• cardiac Surgery
• inflammation
• postoperative complications
• sex differences
• systemic inflammatory response syndrome

• Humans
• Female
• Male
• Systemic Inflammatory Response Syndrome/epidemiology
• Retrospective Studies
• Aged
• Middle Aged
• Sex Factors
• Cardiac Surgical Procedures/adverse effects
• Risk Factors
• Cardiopulmonary Bypass/adverse effects
• Risk Assessment
• Postoperative Complications/epidemiology
• Postoperative Complications/etiology
• Treatment Outcome
• Health Status Disparities
• Time Factors

• C57BL/6 mice
• caerulein
• immunohistochemistry
• macrophages
• pancreatitis
• polarization
• sex

• cardiovascular disease
• estrogen
• gut inflammation
• inflammation
• osteoporosis

• Animals
• Mice
• Cardiomyopathies
• Estrogens
• Inflammation/genetics
• Interleukin-10/genetics
• Mice, Inbred C57BL
• Mice, Knockout
• RNA, Messenger/genetics
• RNA, Messenger/metabolism

• OKL03104 OSU | Oklahoma Agricultural Experiment Station (OAES)
• OKL03105 OSU | Oklahoma Agricultural Experiment Station (OAES)
• 1 #x2010;156560 Oklahoma State University, Jim and Lynn Williams Professorship
• OSU | Oklahoma Agricultural Experiment Station (OAES)
• Oklahoma State University, Jim and Lynn Williams Professorship

• T cells
• aging
• inflammation
• leukocyte trafficking
• sexual dimorphism

• Male
• Female
• Animals
• Mice
• Peritoneal Cavity
• Leukocytes
• Inflammation
• Peritoneum
• Chemotactic Factors

• FS/20/2/34799 British Heart Foundation
• MR/P021220/1 Medical Research Council
• MR/T028025/1 Medical Research Council
• Versus Arthritis
• Royal Society
• a Royal Society Dorothy Hodgkin Fellowship
• a Birmingham Fellowship to A.J.I.

• nuclear receptors
• type 2 diabetes

• Animals
• Female
• Male
• Mice
• Endothelial Cells
• Estrogen Receptor alpha
• Glucose
• Insulin
• Muscle, Skeletal
• Receptors, Estrogen

• R37 DK015556 NIDDK NIH HHS
• R01 EB025841 NIBIB NIH HHS
• R01 DK015556 NIDDK NIH HHS
• T32 HL098040 NHLBI NIH HHS
• R01 HL144572 NHLBI NIH HHS
• R01 CA220284 NCI NIH HHS
• R01 DK126833 NIDDK NIH HHS
• R01 DK110127 NIDDK NIH HHS
• S10 OD021685 NIH HHS
• U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
• American Heart Association (American Heart Association, Inc.)
• Breast Cancer Research Foundation (BCRF)
• U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases)
• U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)
• U.S. Department of Health & Human Services | NIH | National Institute of Biomedical Imaging and Bioengineering (NIBIB)

• ApoE-deficient mice
• Atherosclerosis
• Cholesterol
• Linoleic acid
• Pro-inflammation

• contextual fear
• donepezil
• scopolamine
• sex dimorphism
• spatial memory
• weight drop TBI

• biological sex
• central nervous system
• experimental autoimmune encephalomyelitis
• pregnancy
• sex chromosomes
• sex hormones

• Pregnancy
• Animals
• Female
• Male
• Encephalomyelitis, Autoimmune, Experimental
• Multiple Sclerosis
• Central Nervous System
• Antigens/therapeutic use
• Adjuvants, Immunologic/therapeutic use

• National Health and Medical Research Council

• Depressive symptoms
• General middle-aged and older adults
• Lung function
• Peak expiratory flow (PEF)

• estrogens
• oncogenes
• reactive oxygen species (ROS)
• sex bias
• thyroid cancer

• UTI
• autoimmune hepatitis
• environment
• infection
• oestrogen
• vaccine

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory autoimmune disease that affects about 1% of the global population, with a female–male ratio of 3:1. RA preferably affects the joints, with consequent joint swelling and deformities followed by ankylosis. However, evidence has accumulated showing that patients suffering from RA can also develop extra-articular manifestations, including cardiovascular disease states, neuropathies, and multiorgan dysfunction. In particular, peripheral nerve disorders showed a consistent impact in the course of the disease (prevalence about 20%) mostly associated to vasculitis of the nerve vessels leading to vascular ischemia, axonal degeneration, and neuronal demyelination. The pathophysiological basis of this RA-associated microvascular disease, which leads to impairment of assonal functionality, is still to be better clarified. However, endothelial dysfunction and alterations of the so-called brain-nerve barrier (BNB) seem to play a fundamental role. This review aims to assess the potential mechanisms underlying the impairment of endothelial cell functionality in the development of RA and to identify the role of dysfunctional endothelium as a causative mechanism of extra-articular manifestation of RA. On the other hand, the potential impact of lifestyle and nutritional interventions targeting the maintenance of endothelial cell integrity in patients with RA will be discussed as a potential option when approaching therapeutic solutions in the course of the disease.

