Search

According to the United States Centers for Disease Control and Prevention (CDC), as of July 11, 2016, the reported average incidence of children diagnosed with an autism spectrum disorder (ASD) was 1 in 68 (1.46%) among 8-year-old children born in 2004 and living within the 11 monitoring sites' surveillance areas in the United States of America (USA) in 2012. ASD is a multifaceted neurodevelopmental disorder that is also considered a hidden disability, as, for the most part; there are no apparent morphological differences between children with ASD and typically developing children. ASD is diagnosed based upon a triad of features including impairment in socialization, impairment in language, and repetitive and stereotypic behaviors. The increasing incidence of ASD in the pediatric population and the lack of successful curative therapies make ASD one of the most challenging disorders for medicine. ASD neurobiology is thought to be associated with oxidative stress, as shown by increased levels of reactive oxygen species and increased lipid peroxidation, as well as an increase in other indicators of oxidative stress. Children with ASD diagnosis are considered more vulnerable to oxidative stress because of their imbalance in intracellular and extracellular glutathione levels and decreased glutathione reserve capacity. Several studies have suggested that the redox imbalance and oxidative stress are integral parts of ASD pathophysiology. As such, early assessment and treatment of antioxidant status may result in a better prognosis as it could decrease the oxidative stress in the brain before it can induce more irreversible brain damage. In this review, many aspects of the role of oxidative stress in ASD are discussed, taking into account that the process of oxidative stress may be a target for therapeutic interventions.

Brucellosis is among the most prevalent zoonotic infections in Middle Eastern and North African (MENA) countries, critically impacting human and animal health. A comprehensive review of studies on antibiotic susceptibility and therapeutic regimes for brucellosis in ruminants and humans in the MENA region was conducted to evaluate the current therapeutic management in this region. Different scientific databases were searched for peer-reviewed original English articles published from January 1989 to February 2021. Reports from research organizations and health authorities have been taken into consideration. Brucella melitensis and Brucella abortus have been reported from the majority of MENA countries, suggesting a massive prevalence particularly of B. melitensis across these countries. Several sporadic cases of brucellosis relapse, therapeutic failure, and antibiotic resistance of animal and human isolates have been reported from the MENA region. However, several studies proved that brucellae are still in-vitro susceptible to the majority of antibiotic compounds and combinations in current recommended World Health Organization (WHO) treatment regimens, for example, levofloxacin, tetracyclines, doxycycline, streptomycin, ciprofloxacin, chloramphenicol, gentamicin, tigecycline, and trimethoprim/sulfamethoxazole. The current review presents an overview on resistance development of brucellae and highlights the current knowledge on effective antibiotics regimens for treating human brucellosis.

Mutations in some miRNAs are associated with human recurrent pregnancy loss (RPL). In parallel, Mycoplasma spp. are one of the most common infections in pregnant women. The objective of this study was to identify the relationship between miRNA196a-2 gene polymorphism and Mycoplasma hominis (M. hominis) infection as a possible cause of human abortion. A total of 160 cervical swab specimens were collected from women (80 samples with at least one abortion as case, and 80 samples without abortion as control). A PCR-based method using 16S rRNA gene and tetra primer amplification refractory mutation system-polymerase chain (Tetra-ARMS-PCR) were used to identify the presence of M. hominis infections and miRNA196a-2 genotypes of studied women, respectively. Results showed that 22.5% of women with abortion and 7.5% of women without abortion were infected with M. hominis, thereby suggesting a significant difference between the two groups (P 0.05). Tetra-ARMSPCR indicated that no significant difference in frequency of genotypes existed between women experimenting abortion and control group. Independently to the presence of M. hominis infection, a significant difference (P 0.05) was observed in genotypic frequencies of miRNA196a-2 between RPL women and those with one abortion. Estimation of the Odds Ratios indicated that the chance of recurrent abortions in TT genotypes of miRNA196a-2 was about three times more likely than CC in non-infected individuals and about five times more likely than CC in M. hominis-infected patients. Our results proposed the role of miRNA196a-2 genotypes in RPL either in M. hominis-infected or non-infected individuals.

