Publications by authors named "Maryam Dadar"

105 Publications

Putative Vaccines Based on the Virulence Factors: A Mini-Review.

Front Microbiol 2021 3;12:704247. Epub 2021 Sep 3.

Department of English Language, Zanjan University of Medical Sciences, Zanjan, Iran.

Since the 1960s, the frequency of methicillinresistant as a recurrent cause of nosocomial infections has increased. Since multidrug-resistant has overcome antimicrobial treatment, the development of putative vaccines based on virulence factors could be a great help in controlling the infections caused by bacteria and are actively being pursued in healthcare settings. This mini-review provides an overview of the recent progress in vaccine development, immunogenicity, and therapeutic features of some macromolecules as putative vaccine candidates and their implications against human -related infections. Based on the reviewed experiments, multivalent vaccines could prevent the promotion of the diseases caused by this bacterium and enhance the prevention chance of infections.
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http://dx.doi.org/10.3389/fmicb.2021.704247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447878PMC
September 2021

Isolation of Brucella abortus biovar 1 from human lumbar disc bulging: a case report of brucellar discitis.

BMC Infect Dis 2021 Aug 19;21(1):831. Epub 2021 Aug 19.

Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran.

Background: Brucellosis is an endemic zoonotic disease with rising health and economic concerns in many areas worldwide. Musculoskeletal pains are among the main complications of human brucellosis, which are often difficult to diagnose due to the variability of clinical symptoms. Brucellar discitis is a very disabling problem in some chronic forms of the disease which may lead to serious vertebral and neurological consequences.

Case Presentation: In this case report, we reported the isolation of Brucella abortus from lumbar disc bulging in a woman who had rheumatoid arthritis and diabetes mellitus as underlying conditions. The patient had several negative brucellosis serological tests and dorsolumbar pains with urinary incontinence over a 2-month period. The diagnosis was confirmed by magnetic resonance imaging (MRI) examination of lumbar spine as well as disc culture. MRI examination was performed without intravenous contrast and revealed the presence of disc bulging, left foraminal narrowing at L5-S1, left foraminal narrowing, anterolisthesis grade II at L4-L5. The diagnosis was also confirmed by isolation of B. abortus biovar 1 from bulging disc culture. The isolate was characterized by AMOS PCR, Bruce-ladder PCR and biotyping, resulting in the identification of B. abortus from L4-L5 and L5-S1 disc bulging regions. The patient was treated with two drugs i.e. doxycycline and rifampin for 3 months. In the follow-up, in addition to improving the patient's general condition, low-back pain was also significantly reduced.

Conclusions: MRI, serology, cultural and molecular test along with patient history are important to make a rapid diagnosis of brucellosis' discitis, thereby decreasing the delay for the brucellosis treatment. The present report suggests that the infection by Brucella spp. should be fundamentally considered among the causative agents of back pain especially in the endemic areas of Brucella infections.
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http://dx.doi.org/10.1186/s12879-021-06538-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374416PMC
August 2021

Isolation of Brucella melitensis biovar 1 from human milk confirms breastfeeding as a possible route for infant infection.

Microb Pathog 2021 Aug 21;157:104958. Epub 2021 May 21.

Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran.

Brucellosis during pregnancy is associated with major concerns for mothers but, it is still not clear whether the infection could be transmitted through breastfeeding to newborns. This study aimed at evaluating the shedding of Brucella melitensis through human milk. We describe phenotypic and genotypic characterization of Brucella isolate from human milk. The characterized isolate by Bruce-ladder PCR, AMOS PCR and biotyping confirmed the presence of Brucella melitensis biovar 1 from human milk. However, the breastfeeding of newborn baby induced no serious abnormality, although occasional weakness, loss of appetite and vomiting were reported by the parents. All Brucella serological tests including RBT, SAT and 2 ME test were also positive for the baby and her mother, although the blood culture was negative for the baby. Evaluation of the blood DNA from mother and her baby also confirm the presence of Brucella melitensis in the blood samples. Therefore, the isolation of B. melitensis biovar 1 from human milk as well as presence of Brucella melitensis in the blood samples confirms breastfeeding as a possible route for infant infection.
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http://dx.doi.org/10.1016/j.micpath.2021.104958DOI Listing
August 2021

Brucellosis in Iranian livestock: A meta-epidemiological study.

Microb Pathog 2021 Jun 27;155:104921. Epub 2021 Apr 27.

Department of Environmental Health Engineering, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Brucellosis is a widespread zoonotic disease affecting human and livestock health. This meta-epidemiological study is aiming to draw a comprehensive picture of the Brucella prevalence in Iranian livestock, trying to estimate most affected subgroups as well as the most appropriate methods and sampling conditions for brucellosis screening programs. A literature search was performed among data published between 1 January 1970 and July 2020. Different subgroups were compared according to animal species, gender, age, sampling season, sampling locations as well as the diagnostic method used for brucellosis screening. To determine heterogeneity of studies, Chi-squared test was used and a random effect model (REM) estimated the pooled prevalence among subgroups. A total of 45 publications, comprising 240 studies/data-reports, were evaluated. A significant increase in the number of studies was found over time (Coefficient = 0.151, p value < 0.001). The most studied species in Iran was cow (n = 75), followed by sheep (n = 63), goat (n = 45), camel (n = 40) and Buffalo (n = 16). The most identified Brucella species in livestock were Brucella melitensis (n = 50), Brucella abortus (n = 39), mix infection of B. melitensis and B. abortus (n = 11) and vaccine strain of B. melitensis Rev1 (n = 4). PCR-based tests were the most common applied diagnostic method (n = 140), while the highest prevalence rate of positive samples was obtained by indirect ELISA (69%). The prevalence of brucellosis was significantly higher in females (10.91%) compared to males (8.23%). The meta-epidemiological study of brucellosis in Iranian livestock would help to strengthen surveillance, control and prevention approaches to counter the spread of this zoonotic disease.
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http://dx.doi.org/10.1016/j.micpath.2021.104921DOI Listing
June 2021

Iron Deficiency in Obesity and after Bariatric Surgery.

