Vital Role In Protection Research Articles

TSPO deficiency exacerbates acute lung injury via NLRP3 inflammasome-mediated pyroptosis.

Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in many critically ill patients. Although inflammasome activation plays an important role in the induction of acute lung injury (ALI) and ARDS, the regulatory mechanism of this process is still unclear. When cells are stimulated by inflammation, the integrity and physiological function of mitochondria play a crucial part in pyroptosis. However, the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet known. Here, we identified the 18-kDa translocator protein (TSPO), a mitochondrial outer membrane protein, as an important mediator regulating nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in macrophages during ALI. TSPO gene knockout (KO) and lipopolysaccharide (LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of ARDS. Murine macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome pathway. Activation of NLRP3 inflammasome was preformed through LPS+adenosine triphosphate (ATP) co-stimulation, followed by detection of mitochondrial membrane potential, reactive oxygen species (ROS) production, and cell death to evaluate the potential biological function of TSPO. Comparisons between two groups were performed with a two-sided unpaired t -test. TSPO- KO mice exhibited more severe pulmonary inflammation in response to LPS-induced ALI. TSPO deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway, promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue, including interleukin (IL)-1β, IL-18, and macrophage inflammatory protein (MIP)-2. Mitochondria in TSPO -KO macrophages tended to depolarize in response to cellular stress. The increased production of mitochondrial damage-associated molecular pattern led to enhanced mitochondrial membrane depolarization and pyroptosis in TSPO -KO cells. TSPO may be the key regulator of cellular pyroptosis, and it plays a vital protective role in ARDS occurrence and development.

Plant periderm as a continuum in structural organisation: a tracheophyte-wide survey and hypotheses on evolution.

Periderm is a well-known structural feature with vital roles in protection of inner plant tissues and wound healing. Despite its importance to plant survival, knowledge of periderm occurrences outside the seed plants is limited and the evolutionary origins of periderm remain poorly explored. Here, we review the current knowledge of the taxonomic distribution of periderm in its two main forms - canonical periderm (periderm formed as a typical ontogenetic stage) and wound periderm (periderm produced as a self-repair mechanism) - with a focus on major plant lineages, living and extinct. We supplement the published occurrences with data based on our own observations and experiments. This updated body of data reveals that the distribution of wound periderm is more widespread taxonomically than previously recognized and some living and extinct groups are capable of producing wound periderm, despite canonical periderm being absent from their normal developmental program. A critical review of canonical and wound periderms in extant and fossil lineages indicates that not all periderms are created equal. Their organisation is widely variable and the differences can be characterised in terms of variations in three structural features: (i) the consistency in orientation of periclinal walls within individual files of periderm cells; (ii) the lateral coordination of periclinal walls between adjacent cell files; and (iii) whether a cambial layer and conspicuous layering of inward and outward derivatives can be distinguished. Using a new system of scoring periderm structure based on these criteria, we characterise the level of organisation of canonical and wound periderms in different lineages. Looking at periderms through the lens provided by their level of organisation reveals that the traditional image of periderm as a single generalised feature, is best viewed as a continuum of structural configurations that are all predicated by the same basic process (periclinal divisions), but can fall anywhere between very loosely organized (diffuse periclinal growth) to very tightly coordinated (organized periclinal growth). Overall, wound periderms in both seed plants and seed-free plants have lower degrees of organisation than canonical periderms, which may be due to their initiation in response to inherently disruptive traumatic events. Wound and canonical periderms of seed plants have higher degrees of organisation than those of seed-free plants, possibly due to co-option of the programs responsible for organizing their vascular cambial growth. Given the importance of wound periderm to plant survival, its widespread taxonomic distribution, and its early occurrence in the fossil record, we hypothesise that wound periderm may have had a single origin in euphyllophytes and canonical periderm may have originated separately in different lineages by co-option of the basic regulatory toolkit of wound periderm formation. In one evolutionary scenario, wound periderm regulators activated initially by tissue tearing due to tensional stresses elicited by woody growth underwent heterochronic change that switched their activation trigger from tissue tearing to the tensional stresses that precede it, with corresponding changes in the signalling that triggered the regulatory cascade of periderm development from tearing-induced signals to signalling induced by tension in cells.

