SARS-CoV-2 and dengue virus co-infection: Epidemiology,pathogenesis, diagnosis,treatment, and management

SARS-CoV-2 and dengue virus co-infection cases have been on the rise in dengue-endemic regions as coronavirus disease 2019 (COVID-19) spreads over the world, posing a threat of a co-epidemic. The risk of comorbidity in co-infection cases is greater than that of a single viral infection, which is a cause of concern. Although the pathophysiologies of the two infections are different, the viruses have comparable effects within the body, resulting in identical clinical symptoms in the case of co-infection, which adds to the complexity. Overlapping symptoms and laboratory features make proper differentiation of the infections important. However, specific biomarkers provide precise results that can be utilised to diagnose and treat a co-infection, whether it is simply COVID-19, dengue, or a co-infection. Though their treatment is distinguished, it becomes more complicated in circumstances of co-infection. As a result, regardless of whatever infection the first symptom points to, confirmation diagnosis of both COVID-19 and dengue should be mandatory, particularly in dengue-endemic regions, to prevent health deterioration in individuals treated for a single infection. There is still a scarcity of concise literature on the epidemiology, pathophysiology, diagnosis, therapy, and management of SARS-CoV-2 and dengue virus co-infection. The epidemiology of SARS-CoV-2 and dengue virus co-infection, the mechanism of pathogenesis, and the potential impact on patients are summarised in this review. The possible diagnosis with biomarkers, treatment, and management of the SARS-CoV-2 and dengue viruses are also discussed. This review will shed light on the appropriate diagnosis, treatment, and management of the patients suffering from SARS-CoV-2 and dengue virus co-infection.     

Immunogenicity and efficacy of a bivalent DNA vaccine containing LeIF and TSA genes against murine cutaneous leishmaniasis

There is no effective vaccine for the prevention and elimination of leishmaniasis. For this reason, we assessed the protective effects of DNA vaccines containing LeIF, TSA genes alone, or LeIF–TSA fusion against cutaneous leishmaniasis pEGFP‐N1 plasmid (empty vector) and phosphate buffer saline (PBS) were used as control groups. Therefore, cellular and humoral immune responses were evaluated before and after the challenge with Leishmania major. Lesion diameter was also measured 3–12 weeks after challenge. All immunized mice with plasmid DNA encoding Leishmania antigens induced the partial immunity characterized by increased IFN‐γ and IgG2a levels compared with control groups (p < 0.001). Furthermore, the immunized mice showed significant reduction in mean lesion sizes compared with mice in empty vector and PBS groups (p < 0.05). The reduction in lesion diameter was 29.3%, 34.1%, and 46.2% less in groups vaccinated with LeIF, TSA, and LeIF‐TSA, respectively, than in PBS group at 12th week post infection. IFN/IL‐4 and IgG2a/IgG1 ratios indicated that group receiving LeIF–TSA fusion had the highest IFN‐γ and IgG2a levels. In this study, DNA immunization promoted Th1 immune response characterized by higher IFN‐γ and IgG2a levels and also reduction in lesion size. These results showed that a bivalent vaccine containing two distinct antigens may induce more potent immune responses against leishmaniasis.     

Granulocyte‐macrophage colony‐stimulating factor,a potent adjuvant for polarization to Th‐17 pattern: an experience on HIV‐1 vaccine model

Cytokines are mediators for polarization of immune response in vaccines. Studies show that co‐immunization of DNA vaccines with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) can increase immune responses. Here, experimental mice were immunized with HIV‐1_{tat/pol/gag/env} DNA vaccine with GM‐CSF and boosted with recombinant vaccine. Lymphocyte proliferation with Brdu and CTL activity, IL‐4, IFN‐γ, IL‐17 cytokines, total antibody, and IgG1 and IgG2a isotypes were assessed with ELISA. Results show that GM‐CSF as adjuvant in DNA immunization significantly increased lymphocyte proliferation and IFN‐γ cytokines, but CTL response was tiny increased. Also GM‐CSF as adjuvant decreased IL‐4 cytokine vs mere vaccine group. IL‐17 in the group that immunized with mixture of DNA vaccine/GM‐CSF was significantly increased vs DNA vaccine group. Result of total antibody shows that GM‐CSF increased antibody response in which both IgG1 and IgG2a increased. Overall, results confirmed the beneficial effect of GM‐CSF as adjuvant to increase vaccine immunogenicity. The hallmark result of this study was to increase IL‐17 cytokine with DNA vaccine/GM‐CSF immunized group. This study for the first time provides the evidence of the potency of GM‐CSF in the induction of IL‐17 in response to a vaccine, which is important for control of infection such as HIV‐1.     