Biomolecules 2021 04 21;11(5). Epub 2021 Apr 21.

Faculty of Medicine, Ovidius University of Constanta, 900470 Constanta, Romania.

Iron deficiency (ID) is particularly frequent in obese patients due to increased circulating levels of acute-phase reactant hepcidin and adiposity-associated inflammation. Inflammation in obese subjects is closely related to ID. It induces reduced iron absorption correlated to the inhibition of duodenal ferroportin expression, parallel to the increased concentrations of hepcidin. Obese subjects often get decreased inflammatory response after bariatric surgery, accompanied by decreased serum hepcidin and therefore improved iron absorption. Bariatric surgery can induce the mitigation or resolution of obesity-associated complications, such as hypertension, insulin resistance, diabetes mellitus, and hyperlipidemia, adjusting many parameters in the metabolism. However, gastric bypass surgery and sleeve gastrectomy can induce malabsorption and may accentuate ID. The present review explores the burden and characteristics of ID and anemia in obese patients after bariatric surgery, accounting for gastric bypass technique (Roux-en-Y gastric bypass-RYGB) and sleeve gastrectomy (SG). After bariatric surgery, obese subjects' iron status should be monitored, and they should be motivated to use adequate and recommended iron supplementation.
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http://dx.doi.org/10.3390/biom11050613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142987PMC
April 2021

Environmental barium: potential exposure and health-hazards.

Arch Toxicol 2021 08 19;95(8):2605-2612. Epub 2021 Apr 19.

Council for Nutritional and Environmental Medicine, Toften 24, 8610, Mo i Rana, Norway.

The relatively widespread presence of environmental barium is raising a growing public awareness as it can lead to different health conditions. Its presence in humans may produce several effects, especially among those chronically exposed from low to moderate doses. Barium accumulation can mainly occur by exposure in the workplace or from drinking contaminated water. However, this element is also assumed with the diet, mainly from plant foods. The average amount of barium intake worldwide and its geographical variation is little known due to the lack of research attention. Barium was never considered as an essential nutrient for humans, although it is undoubtedly naturally abundant enough and distinctive in its chemical properties that it might well have some biochemical function, e.g., for regulatory purposes, both in animals and plants. The information on the potential health effects of barium exposure is primarily based on animal studies and reported as comprising kidney diseases, neurological, cardiovascular, mental, and metabolic disorders. The present paper considers exposure and potential health concerns on environmental barium, giving evidence to information that can be used in future epidemiological and experimental studies.
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http://dx.doi.org/10.1007/s00204-021-03049-5DOI Listing
August 2021

The microbiota-mediated dietary and nutritional interventions for COVID-19.

Clin Immunol 2021 05 9;226:108725. Epub 2021 Apr 9.

Council for Nutritional and Environmental Medicine, Mo i Rana, Norway. Electronic address:

Worldwide, scientists are looking for specific treatment for COVID-19. Apart from the antiviral approach, the interventions to support healthy immune responses to the virus are feasible through diet, nutrition, and lifestyle approaches. This narrative review explores the recent studies on dietary, nutritional, and lifestyle interventions that influence the microbiota-mediated immunomodulatory effects against viral infections. Cumulative studies reported that the airway microbiota and SARS-CoV-2 leverage each other and determine the pathogen-microbiota-host responses. Cigarette smoking can disrupt microbiota abundance. The composition and diversification of intestinal microbiota influence the airway microbiota and the innate and adaptive immunity, which require supports from the balance of macro- and micronutrients from the diet. Colorful vegetables supplied fermentable prebiotics and anti-inflammatory, antioxidant phytonutrients. Fermented foods and beverages support intestinal microbiota. In sensitive individuals, the avoidance of the high immunoreactive food antigens contributes to antiviral immunity. This review suggests associations between airway and intestinal microbiota, antiviral host immunity, and the influences of dietary, nutritional, and lifestyle interventions to prevent the clinical course toward severe COVID-19.
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http://dx.doi.org/10.1016/j.clim.2021.108725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8032598PMC
May 2021

The role of B vitamins in stroke prevention.

Crit Rev Food Sci Nutr 2021 Mar 16:1-14. Epub 2021 Mar 16.

Faculty of Medicine, Ovidius University of Constanta, Constanta, Romania.

Elevated plasma levels of homocysteine (Hcy) are a recognized risk factor for stroke. This relationship represents one aspect of the debated `Hcy hypothesis'. Elevated Hcy may be an independent and treatable cause of atherosclerosis and thrombotic vascular diseases. Further observations indicate that proper dietary supplementation with B-vitamins decreases total plasma Hcy concentrations and may be an effective intervention for stroke prevention. Metabolic vitamin B deficiency is a nutritional determinant of total Hcy and stroke risk. Genetic factors may link B vitamins with stroke severity due to the impact on Hcy metabolism of polymorphism in the genes coding for methylenetetrahydrofolate reductase, methionine-synthase, methionine synthase reductase, and cystathionine β-synthase. Several meta-analyses of large randomized controlled trials exist. However, they are not completely in agreement about B vitamins' role, particularly folic acid levels, vitamin B, and B, in lowering the homocysteine concentrations in people at high stroke risk. A very complex relationship exists between Hcy and B vitamins, and several factors appear to modify the preventive effects of B vitamins in stroke. This review highlights the regulating factors of the active role of B vitamins active in stroke prevention. Also, inputs for further large, well-designed studies, for specific, particularly sensitive subgroups are given.
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http://dx.doi.org/10.1080/10408398.2021.1885341DOI Listing
March 2021

Brucella species circulating in rural and periurban dairy cattle farms: a comparative study in an endemic area.

Trop Anim Health Prod 2021 Mar 8;53(2):200. Epub 2021 Mar 8.

Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran.