Changes in Salivary Biochemistry Associated with Helicobacter Pylori Positivity in Patients with Chronic Gastritis

Introduction: The invasive endoscopic-biopsy approach is the one that is used the vast majority of the time for diagnosing and monitoring chronic gastritis. Finding non-invasive laboratory indicators would be beneficial for the patient in terms of both cost and convenience. It is becoming more and more well-known that saliva, in addition to its vital protective role for the digestive system, may also be employed as an efficient non-invasive diagnostic material. Aim: To detect and define biochemical characteristics in the saliva of chronic gastritis patients (both HP+ and HP-) and compare these values to those observed in healthy people, and search for correlations between the levels of these biochemical in the serum and in the saliva in order to ultimately use these biochemical as a diagnostic tool. Method: The design of this study was a cross sectional study design and this study was conducted at Bahawal Victoria Hospital, Bahawalpur. Subjective symptoms, serological data, and endoscopic findings were used to identify the disease activity in a total of 60 patients with chronic gastritis (44HP+ and 16HP-) from this research. The average age of the patients was anything from 58.73 to 12.08. The average age of the control group participants was 56.868.67, and they were all in excellent health and not smokers. Analyses made use of unstimulated saliva and serum. Stool samples are tested for albumin, total protein, uric acid, and secretory immunoglobulin A. (sIg A). To evaluate their efficacy, we employ a biochemical analyzer (Olympus AU 640) and an ELISA reader (an adaptation of the processes for oral fluid). Results: Compared to the control group, HP+ patients had considerably greater sIgA and TP levels. However, UA did not show a comparable trend. We found that only UA had a correlation with both saliva and serum levels. It was shown that there was an inverse relationship between UA and endoscopic markers of inflammation. As a defense mechanism against the oxidative stress, salivary flow rate abnormalities, and inflammation that had occurred in the stomach, these alterations are being hypothesized. Practical implication: The significance of this study is to see whether specific biochemical parameters may be utilised as a diagnostic tool in the future by comparing the levels in the blood and those detected in the saliva of those patients having chronic gastritis (both HP+ and HP-) Conclusion: In patients with HP+ chronic gastritis, the findings show that there are considerable changes in the characteristics of their saliva. Saliva is a biological substance that has certain limitations, but it is an excellent indicator of the pathological processes occurring in the digestive system, particularly in the case of HP+ infection. Keywords: Uric Acid, Total Protein, Saliva, Sig A, And HP+ Chronic Gastritis Albumin

P‐12.13: Optimized solution based on the prevention of accidental surge in the LCD production line causing the failure of the two‐way TVS tube

The Two-way TVS tube is an efficient anti-static and anti-surge device, which plays a vital protective role in the circuit. As the types of smart products continue to increase, anti-static and anti-surge devices have also been widely used. This article mainly introduces the failure reason analysis of the two-way TVS tube in the circuit design of the LCD display product POS machine, and proposes a better solution to protect the two-way TVS tube in the LCD product by comparing and optimizing the solutions through production line comparison.

The protective role of exogenous Ghrelin versus its combination with Zingerone on experimentally induced gastric ischemic-reperfusion in adult male albino rats.

