Pathogenic Conditions Research Articles

Neutrophil extracellular traps contributing to atherosclerosis: From pathophysiology to clinical implications.

Neutrophil extracellular traps (NETs) are network-like structures of chromatin filaments decorated by histones, granules, and cytoplasmic-derived proteins expelled by activated neutrophils under multiple pathogenic conditions. NETs not only capture pathogens in innate immunity but also respond to sterile inflammatory stimuli in atherosclerosis, such as lipoproteins and inflammatory cytokines. Atherosclerosis is a lipid-driven chronic inflammatory disease characterized by the accumulation and transformation of inflammatory cells, and smooth muscle cells in the intimal space. NETs-derived extracellular components possess toxic and proinflammatory properties leading to cellular dysfunction and tissue damage, which may establish a link among lipid metabolism, inflammatory immunity, and atherosclerosis. In this review, we discuss recent advances regarding the role of NETs engaged in the pathogenesis of atherosclerosis, particularly focusing on the interaction with lipids and inflammasomes, crosstalk with smooth muscle cells and inflammatory cells, and the association with aging. We also evaluate the current knowledge on the potential of NETs as biomarkers and therapeutic targets for atherosclerosis and its related diseases in clinical practice.

P30-015-23 Egg Intake Alters Inflammatory Properties of HDL and Immune Cells Under Basal and Pathogenic Conditions, Which Uniquely Correlate With Changes in HDL Composition

P30-015-23 Egg Intake Alters Inflammatory Properties of HDL and Immune Cells Under Basal and Pathogenic Conditions, Which Uniquely Correlate With Changes in HDL Composition

Ascending aortic volume: A feasible indicator for ascending aortic aneurysm elective surgery?

Diameter-based criterion have been widely adopted for preventive surgery of ascending thoracic aortic aneurysm (ATAA). However, recent and growing evidence has shown that diameter-based methods may not be sufficient for identifying patients who are at risk of an ATAA. In this study, fluid-structure interaction (FSI) analysis was performed on one-hundred ATAA geometries reconstructed from clinical data to examine the relationship between hemodynamic conditions, ascending aortic volume (AAV), ascending aortic curvature, and aortic ratios measured from the reconstructed 3D models. The simulated hemodynamic and biomechanical parameters were compared among different groups of ATAA geometries classified based on AAV. The ATAAs with enlarged AAV showed significantly compromised hemodynamic conditions and higher mechanical wall stress. The maximum oscillatory shear index (OSI), particle residence time (PRT) and wall stress (WS) were significantly higher in enlarged ATAAs compared with controls (0.498 [0.497, 0.499] vs 0.499 [0.498, 0.499], p = 0.002, 312.847 [207.445, 519.391] vs 996.047 [640.644, 1573.140], p < 0.001, 769.680 [668.745, 879.795] vs 1072.000 [873.060, 1280.000] kPa, p < 0.001, respectively). Values were reported as median with interquartile range (IQR). AAV was also found to be more strongly correlated with these parameters compared to maximum diameter. The correlation coefficient between AAV and average WS was as high as 0.92 (p < 0.004), suggesting that AAV might be a feasible risk identifier for ATAAs. Statement of SignificanceAscending thoracic aortic aneurysm is associated with the risk of dissection or rupture, creating life-threatening conditions. Current surgical intervention guidelines are mostly diameter based. Recently, many studies proposed to incorporate other morphological parameters into the current clinical guidelines to better prevent severe adverse aortic events like rupture or dissection. The purpose of this study is to gain a better understanding of the relationship between morphological parameters and hemodynamic parameters in ascending aortic aneurysms using fluid-solid-interaction analysis on patient-specific geometries. Our results suggest that ascending aortic volume may be a better indicator for surgical intervention as it shows a stronger association with pathogenic hemodynamic conditions.