Introduction: Brucellar spondylodiscitis is among the most typical forms of osteoarticular involvement that still challenges clinicians and scientists for early diagnosis. Case Presentation: We describe the isolation of Brucella melitensis from vertebrae in a man with spondylodiscitis who had osteoarthritis as an underlying condition. The patient showed negative results on blood samples' serological, molecular, and culture tests and had low-back pain, restricted lumbar movements, headache, poor appetite, and fatigue for the past nine months. He had a history of regular ingestion of raw cow milk and milk products for a long time. First, he was misdiagnosed as lumbar disc herniation and then underwent nonsteroidal anti-inflammatory drugs and myorelaxants treatment. The lack of fast diagnosis and appropriate treatment led to severe complications of the disease. Three months after the first magnetic resonance imaging (MRI), the findings of the second MRI without intravenous contrast showed right lateral recess and canal stenosis at L4 - L5 with narrowing the thecal sac at the disc space. Abnormal enhancement of the endplates at L4 - L5 with relating epidural space-enhancing tissue in the setting of spondylodiscitis and the associated epidural abscess was seen behind L4. Moreover, extensive high signal abnormalities in paraspinal tissues at L3, L4, L5, S1, S2, and S3 were notable. The diagnosis was approved by isolating B. melitensis biovar 1 from the culture of the vertebrate body. The Brucella isolate was characterized by Bruce-ladder PCR, AMOS PCR, and classical biotyping. The patient was treated successfully with surgical intervention and triple-antibiotic, including oral doxycycline 100 mg/12 h plus oral rifampin 300 mg/12 h for three months and intramuscular streptomycin 1 g daily for the first two weeks. The patient’s general condition and low-back pain were remarkably improved in the follow-up. Conclusions: Patient histories and a series of different diagnostic procedures such as MRI, serology, molecular, and cultural tests are essential to make a rapid and accurate diagnosis of brucellar spondylodiscitis, thereby reducing the delay for brucellar spondylodiscitis treatment.

Diazion is a common pesticide which cultured fish can be exposed. There is limited information available on the possible effects of diazinon on reproductive parameters of fish. Therefore, in this study, we focused on the effects of sub-lethal doses (0, 0.8, 1.6, and 3.2 mg/L) of diazinon, an organophosphate insecticide on sex hormones, ovarian morphology, reproductive, immunity, and antioxidant related genes, in female zebrafish (Danio rerio) after 30 days of treatment. The expression of reproductive-related genes (CYP19a, Vtg, and ERα) significantly decreased, while the expression of the immune (TNFα and Il-1β) and antioxidant (SOD and CAT) related genes increased considerably. Among sex steroids, only progesterone significantly decreased after the treatment with Diazinon sub-lethal doses, while 17-β estradiol and testosterone did not change. The ovarian morphology showed a decrease in oocyte development in diazinon-treated groups. Understanding the function and mechanism of action of diazinon on the female reproductive, immune, and oxidant status may provide new strategies to counteract its adverse effects.

Camel brucellosis is a widespread and critical zoonotic infection caused by Brucella abortus and Brucella meli-tensis that negatively impact dairy and meat products.The current meta-analysis covers studies published over a course of 40 years, between 1 January 1980 and 1 April 2021, aiming to investigate the global prevalence of Brucella spp. in camels and related risk factors in different camel-keeping areas. Chi-squared test (I2 index) was applied to evaluate the heterogeneity of studies. A random-effect model (REM) estimated the pooled prevalence among subgroups. The literature search on camel brucellosis was performed among the available databases, including CABI, PubMed, Embase, Web of Science, Cochrane, Scielo, Scopus, and Science Direct. A total of 56 publications, comprising 205 data reports, were evaluated. Our results showed that the overall prevalence of camel brucellosis in the world was 9.23%. The lowest and highest prevalence rates of Brucella spp. infections among camels were reported in Oman (0.34%, 95%CI: 0.18–0.55) and Sudan (37.41%, 95%CI: 25.27–50.31), respectively. According to different risk factors, subgroup analysis showed that the location, sex, herd size, age, and mixed rearing with other animals could be considered the main risk factors impacting the occurrence of brucellosis in camels.The reported Brucella spp. in dromedary camel was Brucella melitensis (Biovar 1, 2, and 3), Brucella abor-tus (Biovar 3, 5, and 6), and Brucella suis. Our study represented remarkable differences between the prevalence of Brucella spp. in male (6.83% in 41 studies) and female (9.64% among 62 studies) camels. However, the present meta-epidemiological study would help improve control and surveillance approaches to prevent the spread of camel brucellosis among herds.

Discoloration of teeth occurs for various reasons. Common ingredients like substances from tea and coffee, as well as antibiotics like tetracycline, or food dyes, can percolate into the teeth, and, as such, these stains may persist in the porous structure of the enamel. Smoking is also contributory to dental discoloration, with toxins of tobacco smoke accumulating in a similar way. With aging, teeth tend to be discolored with accumulation of various stains in addition to the enamel gradually eroding to expose the yellow dentin.This review focused on the effect of several natural ingredients with teeth-whitening properties and their daily clinical application. Metabolic dental bleaching mechanisms, as well as tooth discoloration and decay, were also reviewed. The current scientific literature (mostly from 2000 to 2020) was consolidated from manuscripts retrieved from Scopus, PubMed, ResearchGate, and Google Scholar.Natural teeth whitening effectively lightens the natural color of teeth without eroding dental surfaces. On the other hand, commercially available whiteners containing hydrogen peroxide and carbamide peroxide, in high concentrations, can lead to deproteinization and demineralization of teeth through oxidation processes. If used extensively, these compounds may cause a number of adverse effects. Alternative natural teeth-whiteners include ingredients like lemons, strawberries, oranges, papaya, and other fruits. Such natural ingredients offer a milder and safer way of whitening teeth than whiteners containing hydrogen peroxide or carbamide peroxide.

