Effect of trace elements on the seminal oxidative status and correlation to sperm motility in infertile Saudi males

The impact of trace elements, especially zinc, selenium, copper, and magnesium, on male fertility has gained great interest and significance. Increased oxidative stress and altered trace element levels are probable etiological factors underlying male reproductive dysfunction and infertility. The present study focused on the evaluation of seminal oxidative markers, such as reactive oxygen species (ROS), malondialdehyde (MDA), and total antioxidant capacity (TAC), and trace element levels in the normozoospermic fertile control group (n = 40) and asthenozoospermic infertile group (n = 30). Semen from infertile men exhibited significantly higher ROS and MDA levels accompanied with significant decline in TAC and trace element (zinc and magnesium) levels. Furthermore, a significant correlation was observed between trace elements and oxidative markers with sperm motility. The current study revealed increased lipid peroxidation and oxidant-reductant imbalance that leads to deterioration of semen quality and male infertility. Thus, oxidative stress and trace elements can be considered important biomarkers of male infertility. Measurement of seminal oxidative stress with conventional seminological parameters must be integrated in fertility assessment from early stages to ensure healthy semen characteristics and fertility in men.     

Lycopene is superior to moringa in improving fertility markers in diet-induced obesity male rats

Obesity is a condition of chronic tissue inflammation and oxidative stress that poses as a risk factor for male infertility. Moringa oleifera oil extract is known to have cholesterol-lowering properties and a potential to treat obesity, while lycopene is a potent antioxidant. We hypothesize that Moringa or lycopene may improve male fertility markers in an animal model of diet-induced obesity. Male Albino rats (n = 60) were randomized to receive regular chow (RC) or high-fat diet (HFD) for 12 weeks (n = 30 each). Animals in each arm were further randomized to receive gavage treatment with corn oil (vehicle), lycopene (10 mg/kg), or Moringa (400 mg/kg) for four weeks starting on week 9 (n = 10 each). Animals were sacrificed at 12 weeks, and blood was collected to assess lipid profile, serum testosterone, and gonadotropin levels. The testes and epididymides were removed for sperm analysis, oxidative stress and inflammatory markers, and histopathological assessment. In comparison to their RC littermates, animals on HFD showed an increase in body weights, serum lipids, testosterone and gonadotrophin levels, testicular oxidative stress and inflammatory markers, as well as sperm abnormalities and disrupted testicular histology. Moringa or lycopene reduced body weight, improved oxidative stress, and male fertility markers in HFD-fed animals with lycopene exhibiting better anti-antioxidant and anti-lipidemic effects. Lycopene is superior to Moringa in improving male fertility parameters, possibly by attenuating oxidative stress.     

Novel cerebrospinal fluid and serum autoantibody targets for clinically isolated syndrome

Limited information is available on the identity of antigens targeted by antibodies present in cerebrospinal fluid (CSF) of patients with clinically isolated syndrome (CIS). The aim of this study was to identify novel antigens for CIS and investigate their prognostic potential to predict conversion to multiple sclerosis (MS). We applied serological antigen selection (SAS) to identify antigens interacting with antibodies present in the pooled CSF from four CIS patients, who developed MS. Antibody reactivity towards CIS antigens identified by SAS was tested in CSF and serum from patients with CIS (n = 123/n = 108), MS (n = 65/n = 44), and other (inflammatory) neurological diseases (n = 75/n = 38) as well as in healthy control sera (n = 44). Using SAS, a panel of six novel CIS candidate antigens was identified. CSF antibody reactivity was detected in both CIS and relapsing‐remitting (RR) MS. Serum reactivity was significantly increased in CIS and RR‐MS as compared with controls (p = 0.03). For two antigens, the frequency of antibody‐positive patients was higher in CIS patients who converted to MS as compared with CIS patients without conversion. We identified novel CIS antigens to which antibody reactivity was primarily detected in CIS and RR‐MS as compared to controls. Possible prognostic potential could be demonstrated for two antigens.     