• endothelial dysfunction
• inflammation
• neurological extra-articular manifestations
• polyphenols and Mediterranean diet
• rheumatoid arthritis

Staphylococcus aureus infections remain associated with considerable morbidity and mortality in both hospitals and the community. There is little information regarding the role of ovarian hormones in infections caused by S. aureus. The aim of this study was to evaluate the effects of ovariectomy in the immune response induced by S. aureus.

Female mice BALB/c were ovariectomized (OVX) to significantly reduce the level of ovarian hormones. We also used sham-operated animals. The mice were inoculated intraperitoneally with S. aureus. Blood samples were collected for leukocyte count and bacterial quantification. The uterus and spleen were removed and weighed to calculate the uterine and splenic indexes. Lungs were removed and fractionated for immunohistochemical analysis for macrophage detection (anti-CD68) and relative gene expression of IL-6, IL-1β and TNF-α by RT-PCR.

Ovariectomy enlarged spleen size and generally increased circulating lymphocytes. OVX females experienced a continuation of the initial reduction of lymphocytes and a monocyte and neutrophil late response compared to shams (p ≥ 0.05). Moreover, OVX females showed neutropenia after 168 h of infection (p ≥ 0.05). Macrophage response in the lungs were less pronounced in OVX females in the initial hours of infection (p ≥ 0.01). OVX females showed a higher relative gene expression of IL-1β, IL-6 and TNF-α in the lung at the beginning of the infection compared to sham females (p ≥ 0.01). Among the uninfected females, the OVX control females showed a higher expression of IL-6 in the lung compared to the sham control females (p ≥ 0.05). In this model, the lack of ovarian hormones caused a minor increase in circulating leukocytes during the initial stage of infection by S. aureus and increased pulmonary gene expression of IL-1β, IL-6, and TNF-α. Ovariectomy alone enlarged the spleen and increased circulating lymphocytes. Ovarian hormones acted as immunoprotectors against S. aureus infection.

• GSK3
• adipose tissue
• inflammation
• macrophages
• obesity

• Cerebrovascular disease
• Dementia
• Sex differences
• Sex hormones
• Stroke
• Vascular

• analgesics
• glia
• opioids
• pain

To address the hypothesis that young, gonad-intact female mice have improved long-term recovery associated with decreased neuroinflammation compared to male mice.

Eight to ten week-old male, female, and ovariectomized (OVX) mice underwent closed cranial impact. Gonad-intact female mice were injured only in estrus state. After injury, between group differences were assessed using complementary immunohistochemical staining for microglial cells at 1 h, mRNA polymerase chain reaction for inflammatory markers at 1 h after injury, Rotarod over days 1-7, and water maze on days 28-31 after injury.

Male mice had a greater area of injury (P = 0.0063), F4/80-positive cells (P = 0.032), and up regulation of inflammatory genes compared to female mice. Male and OVX mice had higher mortality after injury when compared to female mice (P = 0.043). No group differences were demonstrated in Rotarod latencies (P = 0.62). OVX mice demonstrated decreased water maze latencies compared to other groups (P = 0.049).

Differences in mortality, long-term neurological recovery, and markers of neuroinflammation exist between female and male mice after moderate traumatic brain injury (MTBI). Unexpectedly, OVX mice have decreased long term neurological function after MTBI when compared to gonad intact male and female mice. As such, it can be concluded that the presence of female gonadal hormones may influence behavioural outcomes after MTBI, though mechanisms involved are unclear.

