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1.
Ann Noninvasive Electrocardiol ; 29(5): e70010, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39205610

ABSTRACT

Arrhythmias are increasingly recognized as severe complications of precapillary pulmonary hypertension, encompassing pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Despite their significant contribution to symptoms, morbidity, in-hospital mortality, and potentially sudden death in PAH/CTEPH, there remains a lack of comprehensive data on epidemiology, pathophysiology, and outcomes to inform the management of these patients. This review provides an overview of the latest evidence on this subject, spanning from the molecular mechanisms underlying arrhythmias in the hypertrophied or failing right heart to the clinical aspects of epidemiology, diagnosis, and treatment.


Subject(s)
Arrhythmias, Cardiac , Hypertension, Pulmonary , Pulmonary Embolism , Humans , Arrhythmias, Cardiac/physiopathology , Arrhythmias, Cardiac/complications , Hypertension, Pulmonary/physiopathology , Hypertension, Pulmonary/complications , Hypertension, Pulmonary/diagnosis , Pulmonary Embolism/physiopathology , Pulmonary Embolism/complications , Chronic Disease , Pulmonary Arterial Hypertension/physiopathology , Pulmonary Arterial Hypertension/complications
2.
BJU Int ; 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39044467

ABSTRACT

OBJECTIVE: To assess the impact of ejaculatory dysfunction (EjD; failure of emission or retrograde ejaculation) on health-related quality of life (HRQoL) after retroperitoneal lymph node dissection (RPLND) for testicular cancer and explore the efficacy of pseudoephedrine hydrochloride as treatment. PATIENTS AND METHODS: In a single arm, phase II trial, patients at ≥6 months after RPLND were invited to complete patient-reported outcome measures (European Organisation for Research and Treatment of Cancer [EORTC] quality of life questionnaire [QLQ]-30-item core, EORTC QLQ-testicular cancer-26, and Brief Male Sexual Function Inventory) evaluating HRQoL and sexual function in follow-up (ACTRN12622000537752/12622000542796). If EjD was reported, post-ejaculatory urine ± semen analysis was undertaken. In eligible patients, pseudoephedrine hydrochloride 60 mg was administered orally every 6 h for six doses. The primary endpoint was sperm count >39 million sperm/ejaculate (>5th centile) following treatment. The trial was powered to detect a clinically relevant 36% achieving sperm count of >39 million sperm/ejaculate. Secondary endpoints included semen volume >1.5 mL, total motile sperm count, safety, and HRQoL impacts. RESULTS: Of the 58 patients enrolled, the median (interquartile range [IQR]) age was 35 (29-41) years, with a median (IQR) of 37 (18-60) months from RPLND. EjD was reported in 33 (57%), including 27/52 (52%) receiving follow-up at our centre. There were no differences in global HRQoL; however, role functioning (P = 0.045), sexual problems (P < 0.005), and sexual enjoyment (P = 0.005) was poorer if EjD was present. In all, 24/33 (73%) patients with EjD consented to pseudoephedrine treatment. Of 22 evaluable patients, four (18%) achieved a sperm count of >39 million/ejaculate (P = 0.20), and four (18%) had a semen volume of >1.5 mL (P = 0.20). There was a mean increase of 105 million sperm/ejaculate (P = 0.051) and 1.47 mL increase in semen volume (P = 0.01). No safety concerns arose. CONCLUSION: Ejaculatory dysfunction is common after RPLND but did not impact global HRQoL in our cohort. Pseudoephedrine improved EjD for some; however, its efficacy was lower than expected. Pseudoephedrine may be considered on an individualised basis.

3.
Int J Mol Sci ; 25(14)2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39063104

ABSTRACT

Acute-phase serum amyloid A (SAA) can disrupt vascular homeostasis and is elevated in subjects with diabetes, cardiovascular disease, and rheumatoid arthritis. Cyclic nitroxides (e.g., Tempo) are a class of piperidines that inhibit oxidative stress and inflammation. This study examined whether 4-methoxy-Tempo (4-MetT) inhibits SAA-mediated vascular and renal dysfunction. Acetylcholine-mediated vascular relaxation and aortic guanosine-3',5'-cyclic monophosphate (cGMP) levels both diminished in the presence of SAA. 4-MetT dose-dependently restored vascular function with corresponding increases in cGMP. Next, male ApoE-deficient mice were administered a vehicle (control, 100 µL PBS) or recombinant SAA (100 µL, 120 µg/mL) ± 4-MetT (at 15 mg/kg body weight via i.p. injection) with the nitroxide administered before (prophylaxis) or after (therapeutic) SAA. Kidney and hearts were harvested at 4 or 16 weeks post SAA administration. Renal inflammation increased 4 weeks after SAA treatment, as judged by the upregulation of IFN-γ and concomitant increases in iNOS, p38MAPK, and matrix metalloproteinase (MMP) activities and increased renal fibrosis (Picrosirius red staining) in the same kidneys. Aortic root lesions assessed at 16 weeks revealed that SAA enhanced lesion size (vs. control; p < 0.05), with plaque presenting with a diffuse fibrous cap (compared to the corresponding aortic root from control and 4-MetT groups). The extent of renal dysfunction and aortic lesion size was largely unchanged in 4-MetT-supplemented mice, although renal fibrosis diminished at 16 weeks, and aortic lesions presented with redistributed collagen networks. These outcomes indicate that SAA stimulates renal dysfunction through promoting the IFN-γ-iNOS-p38MAPK axis, manifesting as renal damage and enhanced atherosclerotic lesions, while supplementation with 4-MetT only affected some of these pathological changes.