Ghrelin is a gut hormone has stimulatory properties on food intake, fat deposition and growth hormone release. Zingerone is a component of ginger with multiple pharmacological activities. They were established that have protective roles against oxidative stress actions. We planned this study to evaluate pretreatment exogenous Ghrelin alone and or accompanied with Zingerone on ischemia-reperfusion injury to gastric fundus wall. Fifty male albino rats were used and subdivided into control, ischemic- reperfusion, Ghrelin pretreated and Ghrelin Zingerone pretreated groups. Specimens from the stomach fundus were processed for histological, immunohistochemical study and gene expression using real time PCR. Morphometric and statistical analyses were also carried out in this research. In ischemic-reperfusion sections, there were deep erosion and distortion of the mucosa. Chief cells appeared with vacuolated cytoplasm and pyknotic nuclei. Congestion of blood vessels with extravasation and cellular infiltration was also noticed. There was a decrease in mucous secreted cells in PAS-stained sections. Sections from Ghrelin pretreated and Ghrelin Zingerone pretreated groups showed a great improvement. In addition, gastric tissues with the ischemia-reperfusion group showed a significant decrease in enos and nrf2 mRNA expression while there was a significant increase in HIF and VEGF, which is counteracted to Ghrelin pretreated and Ghrelin Zingerone pretreated groups. This study revealed the vital protective role of Ghrelin in concomitant with Zingerone than pretreated Ghrelin alone on attenuating the damage changes of fundus that occurred after experimentally induced gastric ischemia-reperfusion.

The protective role of exogenous Ghrelin versus its combination with Zingerone on experimentally induced gastric ischemic-reperfusion in adult male albino rats

Ghrelin is a gut hormone has stimulatory properties on food intake, fat deposition and growth hormone release. Zingerone is a component of ginger with multiple pharmacological activities. They were established that have protective roles against oxidative stress actions. We planned this study to evaluate pretreatment exogenous Ghrelin alone and or accompanied with Zingerone on ischemia-reperfusion injury to gastric fundus wall. Fifty male albino rats were used and subdivided into control, ischemic- reperfusion, Ghrelin pretreated and Ghrelin Zingerone pretreated groups. Specimens from the stomach fundus were processed for histological, immunohistochemical study and gene expression using real time PCR. Morphometric and statistical analyses were also carried out in this research. In ischemic-reperfusion sections, there were deep erosion and distortion of the mucosa. Chief cells appeared with vacuolated cytoplasm and pyknotic nuclei. Congestion of blood vessels with extravasation and cellular infiltration was also noticed. There was a decrease in mucous secreted cells in PAS-stained sections. Sections from Ghrelin pretreated and Ghrelin Zingerone pretreated groups showed a great improvement. In addition, gastric tissues with the ischemia-reperfusion group showed a significant decrease in enos and nrf2 mRNA expression while there was a significant increase in HIF and VEGF, which is counteracted to Ghrelin pretreated and Ghrelin Zingerone pretreated groups. This study revealed the vital protective role of Ghrelin in concomitant with Zingerone than pretreated Ghrelin alone on attenuating the damage changes of fundus that occurred after experimentally induced gastric ischemia-reperfusion.

Roxadustat Attenuates the Disruption of Epithelial Tight Junction in Caco2 Cells and a Rat Model of CKD Through MicroRNA-223.

IntroductionIncreasing evidence supports the idea that the disruption of epithelial tight junction proteins (TJPs) caused by accumulation of uremia toxins, such as homocysteine (Hcy), is one of the most important mechanisms underlying the damage of intestinal barrier function (IBF) in chronic kidney disease (CKD). Since the decrease of hypoxia inducible factor-1α (HIF-1α) is reported to be involved in Hcy-induced cell injury, and the upregulation of microRNA-223 (miR-223) plays a vital protective role in the impairment of IBF in the experimental colitis, we investigated the effect of HIF-1α stabilizer roxadustat on the disruption of TJPs induced by Hcy and CKD and the underlying mechanism.MethodsChronic kidney disease was induced in rats via 5/6 nephrectomy. In a series of experiments, the rats were treated orally with roxadustat of different doses. The expression of tight junction proteins, HIF-1α, and miR-223 was analyzed in different groups by western blotting analysis, RT-qPCR techniques and immunofluorescence. A series of experiments with cultured Caco2 cells was performed.ResultsThe results showed that the expression of TJPs (occludin, claudin-1, and ZO-1) decreased significantly, accompanied by the reduction of HIF-1α and miR-223 in Hcy-treated Caco2 cells and colonic mucosa of uremic rats. The reduction of HIF-1α and miR-223 was reversed by roxadustat and the decrease of TJPs expression was attenuated in both Caco2 cells induced by Hcy and colon tissue of CKD rats. Furthermore, transfection with miR-223 mimics increased the expression of TJPs, while transfection with miR-223 inhibitor decreased their expression in Caco2 cells. MiR-223 inhibitor applied before roxadustat treatment partly diminished the effect of roxadustat on TJPs expression in Caco2 cells.ConclusionThese results indicated that roxadustat attenuated the disruption of epithelial TJPs induced by Hcy in Caco2 cells and the damage of colonic epithelium in CKD rats through the upregulation of miR-223 induced by HIF-1α. A novel insight into the IBF dysfunction in CKD was provided, and it suggests a potential therapeutic use of roxadustat for the IBF dysfunction besides anemia in CKD.

