degradation of the protein of interest fused to a small degron tag. It is often assumed that as a plant hormone, auxin does not significantly affect physiology of animal cells.

Activation of P38 MAPK Signaling Cascade is Linked with Clinical Outcomes and Therapeutic Responses in Human Cancers.

Activation of the p38 mitogen-activated protein kinase (MAPK) pathways is vital in regulating cell growth, differentiation, apoptosis, and stress response, significantly affecting tumorigenesis and cancer progression. We developed a bioinformatic technique to construct an interactome network-based molecular pathways for genes of interest and quantify their activation levels using high-throughput gene expression data. This study is focused on the p38α, p38β, p38γ, and p38δ kinases, examining their activation levels (PALs) based on transcriptomic data and their associations with survival and drug responsiveness across various cancer types.

Exposure to Group B Streptococcus-induced chorioamnionitis alters the proteome of placental extracellular vesicles.

Introduction: Group B Streptococcus (GBS) is an opportunistic pathogen that can induce chorioamnionitis (CA), increasing the risk of neurodevelopmental disorders (NDDs) in the offspring. The placenta facilitates maternal-fetal communication through the release of extracellular vesicles (EVs), which may carry inflammatory molecules such as interleukin (IL)-1. Although the role of EVs in immune modulation is well established, their specific characterization in the context of GBS-induced CA has not yet been investigated.

Identifying Preferred Features of Influenza Vaccination Programs Among Chinese Clinicians Practicing Traditional Chinese Medicine and Western Medicine: Discrete Choice Experiment.

Background: Achieving high vaccine coverage among clinicians is crucial to curb the spread of influenza. Traditional Chinese medicine (TCM), rooted in cultural symbols and concepts without direct parallels in modern Western medicine, may influence perspectives on vaccination. Therefore, understanding the preferences of TCM clinicians towards influenza vaccines is of great importance.

Hypothalamic neural circuits regulating energy expenditure.

The hypothalamus plays a central role in regulating energy expenditure and maintaining energy homeostasis, crucial for an organism's survival. Located in the ventral diencephalon, it is a dynamic and adaptable brain region capable of rapid responses to environmental changes, exhibiting high anatomical and cellular plasticity and integrates a myriad of sensory information, internal physiological cues, and humoral factors to accurately interpret the nutritional state and adjust food intake, thermogenesis, and energy homeostasis. Key hypothalamic nuclei contain distinct neuron populations that respond to hormonal, nutrient, and neural inputs and communicate extensively with peripheral organs like the gastrointestinal tract, liver, pancreas, and adipose tissues to regulate energy production, storage, mobilization, and utilization.

Combined irradiation by gamma-rays and carbon-12 nuclei caused hyperlocomotion and change in striatal metabolism of rats.

Exposure to ionizing radiation during manned deep space missions to Mars could lead to functional impairments of the central nervous system, which may compromise the success of the mission and affect the quality of life for returning astronauts. Along with radiation-induced changes in cognitive abilities and emotional status, the effects of increased motor activity were observed. The mechanisms behind these phenomena still remain unresolved.

Dose measurements with the Pille-ISS thermoluminescent dosimeter system during extravehicular activities (2004-2022).

One of the most problematic goals for radiation safety during spaceflight is an assessment of additional doses received by astronauts during extravehicular activity (EVA). The Pille-ISS thermoluminescent dosimeter developed by the predecessor of the Hungarian Research Network (HUN-REN) Centre for Energy Research (Budapest, Hungary) is designed for the routine dose measurements not only inside the spacecraft compartments, but also for personal dosimetric control for EVA. During almost two decades of the International Space Station (ISS) operation, the unique set of 131 EVA doses were recorded in different conditions, such as: solar activity, ISS trajectory along the South Atlantic Anomaly (SAA), and shielding conditions provided by two kinds of spacesuits: the Extravehicular Mobility Unit (EMU) and Orlan.

Sex-specific effects on the heart from combined exposure to simulated galactic cosmic radiation and hindlimb unloading.

Future long duration space missions will expose astronauts to higher doses of galactic cosmic radiation (GCR) than those experienced on the international space station. Recent studies have demonstrated astronauts may be at risk for cardiovascular complications due to increased radiation exposure and fluid shift from microgravity. However, there is a lack of direct evidence on how the cardiovascular system is affected by GCR and microgravity since no astronauts have been exposed to exploratory mission relevant GCR doses.

The Effects of Cosmic Radiation Exposure on Pregnancy During a Probable Manned Mission to Mars.

Space missions have revealed certain disincentive factors of this unique environment, such as microgravity, cosmic radiation, etc., as the aerospace industry has made substantial progress in exploring deep space and its impacts on human body. Galactic cosmic radiation (GCR), a form of ionizing radiation, is one of those environmental factors that has potential health implications and, as a result, may limit the duration - and possibly the occurrence - of deep-space missions.

The hypercapnic environment on the International Space Station (ISS): A potential contributing factor to ocular surface symptoms in astronauts.

With increasing advancements and efforts towards space exploration, there is a pressing need to understand the impacts of spaceflight on astronauts' health. Astronauts have reported signs and symptoms of dry eye disease upon traveling to the International Space Station (ISS), thus necessitating an evaluation of the factors that contribute to the onset of spaceflight associated dry eye disease. Prior literature describes the hypercapnic environment of the ISS; however, the link between the high CO levels and astronauts' symptoms of dry eye disease remains unexplored.

Epigenetic modulation of doxorubicin resistance and strategies for enhancing chemotherapeutic sensitivity.

With the rising global cancer burden, the dependency on chemotherapy also rises along with the complication of chemoresistance development. Studies on multi-drug resistant proteins provide a wide range of regulators, although the exact mechanism is not yet clearly understood. Epigenetic modifications play a vital role in the regulation of cellular processes and also in determining the efficacy of cancer therapy by modulating resistance development and tumor progression.

The translational potential of epigenetic modulatory bioactive phytochemicals as adjuvant therapy against cancer.

In preclinical studies, bioactive phytochemicals have shown enormous potential therapeutic efficacy against various human malignancies. These natural compounds have been shown to possess an inherent potential to alter the molecular signaling pathways and epigenetic modulatory activity involved in multiple physiological functions. Recently, epigenetic therapy has emerged as an important therapeutic modality due to the reversible nature of epigenetic alterations.

Role of miRNAs as epigenetic regulators of immune checkpoints in lung cancer immunity.

The advent of immunotherapy in cancer has provided new avenues in the treatment of many malignancies at various stages. Specifically, immune checkpoint inhibitors (ICIs) have transformed the field of lung cancer treatment. However, since some tumors can evade the immune system, not all patients respond properly.

Plasma membrane-coated nanoparticles and membrane vesicles to orchestrate multimodal antitumor immunity.

Background: A number of immunotherapeutic approaches have been developed and are entering the clinic. Bispecific antibodies (BsAbs) are one of these modalities and induce robust efficacy by endogenous T cells in several hematological malignancies. However, most of the treated patients experience only a temporary benefit.