Subject(s)
Cyclic N-Oxides , Fibrosis , Kidney , Plaque, Atherosclerotic , Serum Amyloid A Protein , Animals , Mice , Male , Serum Amyloid A Protein/metabolism , Kidney/pathology , Kidney/metabolism , Kidney/drug effects , Cyclic N-Oxides/pharmacology , Plaque, Atherosclerotic/drug therapy , Plaque, Atherosclerotic/pathology , Plaque, Atherosclerotic/metabolism , Collagen/metabolism , Aorta/pathology , Aorta/drug effects , Aorta/metabolism , Cyclic GMP/metabolism , Kidney Diseases/drug therapy , Kidney Diseases/metabolism , Kidney Diseases/pathology , Kidney Diseases/etiology , Oxidative Stress/drug effects , Mice, Inbred C57BL
4.
Int J Mol Sci ; 24(7)2023 Mar 23.
Article in English | MEDLINE | ID: mdl-37047040

ABSTRACT

Dietary selenium (Se) intake within the physiological range is critical to maintain various biological functions, including antioxidant defence, redox homeostasis, growth, reproduction, immunity, and thyroid hormone production. Chemical forms of dietary Se are diverse, including organic Se (selenomethionine, selenocysteine, and selenium-methyl-selenocysteine) and inorganic Se (selenate and selenite). Previous studies have largely investigated and compared the health impacts of dietary Se on agricultural stock and humans, where dietary Se has shown various benefits, including enhanced growth performance, immune functions, and nutritional quality of meats, with reduced oxidative stress and inflammation, and finally enhanced thyroid health and fertility in humans. The emergence of nanoparticles presents a novel and innovative technology. Notably, Se in the form of nanoparticles (SeNPs) has lower toxicity, higher bioavailability, lower excretion in animals, and is linked to more powerful and superior biological activities (at a comparable Se dose) than traditional chemical forms of dietary Se. As a result, the development of tailored SeNPs for their use in intensive agriculture and as candidate for therapeutic drugs for human pathologies is now being actively explored. This review highlights the biological impacts of SeNPs on growth and reproductive performances, their role in modulating heat and oxidative stress and inflammation and the varying modes of synthesis of SeNPs.


Subject(s)
Nanoparticles , Selenium , Animals , Humans , Selenocysteine , Antioxidants , Inflammation/drug therapy
5.
Front Reprod Health ; 4: 782915, 2022.
Article in English | MEDLINE | ID: mdl-36303638

ABSTRACT

Viral infections have been a part of human existence to date, though viruses have posed a huge threat with various outbreaks lately. These threats are associated with reproductive health challenges, especially male infertility. The prime focus of this review is to highlight the mechanisms associated with viral infection-induced male infertility/subfertility and identify new treatment strategies with the aim to preserve male fertility. The reviewed data showed that viral infections stimulate inflammatory responses, resulting in the release of proinflammatory cytokines, which induces oxidative stress. This oxido-inflammatory cycle could continue in a vicious cycle and threaten male fertility. Existing data from human and experimental studies show that viral infection-induced oxido-inflammatory response results in testicular damage, atrophy of the seminiferous tubules and Sertoli cells, and reduced Leydig cell mass. This is accompanied by reduced circulatory testosterone, impaired spermatogenesis, reduced sperm motility, lipid peroxidation, DNA fragmentation and apoptosis of the sperm cells. Based on the available pieces of evidence, antioxidant therapy, in vivo and in vitro, may be beneficial and protects against the potential risk of male infertility from viral infection. It is, however recommended that more clinical studies be conducted to demonstrate the possible protective roles of antioxidants used as adjuvant therapy in viral infections, and in the in vitro treatment of semen samples for those utilizing semen washing and artificial reproductive techniques.