Brucellosis is among the most important zoonotic infectious diseases worldwide affecting both humans and domestic animals. The present study aimed to determine and compare the seroprevalence of brucellosis among rural and periurban dairy cattle farms of four Iranian provinces from 2017 to 2019. We applied different serological tests, including RBT, SAT, and iELISA to evaluate the brucellosis prevalence among 2808 dairy cattle. Species-specific multiplex PCR and biotyping tests were also used to further identify the implicated Brucella species. Serological screening using RBT, SAT, and iELISA led to 157 (5.6%), 112 (3.9%), and 139 (4.9%) positive results among tested cattle, respectively. Brucella abortus biovars 1 (2 cases) and biovars 3 (42 cases) were identified by biotyping experiments and multiplex PCR in all 44 tested lymph node samples. Further, Cohen's kappa statistical analysis revealed that the best degree of agreement was seen between RBT and iELISA (99.4%), followed by SAT/iELISA (98.5%) and finally RBT/SAT (98.4%). Our results also showed a significantly lower seroprevalence of brucellosis in periurban dairy cattle when compared to rural dairy cattle population (p value= 0.01). These results reflect the need for better vaccine coverage using RB51 combined with an appropriate test-and-slaughter program in the rural dairy cattle population.
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http://dx.doi.org/10.1007/s11250-021-02645-yDOI Listing
March 2021

The Role of Diet and Supplementation of Natural Products in COVID-19 Prevention.

Biol Trace Elem Res 2022 Jan 25;200(1):27-30. Epub 2021 Feb 25.

Council for Nutritional and Environmental Medicine (CONEM), Toften 24, 8610, Mo i Rana, Norway.

Recently, a discussion has begun on the global management strategy against COVID-19 based on the hypothesis that individuals' macro- and micronutrient status combined with antiviral drugs and herbs can be an ally against the infection. The hypothesis is that people's nutritional and oxidative scavenging capacity may provide fundamental data to predict severe and acute pulmonary distress following SARS-Cov2 infection. Consequently, the scientific community has addressed the role of balanced diets, nutritional supplements, and micronutrients, including folk herbal formulations, in reducing hospitalization and the severity of pulmonary impact in COVID-19 by preventing the most serious forms of the infection. This led to an animated debate on the potential effectiveness of some vitamins, micronutrients, and traditional Chinese medicine in preventing COVID-19, with some authors convinced that plant extracts could act oppositely, exacerbating the effect of the infection. While current research is still far to assess the suggestions and issues raised in this short communication, it is undoubtedly true that determining an individual's current metabolic status, including macro- and micronutrients, is an essential factor in defining any individuals' deficiencies, which will need to be addressed urgently through a proper diet, specific personalized nutritional supplementation, and lifestyle changes.
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http://dx.doi.org/10.1007/s12011-021-02623-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905195PMC
January 2022

Importance of brucellosis control programs of livestock on the improvement of one health.

Vet Q 2021 Dec;41(1):137-151

Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly, Uttar Pradesh, India.

Brucellosis not only represents an important health restraint on livestock but also causes high economic losses in many developing countries worldwide. Despite considerable efforts made for the control of brucellosis, the disease is still spreading in many regions (such as the Middle East) where it represents one of the most important health hazards impacting both animals and humans. The present review aims to investigate the efficacy of veterinary control programs regarding brucellosis, with a special focus on current prevention, control, and eradication approaches. The reasons for unsuccessful control programs such as the absence of highly effective vaccines and non-certified bulls are also debated, to understand why the prevalence of brucellosis in livestock is not decreasing in many areas despite considerable efforts taken to date. The importance of governmental and regional investment in brucellosis control remains one of the main limiting factors owing to the limited budget allocated to tackle this disease. In this context, one health concept has generated novel comprehensive approaches with multiple economic implications across the livestock industry and public health. However, the implementation of such global preventive strategies appears to be a key issue for many endemic and low-income countries. According to the collected data, epidemiological contexts including management and trade systems along with well-defined agro-ecological zones should be evaluated in brucellosis endemic countries to improve milk production and to enhance the sustainability of the livestock sector at both national and regional levels.
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http://dx.doi.org/10.1080/01652176.2021.1894501DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946044PMC
December 2021

The role of sugar-rich diet and salivary proteins in dental plaque formation and oral health.

J Oral Biosci 2021 06 23;63(2):134-141. Epub 2021 Jan 23.

Council for Nutritional and Environmental Medicine, Mo I Rana, Norway. Electronic address:

Background: Dental plaque is a complex colorless film of bacteria that develops on the surfaces of teeth. Different mechanisms of microbial adhesion to tooth surfaces exist. Both non-specific and specific types of adherence have been anticipated.

Highlight: The present review evaluated the effect of sugar-rich diet and salivary proteins on oral hygiene and dental plaque development.

Conclusion: The oral microbiota is essential for maintaining and reestablishing a healthy oral cavity. Different types of sugars have different effects on the inhibition and formation of dental plaque. The peptides, proteins, and amino acids secreted by parotid glands in the oral cavity facilitate neutralizing the acidity in dental plaque and preventing dental caries. A properly balanced diet is crucial for both a healthy oral cavity and the oral microbiome.
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http://dx.doi.org/10.1016/j.job.2021.01.007DOI Listing
June 2021

The impact of glutathione metabolism in autism spectrum disorder.

Pharmacol Res 2021 04 22;166:105437. Epub 2021 Jan 22.

Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy; CONEM Scientific Secretary, Verona, Italy.

