Epigenetic Modifications and Therapy in Chronic Obstructive Pulmonary Disease (COPD): An Update Review.

Chronic obstructive pulmonary disease (COPD) that is one of the most prevalent chronic adult diseases and the third leading cause of fatality until 2020. Elastase/anti-elastase hypothesis, chronic inflammation, apoptosis, oxidant-antioxidant balance and infective repair cause pathogenesis of COPD are among the factors at play. Epigenetic changes are post-translational modifications in histone proteins and DNA such as methylation and acetylation as well as dysregulation of miRNAs expression. In this update review, we have examined recent studies on the upregulation or downregulation of methylation in different genes associated with COPD. Dysregulation of HDAC activity which is caused by some factors and miRNAs plays a key role in the suppression and reduction of COPD development. Also, some therapeutic approaches are proposed against COPD by targeting HDAC2 and miRNAs, which have therapeutic effects

A novel approach to inhibit HIV-1 infection and enhance lysis of HIV by a targeted activator of complement

<p>Abstract</p> <p>Background</p> <p>The complement system is one of the most potent weapons of innate immunity. It is not only a mechanism for direct protection against invading pathogens but it also interacts with the adaptive immunity to optimize the pathogen-specific humoral and cellular defense cascades in the body. Complement-mediated lysis of HIV is inefficient but the presence of HIV particles results in complement activation by the generation of many C3-fragments, such as C3dg and C3d. It has been demonstrated that activation of complement can enhance HIV infection through the binding of special complement receptor type 2 expression on the surface of mature B cells and follicular dendritic cells.</p> <p>Presentation of the hypothesis</p> <p>Previous studies have proven that the complement-mediated antibody-dependent enhancement of HIV infection is mediated by the association of complement receptor type 2 bound to the C3 fragment and deposited on the surface of HIV virions. Thus, we hypothesize that a new activator of complement, consisting of a target domain (C3-binding region of complement receptor type 2) linked to a complement-activating human IgG1 Fc domain (CR2-Fc), can target and amplify complement deposition on HIV virions and enhance the efficiency of HIV lysis.</p> <p>Testing the hypothesis</p> <p>Our hypothesis was tested using cell-free HIV-1 virions cultivated <it>in vitro </it>and assessment of virus opsonization was performed by incubating appropriate dilutions of virus with medium containing normal human serum and purified CR2-Fc proteins. As a control group, viruses were incubated with normal human serum under the same conditions. Virus neutralization assays were used to estimate the degree of CR2-Fc-enhanced lysis of HIV compared to untreated virus.</p> <p>Implications of the hypothesis</p> <p>The targeted complement activator, CR2-Fc, can be used as a novel approach to HIV therapy by abrogating the complement-enhanced HIV infection of cells.</p

A new therapeutic strategy for lung tissue injury induced by influenza with CR2 targeting complement inhibitior

<p>Abstract</p> <p>Background</p> <p>Influenza is a respiratory disease that seriously threatens human health. In fact, influenza virus itself does not make critical contribution to mortality induced by influenza, but "cytokine storm" produced by the excessive immune response triggered by the virus can result in inflammatory reaction of lung tissues and fatal lung tissue injury, and thus increase influenza mortality. Therefore, besides antiviral drugs, immunosuppression drugs should also be included in infection treatment.</p> <p>Presentation of the hypothesis</p> <p>Complement is the center of inflammatory reaction. If complement system is over activated, the body will have strong inflammatory reaction or tissue injury, resulting in pathological process. Many studies have proved that, inflammatory injury of lung tissues caused by influenza virus is closely related to complement activation. Therefore, inhibiting complement activation can significantly reduce inflammatory injury in lung tissues. As complement is both a physiological defense and pathological damage medium, systematic inhibition may result in side effects including infection. Therefore, we design targeting complement inhibitors for complement activation sites, i.e. with CR2 as targeting vector, complement inhibitors like CD59 and Crry are targeted to inflammatory sites to specially inhibit the complement activation in local injury, thus local inflammatory reaction is inhibited.</p> <p>Testing the hypothesis</p> <p>CR2-CD59 and CR2-Crry targeting complement inhibitors are fusion-expressed, and their biological activity is examined via in <it>vivo </it>and in vitro tests. CR2 targeting complement inhibitors are used to treat mouse influenza viral pneumonia model, with PBS treatment group as the control. The survival and lung tissue injury of the mice is observed and the effect of CR2 targeting complement inhibitors on pneumonia induced by influenza virus is evaluated.</p> <p>Implications of the hypothesis</p> <p>CR2 targeting complement inhibitors are expected to be ideal drugs for viral pneumonia.</p