6.
Inflamm Bowel Dis ; 28(4): 586-598, 2022 03 30.
Article in English | MEDLINE | ID: mdl-34724042

ABSTRACT

BACKGROUND: Intestinal neutrophil recruitment is a characteristic feature of the earliest stages of inflammatory bowel disease (IBD). Neutrophil elastase (NE) and myeloperoxidase (MPO) mediate the formation of neutrophil extracellular traps (NETs); NETs produce the bactericidal oxidant hypochlorous acid (HOCl), causing host tissue damage when unregulated. The project aim was to investigate the relationship between NET formation and clinical IBD in humans. METHODS: Human intestinal biopsies were collected from Crohn's disease (CD) patients, endoscopically categorized as unaffected, transitional, or diseased, and assigned a histopathological score. RESULTS: A significant linear correlation was identified between pathological score and cell viability (TUNEL+). Immunohistochemical analysis revealed the presence of NET markers NE, MPO, and citrullinated histone (CitH3) that increased significantly with increasing histopathological score. Diseased specimens showed greater MPO+-immunostaining than control (P < .0001) and unaffected CD (P < .0001), with transitional CD specimens also showing greater staining than controls (P < .05) and unaffected CD (P < .05). Similarly, NE+-immunostaining was elevated significantly in diseased CD than controls (P < .0001) and unaffected CD (P < .0001) and was significantly higher in transitional CD than in controls (P < .0001) and unaffected CD (P < .0001). The CitH3+-immunostaining of diseased CD was significantly higher than controls (P < .05), unaffected CD (P < .0001) and transitional CD (P < .05), with transitional CD specimens showing greater staining than unaffected CD (P < .01). Multiplex immunohistochemistry with z-stacking revealed colocalization of NE, MPO, CitH3, and DAPI (cell nuclei), confirming the NET assignment. CONCLUSION: These data indicate an association between increased NET formation and CD severity, potentially due to excessive MPO-mediated HOCl production in the extracellular domain, causing host tissue damage that exacerbates CD.


Our data show for the first time that the density of neutrophil extracellular trap formed in the bowel of Crohn's disease patients increases with increasing disease severity, suggesting that myeloperoxidase-mediated host-tissue damage may play a role in disease pathogenesis.


Subject(s)
Crohn Disease , Extracellular Traps , Crohn Disease/pathology , Extracellular Traps/metabolism , Histones , Humans , Neutrophil Infiltration , Neutrophils/metabolism , Peroxidase/metabolism
7.
Int J Mol Sci ; 22(22)2021 Nov 22.
Article in English | MEDLINE | ID: mdl-34830462

ABSTRACT

Acute serum amyloid A (SAA) is an apolipoprotein that mediates pro-inflammatory and pro-atherogenic pathways. SAA-mediated signalling is diverse and includes canonical and acute immunoregulatory pathways in a range of cell types and organs. This study aimed to further elucidate the roles for SAA in the pathogenesis of vascular and renal dysfunction. Two groups of male ApoE-deficient mice were administered SAA (100 µL, 120 µg/mL) or vehicle control (100 µL PBS) and monitored for 4 or 16 weeks after SAA treatment; tissue was harvested for biochemical and histological analyses at each time point. Under these conditions, SAA administration induced crosstalk between NF-κB and Nrf2 transcriptional factors, leading to downstream induction of pro-inflammatory mediators and antioxidant response elements 4 weeks after SAA administration, respectively. SAA treatment stimulated an upregulation of renal IFN-γ with a concomitant increase in renal levels of p38 MAPK and matrix metalloproteinase (MMP) activities, which is linked to tissue fibrosis. In the kidney of SAA-treated mice, the immunolocalisation of inducible nitric oxide synthase (iNOS) was markedly increased, and this was localised to the parietal epithelial cells lining Bowman's space within glomeruli, which led to progressive renal fibrosis. Assessment of aortic root lesion at the study endpoint revealed accelerated atherosclerosis formation; animals treated with SAA also showed evidence of a thinned fibrous cap as judged by diffuse collagen staining. Together, this suggests that SAA elicits early renal dysfunction through promoting the IFN-γ-iNOS-p38 MAPK axis that manifests as the fibrosis of renal tissue and enhanced cardiovascular disease.