O-197 Vertical transmission of maternal mitochondrial DNA via extracellular vesicles (EVs) modulates embryo bioenergetics during the periconceptional period

Abstract Study question Does maternal endometrial mitochondrial (mt) DNA cargo of EVs modulate embryo bioenergetics during embryo implantation? Summary answer We demonstrate the vertical transmission of maternal mtDNA within endometrial-derived EVs and their uptake by the trophoblast which reduces mitochondrial respiration and ATP production. What is known already The release and uptake of membrane-enclosed compartments with specific cargos, commonly known as EVs, represents a novel cell-to-cell communication mechanism in physiological and pathogenic conditions. EVs are generally classified into three populations based on their biogenetic pathways, composition, and physical characteristics: apoptotic bodies (ABs), microvesicles (MVs), and exosomes (EXOs). Among other contents, EVs contain single- and double-stranded DNA, with their relative abundance varying depending on the cell and vesicle type. The vertical transmission of EV-associated DNA has been proposed as a novel genetic material transfer mechanism that may impact genome evolution and tumorigenesis. Study design, size, duration Prospective observational multicenter analysis in which EVs were obtained from endometrial fluid from healthy donors aged 18–35 years (n = 10) during the receptive phase of their natural cycle and under hormonal replacement therapy in pre-receptive (P + 2), receptive (P + 5), post-receptive (P + 8) stages (n = 13). Participants/materials, setting, methods Endometrial EVs isolated using ultracentrifugation and classified according to `parameters obtained from electron microscopy, Western blotting, and size distribution analysis. DNA copy number identified using high throughput sequencing. EV-associated DNA tagged with 5-ethynyl-2’-deoxyuridine was followed by confocal imaging after co-incubation of EVs with murine embryos (n = 200). ATP levels assessed using the FLASC luciferase reporter system, and the Seahorse XFE96 extracellular flux analyzer used to measure embryo oxygen consumption rate (OCR) (n = 400). Main results and the role of chance The human endometrium secretes all three EV types - ABs, MVs, and EXOs - into the human endometrial fluid. Deep sequencing revealed that EVs encapsulated nuclear and mtDNA. When analyzing endometrial biopsies, we observed the reduced mtDNA content of endometrial cells and the activation of mitochondrial clearance mechanisms, which coincided with the time of embryo implantation together with specific enrichment in endometrial MVs secreted during the periconceptional period. EVs were internalized and DNA was transferred to the cytoplasm and nuclei of trophectoderm of murine embryos. We analyzed ATP concentrations in murine embryos and found a significant reduction in ATP levels following the coculture of embryos with a combination of all EVs types compared to control embryos cultured without endometrial EVs (p &amp;lt; 0.001). Finally, we demonstrated a reduction in the OCR in embryos treated with endometrial EVs obtained during the receptive phase compared with the pre-receptive phase. In conclusion, maternal EVs modulate the bioenergetics of the preimplantation embryo by increasing the embryo's metabolic rate and oxygen consumption during the periconceptional period. Limitations, reasons for caution These results were obtained using a combination of a human endometrial model and a murine embryo model. Wider implications of the findings Our results suggest that the vertical transmission of maternal mtDNA encapsulated within EVs to the trophectoderm might energetically assist the preimplantation embryo through the implantation process. Trial registration number N/A

Serum CRP biomarker detection by using carbon nanotube field-effect transistor (CNT-FET) immunosensor

C-reactive protein (CRP) is produced by the liver in response to systemic inflammation caused by bacterial infection, trauma and internal organ failures. CRP serves as a potential biomarker in the precise diagnosis of cardiovascular risk, type-2 diabetes, metabolic syndrome, hypertension and various types of cancers. The pathogenic conditions indicated above are diagnosed by an elevated CRP level in the serum. In this study, we successfully fabricated a highly sensitive and selective carbon nanotube field-effect transistor (CNT-FET) immunosensor for the detection of CRP. The CNTs were deposited on the Si/SiO2 surface, between source-drain electrodes, afterwards modified with well-known linker PBASE and then anti-CRP was immobilized. This anti-CRP functionalized CNT-FET immunosensor exhibits a wide dynamic detection range (0.01–1000 μg/mL) CRP detection, rapid response time (2–3 min) and low variation (<3 %) which can be delivered as a low-cost and rapid clinical detection technology for the early diagnosis of coronary heart disease (CHD). For the clinical applications, our sensor was tested using CRP fortified serum samples and sensing performance was validated using enzyme-linked immune-sorbent assay (ELISA). This CNT-FET immunosensor will be helpful in taking over the complex laboratory-based expensive traditional CRP diagnostic procedures practiced in the hospitals.