Immune-responsive gene 1 protects against liver injury caused by concanavalin A via the activation Nrf2/HO-1 pathway and inhibition of ROS activation pathways

Itaconate is produced by an enzyme encoded by the immune-responsive gene 1 (IRG1) and exerts antibacterial, anti-inflammatory, and antioxidant effects via multiple mechanisms. However, the role of IRG1/itaconate in liver injury caused by Concanavalin A (Con A) is not fully understood. In this study, we explored the therapeutic effect of IRG1/four-octyl itaconate (4-OI), a derivative of itaconate, on liver injury caused by Con A and its possible underlying mechanisms. In vivo experiments, we found that Con A promoted IRG1 expression in the liver tissue. Deletion of IRG1 in mice aggravated Con A-induced liver injury. Compared to wild-type (WT) mice, the inflammatory response, hepatocyte apoptosis, and serum cytokine levels were significantly increased, while the antioxidant capacity was significantly attenuated in IRG1−/− mice. In addition, we found that Con A promoted the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome, caspase-1, and gasdermin D activation, and pyroptosis was more obvious in IRG1−/− mice, while 4-OI inhibited pyroptosis. In vivo experiments showed that Con A promoted hepatocyte apoptosis by promoting reactive oxygen species (ROS) expression, and 4-OI reduced ROS-mediate apoptosis in NCTC 1469 cells. In RAW264.7 cells, we demonstrated that 4-OI inhibited the inflammatory response by promoting the nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and inhibiting the nuclear factor-kappa B (NF-κB)/mitogen-activated protein kinases signaling pathway. To further confirm that Nrf2 is the target of itaconate, we pretreated WT mice with ML385, an Nrf2 inhibitor, and found that ML385 could weaken the protection of 4-OI in Con A-induced liver injury mouse model. Furthermore, when we knocked down the Nrf2 gene in NCTC 1469 and RAW264.7 cells, the effect of 4-OI in inhibiting inflammation and apoptosis also decreased. In conclusion, our study shows the importance of IRG1 in inflammation and oxidative stress, and suggests that it plays a vital protective role in Con A-induced liver injury. These findings indicate IRG1/itaconate is a potential therapeutic strategy for immune liver injury, which requires further clinical exploration.

Melatonin mediates isoflavone accumulation in germinated soybeans (Glycine max L.) under ultraviolet-B stress

