RESUMEN
BACKGROUND: Acute lung injury (ALI) is caused by bacterial, fungal, and viral infections. When pathogens invade the lungs, the immune system responds by producing cytokines, chemokines, and interferons to promote the infiltration of phagocytic cells, which are essential for pathogen clearance. Their excess production causes an overactive immune response and a pathological hyper-inflammatory state, which leads to ALI. Until now, there is no particular pharmaceutical treatment available for ALI despite known inflammatory mediators like neutrophil extracellular traps (NETs) and reactive oxygen species (ROS). OBJECTIVES: Therefore, the primary objective of this review is to provide the clear overview on the mechanisms controlling NETs, ROS formation, and other relevant processes during the pathogenesis of ALI. In addition, we have discussed the significance of epithelial and endothelial damage indicators and several molecular signaling pathways associated with ALI. METHODS: The literature review was done from Web of Science, Scopus, PubMed, and Google Scholar for ALI, NETs, ROS, inflammation, biomarkers, Toll- and nucleotide-binding oligomerization domain (NOD)-like receptors, alveolar damage, pro-inflammatory cytokines, and epithelial/endothelial damage alone or in combination. RESULTS: This review summarized the main clinical signs of ALI, including the regulation and distinct function of epithelial and endothelial biomarkers, NETs, ROS, and pattern recognition receptors (PRRs). CONCLUSION: However, no particular drugs including vaccine for ALI has been established. Furthermore, there is a lack of validated diagnostic tools and a poor predictive rationality of current therapeutic biomarkers. Hence, extensive and precise research is required to speed up the process of drug testing and development by the application of artificial intelligence technologies, structure-based drug design, in-silico approaches, and drug repurposing.
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Lesión Pulmonar Aguda , Biomarcadores , Transducción de Señal , Lesión Pulmonar Aguda/metabolismo , Humanos , Biomarcadores/metabolismo , Animales , Trampas Extracelulares/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Citocinas/metabolismoRESUMEN
Currently, corneal blindness is affecting >10 million individuals worldwide, and there is a significant unmet medical need because only 1.5% of transplantation needs are met globally due to a lack of high-quality grafts. In light of this global health disaster, researchers are developing corneal substitutes that can resemble the human cornea in vivo and replace human donor tissue. Thus, this review examines ROCK (Rho-associated coiled-coil containing protein kinases) inhibitors as a potential corneal wound-healing (CWH) therapy by reviewing the existing clinical and nonclinical findings. The systematic review was done from PubMed, Scopus, Web of Science, and Google Scholar for CWH, corneal injury, corneal endothelial wound healing, ROCK inhibitors, Fasudil, Netarsudil, Ripasudil, Y-27632, clinical trial, clinical study, case series, case reports, preclinical study, in vivo, and in vitro studies. After removing duplicates, all downloaded articles were examined. The literature search included the data till January 2023. This review summarized the results of ROCK inhibitors in clinical and preclinical trials. In a clinical trial, various ROCK inhibitors improved CWH in individuals with open-angle glaucoma, cataract, iris cyst, ocular hypertension, and other ocular diseases. ROCK inhibitors also improved ocular wound healing by increasing cell adhesion, migration, and proliferation in vitro and in vivo. ROCK inhibitors have antifibrotic, antiangiogenic, anti-inflammatory, and antiapoptotic characteristics in CWH, according to the existing research. ROCK inhibitors were effective topical treatments for corneal infections. Ripasudil, Y-27632, H-1152, Y-39983, and AMA0526 are a few new ROCK inhibitors that may help CWH and replace human donor tissue.
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Lesiones de la Cornea , Trasplante de Córnea , Glaucoma de Ángulo Abierto , Humanos , Endotelio Corneal/metabolismo , Glaucoma de Ángulo Abierto/metabolismo , Lesiones de la Cornea/metabolismo , Quinasas Asociadas a rho/metabolismoRESUMEN
OBJECTIVES: In this study, tetramethylpyrazine (TMP) was evaluated for its therapeutic potential as an alternative therapy for epileptogenesis and its associated comorbidities in rats. METHODS: The sub-convulsant dose of pentylenetetrazole (PTZ) (35 mg/kg, intraperitoneally) was injected on alternative days to produce kindling for 32 days and observed for seizure score percent of kindled animals in each group. After kindling, the animals were evaluated in models of anxiety, memory and predictive of depression. The neuroprotective effect of TMP was assessed by estimating the biochemical parameters in the cortex and hippocampus of the brain. Histopathological alterations were also observed in the cortex and hippocampus (CA1, CA3 and DG). KEY FINDINGS: The administration of TMP reduced the seizure score and percentage of kindled animals dose-dependently. Furthermore, TMP significantly improved the behavioural parameters measured in the predictive models of depression but not in the anxiety and cognitive performances of the animals. The oxidative-nitrosative stress, excitotoxicity, neuroinflammation and histological alterations in the brain induced by PTZ were significantly mitigated by administering the TMP high dose of 60 mg/kg. CONCLUSION: In conclusion, the TMP attenuated the depression behaviour in the PTZ-induced kindled rats, and reduced the oxidative-nitrosative stress, excitotoxicity, neuroinflammation and histological alterations of the brain.
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Epilepsia , Excitación Neurológica , Ratas , Animales , Pentilenotetrazol/efectos adversos , Neuroprotección , Roedores , Enfermedades Neuroinflamatorias , Epilepsia/inducido químicamente , Epilepsia/tratamiento farmacológico , Convulsiones/inducido químicamente , HipocampoRESUMEN
OBJECTIVES: Previous studies have been established that persons who experienced a stroke are soon likely to develop several anxiety disorders. In which one of the major anxiety disorders is Post-traumatic Stress Disorder (PTSD). Yet, the likelihood of PTSD in conjunction with cerebral stroke has not been well described. Hence, we evaluated the impact of PTSD on cerebral stroke in rodents subjected to single prolonged stress (SPS) and bilateral common carotid artery occlusion (BCCAo), respectively. METHODS: The relation between PTSD and cerebral stroke is evaluated by performing behavioural, biochemical, histopathological, and brain lesion area measurement studies. RESULTS: Interestingly, SPS + BCCAo induction increased behavioural abnormalities like cognitive impairment and anxiety-like behaviour compared to SPS and BCCAo groups alone. Motor impairment was also observed in SPS + BCCAo rats compared to SPS rats, whereas no change with BCCAo rats. Furthermore, increased brain tissue MDA, acetylcholinesterase, and decreased SOD, catalase, and GSH were observed in SPS + BCCAo subjected rats compared to SPS and BCCAo rats alone. Additionally, SPS + BCCAo induction considerably increased the plasma corticosterone levels and caused severe neurotransmitter alterations. The SPS + BCCAo exposure significantly increased the brain lesion area in comparison with BCCAo rats. Moreover, severe histopathological alterations were observed in the hippocampus (CA1) of SPS + BCCAo rats compared to SPS and BCCAo rats alone. CONCLUSIONS: In conclusion, our study results suggested that SPS-induced PTSD may aggravate the BCCAo induced cerebral ischaemia-reperfusion injury.