Caspase-4/11 promotes hyperlipidemia and chronic kidney disease-accelerated vascular inflammation by enhancing trained immunity.

To determine whether hyperlipidemia and chronic kidney disease (CKD) have a synergy in accelerating vascular inflammation via trained immunity (TI), we performed aortic pathological analysis and RNA-Seq of high-fat diet-fed (HFD-fed) 5/6 nephrectomy CKD (HFD+CKD) mice. We made the following findings: (a) HFD+CKD increased aortic cytosolic LPS levels, caspase-11 (CASP11) activation, and 998 gene expressions of TI pathways in the aorta (first-tier TI mechanism); (b) CASP11-/- decreased aortic neointima hyperplasia, aortic recruitment of macrophages, and casp11-gasdermin D-mediated cytokine secretion; (c) CASP11-/- decreased N-terminal gasdermin D (N-GSDMD) membrane expression on aortic endothelial cells and aortic IL-1B levels; (d) LPS transfection into human aortic endothelial cells resulted in CASP4 (human)/CASP11 (mouse) activation and increased N-GSDMD membrane expression; and (e) IL-1B served as the second-tier mechanism underlying HFD+CKD-promoted TI. Taken together, hyperlipidemia and CKD accelerated vascular inflammation by promoting 2-tier trained immunity.

Ectopic parathyroid adenoma on sternocleidomastoid muscle: a case report.

A 54-year-old woman was admitted to the hospital with a left neck mass. Enhanced CT and ultrasound examinations revealed a lesion in the left sternocleidomastoid muscle. The patient undergone right thyroid lobe resection 8 years ago.

Barnes maze test for spatial memory: A new, sensitive scoring system for mouse search strategies.

The Barnes maze is a task used to assess spatial learning and memory in rodents. It requires animals to learn the position of a hole that can be used as an escape from a bright and open arena. The often-used parameters of latency and path length to measure learning and memory do not reflect the different navigation strategies chosen by the animals.

Four-parameter analysis in modified Rotarod test for detecting minor motor deficits in mice.

Background: The Rotarod test with commercial apparatus is widely used to assess locomotor performance, balance and motor learning as well as the deficits resulting from diverse neurological disorders in laboratory rodents due to its simplicity and objectivity. Traditionally, the test ends when rodents drop from the accelerating, turning rod, and the only parameter used commonly is "latency to fall". The values of individual animals can often vary greatly.

The Autoimmune Rheumatic Disease Related Dry Eye and Its Association with Retinopathy.

Dry eye disease is a chronic disease of the ocular surface characterized by abnormal tear film composition, tear film instability, and ocular surface inflammation, affecting 5% to 50% of the population worldwide. Autoimmune rheumatic diseases (ARDs) are systemic disorders with multi-organ involvement, including the eye, and play a significant role in dry eye. To date, most studies have focused on Sjögren's syndrome (one of the ARDs) since it manifests as two of the most common symptoms-dry eyes and a dry mouth-and attracts physicians to explore the relationship between dry eye and ARDs.

Corrigendum: Therapeutic potential of topical administration of acriflavine against hypoxia-inducible factors for corneal fibrosis.

[This corrects the article DOI: 10.3389/fphar.2022.

Development of a Sensitive Enzyme-Linked Immunosorbent Assay with Three Amplification Antibodies to Detect Low-Abundant Mouse Antibodies in the Mouse Central Nervous System.

Recombinant Abs are gaining increasing importance for the treatment of certain cancers or immunological or neurologic disorders. The ELISA is one of the most used analytical tools for detecting and quantifying Abs of interest. However, the performance of ELISAs often varies because of nonstandard experimental procedures as well as inadequate data analysis.

Intranasal delivery of full-length anti-Nogo-A antibody: A potential alternative route for therapeutic antibodies to central nervous system targets.

Antibody delivery to the CNS remains a huge hurdle for the clinical application of antibodies targeting a CNS antigen. The blood-brain barrier and blood-CSF barrier restrict access of therapeutic antibodies to their CNS targets in a major way. The very high amounts of therapeutic antibodies that are administered systemically in recent clinical trials to reach CNS targets are barely viable cost-wise for broad, routine applications.

Spontaneous suprachoroidal and orbital hemorrhage in an older woman associated with prophylactic antiplatelet therapy: A case report and literature review.

An 80-year-old woman presented to our Ophthalmology Clinic for sudden pain and loss of vision in her right eye for seven days. She had a medical history of atrial fibrillation and cardiac valvular disease and received prophylactic antiplatelet therapy for more than ten years. Spontaneous suprachoroidal and orbital hemorrhage and secondary angle-closure glaucoma was diagnosed according to clinical manifestation and confirmed with B-scan ultrasound and Magnetic Resonance Imaging.

Therapeutic potential of topical administration of acriflavine against hypoxia-inducible factors for corneal fibrosis.