Subject(s)
Apolipoproteins E/genetics , Atherosclerosis/genetics , Interferon-gamma/genetics , Serum Amyloid A Protein/genetics , p38 Mitogen-Activated Protein Kinases/genetics , Animals , Aorta/metabolism , Apolipoproteins E/deficiency , Atherosclerosis/blood , Atherosclerosis/pathology , Humans , Inflammation/blood , Inflammation/genetics , Inflammation/pathology , Kidney Diseases/genetics , Kidney Diseases/pathology , Male , Metalloproteases/genetics , Mice , NF-E2-Related Factor 2/genetics , NF-kappa B/genetics , Nitric Oxide Synthase Type II/genetics , Signal Transduction/genetics
8.
Nutrients ; 13(9)2021 Sep 18.
Article in English | MEDLINE | ID: mdl-34579133

ABSTRACT

Selenium (Se) is a micronutrient essential for life. Dietary intake of Se within the physiological range is critical for human health and reproductive functions. Selenium levels outside the recommended range have been implicated in infertility and variety of other human diseases. However, presently it is not clear how different dietary Se sources are processed in our bodies, and in which form or how much dietary Se is optimum to maintain metabolic homeostasis and boost reproductive health. This uncertainty leads to imprecision in published dietary guidelines and advice for human daily intake of Se and in some cases generating controversies and even adverse outcomes including mortality. The chief aim for this review is to describe the sources of organic and inorganic Se, the metabolic pathways of selenoproteins synthesis, and the critical role of selenprotenis in the thyroid gland homeostasis and reproductive/fertility functions. Controversies on the use of Se in clinical practice and future directions to address these challenges are also described and discussed herein.


Subject(s)
Homeostasis/physiology , Reproduction/physiology , Selenium/physiology , Diet , Female , Fertility/physiology , Humans , Male , Selenium/administration & dosage , Selenium/deficiency , Selenoproteins/biosynthesis , Selenoproteins/physiology , Thyroid Gland/physiology
9.
Int J Mol Sci ; 22(9)2021 Apr 27.
Article in English | MEDLINE | ID: mdl-33925294

ABSTRACT

Intracellular redox imbalance in endothelial cells (EC) can lead to endothelial dysfunction, which underpins cardiovascular diseases (CVD). The acute phase serum amyloid A (SAA) elicits inflammation through stimulating production of reactive oxygen species (ROS). The cyclic nitroxide 4-MethoxyTEMPO (4-MetT) is a superoxide dismutase mimetic that suppresses oxidant formation and inflammation. The aim of this study was to investigate whether 4-MetT inhibits SAA-mediated activation of cultured primary human aortic EC (HAEC). Co-incubating cells with 4-MetT inhibited SAA-mediated increases in adhesion molecules (VCAM-1, ICAM-1, E-selectin, and JAM-C). Pre-treatment of cells with 4-MetT mitigated SAA-mediated increases in transcriptionally activated NF-κB-p65 and P120 Catenin (a stabilizer of Cadherin expression). Mitochondrial respiration and ROS generation (mtROS) were adversely affected by SAA with decreased respiratory reserve capacity, elevated maximal respiration and proton leakage all characteristic of SAA-treated HAEC. This altered respiration manifested as a loss of mitochondrial membrane potential (confirmed by a decrease in TMRM fluorescence), and increased mtROS production as assessed with MitoSox Red. These SAA-linked impacts on mitochondria were mitigated by 4-MetT resulting in restoration of HAEC nitric oxide bioavailability as confirmed by assessing cyclic guanosine monophosphate (cGMP) levels. Thus, 4-MetT ameliorates SAA-mediated endothelial dysfunction through normalising EC redox homeostasis. Subject to further validation in in vivo settings; these outcomes suggest its potential as a therapeutic in the setting of cardiovascular pathologies where elevated SAA and endothelial dysfunction is linked to enhanced CVD.


Subject(s)
Endothelial Cells/drug effects , Nitrogen Oxides/pharmacology , Serum Amyloid A Protein/metabolism , Aorta/pathology , Biomimetics/methods , Cardiovascular Diseases/physiopathology , Cells, Cultured , Endothelial Cells/metabolism , Endothelium, Vascular/metabolism , Humans , Inflammation/pathology , Intercellular Adhesion Molecule-1/metabolism , NF-kappa B/metabolism , Nitric Oxide/metabolism , Nitrogen Oxides/metabolism , Primary Cell Culture , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Superoxide Dismutase/metabolism , Vascular Cell Adhesion Molecule-1/metabolism
10.
Front Pharmacol ; 11: 556020, 2020.
Article in English | MEDLINE | ID: mdl-33041796