Several vaccine candidates for COVID-19 have been developed, and few vaccines received emergency approval with an acceptable level of efficacy and safety. We herein report the development of the first recombinant protein-based vaccine in Iran based on the recombinant SARS-CoV-2 spike protein in its monomeric (encompassing amino acid 1-674 for S1 and 685-1211 for S2 subunits) and trimer form (S-Trimer) formulated in the oil-in-water adjuvant system RAS-01 (Razi Adjuvant System-01). The safety and immunity of the candidate vaccine, referred to as RAZI-COV PARS, were evaluated in Syrian hamster, BALB/c mice, Pirbright guinea pig, and New Zeeland white (NZW) rabbit. All vaccinated animals received two intramuscular (IM) and one intranasal (IN) candidate vaccine at 3-week intervals (days 0, 21, and 51). The challenge study was performed intranasally with 5×106 pfu of SARS-CoV-2 35 days post-vaccination. None of the vaccinated mice, hamsters, guinea pigs, or rabbits showed any changes in general clinical observations; body weight and food intake, clinical indicators, hematology examination, blood chemistry, and pathological examination of vital organs. Safety of vaccine after the administration of single and repeated dose was also established. Three different doses of candidate vaccine stimulated remarkable titers of neutralizing antibodies, S1, Receptor-Binding Domain (RBD), and N-terminal domain (NTD) specific IgG antibodies as well as IgA antibodies compared to placebo and control groups (P

Since the 1960s, the frequency of methicillin-resistant Staphylococcus aureus as a recurrent cause of nosocomial infections has increased. Since multidrug-resistant Staphylococcus 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 S. aureus macromolecules as putative vaccine candidates and their implications against human S. aureus-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 S. aureus infections.

Background Human α-fucosidase (EC 3.2.1.51) is a hydrolase the importance of which has been increasing in the latest years. However, data about its plasma level in children with autoimmune disorders, particularly Sjogren's syndrome (SS), are lacking. In this study, the plasma activity of L-α-fucosidase-1 (α-L-FUCA-1) was assayed in hospitalized children and adults and its association with SS and other rheumatic disorders further evaluated. Methods In total 73 Hungarian hospitalized patients, 32 children (2.5-10 years) and 41 adults (32-68 years), were enrolled in the study and underwent plasma assay of α-L-FUCA1 activity. Linear regression, Durbin-Watson (DW), and Pearson tests were evaluated to investigate the relationship between α-L-FUCA-1 plasma levels and autoimmune manifestations. Results α-L-FUCA-1 correlated with SS both in children (2-sided t test, P = 0.0023) and in adults (2-sided t test, P = 0.00035). Linear regressions showed that in other rheumatic disorders, α-L-FUCA1 did not show any differential distribution related to the particular pathology (r = 0.2042, P = 0.1531, DW test = 2.2139 positive), while this trend was radically opposite for patients with SS (r = 0.1462, P = 0.0032, DW test = 1.3664, negative). Conclusions Alterations in plasma level of α-L-FUCA-1 were significantly associated with SS. This preliminary result should encourage further research on α-L-FUCA-1 as a possible differential serological marker of SS.

This study aimed to compare the protective effect of two geographically distinct propolis against the formation of advanced glycation end products (AGEs). The polyphenol content of propolis extracts (EEPs) was analysed using HPLC‐DAD‐MS profiling and evaluated for their protective effects against pentosidine‐like AGEs. Dicarbonyl trapping capacities of major EEP compounds were determined using a methylglyoxal scavenging in vitro assay. Both propolis samples were characterised with high levels of pinobanksin derivatives exhibiting strong anti‐AGE properties. EEPs reduced AGE formation more effectively than well‐known natural AGE inhibitors such as quercetin or chlorogenic acid. Individual evaluations of the five major compounds in EEPs showed that flavonoids strongly inhibit the formation of AGEs by trapping dicarbonyl intermediates, whereas compounds such as caffeic acid derivatives only act as antioxidant agents. Propolis is thus a promising candidate for the prevention and control of AGE‐related chronic diseases.