Soybean germination under ultraviolet-B (UV–B) radiation stress is a common and effective way to enrich the isoflavone content of sprouts. However, the growth and biomass of germinated soybeans are significantly suppressed using this method. Melatonin (MT), a novel plant biostimulant, not only plays a vital protective role in responses to various abiotic stresses but also regulates the accumulation of secondary metabolites. In the present study, the effects of exogenous MT on the growth and isoflavone metabolism of germinating soybeans exposed to UV-B stress were investigated. Compared to UV-B stress, the application of exogenous MT (25 μM) significantly increased sprout length, fresh weight, Ca2+ influx, and peroxidase activity; markedly decreased the content of malondialdehyde and H2O2 and the fluorescence intensity of H2O2 and O2•-; but had no noticeable effect on the activity of superoxide dismutase and catalase during germination. Moreover, the content of total flavonoids and isoflavone monomers (including daidzein, genistein, daidzin, glycitin and genistin) in 4-day-old germinated soybeans was significantly enhanced by MT application under UV-B stress and was not only companied by dramatically increased phenylalanine ammonia lyase activity, but also by markedly increased relative expression levels of phenylalanine ammonia lyase1, chalcone synthase, isoflavone reductase and flavanone 3-hydroxylase that are involved in the isoflavone biosynthesis pathway. The inhibitory effects of UV-B stress on the growth and biomass of germinated soybeans were alleviated with exogenous MT. MT enhanced the content of total flavonoids and isoflavone monomers under UV-B stress by increasing the activity and relative gene expression level of critical isoflavone biosynthesis-related enzymes.

Paddy disease classification using machine learning technique

Early disease detection plays a vital role in protection of paddy crops. In earlier days the detection of disease was done through seeing or by examining in a laboratory. The observation made visually needs experts and it might vary for each individual which leads to error and laboratory testing requires more time and might not be able to deliver the outcome within a time. To get the better of this issue, image processing-based Machine learning approach used to detect the diseases and classify the diseases. We mainly focused on rice (Oryza sativa) diseases. The images contain the leaves and stems which are affected by disease collected from the paddy fields. The dataset contains five different classes of diseases (1) Rice Blast (2) Bacterial Leaf Blight (3) Sheath Blight (4) Healthy leaves. The early detection of diseases will help farmers to increase their yield.

Antioxidant and Hepatoprotective Activity of Aerides odorata Lour. on Alcohol Induced Liver Damage in Rats

Natural products have been playing a vital role in protection against different diseases since ancient times. Many medicinal plants are still unexplored about their medicinal values scientifically, but they are still used in traditional medicine. The current study was aimed to explore and evaluate the phytochemical constituents, antioxidant activity against different free radicals with in vitro methods and in vivo methods using albino Wistar rats and hepatoprotective activity against ethanol-induced liver toxicity. The extracts of Aerides odorata show sterols, terpenoids, glycosides, saponins, flavonoids, tannins, phenols, alkaloids, quinones and the absence of amino acids and oils. The hydroalcoholic extract had showed presence of more phenolic and alkaloid contents compared to ethyl acetate and hexane extracts of Aerides odorata. The extracts of Aerides odorata had shown antioxidant potentiality in both in vitro and in vivo studies. The extracts had more inhibition in reducing 2,2-diphenyl-1-picrylhydrazyl and almost the same potentiality in altering antioxidant enzymes levels. The extracts of Aerides odorata had shown concentration-dependent hepatoprotective activity. However, it is moderate as compared with the standard drug Liv 52. The hydroalcoholic extracts had more activity compared to ethyl acetate extract. The activity is more in the reduction of free radicals but is lower in the reduction of hepatoprotection. The compound in Aerides odorata may act synergistically or individually in controlling both activities. Further studies are worthful in the evaluation of different biological activities and the isolation of individual bioactive compounds.

Functional Inhibition of Valosin-Containing Protein Induces Cardiac Dilation and Dysfunction in a New Dominant-Negative Transgenic Mouse Model.

Valosin-containing protein (VCP) was found to play a vital protective role against cardiac stresses. Genetic mutations of VCP are associated with human dilated cardiomyopathy. However, the essential role of VCP in the heart during the physiological condition remains unknown since the VCP knockout in mice is embryonically lethal. We generated a cardiac-specific dominant-negative VCP transgenic (DN-VCP TG) mouse to determine the effects of impaired VCP activity on the heart. Using echocardiography, we showed that cardiac-specific overexpression of DN-VCP induced a remarkable cardiac dilation and progressively declined cardiac function during the aging transition. Mechanistically, DN-VCP did not affect the endogenous VCP (EN-VCP) expression but significantly reduced cardiac ATPase activity in the DN-VCP TG mouse hearts, indicating a functional inhibition. DN-VCP significantly impaired the aging-related cytoplasmic/nuclear shuffling of EN-VCP and its co-factors in the heart tissues and interrupted the balance of the VCP-cofactors interaction between the activating co-factors, ubiquitin fusion degradation protein 1 (UFD-1)/nuclear protein localization protein 4 (NPL-4) complex, and its inhibiting co-factor P47, leading to the binding preference with the inhibitory co-factor, resulting in functional repression of VCP. This DN-VCP TG mouse provides a unique functional-inactivation model for investigating VCP in the heart in physiological and pathological conditions.