ABSTRACT

Chronic inflammatory bowel disease (IBD) is a condition with multifactorial pathophysiology. To date, there is no permanent cure and the disease is primarily managed by immunosuppressive drugs; long-term use promotes serious side effects including increased risk malignancies. The current study aimed to target neutrophil-myeloperoxidase, a key contributor to the pathogenesis of IBD, through the use of AZD3241that inhibits extracellular myeloperoxidase. Experimental colitis was induced in C57BL/6 male mice by 2% dextran sodium sulfate in drinking water ad libitum over 9 days. Mice received either normal drinking water and peanut butter (control), 2% DSS in drinking water and peanut butter or 2% DSS in drinking water and AZD3241 (30 mg/kg) dispersed in peanut butter daily for 9 days. Administered AZD3241 attenuated body weight loss (10% p<0.05) and improved clinical score (9 fold p<0.05; a score comprising the time-dependent assessment of stool consistency and extent of rectal bleeding), loss of colonic crypts (p<0.001), preserved surface epithelium (p<0.001) and enhanced expression of the transcription factor Nrf-2 (regulator of antioxidants) and enhanced expression of the downstream antioxidant response element haeoxygenase-1 (HO-1) in the colon tissue. Also, the concentration of fecal hemoglobin and the myeloperoxidase specific oxidative damage biomarker 3-chlorotyrosine in the colon were significantly decreased in the presence of AZD3241. This latter result was consistent with AZD3241 inhibiting MPO activity in vitro. Overall, AZD3241 ameliorated the course and severity of experimental colitis through ameliorating MPO derived tissue damage and could be considered a potential therapeutic option, subject to further validation in chronic IBD models.

11.
Arch Biochem Biophys ; 692: 108490, 2020 10 15.
Article in English | MEDLINE | ID: mdl-32721434

ABSTRACT

Ulcerative colitis is a condition characterised by the infiltration of leukocytes into the gastrointestinal wall. Leukocyte-MPO catalyses hypochlorous acid (HOCl) and hypothiocyanous acid (HOSCN) formation from chloride (Cl-) and thiocyanous (SCN-) anions, respectively. While HOCl indiscriminately oxidises biomolecules, HOSCN primarily targets low-molecular weight protein thiols. Oxidative damage mediated by HOSCN may be reversible, potentially decreasing MPO-associated host tissue destruction. This study investigated the effect of SCN- supplementation in a model of acute colitis. Female mice were supplemented dextran sodium sulphate (DSS, 3% w/v) in the presence of 10 mM Cl- or SCN- in drinking water ad libitum, or with salts (NaCl and NaSCN only) or water only (controls). Behavioural studies showed mice tolerated NaSCN and NaCl-treated water with water-seeking frequency. Ion-exchange chromatography showed increased fecal and plasma SCN- levels in thiocyanate supplemented mice; plasma SCN- reached similar fold-increase for smokers. Overall there was no difference in weight loss and clinical score, mucin levels, crypt integrity and extent of cellular infiltration between DSS/SCN- and DSS/Cl- groups. Neutrophil recruitment remained unchanged in DSS-treated mice, as assessed by fecal calprotectin levels. Total thiol and tyrosine phosphatase activity remained unchanged between DSS/Cl- and DSS/SCN- groups, however, colonic tissue showed a trend in decreased 3-chlorotyrosine (1.5-fold reduction, p < 0.051) and marked increase in colonic GCLC, the rate-limiting enzyme in glutathione synthesis. These data suggest that SCN- administration can modulate MPO activity towards a HOSCN-specific pathway, however, this does not alter the development of colitis within a DSS murine model.


Subject(s)
Colitis , Colon , Dextran Sulfate/toxicity , Peroxidase/metabolism , Thiocyanates/pharmacology , Animals , Colitis/chemically induced , Colitis/drug therapy , Colitis/enzymology , Colitis/pathology , Colon/enzymology , Colon/pathology , Disease Models, Animal , Female , Mice
12.
Reprod Fertil Dev ; 32(7): 637-647, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32234188

ABSTRACT

The 2019 meeting of the Society for Reproductive Biology (SRB) provided a platform for the dissemination of new knowledge and innovations to improve reproductive health in humans, enhance animal breeding efficiency and understand the effect of the environment on reproductive processes. The effects of environment and lifestyle on fertility and animal behaviour are emerging as the most important modern issues facing reproductive health. Here, we summarise key highlights from recent work on endocrine-disrupting chemicals and diet- and lifestyle-induced metabolic changes and how these factors affect reproduction. This is particularly important to discuss in the context of potential effects on the reproductive potential that may be imparted to future generations of humans and animals. In addition to key summaries of new work in the male and female reproductive tract and on the health of the placenta, for the first time the SRB meeting included a workshop on endometriosis. This was an important opportunity for researchers, healthcare professionals and patient advocates to unite and provide critical updates on efforts to reduce the effect of this chronic disease and to improve the welfare of the women it affects. These new findings and directions are captured in this review.