This paper reviews the potential role of glutathione (GSH) in autism spectrum disorder (ASD). GSH plays a key role in the detoxification of xenobiotics and maintenance of balance in intracellular redox pathways. Recent data showed that imbalances in the GSH redox system are an important factor in the pathophysiology of ASD. Furthermore, ASD is accompanied by decreased concentrations of reduced GSH in part caused by oxidation of GSH into glutathione disulfide (GSSG). GSSG can react with protein sulfhydryl (SH) groups, thereby causing proteotoxic stress and other abnormalities in SH-containing enzymes in the brain and blood. Moreover, alterations in the GSH metabolism via its effects on redox-independent mechanisms are other processes associated with the pathophysiology of ASD. GSH-related regulation of glutamate receptors such as the N-methyl-D-aspartate receptor can contribute to glutamate excitotoxicity. Synergistic and antagonistic interactions between glutamate and GSH can result in neuronal dysfunction. These interactions can involve transcription factors of the immune pathway, such as activator protein 1 and nuclear factor (NF)-κB, thereby interacting with neuroinflammatory mechanisms, ultimately leading to neuronal damage. Neuronal apoptosis and mitochondrial dysfunction are recently outlined as significant factors linking GSH impairments with the pathophysiology of ASD. Moreover, GSH regulates the methylation of DNA and modulates epigenetics. Existing data support a protective role of the GSH system in ASD development. Future research should focus on the effects of GSH redox signaling in ASD and should explore new therapeutic approaches by targeting the GSH system.
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http://dx.doi.org/10.1016/j.phrs.2021.105437DOI Listing
April 2021

Investigation of small ruminant brucellosis among smallholder farms: The missing link in control programmes of endemic areas.

Zoonoses Public Health 2021 08 19;68(5):376-383. Epub 2020 Dec 19.

Agricultural Research, Education and Extension Organization (AREEO), Razi Vaccine and Serum Research Institute (RVSRI), Karaj, Iran.

Brucellosis is a neglected zoonotic infection with a worldwide distribution and high levels of endemism in some regions, including the Middle East. In Iran, sheep and goats constitute a major part of the livestock population, often kept by small-scale farmers for their own consumption and economic purposes. This investigation aimed at characterizing the Brucella spp. and biovars circulating in sheep and goats under smallholder farming and their potential spillover across farms. For this purpose, from two randomly selected pastoral districts of Alborz and Fars provinces in Iran, a total of 54 aborted foetuses (38 from sheep and 16 from goats) and 528 blood samples were collected from sheep (n = 435), goats (n = 77), farmers (n = 11) and dogs (n = 5). Then, serological, bacteriological and molecular characterization of Brucella isolates was performed using standard methods. Our results showed the high seroprevalence of brucellosis in pastoral districts of Fars and Alborz provinces reaching 16.3%, 11.7% and 12.7% by using the Rose Bengal plate test (RBPT), serum agglutination test (SAT) and indirect enzyme-linked immunosorbent assay (iELISA) test, respectively. Furthermore, the results of bacterial culture, conventional biotyping and PCR analyses showed the presence of Brucella melitensis biovar 1 and 2 infections among goat, farmers and dog of the Alborz farms and B. melitensis biovars 1, 2 and 3 among sheep of the Fars farms. Among nine seropositive farmer and dog blood samples (four farmers and five dogs), only three (two farmers and one dog) were positive in both culture and PCR tests. These results stress the need to strengthen screening and control measures in small flocks of small ruminants in Iran that could be the starting point of new outbreaks at the livestock/human interface. The present study also suggests that infected dogs may further maintain the risk of exposure to Brucella pathogens in small farms and beyond.
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http://dx.doi.org/10.1111/zph.12796DOI Listing
August 2021

Interrelations between COVID-19 and other disorders.

Clin Immunol 2021 03 14;224:108651. Epub 2020 Dec 14.

Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway. Electronic address:

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory tract virus that causes Coronavirus disease (COVID-19). The virus originated in Wuhan, China, in December 2019 and has spread across the globe to-date. The disease ranges from asymptomatic carriers to symptoms such as fever, sore throat, cough, lung infections, and in severe cases, acute respiratory distress syndrome, sepsis, and death. As many as 50% of patients reported having at least one comorbidities with COVID-19 upon hospital admission. Hypertension, diabetes, chronic obstructive pulmonary disease, obesity, and cardiovascular diseases are among the most commonly reported. Comorbidities are contributing to acute disease prognosis and increased risk of severe symptoms. Around 70% of patients who require ICU care have been observed to have comorbidities. This review intends to understand how some of these comorbidities affect the disease's prognosis and how severe the outcome can be expected.
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http://dx.doi.org/10.1016/j.clim.2020.108651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833539PMC
March 2021

Isolation of Brucella melitensis from seronegative camel: potential implications in brucellosis control.

Prev Vet Med 2020 Dec 2;185:105194. Epub 2020 Nov 2.

Razi Vaccine and Serum Research Institute (RVSRI), Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran. Electronic address:

Brucellosis is a significant zoonotic infection in Iran impacting both humans and animal health status. A number of reasons such as few clinical signs complicate the diagnosis of this infection in Camelidae. Despite the ubiquitous use of serological tests for the first screening of brucellosis in camel, this approach showed several restrictions because of the intracellular properties of this organism as well as decline antibody titers in chronic stage. This study aimed at identifying the presence of Brucella spp. in blood and lymph node samples collected from slaughtered male camels of Sistan-Baluchistan province by serology, culture and polymerase chain reaction (PCR) assay. For this purpose, 2854 blood camel samples were sampled and analyzed for Brucella detection by serological screening tests. The molecular detection of IS711 gene and Bruce-ladder assay as well as culture were performed using the lymph nodes of all seropositive camel (n = 10) and 30 seronegative samples. Results showed that 0.35% (10/2854), 0.24% (7/2854) and 0.21% (6/2854) of blood samples were positive by RBPT, SAT and 2ME, respectively. However, 0% (0/10) and 70% (7/10) of lymph node samples collected from seropositive camels were positive for Brucella infection by culture and PCR, respectively. Furthermore, 6.6% (2/30) of seronegative lymph node specimens showed the presences of Brucella by PCR and culture assay. The results of the present study indicated the low seroprevalence of Brucella infection in male camels of the Sistan-Baluchistan province and highlighted the complementary role of PCR techniques for a better screening of Brucella infection among seronegative camels. Moreover, the potential shedding of Brucella within undiagnosed camel milk and secretions is a serious problem which may result in further spread and maintenance of Brucella infection among both human and livestock. Thus, for brucellosis detection and control, our results suggested that a first PCR screening supported by a bacteriological isolation on positive samples should be performed along with the serological test in endemic countries to identify the source and prevent the uncontrolled spread of the disease among camels.
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http://dx.doi.org/10.1016/j.prevetmed.2020.105194DOI Listing
December 2020

Revisiting Brucellosis in Small Ruminants of Western Border Areas in Pakistan.