This study investigates the effects of Coriander (C. sativum) on the growth, antioxidant, and immune‐associated genes and serum and mucosal immune parameters in zebrafish (D. rerio). The experimental fish were treated with 0 [control], 5, 10 and 20 g/kg coriander supplemented diets for 8 weeks. The results revealed that coriander remarkably increased mucosal immune parameters (the total Immunoglobulin, protease and lysozyme activity). The highest levels of the measured parameters were noticed in 20 g/kg CP treatment. Also, the zebrafish fed 20 g/kg coriander powder showed significantly higher expression gene for lysozyme and TNF‐alpha. The same results were noticed in case of IL‐1B gene expression. In case of sod gene expression there was no significant difference between treatments. However, regarding cat gene expression, significant difference was noticed between 20 g/kg CP treatment and other groups. In addition, no significant changes were observed between coriander fed zebrafish and control treatments regarding GH gene expression level, although IGF‐I remarkable up‐regulate in 20 g/kg coriander powder treatment compared other groups. In conclusion, it can be proposed that dietary Coriander powder can improve mucosal immune parameters and immune and antioxidant genes expression.

Isoniazid is an important antitubercular molecule identified as a drug of choice in tuberculosis treatment. As such, INH is an inactive prodrug; it acquires an active conformation by forming an adduct with NAD. The adduct targets inhA protein, a reductase responsible for fatty acid chain elongation in the cell wall of Mycobacterium tuberculosis. Resistance to INH is majorly contributed by mutations in inhA, katG and geneic and non-geneic regions associated with efflux genes. Despite being widespread, the mechanism of resistance remains unknown in ∼15% of INH-resistant strains. Studies report that an intracellular increase in NADH concentration prevents inhA inhibition, leading to INH resistance. In the pursuit of finding possible resistance mechanisms, we set out to find NAD binding proteins to explore similarities in structure and NAD binding property of these proteins with that of inhA. We identified 172 NAD binding proteins, of which 53 were identified to have sequence or structural similarity to inhA. By performing docking analysis on selected proteins, we identified INH-adduct to have good binding affinity despite very minimal structural similarity to inhA. This analysis was further supported by principal component analysis, which identified 65 proteins with NAD binding conformation similar to that of inhA. These findings prompt us to hypothesize that upon exposure to INH, bacteria tries to reduce inhA susceptibility by inducing expression of these NAD binding proteins through increase in NADH concentration. This in turn favours off-target binding and leads to decreased binding and potency of INH, thus contributing indirectly to INH resistance.Communicated by Ramaswamy H. Sarma.

Despite considerable efforts made to address the issue of brucellosis worldwide, its prevalence in dairy products remains difficult to estimate and represents an important public health issue in many areas of the globe today. This is partly explained by the increasing tendency for consumption of raw dairy products, making the prevention and control of this zoonosis even more critical. This review summarizes reports published since the early 2000s on human brucellosis caused by contaminated dairy products and the systems of evaluation and assessment which are used to improve the diagnosis, surveillance, control and prevention of the disease. For this purpose, five comprehensive electronic databases were investigated and relevant studies were identified for systematic review. The design and quality of the studies revealed notable variation, especially in the methods used for the detection and characterization of Brucella spp. This report provides helpful information about the health risk associated with the consumption of raw milk and relevant preventive strategies.

Chronic fatigue syndrome (CFS) is known as a multi-systemic and complex illness, which induces fatigue and long-term disability in educational, occupational, social, or personal activities. The diagnosis of this disease is difficult, due to lacking a proper and suited diagnostic laboratory test, besides to its multifaceted symptoms. Numerous factors, including environmental and immunological issues, and a large spectrum of CFS symptoms, have recently been reported. In this review, we focus on the nutritional intervention in CFS, discussing the many immunological, environmental, and nutritional aspects currently investigated about this disease. Changes in immunoglobulin levels, cytokine profiles and B- and T- cell phenotype and declined cytotoxicity of natural killer cells, are commonly reported features of immune dysregulation in CFS. Also, some nutrient deficiencies (vitamin C, vitamin B complex, sodium, magnesium, zinc, folic acid, l-carnitine, l-tryptophan, essential fatty acids, and coenzyme Q10) appear to be important in the severity and exacerbation of CFS symptoms. This review highlights a far-driven analysis of mineral and vitamin deficiencies among CFS patients.

Aim: Head and Neck Squamous Cell Carcinoma (HNSCC) is a global health problem whose incidence varies by geographic region and race according to risk factors. Human papillomavirus (HPV) infection is a significant risk factor for HNSCC. HPV-16 and HPV-18 are two forms of HPV that are carcinogenic. HNSCCs that are HPV positive have a better prognosis rather than HPV negative. The purpose of this research was to characterize HPV-16, -18 variations in the saliva of HNSCC patients by examining the genetic diversity of HPV-16, -18 utilizing the full E6, E7, and L1 genes. Methods: The case-control research included 15 patients with HNSCC and 15 healthy volunteers. Unstimulated entire saliva samples were obtained from the case and control groups by spitting method. Genomic DNA was isolated from all saliva samples. A PCR reaction was used to determine the presence of HPV in saliva. HPV-positive samples were genotyped and data were analyzed. We conducted a variant study on the HPV-16, -18 E6, and E7 genes. Results: Three patients with HNSCC were HPVpositive for two HPV genotypes out of 30 people diagnosed with HPV-DNA. HPV-16 and -18 were the most common genotypes. The HPV-16, -18 E6, and E7 genes were sequenced and compared to the HPV-16, -18 (E6, E7) prototype sequence. In all, HPV-16 lineages A1 and HPV-18 lineages A3 were discovered. Conclusion: Regarding the variation of HPV found in Iranian HNSCC patients, the need for further studies in HPV genotyping was seen. Sequencing HPV genes in HNSCC may help answer questions about HPV genotyping in the Iranian population. HPV genotype analysis aids in the development of vaccinations against HNSCC, halting disease progression and preventing HPV-associated HNSCC.