Spondias mombin L. attenuates ventricular remodelling after myocardial infarction associated with oxidative stress and inflammatory modulation

The objective of this study was to evaluate Spondias mombin L. (SM) pulp and its influence on cardiac remodelling after myocardial infarction (MI). Male Wistar rats were assigned to four groups: a sham group (animals underwent simulated surgery) that received standard chow (S; n = 20), an infarcted group that received standard chow (MI; n = 24), an infarcted group supplemented with 100 mg of SM/kg bodyweight/d, (MIS100; n = 23) and an infarcted group supplemented with 250 mg of SM/kg bodyweight/d (MIS250; n = 22). After 3 months of treatment, morphological, functional and biochemical analyses were performed. MI induced structural and functional changes in the left ventricle with worsening systolic and diastolic function, and SM supplementation at different doses did not influence these variables as analysed by echocardiography and an isolated heart study (P > .05). However, SM supplementation attenuated cardiac remodelling after MI, reducing fibrosis (P = .047) and hypertrophy (P = .006). Biomarkers of oxidative stress, inflammatory processes and energy metabolism were further investigated in the myocardial tissue. SM supplementation improved the efficiency of energy metabolism and decreased lipid hydroperoxide in the myocardium [group S (n = 8): 267.26 ± 20.7; group MI (n = 8): 330.14 ± 47.3; group MIS100 (n = 8): 313.8 ± 46.2; group MIS250: 294.3 ± 38.0 nmol/mg tissue; P = .032], as well as decreased the activation of the inflammatory pathway after MI. In conclusion, SM supplementation attenuated cardiac remodelling processes after MI. We also found that energy metabolism, oxidative stress and inflammation are associated with this effect. In addition, SM supplementation at the highest dose is more effective.     

Evoked Potentials and Neuropsychological Tests Validate Positron Emission Topography (PET) Brain Metabolism in Cognitively Impaired Patients

Fluorodeoxyglucose (FDG) Positron Emission Topography (PET) brain hypometabolism (HM) correlates with diminished cognitive capacity and risk of developing dementia. However, because clinical utility of PET is limited by cost, we sought to determine whether a less costly electrophysiological measure, the P300 evoked potential, in combination with neuropsychological test performance, would validate PET HM in neuropsychiatric patients. We found that patients with amnestic and non-amnestic cognitive impairment and HM (n = 43) evidenced significantly reduced P300 amplitudes, delayed latencies, and neuropsychological deficits, compared to patients with normal brain metabolism (NM; n = 187). Data from patients with missing cognitive test scores (n = 57) were removed from the final sample, and logistic regression modeling was performed on the modified sample (n = 173, p = .000004). The logistic regression modeling, based on P300 and neuropsychological measures, was used to validate membership in the HM vs. NM groups. It showed classification validation in 13/25 HM subjects (52.0%) and in 125/148 NM subjects (84.5%), correlating with total classification accuracy of 79.8%. In this paper, abnormal P300 evoked potentials coupled with cognitive test impairment validates brain metabolism and mild/moderate cognitive impairment (MCI). To this end, we cautiously propose incorporating electrophysiological and neuropsychological assessments as cost-effective brain metabolism and MCI indicators in primary care. Final interpretation of these results must await required additional studies confirming these interesting results.     

Oxidative stress and endogenous DNA damage in blood mononuclear cells may predict anti-SARS-CoV-2 antibody titers after vaccination in older adults