• Traumatic brain injury
• Microglia
• Functional recovery
• Inflammation
• Sex

• Estrogen receptors
• Immune system
• Sex hormones
• Teleosts
• microRNAs

• Animals
• Estrogens/metabolism
• Fishes/genetics
• Fishes/immunology
• Gene Expression Regulation
• Immune System/immunology

• Annexin A1
• Blood–brain barrier
• Inflammation
• Metabolism
• Multiple sclerosis
• Stroke

• Fondazione Italiana Sclerosi Multipla
• Society for Endocrinology
• Ministério da Educação (BR) CAPES
• Regional Technology Clusters, Regione Puglia 2015
• FCRP-Fondazione Cassa di Risparmio di Puglia

• coronary microvascular disorder
• cytochrome P-450 2C19
• genetic polymorphism
• low-grade inflammation
• sex difference

• Anxiety
• Glucose intolerance
• Hepatic inflammation
• High-fat diet
• Hypoactivity
• Insulin sensitivity

• COX-2
• EGFR
• GPR30
• Oviductal epithelial cells
• Src kinase

• Animals
• Cyclooxygenase 2/metabolism
• Epithelial Cells/cytology
• Epithelial Cells/metabolism
• ErbB Receptors/metabolism
• Female
• Oviducts/cytology
• Oviducts/enzymology
• Phosphorylation
• Proto-Oncogene Proteins c-akt/metabolism
• Rats
• Rats, Sprague-Dawley
• Receptors, G-Protein-Coupled/metabolism
• Signal Transduction
• src-Family Kinases/metabolism

• CYP2C8
• CYP2J2
• Coronary artery disease
• Essential hypertension

Sex differences in incidence of cardiovascular disease may reflect age-associated intravascular cellular activation resulting in shedding of cell membrane-derived bioactive microvesicles (MV or microparticles) into the blood. Concentrations of cell-specific MV in blood have the potential to be a diagnostic/prognostic marker of pathology, but ranges of MV must first be established in healthy individuals. This study identified cellular origin of blood-borne MV >0.2 μm in blood of apparently healthy women and men aged from 20–70 years.

Venous blood from apparently healthy participants in the Mayo Clinic Biobank was collected into tubes containing protease inhibitors as the anticoagulant. MV were isolated by standardized differential centrifugation and characterized by digital flow cytometer. Each cellular origin of MV was verified by two different antibodies with strong correlation between the two distinct antibodies (e.g., for platelet-derived MV, r² = 0.97).

MV derived from platelets were the most abundant type of MV in blood from women and men in all age groups. Total numbers of phosphatidylserine, P-selectin, and platelet- and endothelium-derived MV were significantly (P < 0.05) greater in women than men. Numbers of MV from erythrocytes and stem/progenitor cells were significantly lower in premenopausal women than age-matched men. Number of tissue factor pathway inhibitor positive MV were significantly (P < 0.05) lower whereas erythrocyte-derived MV were significantly higher in postmenopausal women compared to premenopausal women. In women, there was a positive relationship between age and erythrocyte-derived MV (ρ = 0.28; P = 0.009), while in men adipocyte-derived MV increased with age (ρ = 0.33; P = 0.01).

This study provides ranges for cellular origin of blood-borne MV in age-matched, apparently healthy women and men from which to compare diagnostic and prognostic uses of blood-borne MV in larger studies and patient population. In addition, sex- and age-specific differences in phosphatidylserine, platelet-, endothelium-, erythrocyte-, and adipocyte-derived blood-borne MV may contribute to differential progression of cardiovascular disease in women compared to men.

• Anticoagulant vesicles
• Extracellular vesicles
• Flow cytometry
• Microparticles
• Procoagulant vesicles
• Sex differences

Gender-related physiological variations in gastrointestinal (GI) symptomatology have been observed in women of reproductive age. Many women experience cyclical changes in GI symptomatology during their menstrual cycle, particularly alteration in their bowel habits. Physiological studies of healthy women during the menstrual cycle showed a prolonged GI transit time during the luteal phase, either in the oro-cecum route or in the colon. Worsened GI symptoms, such as abdominal pain, bloating or diarrhea are observed in patients with irritable bowel syndrome (IBS) during menses. This may be due to elevated prostaglandin levels during menses, with an enhanced perception of viscera-somatic stimuli resulting in nausea, abdominal distension and pain. Also patients with IBS or IBD demonstrate a cyclical pattern more closely related to their bowel habits than healthy controls. Women with inflammatory bowel disease (IBD) also have exacerbated symptoms during menses; however, it is unclear whether this relates to physiological variation or disease exacerbation in IBS or IBD. Studies examining the association of the menstrual cycle and GI symptomatology in patients with IBS or IBD, have not yet clarified the underlying mechanisms. Moreover medications—such as non-steroidal anti-inflammatory drugs and oral contraceptive pills used for dysmenorrhea and menstrual migraine in those patients have not well been controlled for in the previous studies, which can contribute to further bias. Understanding changes in GI symptomatology during the menstrual cycle may help to determine the true extent of disease exacerbation and proper management strategy.