Background: RNA polymerase beta subunit (rpoB) gene analysis in bacterial communities is known as a method for determining rifampin sensitivity and genetic diversity among Brucella spp. Detection of antibiotic resistance among Brucella isolates can be a critical approach to control brucellosis. However, rpoB gene analysis of Brucella melitensis for assessing rifampicin resistance has not yet been performed in Iran, which is considered an endemic area for brucellosis. Objectives: The aim of this study was to analyze the whole sequence of rpoB genes of different B. melitensis isolates from humans to identify the single-nucleotide polymorphisms (SNPs) and mutations related to rifampin resistance and to analyze the genetic diversity of these bacteria in Iran. Methods: Between 2017 and 2019, a total of 156 blood samples along with 12 synovial fluid specimens were collected from brucellosis patients in different Iranian provinces and subjected to bacterial culture in Brucella selective media. Brucella identification was carried out using classical biotyping and molecular examinations. Polymerase chain reaction (PCR)-based amplification of the rpoB gene was performed by specific rpoB primers for whole gene sequencing. The antimicrobial susceptibility of Brucella isolates was assessed using disk diffusion susceptibility tests and minimal inhibitory concentration (MIC) methods. The presence of rifampin-binding sites and SNPs were investigated through rpoB whole gene sequencing. Results: Clinical B. melitensis isolates were obtained from blood (13) and synovial fluid (1) samples of patients from different regions of Iran. The results of MIC and disk diffusion susceptibility tests showed that all the isolates were sensitive to rifampin except for one isolate showing intermediate rifampin resistance based on the standards defined for slow-growing bacteria by the Clinical and Laboratory Standards Institute (CLSI). Gene analysis for identifying the mutations related to rifampin resistance and investigating genetic diversity showed that none of the B. melitensis isolates had missense mutations, confirming the susceptibility of all the studied isolates to rifampin. Conclusions: The present study revealed that rpoB gene analysis could be used for the efficient and precise identifying of the mutations related to rifampin resistance, investigating rifampin binding sites, and genotyping Brucella species. Furthermore, the identification of B. melitensis isolates with intermediate resistance to rifampicin highlighted the importance of periodically carrying out antibiotic susceptibility testing. The molecular detection of rpoB mutations in different Brucella isolates may help to prevent the spread of rifampin-resistant Brucella spp. among humans and livestock.

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.

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.

Probiotics improve the immune system and help to fight with different infection. The LAB ability in eliciting the immune response against foreign antigens has led to their use as candidate vectors for mucosal vaccines. Here, the use of LAB as oral vaccine carriers and various expression systems intended to the production of heterologous proteins are reviewed and discussed. Lactococcus lactis, Lactobacillus strains, and Streptococcus gordonii are lactic acid bacteria (LAB) currently being advocated for use as live antigen delivery vehicles to mucosal sites. Since these vehicles differ in their life span and mode of antigen delivery within the small intestine, in this chapter we tried to determine the promising LAB candidates for the development of oral vaccines.

The performance of probiotic bacteria and their metabolites in the control and treatment of various cancers has been shown by a number of clinical studies. Among probiotic bacteria, lactic acid bacteria are well known for their beneficial role in colonic health, where they also exert anticarcinogenic effects. These beneficial bacteria can inhibit the occurrence of cancer by (1) lowering PH, (2) reducing the level of pro-carcinogenic enzymes, (3) enhancing cell proliferation by inhibiting normal cell apoptosis and by promoting cell differentiation and cytoprotective activities, (4) suppressing inflammation-induced cell apoptosis, (5) enhancing innate immunity, (6) promoting various gut homeostasis, and (7) displaying antioxidant activity. Several research findings showed that probiotic metabolites (postbiotics) can regulate cell proliferation in colorectal cancer and might be considered a therapeutic alternative for treating chemoresistant colorectal cancer. These metabolites including short-chain fatty acids, exopolysaccharides, vitamins, bacteriocin, H2O2, etc. are known to be involved in decreasing the viability of cancer cells and the induction of apoptosis by influencing different signaling pathway. Despite the general definition that probiotics are live microorganisms, a variety of biological responses have been reported from administering dead and frequently heat-killed (Paraprobiotic) probiotic bacterial cultures to various mammalians. The preparations of dead cells have also been fractionated and various cellular components shown to produce a range of biological responses. Many of the biological responses found with the heat-killed probiotic bacterial cells are not antimicrobial effects but are, rather, immunomodulating effects. Owing to the fact that probiotics, paraprobiotics and metabiotics or postbiotics metabolites are the most widely studied biological therapeutic alternatives for the treatment of cancer; hence in this chapter their functions and mechanism of action would be elucidated.