Immune senescence in the elderly has been associated with chronic oxidative stress and DNA damage accumulation. Herein we tested the hypothesis that increased endogenous DNA damage and oxidative stress in peripheral blood mononuclear cells of older adults associate with diminished humoral immune response to SARS-CoV-2 vaccination. Increased oxidative stress and DNA double-strand breaks (DSBs) were detected in 9 non-immunocompromised individuals aged 80–96 years compared to 11 adults aged 27–44 years, before, as well as on days 1 and 14 after the first dose, and on day 14 after the second dose of the BNT162B2-mRNA vaccine (all p < 0.05). SARS-CoV-2 vaccination induced a resolvable increase in oxidative stress and DNA damage, but individual DSB-repair efficiency was unaffected by vaccination irrespective of age, confirming vaccination safety. Individual titers of anti-Spike-Receptor Binding Domain (S-RBD)-IgG antibodies, and the neutralizing capacity of circulating anti-SARS-CoV-2 antibodies, measured on day 14 after the second dose in all participants, correlated inversely with the corresponding pre-vaccination endogenous oxidative stress and DSB levels (all p < 0.05). In particular, a strong inverse correlation of individual pre-vaccination DSB levels with both the respective anti-S-RBD-IgG antibodies titers (r = ?0.867) and neutralizing capacity of circulating anti-SARS-CoV-2 antibodies (r = ?0.983) among the 9 older adults was evident. These findings suggest that humoral responses to SARS-CoV-2 vaccination may be weaker when immune cells are under oxidative and/or genomic stress. Whether such measurements may serve as biomarkers of vaccine efficacy in older adults warrants further studies.     

Relationship between the capacity to repair 8-oxoguanine, biomarkers of genotoxicity and individual susceptibility in styrene-exposed workers

Genotoxic effects related to exposure to styrene have been a matter of investigation for many years by employing markers of exposure, effect and susceptibility. The role of individual DNA-repair capacity in response to exposure to styrene may explain the controversial results so far obtained, but it is still scarcely explored. In the present study, we measured capacity to repair oxidative DNA damage in cell extracts obtained from 24 lamination workers occupationally exposed to styrene and 15 unexposed controls. The capacity to repair oxidative DNA damage was determined by use of a modified comet assay, as follows: HeLa cells, pre-treated with photosensitizer and irradiated with a halogen lamp in order to induce 7,8-dihydroxy-8-oxoguanine, were incubated with cell extracts from mononuclear leukocytes of each subject. The level of strand breaks reflects the removal of 7,8-dihydroxy-8-oxoguanine from substrate DNA by the enzymatic extract.In styrene-exposed subjects a moderate, non-significant increase in oxidative DNA repair was observed. Stratification for sex and smoking habit showed that unexposed males (P = 0.010) and unexposed smokers (P = 0.037) exhibited higher DNA-repair rates. The repair capacity did not correlate with parameters of styrene exposure and biomarkers of genotoxic effects (DNA strand breaks, N1-styrene-adenine DNA adducts, chromosomal aberrations and mutant frequencies at the HPRT locus). Significantly higher levels of DNA-repair capacity were observed in carriers of GSTM1-plus, compared to those with a deletion in GSTM1. The DNA-repair capacity was significantly lower in individuals with variant Gln/Gln genotype in XRCC1 Arg399Gln than in those with heterozygous Arg/Gln and wild-type Arg/Arg genotypes. Significantly lower repair capacity was also found in individuals with the wild-type Lys/Lys genotype in XPC Lys939Gln as compared with those homozygous for the Gln/Gln variant genotype.     

Beneficial effect of Burdock complex on asymptomatic Helicobacter pylori‐infected subjects: A randomized,double‐blind placebo‐controlled clinical trial

Background

Burdock complex (BC) constitutes of burdock (Arctium lappa), angelica (Angelica sinensis), gromwell (Lithospermum erythrorhizon), and sesame (Sesamum indicum) oil, which are commonly used in traditional Chinese medicine (TCM) for treating various disorders. This study intended to examine the anti‐H. pylori activity of BC on AGS cell model as well as in asymptomatic H. pylori‐infected subjects.

Materials and Methods

AGS cell incubated with H. pylori and treated with BC to evaluate the minimum inhibition concentration (MIC), cell viability (MTT) anti‐adhesion activity, and inflammatory markers. In case of clinical trial, H. pylori‐positive subjects (urea breath test [UBT] >10%, n = 36) were enrolled and requested to intake BC (n = 19) or placebo (n = 17) for 8 weeks. Antioxidant capacity, total phenol, UBT, inflammatory markers were analyzed at the initial, 4th, 8th, and 10th weeks. Moreover, the endoscopic examination was carried out on baseline and 10th week.