Pathogens 2020 Nov 10;9(11). Epub 2020 Nov 10.

Institute of Bacterial Infections and Zoonoses, Friedrich-Loeffler-Institut, 07743 Jena, Germany.

Brucellosis, globally known bacterial zoonosis, is endemic to Pakistan. in bovines, in small ruminants and in dogs mainly cause this disease. A total of 1821 sera (1196 from sheep and 625 from goats) from animal herds near the Pakistan-Afghanistan border were collected. In parallel testing of sera for anti- antibodies ( and ) was carried out by RBPT and indirect ELISA. The presence of DNA in sera was tested by real-time PCR. The overall percentage of seropositive samples was 0.99 (18/1821) by both tests. All positive samples originated from Baluchistan territory which translated into 1.76% (18/1021). None of the positive sera had signals for DNA and none of sera from goats carried detectable antibodies. Both tests showed an almost perfect agreement with Kappa statistics. The flock size was found to be associated with the presence of anti- antibodies. The samples of Khyber Pakhtunkhwa (KPK) tested negative in both serological tests and hence were not processed for real-time PCR. The present study shows the presence of anti- antibodies in sheep in the Baluchistan region of Pakistan. Diagnostic services need to be improved and test and slaughter policies might be implemented for eradication of infection in these areas. Awareness about the infection is needed at the farmer's level. Isolation and molecular biology of the isolates could help with understanding the prevailing etiology in a better way.
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http://dx.doi.org/10.3390/pathogens9110929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697571PMC
November 2020

The glutathione system in Parkinson's disease and its progression.

Neurosci Biobehav Rev 2021 01 14;120:470-478. Epub 2020 Oct 14.

Faculty of Medicine, Ovidius University of Constanta, Constanta, Romania.

Redox dysfunctions and neuro-oxidative stress play a major role in the pathophysiology and progression of Parkinson's disease (PD). Glutathione (GSH) and the reduced/oxidized glutathione (GSH/GSSG) ratio are lowered in oxidative stress conditions and may lead to increased oxidative toxicity. GSH is involved not only in neuro-immune and neuro-oxidative processes, including thiol redox signaling, but also in cell proliferation and differentiation and in the regulation of cell death, including apoptotic pathways. Lowered GSH metabolism and a low GSH/GSSG ratio following oxidative stress are associated with mitochondrial dysfunctions and constitute a critical factor in the neuroinflammatory and neurodegenerative processes accompanying PD. This review provides indirect evidence that GSH redox signaling is associated with the pathophysiology of PD. Nevertheless, it has not been delineated whether GSH redox imbalances are a causative factor in PD or whether PD-associated pathways cause the GSH redox imbalances in PD. The results show that antioxidant approaches, including neuroprotective and anti-neuroinflammatory agents, which neutralize reactive oxygen species, may have therapeutic efficacy in the treatment of PD and its progression.
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http://dx.doi.org/10.1016/j.neubiorev.2020.10.004DOI Listing
January 2021

Neurological Involvements of SARS-CoV2 Infection.

Mol Neurobiol 2021 Mar 16;58(3):944-949. Epub 2020 Oct 16.

Council for Nutritional and Environmental Medicine (CONEM), Toften 24, 8610, Mo i Rana, Norway.

COVID-19 is a pandemic viral infection caused by a novel coronavirus, SARS-CoV2, which is a global concern of the twenty-first century for its rapid spreading in a short period. Apart from its known acute respiratory involvements, the CNS manifestations of COVID-19 are common. These neurological symptoms are diverse and could range from mild nonspecific or specific symptoms such as the loss of various sensory perceptions, the worrying autoimmune Guillain-Barré syndrome, to the life-threatening acute disseminated encephalomyelitis, and the CNS-mediated respiratory distress. An autopsy report documented the presence of SARS-CoV2 in brain tissues of a COVID-19 patient. However, there is no definite conclusion on the mechanisms of SARS-CoV2 neuroinvasion. These proposed mechanisms include the direct viral invasion, the systemic blood circulation, or the distribution of infected immune cells. Concerning these different neuropathophysiologies, COVID-19 patients who are presenting with either the early-onset, multiple, and severe CNS symptoms or rapid respiratory deterioration should be suspected for the direct viral neuroinvasion, and appropriate management options should be considered. This article reviews the neurological manifestations, the proposed neuroinvasive mechanisms, and the potential neurological sequelae of SARS-CoV2.
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http://dx.doi.org/10.1007/s12035-020-02070-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7562688PMC
March 2021

Brucella melitensis infection in dog: a critical issue in the control of brucellosis in ruminant farms.

Comp Immunol Microbiol Infect Dis 2020 Dec 17;73:101554. Epub 2020 Sep 17.

Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran. Electronic address:

Canine brucellosis is a contagious disease associated with health implications for humans as well as for a wide range of wild and domesticated animals. In this study, 173 dog blood specimens were sampled from herding dogs in three different provinces including Tehran (n = 127), Qom (n = 40) and Alborz (n = 6) provinces. The presence of Brucella antibodies was determined using Rose Bengal plate test (RBPT), slow agglutination test (SAT) and 2-mercaptoethanol (2-ME), respectively. The seropositive samples were further screened using blood culture and PCR tests to identify and differentiate the implicated Brucella species. According to our results, 24.3% (42/173), 13.8% (24/173) and 6.3% (11/173) of blood samples were tested positive using RBPT, SAT and 2-ME, respectively. However, among 42 seropositive samples, only 38.1% (16/42) and 14.2% (6/42) were positive by PCR and culture, respectively. Brucella melitensis biovar 1 and biovar 2 was isolated from the bacterial cultures of 6 blood samples and confirmed by biotyping, AMOS PCR and Bruce-ladder PCR assays. These findings highlight the potential risk of Brucella transmission from dog to humans along with other livestock and reflect the critical role of infected dogs in the persistence of Brucella infections among ruminant farms. This study stresses the need for further epidemiological investigations on canine brucellosis among herding dogs and suggests the systematic screening of the disease among companion animals such as dogs in order to improve brucellosis surveillance and control programs.
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http://dx.doi.org/10.1016/j.cimid.2020.101554DOI Listing
December 2020

Biomarkers of Senescence during Aging as Possible Warnings to Use Preventive Measures.