The significant increase in food allergy severity and prevalence stresses the need for efficient preventive strategies to reduce life-threatening allergic reactions, particularly among children. At present, there is no cure for food allergy and the eviction of triggers remains the main preventive strategy. The gut microbiome was found to play a key role in the development and pathogenesis of food allergy, opening new therapeutic possibilities. Differences in gut microbiomes were reported between allergic and healthy individuals, suggesting that imbalances in the gut microbial environment likely precede the development of food allergy. The administration of probiotics and prebiotics has been proposed as a safe non-allergen specific therapy with promising outcomes for food allergy treatment. Although numerous studies support the effective role of the probiotics and prebiotics against different allergy conditions, these beneficial impacts appeared to be highly strain specific and particularly observed in pediatric studies. This chapter tries to address the potentials of prebiotics and probiotics in the prevention or treatment of food allergy in the light of preclinical and clinical investigations.

Abstract:: 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.

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.

Brucellosis is an endemic infection in Iran and represents a serious health problem in humans and livestock causing important economic losses. The objective of this study was to undertake molecular characterization of Brucella spp. isolated from humans and livestock in several provinces of Iran including by multi-locus sequence typing (MLST), in order to understand the genotypes circulating in Iran and their relationship to genotypes globally. A total of 23 Brucella isolates were isolated from eight milk samples (seven cows, and one camel), human blood samples (seven), bovine lymph nodes (two), and samples from aborted fetuses (three sheep, two cows, and one goat). Phenotypic and molecular identification of Brucella isolates was performed on all isolated bacteria and showed that all were either Brucella melitensis or Brucella abortus. B. melitensis was associated with ovine/caprine and camel samples, most human isolates, and a significant minority of cattle isolates. In contrast B. abortus from livestock was associated only with isolations from bovine samples, as well as a single human sample. These results indicate that both B. melitensis and B. abortus contribute to the human brucellosis burden in Iran. B. melitensis isolates comprised three MLST-9 genotypes, the common and globally distributed ST8, a single representative of ST7, and several additional examples of ST102, a genotype previously only reported in a single isolate from a human brucellosis case believed to be acquired through travel to Iran. B. abortus isolates represented two globally common MLST-9 genotypes (ST1 and ST2), with relationships to biotype and other PCR-based typing methods consistent with previous observations. The results provide the basis for further studies examining the molecular epidemiology of Brucella circulating in Iran and the relationships of local isolates to those present globally.

The development of COVID-19 vaccines was promptly regulated to ensure the best possible approach. By January 2022, 75 candidates reached preclinical evaluation in various animal models, 114 vaccines were in clinical trials on humans, and 48 were in the final testing stages. Vaccine platforms range from whole virus vaccines to nucleic acid vaccines, which are the most promising in prompt availability and safety. The USA and Europe have approved vaccines developed by Pfizer-BioNTech (BNT162b2) and Moderna (mRNa1273). So far, Pfizer-BioNTech, Moderna, JohnsonJohnson, AstraZeneca-University of Oxford, Sinopharm, Sinovac Biotech Gamaleya, Bharat Biotech, and Novavax have documented effective vaccines. Even with technological advances and a fast-paced development approach, many limitations and problems need to be overcome before a large-scale production of new vaccines can start. The Key is to ensure equal and fair distribution globally through regulatory measures. Recent studies link Bacillus Calmette-Guérin (BCG) vaccination programs and lower disease severity.

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

The presence of Brucella infections was documented in a large number of aquatic mammals, affecting wild animals living in oceans, seas, lakes and rivers within both northern and southern hemispheres. Through meta‑regression analysis, this study provides acom prehensive view of the prevalence of Brucella spp. in aquatic mammals, identifying risksu bgroups as well as most common sampling and testing methods. Brucella ceti and Brucella pinnipedialis represent the main marine Brucella spp., with documented enzootic potential, for which information on standardized diagnostic methods for the implementation of efficient screening and monitoring programs is needed. A total of 71 articles investigating the occurrence of brucellosis in aquatic mammals have been reported since 1987. The prevalence of brucellosis in males (30.42%) was significantly higher than females (18.59%). The family of Delphinidae was the most studied among aquatic mammals with a total prevalence of 39.66%. Our meta‑regression analysis showed a strong and significant association between the prevalence of Brucella spp. in mammals and water temperature (C = 0.02, p value = 0.003), while no significant correlation was found with water salinity (C = ‑ 0.09; p value = 0.10). At least 130 species of aquatic mammals have been identified as potential hosts for Brucella spp. There is no systematic veterinary inspection and global or local requirements for the monitoring of brucellosis in aquatic mammals. The association of brucellosis prevalence and water temperature warrants further studies to assess the potential direct and indirect impacts of climate change on brucellosis in aquatic mammals. This study would help to determine the basis of adaptive management strategies in order to control enzootic brucellosis in wild aquatic mammals.