Results

In vitro studies showed that BC treatment significantly inhibited (P < .05) the inflammatory markers and adhesion of H. pylori to AGS cell. However, H. pylori‐infected subject ingested with BC for 8 weeks significantly decreased (P < .05) the UBT value, inflammatory markers with improved antioxidant activity, and phenolic levels as compared to placebo. Also, consumption of BC considerably healed the ulcer wound.

Conclusion

Overall, the BC could attenuate H. pylori infection by inhibiting H. pylori adhesion and subsequent inflammatory response on the gastric epithelial cell (AGS) as well as clinically ameliorated UBT, antioxidant capacity, and alleviated inflammation to display its anti‐H. pylori activity.     

Lipid accumulation and mitochondrial abnormalities are associated with fiber atrophy in the skeletal muscle of rats with collagen-induced arthritis

Rheumatoid arthritis (RA) has a negative impact on muscle mass, and reduces patient's mobility and autonomy. Furthermore, RA is associated with metabolic comorbidities, notably in lipid homeostasis by unknown mechanisms. To understand the links between the loss in muscle mass and the metabolic abnormalities, arthritis was induced in male Sprague Dawley rats (n = 11) using the collagen-induced arthritis model. Rats immunized with bovine type II collagen were compared to a control group of animals (n = 11) injected with acetic acid and complete Freund's adjuvant. The clinical severity of the ensuing arthritis was evaluated weekly by a semi-quantitative score. Skeletal muscles from the hind limb were used for the histological analysis and exploration of mitochondrial activity, lipid accumulation, metabolism and regenerative capacities. A significant atrophy in tibialis anterior muscle fibers was observed in the arthritic rats despite a non-significant decrease in the weight of the muscles. Despite moderate inflammation, accumulation of triglycerides (P < 0.05), reduced mitochondrial DNA copy number (P < 0.05) and non-significant dysfunction in mitochondrial cytochrome c oxidase activity were found in the gastrocnemius muscle. Concomitantly, our results suggested an activation of the muscle specific E3 ubiquitin ligases MuRF-1 and MAFbx. Finally, the adipose tissue from the arthritic rats exhibited decreased PPARγ mRNA suggesting reduced adipogenic capacities. In conclusion, the reduced adipose tissue adipogenic capacity and skeletal muscle mitochondrial capacity are probably involved in the activation of protein catabolism, inhibition of myogenesis, accumulation of lipids and fiber atrophy in the skeletal muscle during RA.     

Mangiferin ameliorates aluminium chloride-induced cognitive dysfunction via alleviation of hippocampal oxido-nitrosative stress,proinflammatory cytokines and acetylcholinesterase level

Mangiferin is a phytochemical primarily present in the stem, leaves and bark of Mangifera indica. It offers neuroprotection mainly through inhibition of oxidative stress, and decreasing proinflammatory cytokines level in the brain. Aluminium has been reported to cause oxidative stress-associated damage in the brain. In the present investigation, protective effect of mangiferin against aluminium chloride (AlCl₃)-induced neurotoxicity and cognitive impairment was studied in male Swiss albino mice. AlCl₃ (100 mg/kg) was administered once daily through oral gavage for 42 days. Mangiferin (20 and 40 mg/kg, p.o.) was given to mice for last 21 days of the study. We found cognitive dysfunction in AlCl₃-treated group, which was assessed by Morris water maze test, and novel object recognition test. AlCl₃-treated group showed elevated level of oxidative stress markers, proinflammatory cytokines level and lowered hippocampal brain-derived neurotrophic factor (BDNF) content. Mangiferin (40 mg/kg) prevented the cognitive deficits, hippocampal BDNF depletion, and biochemical anomalies induced by AlCl₃-treatment. In conclusion, our data demonstrated that mangiferin offers neuroprotection in AlCl₃-induced neurotoxicity and it may be a potential therapeutic approach in the treatment of oxido-nitrosative stress and inflammation-associated neurotoxicity.     

Shorter leukocyte telomere length is associated with severity of COVID-19 infection.