• inflammatory bowel disease
• irritable bowel syndrome
• menstrual cycle
• symptomatology

• Autoimmunity
• Estrous cycle
• MS/EAE
• Sex hormones
• Uterine cycle

• Escherichia coli/metabolism
• Humans
• Interleukin-6/biosynthesis
• Lipopolysaccharides/pharmacology
• Periodontal Ligament/cytology
• Periodontal Ligament/drug effects
• Periodontal Ligament/metabolism
• Porphyromonas gingivalis/metabolism

• stroke
• brain
• sex differences
• estrogen
• cerebral ischemia
• gender differences
• middle cerebral artery occlusion
• hypoxia-ischemia

• Brain Ischemia/genetics
• Brain Ischemia/immunology
• Brain Ischemia/therapy
• Cytoprotection/drug effects
• Cytoprotection/genetics
• Cytoprotection/physiology
• Encephalitis/etiology
• Encephalitis/genetics
• Encephalitis/immunology
• Encephalitis/prevention & control
• Estrogens/pharmacology
• Estrogens/therapeutic use
• Female
• Humans
• Immunity, Cellular/drug effects
• Immunity, Cellular/genetics
• Immunity, Cellular/physiology
• Male
• MicroRNAs/genetics
• MicroRNAs/physiology
• Models, Biological
• Sex Factors
• Stroke/etiology
• Stroke/genetics
• Stroke/immunology
• Stroke/physiopathology

• F31 NS083244 NINDS NIH HHS
• R01 NS055215 NINDS NIH HHS
• R21 NS066406 NINDS NIH HHS
• R21 NS076293 NINDS NIH HHS

• Anti-Inflammatory Agents/therapeutic use
• Anti-Inflammatory Agents, Non-Steroidal/therapeutic use
• Aspirin/therapeutic use
• Cyclooxygenase 2 Inhibitors/therapeutic use
• Female
• Humans
• Inflammation/drug therapy
• Inflammation/epidemiology
• Male
• Sex Characteristics
• Tumor Necrosis Factor-alpha/antagonists & inhibitors

Sex differences in obesity-induced complications such as type 2 diabetes have been reported. The aim of the study was to pinpoint the mechanisms resulting in different outcome of female and male mice on a high-fat diet (HFD). Mice fed control or HFD were monitored for weight, blood glucose, and insulin for 14 weeks. Circulating chemokines, islet endocrine function and blood flow, as well as adipose tissue populations of macrophages and regulatory T-lymphocytes (T_reg) were thereafter assessed. Despite similar weight (43.8±1.0 and 40.2±1.5 g, respectively), male but not female mice developed hyperinsulinemia on HFD as previously described (2.5±0.7 and 0.5±0.1 pmol/l, respectively) consistent with glucose intolerance. Male mice also exhibited hypertrophic islets with intact function in terms of insulin release and blood perfusion. Low-grade, systemic inflammation was absent in obese female but present in obese male mice (IL-6 and mKC, males: 77.4±17 and 1795±563; females: 14.6±4.9 and 240±22 pg/ml), and the population of inflammatory macrophages was increased in intra-abdominal adipose tissues of high-fat-fed male but not female mice. In contrast, the anti-inflammatory T_reg cell population increased in the adipose tissue of female mice in response to weight gain, while the number decreased in high-fat-fed male mice. In conclusion, female mice are protected against HFD-induced metabolic changes while maintaining an anti-inflammatory environment in the intra-abdominal adipose tissue with expanded T_reg cell population, whereas HFD-fed male mice develop adipose tissue inflammation, glucose intolerance, hyperinsulinemia, and islet hypertrophy.

• Actins/genetics
• Actins/metabolism
• Animals
• Cells, Cultured
• Computer Simulation
• Estrogens/pharmacology
• Expressed Sequence Tags
• Fish Proteins/genetics
• Fish Proteins/metabolism
• Gene Expression/drug effects
• Gene Expression Profiling
• Genes, MHC Class I
• Intercellular Signaling Peptides and Proteins/genetics
• Intercellular Signaling Peptides and Proteins/metabolism
• Macrophages/drug effects
• Matrix Metalloproteinase 13/genetics
• Matrix Metalloproteinase 13/metabolism
• Receptors, Immunologic/genetics
• Receptors, Immunologic/metabolism
• Reverse Transcriptase Polymerase Chain Reaction
• Sea Bream/genetics
• Sequence Analysis, DNA
• Transcription, Genetic/drug effects