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.

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. In vivo, 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(2+), CH(3)Hg(+), C(2)H(5)Hg(+), C(6)H(5)Hg(+)) protein. At the Cys(34) residue, Hg(2+) 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(196)), thioredoxin reductase (TrxR) (Cys(497)) activity, as well as limiting GSH (GS-HgCH(3)) and Trx (Cys(32, 35, 62, 65, 73)) 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.

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.

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 × 1010 cfu/g and 1 × 108 cfu/g recombinant L. lactis NZ3900, two groups of fish were fed 1 × 1010 cfu/g and 1 × 108 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 108 cfu/g 1010 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.

Background and Objectives: Brucellosis is a widespread zoonotic disease with a high prevalence in both animals and humans. The present study was aimed to evaluate the susceptibility of Brucella strains isolated from human clinical specimens against commonly used antimicrobial agents. Materials and Methods: A total of 360 blood specimens were collected during 2016–2018 and subjected to culture and Brucella spp. identification. The classical biotyping for Brucella isolates was performed according to Alton and coworker’s guidelines. Antimicrobials susceptibility test carried out using disk diffusion and minimal inhibitory concentration (MIC) methods. Results: In this study, sixty B. melitensis strains were isolated from blood samples (16%) and all them belonged to biovar 1. Majority of the tested antibacterial agents, excepting ampicillin-sulbactam had an effective activity against B. melitensis isolates in E-test (MIC) and disk diffusion method. Moreover, probable resistance to rifampin and ampicillin-sulbactam were observed in 60 (100%), 1 (1.7%), 11 (18.4%) and 2 (3.4%) isolates, respectively. Conclusion: Our data suggest that the efficacy of commonly used antibiotics for brucellosis treatment should be regularly monitored. In conclusion, appropriate precaution should be exercised in the context of antibiotic administration to prevent future antibiotic resistance.

There is an emerging body of evidence associating children having autism spectrum disorder (ASD) with gastrointestinal (GI) symptoms, such as abdominal pain, chronic diarrhea, constipation, vomiting, gastroesophageal reflux, intestinal infections, and increased intestinal permeability. Moreover, in many studies, large differences in the composition of intestinal microbiota and metabolic products between ASD patients and controls were reported. Deepening the role and the biology of the gut microbiome may be fundamental to elucidate the onset of GI symptoms in ASD individuals and their etiopathogenetic causes. The gut-brain axis may affect brain development and behaviors through the neuroendocrine, neuroimmune, and autonomic nervous systems.

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.

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.

Mercury (Hg) is widely recognized as a neurotoxic metal, besides it can also act as a proinflammatory agent and immunostimulant, depending on individual exposure and susceptibility. Mercury exposure may arise from internal body pathways, such as via dental amalgams, preservatives in drugs and vaccines, and seafood consumption, or even from external pathways, i.e., occupational exposure, environmental pollution, and handling of metallic items and cosmetics containing Hg. In susceptible individuals, chronic low Hg exposure may trigger local and systemic inflammation, even exacerbating the already existing autoimmune response in patients with autoimmunity. Mercury exposure can trigger dysfunction of the autoimmune responses and aggravate immunotoxic effects associated with elevated serum autoantibodies titers. The purpose of the present review is to provide a critical overview of the many issues associated with Hg exposure and autoimmunity. In addition, the paper focuses on individual susceptibility and other health effects of Hg.

Uranium (U) has no known essential biological functions. Furthermore, it is well known for its toxicity, radioactivity, and carcinogenic potency. Impacts on human health due to U exposure have been studied extensively by many researchers. Chronic exposure to low-level U isotopes (radionuclides) may be interlinked with cancer etiology and at high exposure levels, also kidney disease. Other important issues covered U and fertilizers, and also U in soils or human tissues as an easily measurable indicator element in a pathophysiological examination. Furthermore, phosphate fertilization is known as the important source of contamination with U in the agricultural land, mainly due to contamination in the phosphate rock applied for fertilizer manufacture. Therefore, long-term usage of U-bearing fertilizers can substantially increase the concentration of U in fertilized soils. It should also be noted that U is an active redox catalyst for the reaction between DNA and H2O2. This review is aimed to highlight a series on various hydro-geochemical aspects in different water sources and focused on the comparison of different U contents in the drinking water sources and presentation of data in relation to health issues.

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.

