\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,english]{babel}



\usepackage{float}








\begin{document}

\title{PROTECTIVE ROLE OF CORTISTATIN IN PULMONARY INFLAMMATION AND FIBROSIS}



\author[1]{Margarita Barriga}%
\author[1]{Raquel Benitez}%
\author[2]{Viviane Ferraz-de-Paula}%
\author[1]{Marta Caro}%
\author[3]{Gema Robledo}%
\author[4]{Francisco O'Valle}%
\author[1]{Jenny Campos-Salinas}%
\author[3]{Mario Delgado}%
\affil[1]{Instituto de Parasitologia y Biomedicina Lopez-Neyra}%
\affil[2]{School of Veterinary Medicine, University of São Paulo}%
\affil[3]{Institute of Parasitology and Biomedicine López-Neyra}%
\affil[4]{University ofGranada}%


\vspace{-1em}



  
  \date{May 24, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Background and Purpose: Acute lung injury (ALI), acute respiratory
distress syndrome (ARDS) and pulmonary fibrosis remain major causes of
morbidity, mortality and healthcare burden in the critically ill
patient. There is an urgent medical need for identifying factors of
susceptibility and prognosis and for designing new therapeutic tools for
treating these disorders. Here, we evaluate the capacity of the
immunomodulatory neuropeptide cortistatin to regulate pulmonary
inflammation and fibrosis in vivo. Experimental Approach: ALI/ARDS and
pulmonary fibrosis were induced experimentally in wild-type and
cortistatin-deficient mice by pulmonary infusion of the bacterial
endotoxin LPS or the chemotherapeutic drug bleomycin, and the
histopathological signs, pulmonary leukocyte infiltration and cytokines
and fibrotic markers were evaluated. Key Results: Partially-deficient
mice in cortistatin showed exacerbated pulmonary damage, pulmonary
inflammation, alveolar oedema and fibrosis, and subsequent increased
respiratory failure and mortality when challenged to LPS or bleomycin,
even at low doses. Treatment with cortistatin reversed these aggravated
phenotypes and protected from progression to severe ARDS and fibrosis
after high-exposition to both injury agents. Moreover,
cortistatin-deficient pulmonary macrophages and fibroblasts showed
exaggerated ex vivo inflammatory and fibrotic responses. The
anti-fibrotic protective effect of cortistatin was also observed in
experimental scleroderma, in which lack of cortistatin predisposes to
develop more severe dermal lesions and associated pulmonary fibrosis.
Conclusion and Implications: We identify to cortistatin as an endogenous
break of pulmonary inflammation and fibrosis. Deficiency in cortistatin
could be a marker of poor-prognosis in inflammatory/fibrotic pulmonary
disorders. Cortistatin-based therapies emerge as attractive candidates
to treat severe ALI/ARDS, including SARS-Cov-2-associated ARDS.%
\end{abstract}%



\sloppy


\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-3/Figure-3}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-4/Figure-4}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-5/Figure-5}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-6/Figure-6}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-7/Figure-7}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-8/Figure-8}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-9/Figure-9}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Fig-10/Fig-10}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