<Emphasis Type="Italic">Iranian johnsongrass mosaic virus</Emphasis>: the complete genome sequence,molecular and biological characterization,and comparison of coat protein gene sequences

Iranian johnsongrass mosaic virus (IJMV) is one of the most prevalent viruses causing maize mosaic disease in Iran. An IJMV isolate, Maz-Bah, was obtained from the maize showing mosaic symptoms in Mazandaran, north of Iran. The complete genomic sequence of Maz-Bah is 9544 nucleotides, excluding the poly(A) tail. It contains one single open reading frame of 9165 nucleotides and encodes a large polyprotein of 3054 amino acids, flanked by a 5′-untranslated region (UTR) of 143 nucleotides and a 3′-UTR of 236 nucleotides. The entire genomic sequence of Maz-Bah isolate shares identities of 84.9 and 94.2 % with the IJMV (Shz) isolate, the lone complete genome sequence available in the GenBank at the nucleotide (nt) and deduced amino acid (aa) levels, respectively. The whole genome sequences share identities of 51.5–69.8 and 44.9–74.3 % with those of other Sugarcane mosaic virus (SCMV) subgroup potyviruses at nt and aa levels, respectively. In phylogenetic trees based on the multiple alignments of the entire nt and aa sequences, IJMV isolates formed a separate sublineage of the tree with potyviruses infecting monocotyledons of cereals, indicating that IJMV is a member of SCMV subgroup of potyviruses. IJMV is most closely related to Sorghum mosaic virus and Maize dwarf mosaic virus and less closely related to the Johnsongrass mosaic virus and Cocksfoot streak virus. To further investigate the genetic relationship of IJMV, 9 other isolates from different hosts were cloned and sequenced. The identity of IJMV CP nt and aa sequences of 11 Iranian isolates ranged from 86.4 to 99.8 % and 90.5 to 99.7 %, respectively, indicating a high nt variability in CP gene. Furthermore, in the CP-based phylogenetic tree, IJMV isolates were clustered together with a maize potyvirus described as Zea mosaic virus from Israel (with 86–89 % nt identity), indicating that both isolates probably are the strains of the same virus.     

Expression of recombinant parvalbumin from wolf-herring fish and determination of its IgE-binding capability

In this study, we produced the recombinant form of parvalbumin from wolf-herring fish and determined its IgE reactivity. Parvalbumin cDNA was sub-cloned into pET28 and expressed in Escherichia coli BL-21. The immunoreactivities of the recombinant and native parvalbumins were compared, and the effect of calcium binding was determined by sera from 25 fish-allergic patients. ELISA and Western blotting confirmed similar IgE-reactivities of the recombinant and native proteins and confirmed that this phenomenon is highly dependent on calcium binding. The recombinant protein was 94.5% similar to carp parvalbumin (Cyp c1). Approximately 72% of patients reacted strongly with recombinant parvalbumin, 80% of them reacted with the native form and only 56% showed IgE reactivity with crude extract. Because the IgE-binding capacity of recombinant wolf-herring parvalbumin is retained and is highly similar to Cyp c1, the wild and hypoallergenic forms of this allergen could be used for diagnosis and immunotherapy of fish allergy, respectively.     

A microfluidic device for quantitative investigation of zebrafish larvae’s rheotaxis

Zebrafish is a model organism for various sensory-motor biological studies. Rheotaxis, or the ability of zebrafish to orient and swim against the water stream, is a common behavior that involves multiple sensory-motor processes such as their lateral line and visual systems. Due to the lack of a controllable and easy-to-use assay, zebrafish rheotaxis at larval stages is not well-understood. In this paper, we report a microfluidic device that can be used to apply the flow stimulus precisely and repeatedly along the longitudinal axis of individual zebrafish larvae to study their coaxial rheotaxis. We quantified rheotaxis in terms of the response rate and location along the channel at various flow velocities (9.5–38 mm.sec^?1). The larvae effectively exhibited a similarly high rheotactic response at low and medium velocities (9.5 and 19 mm.sec^?1); however, at high velocity of 38 mm.sec^?1, despite sensing the flow, their rheotactic response decreased significantly. The flow velocity also affected the response location along the channel. At 9.5 mm.sec^?1, responses were distributed evenly along the channel length while, at 19 and 38 mm.sec^?1, the larvae demonstrated higher rheotaxis responses at the anterior and posterior ends of the channel, respectively. This result shows that although the response is similarly high at low and medium flow velocities, zebrafish larvae become more sensitive to the flow at medium velocity, demonstrating a modulated rheotactic behavior. Employing our device, further investigations can be conducted to study the sensory-motor systems involved in rheotaxis of zebrafish larvae and other fish species.     