Coronaviruses are the well-known cause of severe respiratory, enteric and systemic infections in a wide range of hosts including man, mammals, fish, and avian. The scientific interest on coronaviruses increased after the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreaks in 2002-2003 followed by Middle East Respiratory Syndrome CoV (MERS-CoV). This decade’s first CoV, named 2019-nCoV, emerged from Wuhan, China, and declared as ‘Public Health Emergency of International Concern’ on January 30th, 2020 by the World Health Organization (WHO). As on February 4, 2020, 425 deaths reported in China only and one death outside China (Philippines). In a short span of time, the virus spread has been noted in 24 countries. The zoonotic transmission (animal-to-human) is suspected as the route of disease origin. The genetic analyses predict bats as the most probable source of 2019-nCoV though further investigations needed to confirm the origin of the novel virus. The ongoing nCoV outbreak highlights the hidden wild animal reservoir of the deadly viruses and possible threat of spillover zoonoses as well. The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas.

As a major neurodevelopmental disorder, Autism Spectrum Disorder (ASD) encompasses deficits in communication and repetitive and restricted interests or behaviors in childhood and adolescence. Its etiology may come from either a genetic, epigenetic, neurological, hormonal, or an environmental cause, generating pathways that often altogether play a synergistic role in the development of ASD pathogenesis. Furthermore, the metabolic origin of ASD should be important as well. A balanced diet consisting of the essential and special nutrients, alongside the recommended caloric intake, is highly recommended to promote growth and development that withstand the physiologic and behavioral challenges experienced by ASD children. In this review paper, we evaluated many studies that show a relationship between ASD and diet to develop a better understanding of the specific effects of the overall diet and the individual nutrients required for this population. This review will add a comprehensive update of knowledge in the field and shed light on the possible nutritional deficiencies, metabolic impairments (particularly in the gut microbiome), and malnutrition in individuals with ASD, which should be recognized in order to maintain the improved socio-behavioral habit and physical health.

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.

Viral hemorrhagic septicemia virus (VHSV) is a most serious systemic finfish virus that is transported through at least 50 species of freshwater and marine host located in the northern hemisphere. The virus is an enveloped RNA virus in the order, Mononegavirales, family Rhabdoviridae, and genus Novirhabdovirus. The disease was first reported from Denmark by Schaperclaus following mortality at Danish rainbow trout farms in 1938 with what he reported as infectious kidney swelling and liver degeneration. The economically most important pathogenic Rhabdoviridae is VHS that shares six genes named as (nucleoprotein) N, (phosphoprotein) P, (matrix protein) M, (glycoprotein) G, (nonstructural viral protein) NV, and (RNA polymerase) L. The arrangement of genes contains the order 3′-N-P-M-G-NV-L-5′. Serotyping was the most used approach for the identification of subgroup isolates, but currently, genotyping is done with the genes of G and N. According to the various studies, isolates of VHSV are divided into four genotypes (I–IV), which contain different sublineages within genotypes I (minimum Ia–Ie), which include isolates from the mortality of rainbow trout in the continental Europe, as well as isolates of wild marine fish. In addition, the sublineages of IV contain IVa–IVb, which thought to be related to the geographical regions of isolations. This chapter describes the molecular and epidemiological features of VHSV and presents up to date information about the VHSV distribution.

Research on the etiopathogenesis of Parkinson's disease (PD) has in the very recent years earned many insightful cues about the involvement of xenobiotics and metal pollutants in the onset and exacerbation of this neurodegenerative disorder. Furthermore, particularly for metal pollutants, the hypothesis about the role exerted by impaired mitochondrial function is gaining a leading causative role. In this review, we outline the role of environmental pollution in the pathogenesis of PD, as the prolonged exposure to xenobiotics may account for the majority of PD reported cases, expanding the debate also about some suggested therapeutic approaches.

Inflammation is part of the regular host reaction to injury or infection caused by toxic factors, pathogens, damaged cells, irritants, and allergens. Antiinflammatory peptides (AIPs) are present in all living organisms, and many peptides from herbal, mammalian, bacterial, and marine origins have been shown to have antimicrobial and/or antiinflammatory properties. In this study, we investigated the effects of antiinflammatory peptides on inflammation, and highlighted the underlying mechanisms responsible for these effects. In multicellular organisms, including humans, AIPs constitute an essential part of their immune system. In addition, numerous natural and synthetic AIPs are effective immunomodulators and can interfere with signal transduction pathways involved in inflammatory cytokine expression. Among them, some peptides such as antiflammin, N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), and those derived from velvet antler proteins, bee venom, horse fly salivary gland, and bovine β-casein have received considerable attention over the past few years. This article presents an overview on the major properties and mechanisms of action associated with AIPs as immunomodulatory, chemotactic, antioxidant, and antimicrobial agents. In addition, the results of various studies dealing with effects of AIPs on numerous classical models of inflammation are reviewed and discussed.