#4947 LMO7 IN URINE AS A SPECIFIC MARKER OF COMPROMISED RENAL EPITHELIAL INTEGRITY

Abstract Background and Aims Renal epithelial barrier (REB) are the physical isolator as well as physiological interface mediating body fluid and electrolytes homeostasis. Maintaining epithelial integrity is tightly related to REB biological function. LMO7 (LIM domain only 7) is a protein associated with the cell–cell junctional complex and is predominantly distributed in renal tubular epithelial cells. Previously, we reported that the LMO7 is associated with the maintenance of renal epithelial integrity, and that LMO7 releases to conditioned medium when the epithelial integrity was lost. In this study, we attempt to characterize roles of LMO7 and its functional interacting protein in maintaining epithelial integrity, and relevance of the LMO7 released from plasma membrane and the loss of tubular epithelial integrity. Method Renal ischemia-reperfusion injury (IRI) in mice as a model of acute kidney injury (AKI) were settled as a platform to investigate the the roles of LMO7 and its functional interacting protein in the pathological progression of compromised tubular epithelial integrity. Additionally, renal epithelial cells cultured in hypoxia as the pathogenic condition equivalent to AKI were also employed to investigate the role of LMO7. We also search the STRING database with LMO7 as query to find out its functional interacting proteins. Pathological pattern associated with LMO7 and its functional interacting protein in mice suffering from AKI as well as loss of tubular epithelial integrity were examined by immunofluorescent visualization. The LMO7 in urine as well as in conditioned medium derived from medium of hypoxia culture were quantified by Western blot analysis. Results Renal damage in IRI mice showed loss of epithelial integrity by histochemical staining, presence of LMO7 in urine, and high serum creatinine on the third day post IRI. Under the periodic acid-schiff (PAS) staining, loss of epithelial integrity is visible in proximal tubules, Henle's loops, and collecting ducts at the third day after reperfusion, and brush border impairment is observed in the outer stripe of the outer medulla. Most severe damages in renal tubules are present in Henle's loops where the epithelia express abundant LMO7. In the AKI mice, the LMO7 in renal tubules was apparently lower in Henle's loops. Additionally, the VANGL1, a LMO7 interacting protein participated in epithelial integrity and planar cell polarity in kidney, is also absent in Henle's loop of AKI mice. Hypoxia and glucose deprivation in cultured renal epithelial cells resulted in loss of epithelial integrity, and down-regulation of LMO7 and VANGL1. LMO7 was also identified in conditioned medium in which cells exposed to hypoxia but not normoxia. Additionally, the LMO7 was detected in urine of some patients with chronic kidney disease. Conclusion Presence of LMO7 in urine has been promising in experimental models holding compromised epithelial integrity. These approaches identified the role of LMO7 in maintaining epithelial integrity and that LMO7 being released into urine after renal epithelial damage as a novel marker for loss of REB.

Nodular gill disease in Northeastern Italy: An investigation on the prevalence of the disease and the risks of introduction in rainbow trout farms.

Nodular Gill Disease (NGD) is an emerging pathogenic condition that causes gill damage and mainly affects farmed freshwater fish, rainbow trout (Oncorhynchus mykiss) in particular, and this inevitably generates noticeable economic losses for the industry. The present study aimed to assess the prevalence of NGD in the Autonomous Province of Trento, a highly productive area located in Northeastern Italy, traditionally suited to rainbow trout production, and to identify possible risk factors for the introduction of this disease in trout farms. The necessary data were obtained through a questionnaire and the collection of fish samples. According to the data analysis, 42% of the investigated farms tested positive for NGD. The two possible risk factors identified for its introduction in farms are the presence of other diseases in the same farm (OR = 17.5; 95% CI = 2.7; 111.5) and having farms located 5 km upstream (OR = 24.8; 95% CI = 2.9; 211.1). These results highlight (i) a possible impairment of the immune system caused by other diseases as a predisposing factor to the manifestation of the pathology and (ii) the role of water in spreading pathogens.