Is autoimmunology a discipline of its own? A big data-based bibliometric and scientometric analyses

Autoimmunology is a super-specialty of immunology specifically dealing with autoimmune disorders. To assess the extant literature concerning autoimmune disorders, bibliometric and scientometric analyses (namely, research topics/keywords co-occurrence, journal co-citation, citations, and scientific output trends – both crude and normalized, authors network, leading authors, countries, and organizations analysis) were carried out using open-source software, namely, VOSviewer and SciCurve. A corpus of 169,519 articles containing the keyword “autoimmunity” was utilized, selecting PubMed/MEDLINE as bibliographic thesaurus. Journals specifically devoted to autoimmune disorders were six and covered approximately 4.15% of the entire scientific production. Compared with all the corpus (from 1946 on), these specialized journals have been established relatively few decades ago. Top countries were the United States, Japan, Germany, United Kingdom, Italy, China, France, Canada, Australia, and Israel. Trending topics are represented by the role of microRNAs (miRNAs) in the ethiopathogenesis of autoimmune disorders, contributions of genetics and of epigenetic modifications, role of vitamins, management during pregnancy and the impact of gender. New subsets of immune cells have been extensively investigated, with a focus on interleukin production and release and on Th17 cells. Autoimmunology is emerging as a new discipline within immunology, with its own bibliometric properties, an identified scientific community and specifically devoted journals.     

Preclinical and pharmacotoxicology evaluation of α-l-guluronic acid (G2013) as a non-steroidal anti-inflammatory drug with immunomodulatory property

Context: Therapeutic effects of α-l-guluronic acid with the greatest tolerability and efficacy (G2013) have been shown in experimental model of multiple sclerosis and other in vitro and in vivo examinations regarding α-l-guluronic acid; there are no toxicological researches on its safety although the pharmacological impacts have been recorded.

Objective: This study was designed to determine the acute and sub chronic toxicity of α-l-guluronic acid in healthy male and female BALB/c mice.

Materials and methods: For the acute toxicity study, the animals orally received five different single doses of α-l-guluronic acid and were kept under observation for 14?d. In the sub-chronic study, 24 male and female BALB/c mice were divided into four groups and treated daily with test substance preparation at dose levels of 0, 50, 250, and 1250?mg/kg body weight for at least 90 consecutive days. The mortality, body weight changes, clinical signs, hematological and biochemical parameters, gross findings, histopathological, and organs weight determinants were monitored during this study.

Results: The results of acute toxicity indicated that the LD50 of α-l-guluronic acid is 4.8?g/kg. We found no mortality or abnormality in clinical signs, body weight, relative organs weight, or necropsy in any of the animals in the subchronic study. Additionally, the results showed no significant difference in hematological, biochemical, and histopathological parameters in rats.

Conclusions: Our results suggest that α-l-guluronic acid has high safety when administered orally in animals.     

A dermal equivalent developed from adipose-derived stem cells and electrospun polycaprolactone matrix: an in vitro and in vivo study

Polycaprolactone (PCL) is used as a material of choice for surgical sutures, wound dressings, contraceptives, fixation devices and dentistry in paramedical sciences. In addition, adipose-derived stem cells (ASCs) have been shown to be effective in the treatment of acute and chronic wounds. This study aimed to evaluate the effect of electrospun PCL fibers on keratinocyte differentiation of ASCs and wound healing. PCL solution was electrospun and characterized. Isolated and characterized ASCs were differentiated into keratinocyte-like cells on a tissue culture plate (TCP) and PCL matrices and compared. PCL nano-/microfibers cultured with ASCs (test group) or alone (control) were implanted as a dermal substitute for wound healing. There were significant increases in the proliferation rate and expression level of cytokeratin 14, filaggrin and involucrin in cells cultured on PCL matrices compared to TCP (p < 0.05). After histological and immunological evaluation of the reconstituted skin, a thick epidermal layer with several skin appendages was evidently observed in the ASC/PCL group, whereas no real and mature epidermis was formed, especially in the central area of the healing wound in the pure PCL group on day 14. Pure PCL, if possessing suitable properties including good adhesiveness, high proliferative capability, inductive elasticity and stiffness for migration and differentiation, could drive the keratinocyte differentiation of ASCs and act as an efficient dermal equivalent to promote wound healing.