The infection by COVID-19 is a serious global public health problem. An efficient way to improve this disease's clinical management would be to characterize patients at higher risk of progressing to critically severe infection using prognostic biomarkers. The telomere length could be used for this purpose. Telomeres are responsible for controlling the number of maximum cell divisions. The telomere length is a biomarker of aging and several diseases. We aimed to compare leukocyte telomere length (LTL) between patients without COVID-19 and patients with different clinical severity of the infection. Were included 53 patients who underwent SARS-CoV-2 PCR divided in four groups. The first group was composed by patients with a negative diagnosis for COVID-19 (n = 12). The other three groups consisted of patients with a confirmed diagnosis of COVID-19 divided according to the severity of the disease: mild (n = 15), moderate (n = 17) and severe (n = 9). The LTL was determined by Q-PCR. The severe group had the shortest LTL, followed by the moderate group. The negative and mild groups showed no differences. There is an increase of patients with hypertension (p = 0.0099) and diabetes (p = 0.0067) in moderate and severe groups. Severe group was composed by older patients in comparison with the other three groups (p = 0.0083). Regarding sex, there was no significant difference between groups (p = 0.6279). In an ordinal regression model, only LTL and diabetes were significantly associated with disease severity. Shorter telomere length was significantly associated with the severity of COVID-19 infection, which can be useful as a biomarker or to better understand the SARS-CoV-2 pathophysiology.     

Low plasma lysophosphatidylcholines are associated with impaired mitochondrial oxidative capacity in adults in the Baltimore Longitudinal Study of Aging

The decrease in skeletal muscle mitochondrial oxidative capacity with age adversely affects muscle strength and physical performance. Factors that are associated with this decrease have not been well characterized. Low plasma lysophosphatidylcholines (LPC), a major class of systemic bioactive lipids, are predictive of aging phenotypes such as cognitive impairment and decline of gait speed in older adults. Therefore, we tested the hypothesis that low plasma LPC are associated with impaired skeletal muscle mitochondrial oxidative capacity. Skeletal muscle mitochondrial oxidative capacity was measured using in vivo phosphorus magnetic resonance spectroscopy (³¹P‐MRS) in 385 participants (256 women, 129 men), aged 24–97 years (mean 72.5) in the Baltimore Longitudinal Study of Aging. Postexercise recovery rate of phosphocreatine (PCr), k_PCr, was used as a biomarker of mitochondrial oxidative capacity. Plasma LPC were measured using liquid chromatography–tandem mass spectrometry. Adults in the highest quartile of k_PCr had higher plasma LPC 16:0 (p = 0.04), 16:1 (p = 0.004), 17:0 (p = 0.01), 18:1 (p = 0.0002), 18:2 (p = 0.002), and 20:3 (p = 0.0007), but not 18:0 (p = 0.07), 20:4 (p = 0.09) compared with those in the lower three quartiles in multivariable linear regression models adjusting for age, sex, and height. Multiple machine‐learning algorithms showed an area under the receiver operating characteristic curve of 0.638 (95% confidence interval, 0.554, 0.723) comparing six LPC in adults in the lower three quartiles of k_PCr with the highest quartile. Low plasma LPC are associated with impaired mitochondrial oxidative capacity in adults.     

Increased Oxidative Damage and Decreased Antioxidant Function in Aging Human Substantia Nigra Compared to Striatum: Implications for Parkinson’s Disease

Parkinson’s disease (PD) is characterized by selective degeneration and loss of dopaminergic neurons in the substantia nigra (SN) of the ventral mid brain leading to dopamine depletion in the striatum. Oxidative stress and mitochondrial damage have been implicated in the death of SN neurons during the evolution of PD. In our previous study on human PD brains, we observed that compared to SN, striatum was significantly protected against oxidative damage and mitochondrial dysfunction. To understand whether brain aging contributes to the vulnerability of midbrain to neurodegeneration in PD compared to striatum, we assessed the status of oxidant and antioxidant markers, glutathione metabolic enzymes, glial fibrillary acidic protein (GFAP) expression and mitochondrial complex I(CI) activity in SN (n = 23) and caudate nucleus (n = 24) during physiological aging in human brains. We observed a significant increase in protein oxidation (P < 0.001), loss of CI activity (P = 0.04) and increased astrocytic proliferation indicated by GFAP expression (P < 0.001) in SN compared to CD with increasing age. These changes were attributed to significant decrease in antioxidant function represented by superoxide dismutase (SOD) (P = 0.03), glutathione (GSH) peroxidase (GPx) (P = 0.02) and GSH reductase (GR) (P = 0.03) and a decreasing trend in total GSH and catalase with increasing age. However, these parameters were relatively unaltered in CD. We propose that SN undergoes extensive oxidative damage, loss of antioxidant and mitochondrial function and increased GFAP expression during physiological aging which might make it more vulnerable to neurotoxic insults thus contributing to selective degeneration during evolution of PD.     