Curr Med Chem 2021 ;28(8):1471-1488

Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway.

Human life expectancy is increasing significantly over time thanks to the improved possibility for people to take care of themselves and the higher availability of food, drugs, hygiene, services, and assistance. The increase in the average age of the population worldwide is, however, becoming a real concern, since aging is associated with the rapid increase in chronic inflammatory pathologies and degenerative diseases, very frequently dependent on senescent phenomena that occur alongside with senescence. Therefore, the search for reliable biomarkers that can diagnose the possible onset or predict the risk of developing a disease associated with aging is a crucial target of current medicine. In this review, we construct a synopsis of the main addressable biomarkers to study the development of aging and the associated ailments.
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http://dx.doi.org/10.2174/0929867327999200917150652DOI Listing
May 2021

Sulfhydryl groups as targets of mercury toxicity.

Coord Chem Rev 2020 Aug 7;417. Epub 2020 May 7.

Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway.

The present study addresses existing data on the affinity and conjugation of sulfhydryl (thiol; -SH) groups of low- and high-molecular-weight biological ligands with mercury (Hg). The consequences of these interactions with special emphasis on pathways of Hg toxicity are highlighted. Cysteine (Cys) is considered the primary target of Hg, and link its sensitivity with thiol groups and cellular damage. , Hg complexes play a key role in Hg metabolism. Due to the increased affinity of Hg to SH groups in Cys residues, glutathione (GSH) is reactive. The geometry of Hg(II) glutathionates is less understood than that with Cys. Both Cys and GSH Hg-conjugates are important in Hg transport. The binding of Hg to Cys mediates multiple toxic effects of Hg, especially inhibitory effects on enzymes and other proteins that contain free Cys residues. In blood plasma, albumin is the main Hg-binding (Hg, CHHg, CHHg, CHHg) protein. At the Cys residue, Hg binds to albumin, whereas other metals likely are bound at the N-terminal site and multi-metal binding sites. In addition to albumin, Hg binds to multiple Cys-containing enzymes (including manganese-superoxide dismutase (Mn-SOD), arginase I, sorbitol dehydrogenase, and δ-aminolevulinate dehydratase, etc.) involved in multiple processes. The affinity of Hg for thiol groups may also underlie the pathways of Hg toxicity. In particular, Hg-SH may contribute to apoptosis modulation by interfering with Akt/CREB, Keap1/Nrf2, NF-κB, and mitochondrial pathways. Mercury-induced oxidative stress may ensue from Cys-Hg binding and inhibition of Mn-SOD (Cys), thioredoxin reductase (TrxR) (Cys) activity, as well as limiting GSH (GS-HgCH) and Trx (Cys) availability. Moreover, Hg-thiol interaction also is crucial in the neurotoxicity of Hg by modulating the cytoskeleton and neuronal receptors, to name a few. However, existing data on the role of Hg-SH binding in the Hg toxicity remains poorly defined. Therefore, more research is needed to understand better the role of Hg-thiol binding in the molecular pathways of Hg toxicology and the critical role of thiols to counteract negative effects of Hg overload.
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http://dx.doi.org/10.1016/j.ccr.2020.213343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470069PMC
August 2020

The association between the incidence of COVID-19 and the distance from the virus epicenter in Iran.

Arch Virol 2020 Nov 2;165(11):2555-2560. Epub 2020 Sep 2.

Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran.

Since the first official report of the spread of SARS-CoV-2 infections in the city of Qom in mid-February, Iran has become the country most affected by the COVID-19 epidemic in the Middle East. All Iranian provinces are now affected, although to a different extent. The aim of the present study was to evaluate whether the distance from the epicenter of the infection (Qom) or demographic factors such as population density and the ratio of the elderly population are associated with the incidence of COVID-19 in different Iranian provinces. For the purpose of determining whether the distance from the virus epicenter could be associated with the spread of infection, linear regression analysis was performed using STATA 12.0 software. The association of the incidence of COVID-19 with the population density and the ratio of the population over 65 years old in 31 Iranian provinces was also evaluated. According to our results, a strong association was found between the incidence of COVID-19 in Iranian provinces and their respective distance from Qom (p < 0.001; C = -0.68). The incidence of COVID-19 in Iranian provinces was also positively associated with the ratio of the population over 65 years old (p = 0.002; C = 0.53), while no significant association with population density was found (p = 0.39; C = 0.16). These results suggest that the implementation of travel restrictions from highly affected areas to other provinces could considerably reduce the rate of transmission of the disease throughout the country. Also, provinces with a higher proportion of elderly people (over 65) were identified as particularly at risk for the spread of SARS-CoV-2 infections. These results will contribute to better management of the COVID-19 outbreak in Iran, taking into account demographic and geographic characteristics of different provinces.
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http://dx.doi.org/10.1007/s00705-020-04774-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466924PMC
November 2020

Association between the gut and oral microbiome with obesity.

Anaerobe 2021 Aug 14;70:102248. Epub 2020 Aug 14.

Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway. Electronic address:

In recent decades, obesity has become one of the most common lifestyle-associated disorders. Obesity is a major contributing factor for several other lifestyles associated disorders such as type 2 diabetes mellitus, hypertension, and cardiovascular disease. Although genetics and lifestyle have been directly implicated in the onset and progression of obesity, recent studies have established that gut microbiome plays a crucial role in obesity progression. A higher proportion of Firmicutes and a skewed Firmicutes/Bacteroidetes ratio may contribute to gut dysbiosis and subsequent disturbances in the overall body metabolisms. Like gut microbiome, the oral cavity of humans also harbors a characteristic microbial population called "oral microbiome". The oral microbiome has also been implicated in the development of obesity due to its modulating effects on the gut microbiome. Due to its critical role in obesity, alteration in the gut microbiome has been suggested as one of the therapeutic strategies to manage obesity itself. For example, fecal microbiome transfer, or the use of probiotics and prebiotics have been suggested. These therapies not only restore the gut microbiome to the "pre-obese stage" but also ameliorate many functional aspects of the metabolic syndrome such as systemic inflammation, insulin resistance, and fat accumulation. However, the efficacy and safety of some of the methods have not been tested for their long-term implications, and further research in this area is warranted to understand the molecular mechanisms involved in this process completely.
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http://dx.doi.org/10.1016/j.anaerobe.2020.102248DOI Listing
August 2021

Environmental, Neuro-immune, and Neuro-oxidative Stress Interactions in Chronic Fatigue Syndrome.

Mol Neurobiol 2020 Nov 6;57(11):4598-4607. Epub 2020 Aug 6.

Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS) is a complex, multisystem disease that is characterized by long-term fatigue, exhaustion, disabilities, pain, neurocognitive impairments, gastrointestinal symptoms, and post-exertional malaise, as well as lowered occupational, educational, and social functions. The clinical and biomarker diagnosis of this disorder is hampered by the lack of validated diagnostic criteria and laboratory tests with adequate figures of merit, although there are now many disease biomarkers indicating the pathophysiology of CFS. Here, we review multiple factors, such as immunological and environmental factors, which are associated with CFS and evaluate current concepts on the involvement of immune and environmental factors in the pathophysiology of CFS. The most frequently reported immune dysregulations in CFS are modifications in immunoglobulin contents, changes in B and T cell phenotypes and cytokine profiles, and decreased cytotoxicity of natural killer cells. Some of these immune aberrations display a moderate diagnostic performance to externally validate the clinical diagnosis of CFS, including the expression of activation markers and protein kinase R (PKR) activity. Associated with the immune aberrations are activated nitro-oxidative pathways, which may explain the key symptoms of CFS. This review shows that viral and bacterial infections, as well as nutritional deficiencies, may further aggravate the immune-oxidative pathophysiology of CFS. Targeted treatments with antioxidants and lipid replacement treatments may have some clinical efficacy in CFS. We conclude that complex interactions between immune and nitro-oxidative pathways, infectious agents, environmental factors, and nutritional deficiencies play a role in the pathophysiology of CFS.
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http://dx.doi.org/10.1007/s12035-020-01939-wDOI Listing
November 2020

The role of glutathione redox imbalance in autism spectrum disorder: A review.

Free Radic Biol Med 2020 11 31;160:149-162. Epub 2020 Jul 31.

IM Sechenov First Moscow State Medical University, Moscow, Russia; Federal Research Centre of Biological Systems, Agro-technologies of the Russian Academy of Sciences, Orenburg, Russia.

The role of glutathione in autism spectrum disorder (ASD) is emerging as a major topic, due to its role in the maintenance of the intracellular redox balance. Several studies have implicated glutathione redox imbalance as a leading factor in ASD, and both ASD and many other neurodevelopmental disorders involve low levels of reduced glutathione (GSH), high levels of oxidized glutathione (GSSG), and abnormalities in the expressions of glutathione-related enzymes in the blood or brain. Glutathione metabolism, through its impact on redox environment or redox-independent mechanisms, interferes with multiple mechanisms involved in ASD pathogenesis. Glutathione-mediated regulation of glutamate receptors [e.g., N-methyl-d-aspartate (NMDA) receptor], as well as the role of glutamate as a substrate for glutathione synthesis, may be involved in the regulation of glutamate excitotoxicity. However, the interaction between glutathione and glutamate in the pathogenesis of brain diseases may vary from synergism to antagonism. Modulation of glutathione is also associated with regulation of redox-sensitive transcription factors nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1) and downstream signaling (proinflammatory cytokines and inducible enzymes), thus providing a significant impact on neuroinflammation. Mitochondrial dysfunction, as well as neuronal apoptosis, may also provide a significant link between glutathione metabolism and ASD. Furthermore, it has been recently highlighted that glutathione can affect and modulate DNA methylation and epigenetics. Review analysis including research studies meeting the required criteria for analysis showed statistically significant differences between the plasma GSH and GSSG levels as well as GSH:GSSG ratio in autistic patients compared with healthy individuals (P = 0.0145, P = 0.0150 and P = 0.0202, respectively). Therefore, the existing data provide a strong background on the role of the glutathione system in ASD pathogenesis. Future research is necessary to investigate the role of glutathione redox signaling in ASD, which could potentially also lead to promising therapeutics.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.07.017DOI Listing
November 2020

Micronutrients as immunomodulatory tools for COVID-19 management.

Clin Immunol 2020 11 22;220:108545. Epub 2020 Jul 22.

Council for Nutritional and Environmental Medicine (CONEM), Mo i Rana, Norway. Electronic address:

COVID-19 rapidly turned to a global pandemic posing lethal threats to overwhelming health care capabilities, despite its relatively low mortality rate. The clinical respiratory symptoms include dry cough, fever, anosmia, breathing difficulties, and subsequent respiratory failure. No known cure is available for COVID-19. Apart from the anti-viral strategy, the supports of immune effectors and modulation of immunosuppressive mechanisms is the rationale immunomodulation approach in COVID-19 management. Diet and nutrition are essential for healthy immunity. However, a group of micronutrients plays a dominant role in immunomodulation. The deficiency of most nutrients increases the individual susceptibility to virus infection with a tendency for severe clinical presentation. Despite a shred of evidence, the supplementation of a single nutrient is not promising in the general population. Individuals at high-risk for specific nutrient deficiencies likely benefit from supplementation. The individual dietary and nutritional status assessments are critical for determining the comprehensive actions in COVID-19.
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http://dx.doi.org/10.1016/j.clim.2020.108545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833875PMC
November 2020

The global epidemiology of Brucella infections in terrestrial wildlife: A meta-analysis.