Spatial and temporal monitoring of wildfires in Golestan province using remote sensing data

Wildfires are one of the most significant factors of ecosystem change. Knowing the wildfire regime (frequency, intensity, and distribution pattern) is essential in wildfire management. This research aims to analyze the spatiotemporal pattern of wildfires in Golestan in 2001-2021 using MODIS data, burned area product (MCD64A1). For this purpose, the annual and monthly frequency, as well as the trend of wildfires based on types of forest, pasture, and crop cover, were statistically analyzed. The local Moran pattern analysis method and kernel density function were used to analyze the spatial dynamics of wildfire. The results showed that 18,462 wildfires occurred in Golestan, the highest of which was in 2010, with 2,517 wildfires (13.8%). The lowest number of wildfires, with only 57 events (0.5%), was in 2001. Based on the local Moran model results and the kernel density function, the wildfires' extent and intensity were greater in the plains and foothills to the south and southeast of Golestan. The lowest extent and intensity of the wildfire corresponded to the eastern parts of the province. The frequency of wildfires was higher in the hot period of the year (spring and summer). However, the period of occurrence of wildfire and the peak of wildfire changes in different uses. The wildfire zones in June were wider and more intense than in other months. The frequency and spatial extent of wildfires in agricultural lands from May to July, pasture lands in July, August, and September, and forest lands in November and December were more than in other months. Weather conditions play a significant role in the occurrence of wildfire in the forest lands of Golestan. The results of this research help understand wildfire risk areas and provide a scientific basis for predicting and controlling wildfires and reducing carbon emissions related to them

A novel trifunctional IgG-like bispecific antibody to inhibit HIV-1 infection and enhance lysis of HIV by targeting activation of complement

BACKGROUND: The complement system is not only a key component of innate immunity but also provides a first line of defense against invading pathogens, especially for viral pathogens. Human immunodeficiency virus (HIV), however, possesses several mechanisms to evade complement-mediated lysis (CoML) and exploit the complement system to enhance viral infectivity. Responsible for this intrinsic resistance against complement-mediated virolysis are complement regulatory membrane proteins derived from the host cell that inherently downregulates complement activation at several stages of the cascade. In addition, HIV is protected from complement-mediated lysis by binding soluble factor H (fH) through the viral envelope proteins, gp120 and gp41. Whereas inhibition of complement activity is the desired outcome in the vast majority of therapeutic approaches, there is a broader potential for complement-mediated inhibition of HIV by complement local stimulation. PRESENTATION OF THE HYPOTHESIS: Our previous studies have proven that the complement-mediated antibody-dependent enhancement of HIV infection is mediated by the association of complement receptor type 2 bound to the C3 fragment and deposited on the surface of HIV virions. Thus, we hypothesize that another new activator of complement, consisting of two dsFv (against gp120 and against C3d respectively) linked to a complement-activating human IgG1 Fc domain ((anti-gp120 × anti-C3d)-Fc), can not only target and amplify complement activation on HIV virions for enhancing the efficiency of HIV lysis, but also reduce the infectivity of HIV through blocking the gp120 and C3d on the surface of HIV. TESTING THE HYPOTHESIS: Our hypothesis was tested using cell-free HIV-1 virions cultivated in vitro and assessment of virus opsonization was performed by incubating appropriate dilutions of virus with medium containing normal human serum and purified (anti-gp120 × anti-C3d)-Fc proteins. As a control group, viruses were incubated with normal human serum under the same conditions. Virus neutralization assays were used to estimate the degree of (anti-gp120 × anti-C3d)-Fc lysis of HIV compared to untreated virus. IMPLICATIONS OF THE HYPOTHESIS: The targeted complement activator, (anti-gp120 × anti-C3d)-Fc, can be used as a novel approach to HIV therapy by abrogating the complement-enhanced HIV infection of cells