Subject(s)
Reproductive Health , Australia , Biomedical Research , Chronic Pain , Endometriosis/physiopathology , Female , Humans , Infertility , New Zealand , Pelvic Pain , Pregnancy , Reproduction , Reproductive Techniques, Assisted
13.
Int J Mol Sci ; 21(4)2020 Feb 15.
Article in English | MEDLINE | ID: mdl-32075280

ABSTRACT

Serum amyloid A (SAA) promotes endothelial inflammation and dysfunction that is associated with cardiovascular disease and renal pathologies. SAA is an apoprotein for high-density lipoprotein (HDL) and its sequestration to HDL diminishes SAA bioactivity. Herein we investigated the effect of co-supplementing HDL on SAA-mediated changes to vascular and renal function in apolipoprotein E-deficient (ApoE-/-) mice in the absence of a high-fat diet. Male ApoE-/- mice received recombinant human SAA or vehicle (control) by intraperitoneal (i.p.) injection every three days for two weeks with or without freshly isolated human HDL supplemented by intravenous (i.v.) injection in the two weeks preceding SAA stimulation. Aorta and kidney were harvested 4 or 18 weeks after commencement of treatment. At 4 weeks after commencement of treatment, SAA increased aortic vascular cell adhesion molecule (VCAM)-1 expression and F2-isoprostane level and decreased cyclic guanosine monophosphate (cGMP), consistent with SAA stimulating endothelial dysfunction and promoting atherosclerosis. SAA also stimulated renal injury and inflammation that manifested as increased urinary protein, kidney injury molecule (KIM)-1, and renal tissue cytokine/chemokine levels as well as increased protein tyrosine chlorination and P38 MAPkinase activation and decreased in Bowman's space, confirming that SAA elicited a pro-inflammatory phenotype in the kidney. At 18 weeks, vascular lesions increased significantly in the cohort of ApoE-/- mice treated with SAA alone. By contrast, pretreatment of mice with HDL decreased SAA pro-inflammatory activity, inhibited SAA enhancement of aortic lesion size and renal function, and prevented changes to glomerular Bowman's space. Taken together, these data indicate that supplemented HDL reduces SAA-mediated endothelial and renal dysfunction in an atherosclerosis-prone mouse model.


Subject(s)
Atherosclerosis/drug therapy , Inflammation/drug therapy , Lipoproteins, HDL/pharmacology , Serum Amyloid A Protein/toxicity , Animals , Aorta/drug effects , Aorta/pathology , Apolipoproteins E/deficiency , Apolipoproteins E/genetics , Atherosclerosis/chemically induced , Atherosclerosis/genetics , Atherosclerosis/pathology , Disease Models, Animal , Gene Expression Regulation/drug effects , Hepatitis A Virus Cellular Receptor 1/genetics , Humans , Inflammation/chemically induced , Inflammation/genetics , Kidney/drug effects , Kidney/pathology , Mice , Mice, Knockout , p38 Mitogen-Activated Protein Kinases/genetics
14.
J Clin Lab Anal ; 34(6): e23212, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31950567

ABSTRACT

BACKGROUND: Tobacco smoking is a major health issue worldwide. In addition to several health problems, smoking can also cause buccal cavity ulcers and buccal cavity cancer in case of chronic smoking. Tobacco smoking may also lead to deranged morphology of red blood cells (RBCs), which results in reduced oxygen carrying capacity of the blood. AIM: (a) To investigate and compare the changes in the RBC morphology of smokers and nonsmokers. (b) To investigate and compare the normal buccal flora of smokers and nonsmokers. METHODOLOGY: A total of 81 men were included in the study. Study population was divided into two groups: group 1; smokers (n = 50) and group 2; nonsmokers, which served as control (n = 31). After informed written consent from the study participants, a 5 mL of venous blood was drawn under sterile conditions for complete blood analysis and RBC morphology. Samples from buccal cavity were collected by cotton swab and cultured in sterile petri dishes to identify the bacterial growth. Data of RBC morphology and buccal microbiota were compared between smokers and nonsmokers. RESULTS: Buccal microflora results showed heavy growth in smokers compared with nonsmokers. Mean values of RBCs, Platelets, WBCs, HGB (hemoglobin), and MCV (mean corpuscular volume) did not differ between smokers and nonsmokers. Mean red cell distribution (RDW) width significantly was lower in smokers than nonsmokers. Macrocytic RBCs was more in smokers (60%) compared with nonsmokers (4%). CONCLUSIONS: Our results showed an increase in the percentage of macrocytic RBCs and a decrease in the red cell distribution width (RDW) in smokers compared with nonsmokers. Buccal Microflora was significantly higher in smoker group in contrast to nonsmoker group.