Transbound Emerg Dis 2021 Mar 3;68(2):715-729. Epub 2020 Aug 3.

Department of Arctic and Marine Biology, Faculty of Biosciences, Fisheries and Economics, Tromsø, Norway.

Brucellosis is a widespread zoonotic disease with serious consequences on human and animal health. Brucella infections were reported in many terrestrial wild animals, from subtropical and temperate regions to arctic regions. In many areas, the epidemiology of brucellosis in wildlife is closely associated with the occurrence of the disease in livestock. Some wild species may contribute to the re-introduction of Brucella infections in livestock (spillback), even in officially brucellosis-free (OBF) regions. Through meta-regression analysis, this study draws a global picture of the prevalence of Brucella spp. in terrestrial wild animals, trying to determine most affected subgroups as well as preferential sampling and screening methods. For this purpose, a literature search was carried out among publications published from 1983 to 2019. Different subgroups were compared according to animal species, feeding, gender, age as well as the method used for sampling and for brucellosis diagnostic. To determine heterogeneity of studies, chi-squared test was used and a random-effects model (REM) estimated the pooled prevalence among subgroups. A total of 68 publications, comprising 229 data reports/studies, were selected. The most-reported Brucella species in wildlife was Brucella abortus, and the highest prevalence rate was found in American bison, Bison bison (39.9%) followed by Alpine ibex, Capra ibex (33%). Serology was the most widely applied diagnostic approach (66%), while PCR appeared to be highly sensitive (36.62% of positive results). The gender of animals showed no significant association with the prevalence of brucellosis (p > .05). Blood samples and visceral organs constituted the great majority of specimen used for the detection of Brucella spp., while lymph nodes showed a high prevalence of positive samples (94.6%). The present study provides insight into the global epidemiology and enzootic potential of brucellosis in wild terrestrial animals worldwide, aiming at helping the appropriate authorities to strengthen prevention, surveillance and control strategies.
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http://dx.doi.org/10.1111/tbed.13735DOI Listing
March 2021

Preventive treatments to slow substantia nigra damage and Parkinson's disease progression: A critical perspective review.

Pharmacol Res 2020 11 8;161:105065. Epub 2020 Jul 8.

Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Impact Research Center, Deakin University, Geelong, Australia.

Restoring the lost physiological functions of the substantia nigra in Parkinson's disease (PD) is an important goal of PD therapy. The present article reviews a) novel drug targets that should be targeted to slow PD progression, and b) clinical and experimental research data reporting new treatments targeting immune-inflammatory and oxidative pathways. A systematic search was performed based on the major databases, i.e., ScienceDirect, Web of Science, PubMed, CABI Direct databases, and Scopus, on relevant studies performed from 1900 to 2020. This review considers the crucial roles of mitochondria and immune-inflammatory and oxidative pathways in the pathophysiology of PD. High levels of oxidative stress in the substantia nigra, as well as modifications in glutathione regulation, contribute to mitochondrial dysfunction, with a decline in complex I of the mitochondrial electron transport chain reported in PD patients. Many papers suggest that targeting antioxidative systems is a crucial aspect of preventive and protective therapies, even justifying the utilization of N-acetylcysteine (NAC) supplementation to fortify the protection afforded by intracellular glutathione. Dietary recommended panels including ketogenetic diet, muscular exercise, nutraceutical supplementation including NAC, glutathione, nicotine, caffeine, melatonin, niacin, and butyrate, besides to nonsteroidal anti-inflammatory drugs (NSAIDs), and memantine treatment are important aspects of PD therapy. The integration of neuro-immune, antioxidant, and nutritional approaches to treatment should afford better neuroprotection, including by attenuating neuroinflammation, nitro-oxidative stress, mitochondrial dysfunction, and neurodegenerative processes. Future research should clarify the efficacy, and interactions, of nicotine receptor agonists, gut microbiome-derived butyrate, melatonin, and NSAIDs in the treatment of PD.
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http://dx.doi.org/10.1016/j.phrs.2020.105065DOI Listing
November 2020

Oral immunization of trout fry with recombinant Lactococcus lactis NZ3900 expressing G gene of viral hemorrhagic septicaemia virus (VHSV).

Fish Shellfish Immunol 2020 Oct 6;105:62-70. Epub 2020 Jul 6.

Iranian Veterinary Organization, Central Veterinary Laboratory, Tehran, Iran.

This study has investigated the ability of Lactococcus lactic (NZ3900) carried G gene of viral haemorrhagic septicaemia virus (VHSV) under nisin-controlled gene expression (NICE) system in rainbow trout (O.Mykiss). Two groups of trout fry (7 ± 0.65 g) were immunized with 1 × 10 cfu/g and 1 × 10 cfu/g recombinant L. lactis NZ3900, two groups of fish were fed 1 × 10 cfu/g and 1 × 10 cfu/g L. lactis vector free, and one group was fed by the basal diet as a control. Oral immunization was done on days 1-7 and boosting was performed on days 15-21. The relative expression of IFN-1 and MX-1 genes significantly increased in head kidney of vaccinated fish depend on vaccine dosage compared to the control group. Fish in vaccinated group also showed elevated VHSV-specific antibody levels compared to the control groups. Relative percent survival (RPS), under virulent isolate VHSV challenge were estimated 62%, 78% for 10 cfu/g 10 cfu/g feed vaccinated groups 21 days post-vaccination, while groups fed similar doses of L. lactis vector free illustrated 22% and 27% RPSs, respectively. The significant reduction of viral loads (transcript levels of N gene) were detected in the immunized groups. Increased weight gain and decreased feed consumption in vaccinated group attributed to the probiotic effect were also observed. In conclusion, our results demonstrate the ability of recombinant L. lactis as oral vaccine against VHS in rainbow trout, which can be considered as effective method against different fish pathogens.
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http://dx.doi.org/10.1016/j.fsi.2020.07.007DOI Listing
October 2020
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