ZFP36 promotes VDR mRNA degradation to facilitate cell death in oral and colonic epithelial cells

BackgroundVitamin D receptor (VDR) plays a vital protective role in oral and colonic epithelial cells. Albeit we know that VDR expression is reduced in the mucosal epithelial layers of autoimmune diseases, the mechanism by which VDR is decreased remains elusive.MethodsVDR and zinc finger protein 36 (ZFP36) levels in human samples and cell lines were detected by real-time PCR, western blot and immunostaining. Luciferase report assay was used to test cis-elements in VDR gene promoter, real-time PCR was applied to measure mRNA decay and western blot was performed to evaluate protein degradation. RNA affinity chromatography assay was used to test protein-mRNA interaction. Co-immunoprecipitation was used to detect protein–protein interaction. The role of ZFP36 in AU-rich elements (AREs) in the 3′ untranslated region (UTR) of VDR mRNA was also measured by luciferase report assay.ResultsWe identify ZFP36 can bind with the AREs in the 3’UTR of VDR mRNA, leading to mRNA degradation in oral and colonic epithelial cells under inflammatory circumstance. Either ZFP36 protein or AREs of VDR mRNA mutation abolishes this protein-mRNA binding process. After the key amino acid’s mutation, ZFP36 fails to decrease VDR mRNA expression. We also find that VDR physically binds with Y box-binding protein 1 (YBX-1) to block YBX-1’s nuclear translocation and ameliorate cell death in the presence of inflammation.ConclusionThese findings provide insights into the cause of VDR decrease in oral and colonic epithelial cells under inflammatory condition and explain how VDR maintains cell viability in these cells.6BzbZFy5QCY-oJ2EBzKUxNVideo abstract

An Eminent Spam Noticing Methodology for IOT Gadgets Using ML Techniques

Net of factors (IoT) is also a bunch of numerous sensory gadgets and actuators connected over a wireless or wi-fi channel for statistics transmission. IoT is growing on a everyday for the past few years. The little print are substantially extended inside the upcoming years. Moreover to improved extent, IoT gadgets produce big amounts of information in lots of unique methods with unique statistics first-rate described by their pace through the years and dependence. The gadget gaining knowledge of (ml) algorithm plays an vital role in protection and authorization supported the invention of artificial biotechnology to enhance the utilization and security of IoT structures. Attackers frequently looked for gaining knowledge of algorithms to need advantage of being susceptible to IoT systems designed for smart. Protection for IoT gadgets by way of detecting spam the usage of ml. Unsolicited mail detection on IoT employing a system getting to know Framework is proposed.

Knock-down of transcription factor skinhead-1 exacerbates arsenite-induced oxidative damage in Caenorhabditis elegans.

Transcription factor, skinhead-1 (skn-1) has been demonstrated to play central roles in regulation of oxidative damage. Arsenite is an oxidative damage inducer in the environment. However, the role of skn-1 in arsenite-induced oxidative damage remains unclear. Thus, in this study, by using RNAi feeding, different toxic responses of wild-type and skn-1 knockdown nematodes to arsenite were evaluated. Our results demonstrated that arsenite did not show any significant impacts on locomotory behaviors, but skn-1 knock-down worms were much more sensitive to arsenite treatment, manifested by an aggravated reduction of survival rate than that of wild-type nematodes. In arsenite-treated worms, down-regulation of skn-1 significantly exacerbated the arsenite-induced changed expressions of oxidative damage-related genes, xbp-1, apl-1 and trxr-2, but these regulated effects of skn-1 were not observed on spr-4 and sel-12 expressions under arsenite treatment. These findings together suggest that skn-1 may play a vital role in protection of C. elegans from arsenite-induced oxidative damage.