Human SAMD9 is a poxvirus-activatable anticodon nuclease inhibiting codon-specific protein synthesis.

As a defense strategy against viruses or competitors, some microbes use anticodon nucleases (ACNases) to deplete essential tRNAs, effectively halting global protein synthesis. However, this mechanism has not been observed in multicellular eukaryotes. Here, we report that human SAMD9 is an ACNase that specifically cleaves phenylalanine tRNA (tRNAPhe), resulting in codon-specific ribosomal pausing and stress signaling. While SAMD9 ACNase activity is normally latent in cells, it can be activated by poxvirus infection or rendered constitutively active by SAMD9 mutations associated with various human disorders, revealing tRNAPhe depletion as an antiviral mechanism and a pathogenic condition in SAMD9 disorders. We identified the N-terminal effector domain of SAMD9 as the ACNase, with substrate specificity primarily determined by a eukaryotic tRNAPhe-specific 2'-O-methylation at the wobble position, making virtually all eukaryotic tRNAPhe susceptible to SAMD9 cleavage. Notably, the structure and substrate specificity of SAMD9 ACNase differ from known microbial ACNases, suggesting convergent evolution of a common immune defense strategy targeting tRNAs.

Environmental ethics and sustainability of techniques. From hyper-specialisation to multifunctionality for a resilient inhabitable space

Crises represent crucial global dynamics events, which were predictable and have been with us for some time. In the new context caused by epidemic and pathogenic conditions, not only must it be reaffirmed that planetary society is an integral part of nature, but that the production processes of anthropogenic metabolism are part of the more general metabolism of nature. Climate change, a significant element of the contemporary environmental crisis, will orient living conditions within the global ecological crisis in a different way. The concept of habitable space, which is, above all, a space of correlation between society and the environment, considers technology as a factor in the reconstitution of a process that is symbiotic and no longer of exploitation of environmental resources. Recently, there has been a renewed awareness of place consciousness and of inhabitants/producers who, through a co-evolutionary principle, are called upon to develop “neo-ecosystems” according to a territorial identity principle. Rather than representing levels of identity that nevertheless express borders, the “local” category constitutes what is discussed and argued in common through a measure of involvement and intensity. So, the relationship between transition cities and urban resilience is part of the governance of the new phenomena of non-linearity. In metropolitan areas, the spread of new urban polarities evolves the concept of resilience towards a multi-scalar and multi-sectoral condition of adaptation and mitigation of anthropogenic and environmental risks. Inside this scenario, hyper-specialisation still represents the tendency of a technical character that induces the development of deep competencies but loses the critical sense of technique in its ethical and socio-economic interactions. Inhabiting and building evolved scenarios of society need a multifunctional thought that can develop and critically manage the choices and uses of technology in a design scenario capable of coherently integrating its contributions.

Global analysis of contact-dependent human-to-mouse intercellular mRNA and lncRNA transfer in cell culture.

Full-length mRNAs transfer between adjacent mammalian cells via direct cell-to-cell connections called tunneling nanotubes (TNTs). However, the extent of mRNA transfer at the transcriptome-wide level (the 'transferome') is unknown. Here, we analyzed the transferome in an in vitro human-mouse cell co-culture model using RNA-sequencing. We found that mRNA transfer is non-selective, prevalent across the human transcriptome, and that the amount of transfer to mouse embryonic fibroblasts (MEFs) strongly correlates with the endogenous level of gene expression in donor human breast cancer cells. Typically, <1% of endogenous mRNAs undergo transfer. Non-selective, expression-dependent RNA transfer was further validated using synthetic reporters. RNA transfer appears contact-dependent via TNTs, as exemplified for several mRNAs. Notably, significant differential changes in the native MEF transcriptome were observed in response to co-culture, including the upregulation of multiple cancer and cancer-associated fibroblast-related genes and pathways. Together, these results lead us to suggest that TNT-mediated RNA transfer could be a phenomenon of physiological importance under both normal and pathogenic conditions.