Relationships between Inflammation,Adiponectin, and Oxidative Stress in Metabolic Syndrome

Metabolic syndrome (MS) represents a cluster of physiological and anthropometric abnormalities. The purpose of this study was to investigate the relationships between the levels of inflammation, adiponectin, and oxidative stress in subjects with MS. The inclusion criteria for MS, according to the Taiwan Bureau of Health Promotion, Department of Health, were applied to the case group (n = 72). The control group (n = 105) comprised healthy individuals with normal blood biochemical values. The levels of inflammatory markers [high sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6), adiponectin, an oxidative stress marker (malondialdehyde), and antioxidant enzymes activities [catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx)] were measured. Subjects with MS had significantly higher concentrations of inflammatory markers and lower adiponectin level, and lower antioxidant enzymes activities than the control subjects. The levels of inflammatory markers and adiponectin were significantly correlated with the components of MS. The level of hs-CRP was significantly correlated with the oxidative stress marker. The IL-6 level was significantly correlated with the SOD and GPx activities, and the adiponectin level was significantly correlated with the GPx activity. A higher level of hs-CRP (≥1.00 mg/L), or IL-6 (≥1.50 pg/mL) or a lower level of adiponectin (<7.90 µg/mL) were associated with a significantly greater risk of MS. In conclusion, subjects suffering from MS may have a higher inflammation status and a higher level of oxidative stress. A higher inflammation status was significantly correlated with decreases in the levels of antioxidant enzymes and adiponectin and an increase in the risk of MS.     

Age- and gender-related oxidative status determined in healthy subjects by means of OXY-SCORE,a potential new comprehensive index

Oxidative stress has been related to various diseases, gender and ageing, and has been measured by various markers. The authors developed a procedure to compute a global oxidative stress index (OXY-SCORE), reflecting both oxidative and antioxidant markers in healthy subjects. Its performance was tested in relation to age and gender and in coronary artery disease (CAD) patients. Eighty-two healthy subjects and 20 CAD patients were enrolled. Plasma free and total malondialdehyde (F- and T-MDA), glutathione disulphide/reduced form ratio (GSSG/GSH) and urine isoprostanes (iPF_2α-III) levels were combined as oxidative damage markers (damage score). GSH, α- and γ-tocopherol (TH) levels, and individual antioxidant capacity were combined as antioxidant defence indexes (protection score). The OXY-SCORE was computed by subtracting the protection score from the damage score. Among single parameters, T-MDA and iPF_2α-III significantly correlated with age; only GSH and both tocopherols correlated with male gender in healthy subjects. The OXY-SCORE was positively associated with age (p=0.004) and male gender (p=0.03). As expected, the OXY-SCORE was higher in CAD with a very significant p-value (<0.0001), after adjusting for age, gender and smoking. Combining different markers can potentially provide a powerful index in the evaluation of oxidative stress related to age, gender and CAD status.     