Subject(s)
Erythrocytes/drug effects , Mouth Mucosa/microbiology , Smoking/adverse effects , Adult , Case-Control Studies , Erythrocyte Indices , Erythrocytes/physiology , Humans , Young Adult
15.
World J Mens Health ; 38(2): 198-207, 2020 Apr.
Article in English | MEDLINE | ID: mdl-30588784

ABSTRACT

PURPOSE: Patients with non-seminoma testicular cancer (NSTC) cancer can be subfertile or infertile, and present reduced sperm quality, but the underlying mechanisms are unknown. The aim of this study was to compare the sperm proteome of patients with NSTC, who cryopreserved their sperm before starting cancer treatment, with that from healthy fertile men. MATERIALS AND METHODS: Semen volume, sperm motility and sperm concentration were evaluated before the cryopreservation of samples from patients with NSTC (n=15) and the control group (n=15). Sperm proteomic analysis was performed by liquid chromatography-tandem mass spectrometry and the differentially expressed proteins (DEPs) between the two groups were identified using bioinformatic tools. RESULTS: A total of 189 DEPs was identified in the dataset, from which five DEPs related to sperm function and fertilization were selected for validation by Western blot. We were able to validate the underexpression of the mitochondrial complex subunits NADH:Ubiquinone Oxidoreductase Core Subunit S1 (NDUFS1) and ubiquinol-cytochrome C reductase core protein 2 (UQCRC2), as well as the underexpression of the testis-specific sodium/potassium-transporting ATPase subunit alpha-4 (ATP1A4) in the NSTC group. CONCLUSIONS: Our results indicate that sperm mitochondrial dysfunction may explain the observed decrease in sperm concentration, total sperm count and total motile count in NSTC patients. The identified DEPs may serve as potential biomarkers for the pathophysiology of subfertility/infertility in patients with NSTC. Our study also associates the reduced fertilizing ability of NSTC patients with the dysregulation of important sperm molecular mechanisms.

16.
J Clin Lab Anal ; 34(2): e23048, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31568604

ABSTRACT

BACKGROUND: Vitamin D (mainly 25-hydroxyvitamin D, 25[OH]D) has stimulated increasing interest in Saudi Arabia over the current years due to its association with several different chronic diseases such as diabetes. This study aims to ascertain whether the vitamin D level has any influence on glycemic control in Saudi patients with type 2 diabetes (T2DM). METHOD: This retrospective study included 200 patients with T2DM who visited Prince Sattam Bin Abdulaziz University Hospital between January 2015 and December 2015. Venous blood was collected and examined for "serum/plasma levels of 25(OH)D" and related variables using kit methods. HbA1C levels <7% and ≥7% were taken as indicators of good and poor glycemic control, respectively. An association between vitamin D deficiency and poor glycemic control was determined using multinomial logistic regression analysis. RESULTS: Among the total of 200 patients with type 2 diabetes, 118 (59%) were female and 82 (41%) were males with the mean age 42.4 ± 14.8 years. Good glycemic control (HbA1c < 7) was observed in 127 (63.5%), and poor glycemic control (HbA1c > 7) was found in 73(36.5%). The mean serum 25(OH)vit D was 20.27 ± 8.66 ng/mL, with (52% vs 82%; P ≤ .001) of subjects identified to have vitamin D deficiency in good and poor glycemic control groups, respectively. CONCLUSION: Taken together, our results demonstrated an association of vitamin D level with poor glycemic control in patients with type 2 diabetes. However, additional studies with larger sample size from local population are warranted in future to confirm and extend the findings of the present study.


Subject(s)
Diabetes Mellitus, Type 2/blood , Glycerides/blood , Vitamin D/blood , Adolescent , Adult , Aged , Aged, 80 and over , Body Mass Index , Female , Glycated Hemoglobin/analysis , Hospitals, University , Humans , Logistic Models , Male , Middle Aged , Retrospective Studies , Saudi Arabia , Vitamin D/analogs & derivatives , Vitamin D Deficiency/blood , Young Adult
17.
World J Mens Health ; 38(4): 521-534, 2020 Oct.
Article in English | MEDLINE | ID: mdl-31385466

ABSTRACT

PURPOSE: Hodgkin's disease (HD) is a type of cancer affecting men in the reproductive age with potential consequences on their fertility status. This study aims to analyze sperm parameters, alterations in proteomic profiles and validate selected protein biomarkers of spermatozoa in men with HD undergoing sperm banking before cancer therapy. MATERIALS AND METHODS: Semen analysis was carried out in healthy fertile donors (control, n=42), and patients diagnosed with HD (patients, n=38) before cancer therapy. We compared proteomic profiles of spermatozoa from donors (n=3) and patients (n=3) using LTQ-Orbitrap Elite hybrid MS system. RESULTS: A total of 1,169 proteins were identified by global proteomic in both groups. The ingenuity pathway analysis revealed that differentially expressed proteins involved in capacitation, acrosome reaction, binding of sperm to the zona pellucida, sperm motility, regulation of sperm DNA damage, and apoptosis were significantly downregulated in HD patients. Validation of proteins implicated in sperm fertility potential by Western Blot demonstrated that peroxiredoxin 2 (PRDX 2) was underexpressed (p=0.015), and transferrin (p=0.045) and SERPIN A5 (p=0.010) protein levels were overexpressed in spermatozoa of men with HD. CONCLUSIONS: Findings of this study indicates that the key proteins involved in sperm fertility potential are significantly altered in men with HD, which provides substantial explanation for the observed low sperm quality in HD subjects prior to cancer therapy. Furthermore, our results suggest PRDX 2, transferrin and SERPIN A5 as possible candidate proteins for assessing sperm quality in HD patients prior to cancer therapy.