Transdifferentiation of keratocytes into fibroblasts or further into myofibroblasts, which produced denser and more disorganized extracellular matrix, is the major cause of corneal fibrosis and scarring, leading to corneal blindness. TGF-β1 is the critical cytokine for the myofibroblast's transdifferentiation and survival. Hypoxia Inducible Factor (HIF) was found to play an important role in promoting fibrosis in lung, kidney, and dermal tissues recently.

Viral keratitis after the second and third doses of inactivated COVID-19 vaccination: A case report.

Rare cases of viral keratitis after coronavirus disease 2019 (COVID-19) vaccination have been reported. Furthermore, to our knowledge, cases of viral keratitis after two rounds of COVID-19 vaccination have not yet been reported. We report the case of a 19-year-old man without a history of keratitis, who developed viral keratitis soon after receiving the second and third doses of inactivated COVID-19 vaccines.

Blocking C3d/GFAP A1 Astrocyte Conversion with Semaglutide Attenuates Blood-Brain Barrier Disruption in Mice after Ischemic Stroke.

Astrocytes play an essential role in the modulation of blood-brain barrier function. Neurological diseases induce the transformation of astrocytes into a neurotoxic A1 phenotype, exacerbating brain injury. However, the effect of A1 astrocytes on the BBB dysfunction after stroke is unknown.

29 mA-RNA Methylation (Epitranscriptomic) Regulators Are Regulated in 41 Diseases including Atherosclerosis and Tumors Potentially via ROS Regulation - 102 Transcriptomic Dataset Analyses.

We performed a database mining on 102 transcriptomic datasets for the expressions of 29 mA-RNA methylation (epitranscriptomic) regulators (mA-RMRs) in 41 diseases and cancers and made significant findings: (1) a few mA-RMRs were upregulated; and most mA-RMRs were downregulated in sepsis, acute respiratory distress syndrome, shock, and trauma; (2) half of 29 mA-RMRs were downregulated in atherosclerosis; (3) inflammatory bowel disease and rheumatoid arthritis modulated mA-RMRs more than lupus and psoriasis; (4) some organ failures shared eight upregulated mA-RMRs; end-stage renal failure (ESRF) downregulated 85% of mA-RMRs; (5) Middle-East respiratory syndrome coronavirus infections modulated mA-RMRs the most among viral infections; (6) proinflammatory oxPAPC modulated mA-RMRs more than DAMP stimulation including LPS and oxLDL; (7) upregulated mA-RMRs were more than downregulated mA-RMRs in cancer types; five types of cancers upregulated ≥10 mA-RMRs; (8) proinflammatory M1 macrophages upregulated seven mA-RMRs; (9) 86% of mA-RMRs were differentially expressed in the six clusters of CD4Foxp3 immunosuppressive Treg, and 8 out of 12 Treg signatures regulated mA-RMRs; (10) immune checkpoint receptors TIM3, TIGIT, PD-L2, and CTLA4 modulated mA-RMRs, and inhibition of CD40 upregulated mA-RMRs; (11) cytokines and interferons modulated mA-RMRs; (12) NF-B and JAK/STAT pathways upregulated more than downregulated mA-RMRs whereas TP53, PTEN, and APC did the opposite; (13) methionine-homocysteine-methyl cycle enzyme Mthfd1 downregulated more than upregulated mA-RMRs; (14) mA writer RBM15 and one mA eraser FTO, H3K4 methyltransferase MLL1, and DNA methyltransferase, DNMT1, regulated mA-RMRs; and (15) 40 out of 165 ROS regulators were modulated by mA eraser FTO and two mA writers METTL3 and WTAP. Our findings shed new light on the functions of upregulated mA-RMRs in 41 diseases and cancers, nine cellular and molecular mechanisms, novel therapeutic targets for inflammatory disorders, metabolic cardiovascular diseases, autoimmune diseases, organ failures, and cancers.

IL-35 promotes CD4+Foxp3+ Tregs and inhibits atherosclerosis via maintaining CCR5-amplified Treg-suppressive mechanisms.

Tregs play vital roles in suppressing atherogenesis. Pathological conditions reshape Tregs and increase Treg-weakening plasticity. It remains unclear how Tregs preserve their function and how Tregs switch into alternative phenotypes in the environment of atherosclerosis.

CcPmk1 is a regulator of pathogenicity in Cytospora chrysosperma and can be used as a potential target for disease control.

Fus3/Kss1, also known as Pmk1 in several pathogenic fungi, is a component of the mitogen-activated protein kinase (MAPK) signalling pathway that functions as a regulator in fungal development, stress response, mating, and pathogenicity. Cytospora chrysosperma, a notorious woody plant-pathogenic fungus, causes canker disease in many species, and its Pmk1 homolog, CcPmk1, is required for fungal development and pathogenicity. However, the global regulation network of CcPmk1 is still unclear.

A Novel Subset of CD95 Pro-Inflammatory Macrophages Overcome miR155 Deficiency and May Serve as a Switch From Metabolically Healthy Obesity to Metabolically Unhealthy Obesity.