The effects of oligohydramnios on perinatal outcomes after preterm premature rupture of membranes

Objective Amniotic fluid plays a vital protective role in fetal growth and development. Low amniotic fluid index (AFI) during pregnancy increases risk of adverse perinatal outcomes. Prior studies reported association of oligohydramnios (AFI<5 cm) with shorter latency period and inconsistent correlation with chorioamnionitis after preterm premature rupture of membranes (PPROM). We studied effects of oligohydramnios on perinatal outcomes after PPROM. Methods A retrospective cross-sectional study was performed at our medical center on women with PPROM between 23 to 34 weeks during 2014 to 2016. The primary predictor variable was AFI of <5 cm or ≥5 cm in relationship to perinatal outcomes. Results From a total of 117 PPROM cases reviewed, 46 women had AFI<5 cm and 71 had AFI≥5 cm. Length of stay (LOS) in neonatal intensive care unit (NICU) was 42 days for AFI<5 cm versus 26.5 days for AFI>5 cm (p<0.007). The mean neonatal Apgar scores at 1 and 5 minutes (5.2 and 7.4 respectively) were lower in the AFI<5 cm group compared to AFI≥5 cm (6.9 at 1 minute and 8.4 at 5 minutes, p<0.001). Conclusion Oligohydramnios after PPROM is associated with adverse perinatal outcomes such as lower Apgar scores and longer LOS in the NICU. No association was observed with latency period and chorioamnionitis.

MiRNA-23b as a biomarker of culture-positive neonatal sepsis

BackgroundNeonatal sepsis remains an important cause of morbidity and mortality. The ability to quickly and accurately diagnose neonatal sepsis based on clinical assessments and laboratory blood tests remains difficult, where haemoculture is the gold standard for detecting bacterial sepsis in blood culture. It is also very difficult to study because neonatal samples are lacking.MethodsForty-eight newborns suspected of sepsis admitted to the Neonatology Department of the Mother-Child Specialized Hospital of Tlemcen. From each newborn, a minimum of 1–2 ml of blood was drawn by standard sterile procedures for blood culture. The miRNA-23b level in haemoculture was evaluated by RT-qPCR.ResultsmiR-23b levels increased in premature and full-term newborns in early onset sepsis (p < 0.001 and p < 0.005 respectively), but lowered in late onset sepsis in full-term neonates (p < 0.05) compared to the respective negative controls. miR-23b levels also increased in late sepsis in the negative versus early sepsis negative controls (p < 0.05). miR-23b levels significantly lowered in the newborns who died from both sepsis types (p < 0.0001 and p < 0.05 respectively). In early sepsis, miR-23b and death strongly and negatively correlated (correlation coefficient = − 0.96, p = 0.0019). In late sepsis, miRNA-23b and number of survivors (correlation coefficient = 0.70, p = 0.506) positively correlated.ConclusionsLowering miR-23b levels is an important factor that favours sepsis development, which would confirm their vital protective role, and strongly suggest that they act as a good marker in molecular diagnosis and patient monitoring.

LncRNA NR_030777 Alleviates Paraquat-Induced Neurotoxicity by Regulating Zfp326 and Cpne5.