High central venous oxygen saturation is associated with mitochondrial dysfunction in septic shock: A prospective observational study

To test the hypothesis that an impaired mitochondrial function is associated with altered central venous oxygen saturation (ScvO₂), venous-to-arterial carbon dioxide tension difference (delta PCO₂) or serum lactate in sepsis patients. This prospective cohort study was conducted in a single tertiary emergency department between April 2017 and March 2019. Patients with suspected sepsis were included in the study. Serum lactate was obtained in sepsis, ScvO₂ and delta PCO₂ were evaluated in septic shock patients. Mitochondrial function was determined from the peripheral blood mononuclear cells. Forty-six patients with suspected sepsis were included. Of these, twenty patients were septic shock. Mitochondrial oxidative stress levels were increased in the high ScvO₂ group (ScvO₂ > 80%, n = 6), compared with the normal (70%-80%, n = 9) and low ScvO₂ (<70%, n = 5) groups. A strong linear relationship was observed between the mitochondrial oxidative stress and ScvO₂ (r = .75; P = .01). However, mitochondrial respiration was increased in the low ScvO₂ group. In addition, mitochondrial complex II protein levels were significantly decreased in the high ScvO₂ group (P < .05). Additionally, there was no correlation between serum lactate, delta PCO₂, and mitochondria oxidative stress or mitochondria function. ScvO₂ can be potentially useful for developing new therapeutics to reduce mitochondrial dysfunction in septic shock patient.     

BDNF VAL66MET polymorphism and memory decline across the spectrum of Alzheimer's disease

The brain-derived neurotrophic factor (BDNF) Val66Met (rs6265) polymorphism has been shown to moderate the extent to which memory decline manifests in preclinical Alzheimer's disease (AD). To date, no study has examined the relationship between BDNF and memory in individuals across biologically confirmed AD clinical stages (i.e., Aβ+). We aimed to understand the effect of BDNF on episodic memory decline and clinical disease progression over 126 months in individuals with preclinical, prodromal and clinical AD. Participants enrolled in the Australian Imaging, Biomarkers and Lifestyle (AIBL) study who were Aβ + (according to positron emission tomography), and cognitively normal (CN; n = 238), classified as having mild cognitive impairment (MCI; n = 80), or AD (n = 66) were included in this study. Cognition was evaluated at 18 month intervals using an established episodic memory composite score over 126 months. We observed that in Aβ + CNs, Met66 was associated with greater memory decline with increasing age and were 1.5 times more likely to progress to MCI/AD over 126 months. In Aβ + MCIs, there was no effect of Met66 on memory decline or on disease progression to AD over 126 months. In Aβ + AD, Val66 homozygotes showed greater memory decline, while Met66 carriers performed at a constant and very impaired level. Our current results illustrate the importance of time and disease severity to clinicopathological models of the role of BDNF Val66Met in memory decline and AD clinical progression. Specifically, the effect of BDNF on memory decline is greatest in preclinical AD and reduces as AD clinical disease severity increases.     

Durability of the humoral immune response in recovered COVID-19 patients

BackgroundThe immunological factors involved in protection against the disease caused by SARS-CoV-2 are insufficiently defined and understood. However, previous knowledge pertaining to the related SARS virus and other human coronaviruses may prove useful. Population-based serosurveys measuring anti-SARS-CoV-2 antibodies may provide a pattern for estimating infection degrees and observing the development of the epidemic. In this study, we aimed to investigate the persistence of antibody against the SARS-CoV-2 in recovered patients in Al Madinah region of Saudi Arabia.Materials and methodsA total of 150 recovered COVID-19 patients participated in this study. All the patients tested positive for the presence of SARS-CoV-2 RNA, using qualitative RT-PCR. An ELISA was used to measure anti-Spike (S) IgG antibodies in serum samples and screen for their persistence at various time points post-infection.ResultsThe patients were categorized as asymptomatic (27.3%), mild (28%) and moderate (44.7%) according to the disease severity. Amongst them, 35.3% were females (n = 53) and 64.7% were males (n = 97). Significant anti-S IgG antibody levels were observed among the different groups, with the patients in moderate group exhibiting the highest levels followed by the mild group; while the lowest levels were detected among the asymptomatic. There was a significant positive correlation between the patients’ age and anti-S IgG antibody concentrations (Pearson r = 0.45; p < 0.001).ConclusionOur findings provide a solid evidence to support the use of an anti-S IgG ELISA as a diagnostic tool to indicate SARS-CoV-2 infection. IgG seropositivity was sustained in recovered patients up to a hundred days' post-infection, the latest time point for antibody measurement in our study. Ours is the first report in Saudi Arabia to investigate the durability of humoral immune response in recovered COVID-19 patients.     