Metabolically healthy obesity (MHO) accounts for roughly 35% of all obese patients. There is no clear consensus that has been reached on whether MHO is a stable condition or merely a transitory period between metabolically healthy lean and metabolically unhealthy obesity (MUO). Additionally, the mechanisms underlying MHO and any transition to MUO are not clear.

BM-MSC Transplantation Alleviates Intracerebral Hemorrhage-Induced Brain Injury, Promotes Astrocytes Vimentin Expression, and Enhances Astrocytes Antioxidation via the Cx43/Nrf2/HO-1 Axis.

Intracerebral hemorrhage (ICH) is a particularly severe form of stroke, and reactive astrogliosis is a common response following injury to the central nervous system (CNS). Mesenchymal stem cells (MSCs) are reported to promote neurogenesis and alleviate the late side effects in injured brain regions. Gap junctions (Gjs) are abundant in the brain, where the richest connexin (Cx) is Cx43, most prominently expressed in astrocytes.

Farnesoid X receptor knockout protects brain against ischemic injury through reducing neuronal apoptosis in mice.

Background: Farnesoid X receptor (FXR) is a nuclear receptor that plays a critical role in controlling cell apoptosis in diverse diseases. Previous studies have shown that knocking out FXR improved cardiac function by reducing cardiomyocyte apoptosis in myocardial ischemic mice. However, the role of FXR after cerebral ischemia remains unknown.

Ly6C Inflammatory Monocyte Differentiation Partially Mediates Hyperhomocysteinemia-Induced Vascular Dysfunction in Type 2 Diabetic db/db Mice.

Objective: Hyperhomocysteinemia (HHcy) is a potent risk factor for diabetic cardiovascular diseases. We have previously reported that hyperhomocysteinemia potentiates type 1 diabetes mellitus-induced inflammatory monocyte differentiation, vascular dysfunction, and atherosclerosis. However, the effects of hyperhomocysteinemia on vascular inflammation in type 2 diabetes mellitus (T2DM) and the underlying mechanism are unknown.

L-glutamine protects mouse brain from ischemic injury via up-regulating heat shock protein 70.

Introduction: L-glutamine is an antioxidant that plays a role in a variety of biochemical processes. Given that oxidative stress is a key component of stroke pathology, the potential of L-glutamine in the treatment of ischemic stroke is worth exploring.

Aims: In this study, we investigated the effect and mechanisms of action of L-glutamine after cerebral ischemic injury.

Evaluating the sustainable traffic flow operational features of an exclusive spur dike U-turn lane design.

The traditional U-turn design has significantly improved traffic operations for relieving traffic congestion. However, the U-turn diversion and merge segments still cause traffic conflicts and delays. In this paper, an exclusive spur dike U-turn lane (ESUL) is proposed with the aim of addressing the disadvantages of the traditional U-turn design.

Hyperhomocysteinemia potentiates diabetes-impaired EDHF-induced vascular relaxation: Role of insufficient hydrogen sulfide.

Unlabelled: Insufficient hydrogen sulfide (HS) has been implicated in Type 2 diabetic mellitus (T2DM) and hyperhomocysteinemia (HHcy)-related cardiovascular complications. We investigated the role of HS in T2DM and HHcy-induced endothelial dysfunction in small mesenteric artery (SMA) of db/db mice fed a high methionine (HM) diet. HM diet (8 weeks) induced HHcy in both T2DM db/db mice and non-diabetic db/+ mice (total plasma Hcy: 48.

MicroRNA-155 Deficiency Leads to Decreased Atherosclerosis, Increased White Adipose Tissue Obesity, and Non-alcoholic Fatty Liver Disease: A NOVEL MOUSE MODEL OF OBESITY PARADOX.

Obesity paradox (OP) describes a widely observed clinical finding of improved cardiovascular fitness and survival in some overweight or obese patients. The molecular mechanisms underlying OP remain enigmatic partly due to a lack of animal models mirroring OP in patients. Using apolipoprotein E knock-out (apoE) mice on a high fat (HF) diet as an atherosclerotic obesity model, we demonstrated 1) microRNA-155 (miRNA-155, miR-155) is significantly up-regulated in the aortas of apoE mice, and miR-155 deficiency in apoE mice inhibits atherosclerosis; 2) apoE/miR-155 (double knock-out (DKO)) mice show HF diet-induced obesity, adipocyte hypertrophy, and present with non-alcoholic fatty liver disease; 3) DKO mice demonstrate HF diet-induced elevations of plasma leptin, resistin, fed-state and fasting insulin and increased expression of adipogenic transcription factors but lack glucose intolerance and insulin resistance.

Mitochondrial Reactive Oxygen Species Mediate Lysophosphatidylcholine-Induced Endothelial Cell Activation.

Objective: Hyperlipidemia-induced endothelial cell (EC) activation is considered as an initial event responsible for monocyte recruitment in atherogenesis. However, it remains poorly defined what is the mechanism underlying hyperlipidemia-induced EC activation. Here, we tested a novel hypothesis that mitochondrial reactive oxygen species (mtROS) serve as signaling mediators for EC activation in early atherosclerosis.