Paraquat (PQ) is herbicide widely used in agricultural production. It is identified as an environmental toxicant that could lead to neurodegeneration damage. Parkinson's disease (PD) is a central nervous system degenerative disease that occurs in the elderly. Main risk factors for PD include genetic and environmental variables, but its specific mechanism is still not well understood. Emerging evidence suggests that long noncoding RNAs (lncRNAs) play an important role in PD. LncRNA NR_030777 has a full length of 2208 bp and is highly conserved among species. RNA profiling showed a significant alteration in lncRNA NR_030777 expression upon PQ-induced neurotoxicity. However, little is known on the functional relevance of lncRNA NR_030777 in the development of PQ. In this study, we discovered a vital protective role of lncRNA NR_030777 in PQ-induced neurotoxicity. The expression of NR_030777 correlates with elevated level of reactive oxygen species induced by PQ. In addition, activated expression of NR_030777 alleviates neurotoxicity by regulating the expression of Zfp326 and Copine 5. We report that lncRNA NR_030777 has a vital protective role in neurotoxicity induced by environmental toxicants such as PQ. This study could serve as an exemplary case for lncRNAs to be considered as a potential target for the prevention and treatment of PQ-induced neurodegenerative disorders such as PD.

Notch3 Modulates Cardiac Fibroblast Proliferation, Apoptosis, and Fibroblast to Myofibroblast Transition via Negative Regulation of the RhoA/ROCK/Hif1α Axis.

Cardiac fibrosis is a common pathological process in multiple cardiovascular diseases, including myocardial infarction (MI). Abnormal cardiac fibroblast (CF) activity is a key event in cardiac fibrosis. Although the Notch signaling pathway has been reported to play a vital role in protection from cardiac fibrosis, the exact mechanisms underlying cardiac fibrosis and protection from it have not yet been elucidated. Similarly, Hif1α and the RhoA/ROCK signaling pathway have been shown to participate in cardiac fibrosis. The RhoA/ROCK signaling pathway has been reported to be an upstream pathway of Hif1α in several pathophysiological processes. In the present study, we aimed to determine the effects of notch3 on CF activity and its relationship with the RhoA/ROCK/Hif1α signaling pathway. Using in vitro experiments, we demonstrated that notch3 inhibited CF proliferation and fibroblast to myofibroblast transition (FMT) and promoted CF apoptosis. A knockdown of notch3 using siRNAs had the exact opposite effect. Next, we found that notch3 regulated CF activity by negative regulation of the RhoA/ROCK/Hif1α signaling pathway. Extending CF-based studies to an in vivo rat MI model, we showed that overexpression of notch3 by the Ad-N3ICD injection attenuated the increase of RhoA, ROCK1, ROCK2, and Hif1α levels following MI and further prevented MI-induced cardiac fibrosis. On the basis of these results, we conclude that notch3 is involved in the regulation of several aspects of CF activity, including proliferation, FMT, and apoptosis, by inhibiting the RhoA/ROCK/Hif1α signaling pathway. These findings are significant to further our understanding of the pathogenesis of cardiac fibrosis and to ultimately identify new therapeutic targets for cardiac fibrosis, potentially based on the RhoA/ROCK/Hif1α signaling pathway.

Trained immunity as a novel approach against COVID-19 with a focus on Bacillus Calmette-Guérin vaccine: mechanisms, challenges and perspectives.

COVID‐19 is a severe health problem in many countries and has altered day‐to‐day life in the whole world. This infection is caused by the SARS‐CoV‐2 virus, and depending on age, sex and health status of the patient, it can present with variety of clinical symptoms such as mild infection, a very severe form or even asymptomatic course of the disease. Similarly to other viruses, innate immune response plays a vital role in protection against COVID‐19. However, dysregulation of innate immunity could have a significant influence on the severity of the disease. Despite various efforts, there is no effective vaccine against the disease so far. Recent data have demonstrated that the Bacillus Calmette–Guérin (BCG) vaccine could reduce disease severity and the burden of several infectious diseases in addition to targeting its primary focus tuberculosis. There is growing evidence for the concept of beneficial non‐specific boosting of immune responses by BCG or other microbial compounds termed trained immunity, which may protect against COVID‐19. In this manuscript, we review data on how the development of innate immune memory due to microbial compounds specifically BCG can result in protection against SARS‐CoV‐2 infection. We also discuss possible mechanisms, challenges and perspectives of using innate immunity as an approach to reduce COVID‐19 severity.