Osteochondral regeneration by a bilayered construct in a cell-free or cell-based approach

A bilayered construct with or without adipose-derived stem cells (ASCs) was applied to repair full-thickness defects in the patellar groove of 18 rabbits. Non-treated and treated defects were divided into three groups: a control group (n = 12), a cell-free group (n = 12) and a cell-based group (n = 12). Histological appearance and grading were evaluated at 8 and 12 weeks. At 12 weeks, osteochondral-like tissues completely filled in the defects and integrated with host tissues in the cell-based group. The semi-quantitative score of the cell-based group (4.2 ± 1.2), which is a total score ranging from 0 (best) to 20 (worst), was significantly better than that of the other two groups (cell-free: 13.8 ± 2.5; control: 10.3 ± 2.4). This finding indicated that the bilayered constructs combined with ASCs could be an effective way to enhance osteochondral regeneration.     

Flaxseed oil modulates testicular biometrics,hormone, libido,antioxidant and semen profiles in endangered Teressa goat of Andaman and Nicobar Islands

Teressa goat is a unique goat breed in Andaman and Nicobar Islands (ANI) of India. Effects of Flaxseed oil (FSO) supplementation in body weight (BW), scrotal circumference (SC), testicular volume (TV) and testicular weight (TW), endocrinological profiles, sex behavioural profiles (SBPs), oxidative stress markers and semen production and its quality profiles in rainy and dry summer season were studied in Teressa goat. Male goats (n = 12) of 3–4 years old were equally divided into control and treated groups. Treated animals received 25 mL FSO per day. Oral drenching of FSO was done in the morning before feeding the concentrate ration. Body weight, scrotal circumference, TV and TW were measured in bucks of FSO treated and untreated during rainy and dry summer seasons. Blood follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, thyroid stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), cortisol and prolactin, total antioxidant capacity (TAC), superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA) were measured in bucks of FSO treated and untreated during rainy and dry summer seasons. Libido score (LS), mating ability score (MAS) and sex behavioural score (SBS) were estimated at time of semen collection in bucks of FSO treated and untreated during rainy and dry summer seasons. Semen samples (n = 100; 50 semen samples from each season; each 25 semen samples from control and treatment groups per season) were collected and analysed for semen quality profiles. One-way ANOVA (control rainy, control dry, treated rainy and treated dry) revealed that BW, SC, TV and TW, FSH, LH, testosterone, TSH, T3 and T4 were higher (P < 0.05) and cortisol and prolactin were lower (P < 0.05) in FSO treated bucks of rainy season followed by untreated bucks of rainy season, FSO treated bucks of dry summer season and were lower (P < 0.05) in untreated bucks of dry summer season. Similarly, TAC, CAT, SOD and GSH, LS, MAS and SBS, and volume, pH, sperm concentration, mass activity, total motility (TM), viability, acrosomal integrity (AcI), plasma membrane integrity (PMI) and nuclear integrity (NI) were higher (P < 0.05) and MDA and TSA were lower (P < 0.05) in FSO treated bucks of rainy season followed by FSO treated bucks of dry summer season, untreated bucks of rainy season and were lower (P < 0.05) in untreated bucks of dry summer season. The results of the present study indicated that the breeding bucks suffered physiological stress (higher cortisol), oxidative stress (higher MDA and deficiency of antioxidants), hormonal imbalance (higher prolactin and cortisol and deficiency of gonadotropins, gonadal hormone and thyroid hormones) and infertility due to poor libido and poor semen production and its quality profiles during dry summer season. Thus, dry summer was more stressful season compared to rainy season for the goat bucks. FSO supplementation mitigated these stresses and improved the scrotal and testicular biometrics, libido, antioxidants, hormones and semen quality profiles in Teressa goat bucks. The current study concluded that FSO effectively improved the hormones, libido, antioxidant profiles, and scrotal and testicular biometrics with cascading beneficial effects on semen quality profiles in Teressa goat bucks under humid tropical island ecosystem of Andaman and Nicobar Islands.