18.
Asian J Androl ; 22(1): 88-93, 2020.
Article in English | MEDLINE | ID: mdl-31006710

ABSTRACT

Testicular cancer seminoma is one of the most common types of cancer among men of reproductive age. Patients with this condition usually present reduced semen quality, even before initiating cancer therapy. However, the underlying mechanisms by which testicular cancer seminoma affects male fertility are largely unknown. The aim of this study was to investigate alterations in the sperm proteome of men with seminoma undergoing sperm banking before starting cancer therapy, in comparison to healthy proven fertile men (control group). A routine semen analysis was conducted before cryopreservation of the samples (n = 15 per group). Men with seminoma showed a decrease in sperm motility (P = 0.019), total motile count (P = 0.001), concentration (P = 0.003), and total sperm count (P = 0.001). Quantitative proteomic analysis identified 393 differentially expressed proteins between the study groups. Ten proteins involved in spermatogenesis, sperm function, binding of sperm to the oocyte, and fertilization were selected for validation by western blot. We confirmed the underexpression of heat shock-related 70 kDa protein 2 (P = 0.041), ubiquinol-cytochrome C reductase core protein 2 (P = 0.026), and testis-specific sodium/potassium-transporting ATPase subunit alpha-4 (P = 0.016), as well as the overexpression of angiotensin I converting enzyme (P = 0.005) in the seminoma group. The altered expression levels of these proteins are associated with spermatogenesis dysfunction, reduced sperm kinematics and motility, failure in capacitation and fertilization. The findings of this study may explain the decrease in the fertilizing ability of men with seminoma before starting cancer therapy.


Subject(s)
Proteomics , Seminoma/metabolism , Sperm Count , Sperm Motility , Spermatozoa/metabolism , Testicular Neoplasms/metabolism , Acrosin/metabolism , Adult , Case-Control Studies , Chaperonin Containing TCP-1/metabolism , Electron Transport Complex III/metabolism , HSP70 Heat-Shock Proteins/metabolism , Humans , Male , Peptidyl-Dipeptidase A/metabolism , Proteasome Endopeptidase Complex/metabolism , Semen Analysis , Sodium-Potassium-Exchanging ATPase/metabolism
19.
BMC Fam Pract ; 20(1): 150, 2019 11 05.
Article in English | MEDLINE | ID: mdl-31690280

ABSTRACT

The editors have retracted this article [1] because it contains extensive overlap with an article published by the same authors in the Journal of Family & Community Medicine [2] and is therefore redundant.

20.
Cureus ; 11(7): e5249, 2019 Jul 27.
Article in English | MEDLINE | ID: mdl-31572634

ABSTRACT

Introduction Dengue viral infections are a major cause of morbidity and mortality in tropical/subtropical countries. Early and prompt detection of dengue hemorrhagic fever (DHF), though challenging, is helpful to identify an individual that would benefit from intensive therapy. Objective The goal of this study was to determine the plasma interleukin-10 (IL-10) levels in DHF patients at four to seven days of disease onset and 24 hours after the first sample. We also aimed to determine the association of plasma IL-10 levels and abdominopelvic ultrasound findings. Methods A total of 50 registered DHF patients aged 15 to 50 years were recruited. Plasma IL-10 concentration measurements and abdominopelvic ultrasounds were performed. Patients were also categorized based on ultrasound grading I to IV (based on severity). Outcomes were described as recovery and shock. Platelet count and hematocrit percentages were also recorded. Results Plasma IL-10 levels were elevated in DHF patients and associated with fatal outcomes (p = 0.00). Binary regression-coefficient showed the direct effect of high levels of plasma IL-10 on the fatal outcome of patients 24 hours after the first sample (p = 0.04). Disease severity was predicted by a positive correlation between ultrasound grades and outcomes (p = 0.00). Spearman's correlation coefficient found a highly significant inverse relationship between plasma IL-10 levels and platelet count after 24 hours (p = 0.01). However, a significant positive relationship was observed between elevated plasma IL-10 levels and hematocrit percentage after 24 hours (p = 0.01). Conclusion Elevated plasma IL-10 levels and abdominopelvic ultrasonography are promising potential predictors of disease progression and fatal outcome in DHF patients.

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