Deciphering the RNA-binding protein interaction with the mRNAs encoded from human chromosome 15q11.2 BP1-BP2 microdeletion region.

Microdeletion of the 15q11.2 BP1-BP2 region, also known as Burnside-Butler susceptibility region, is associated with phenotypes like delayed developmental language abilities along with motor skill disabilities, combined with behavioral and emotional problems. The 15q11.2 microdeletion region harbors four evolutionarily conserved and non-imprinted protein-coding genes: NIPA1, NIPA2, CYFIP1, and TUBGCP5. This microdeletion is a rare copy number variation frequently associated with several pathogenic conditions in humans. The aim of this study is to investigate the RNA-binding proteins binding with the four genes present in 15q11.2 BP1-BP2 microdeletion region. The results of this study will help to better understand the molecular intricacies of the Burnside-Butler Syndrome and also the possible involvement of these interactions in the disease aetiology. Our results of enhanced crosslinking and immunoprecipitation data analysis indicate that most of the RBPs interacting with the 15q11.2 region are involved in the post-transcriptional regulation of the concerned genes. The RBPs binding to this region are found from the in silico analysis, and the interaction of RBPs like FASTKD2 and EFTUD2 with exon-intron junction sequence of CYFIP1 and TUBGCP5 has also been validated by combined EMSA and western blotting experiment. The exon-intron junction binding nature of these proteins suggests their potential involvement in splicing process. This study may help to understand the intricate relationship of RBPs with mRNAs within this region, along with their functional significance in normal development, and lack thereof, in neurodevelopmental disorders. This understanding will help in the formulation of better therapeutic approaches.

Simultaneous detection of 7 important Rickettsiales pathogens by TaqMan-probe quantitative real-time PCR

Objective: To establish and optimize a TaqMan-probe quantitative real-time PCR (qPCR) assay for the detection of 7 important Rickettsiales pathogens and simultaneous identification of the infection types. Methods: Based on the ompB gene of Rickettsia prowazekii, Rickettsia mooseri and spotted fever group rickettsiae, the groEL gene of Orientia tsutsugamushi, the 16S rRNA of Ehrlichia chaffeensis, the gltA gene of Anaplasma phagocytophilum and the com1 gene of Coxiella burnetii, we synthesized primers and TaqMan-probes and optimized the reaction system and reaction process to same solution. The sensitivity, specificity and reproducibility of this assay were evaluated and the assay was used for the detection of simulated and actual samples. Results: The Ct value of the standard curves of the 7 pathogens showed a good linear relationship with the number of DNA copies (all R2 >0.990 0), the minimum detection limit was 10 copies/μl, showing good specificity. In the 96 tick nucleic acid extracts, Coxiella burnetii was detected in 1 sampleand spotted fever group Rickettsiae was detected in 3 samples. In the 80 blood samples from patients with undefined febrile illness, Orientia tsutsugamushi was detected in 1 sample and spotted fever group rickettsiae was detected in 2 samples. Conclusions: In this study, based on the established TaqMan-probe qPCR assay, the reaction system and reaction condition of the 7 important pathogens of Rickettsiales were optimized to the same solution. This method overcomes the shortcomings of using different reaction systems and reaction conditions for different pathogens, which can precisely identify the species of 7 important pathogens of Rickettsiales in clinical sample detections and is important for the infection type identification and laboratory detection time reduction to facilitate precise treatment of the patients.

The Prevalence of Chest Infection in Patients with Heart Failure in Al-Wahadah Teaching Hospital, Dhamar, Yemen

Background: Heart failure is a common clinical manifestation of most organic heart diseases that progress to the end stage. Patients with heart failure are often accompanied by secondary conditions such as pulmonary circulatory congestion and pulmonary edema, which can lead to dyspnea, gas exchange disorders, and other consequences, creating certain conditions for pathogens to invade and colonize the lungs. Therefore, patients with heart failure may have higher risk of pulmonary infection. Aim: This study aimed to assess the prevalence of chest infection among patients with heart failure and to determine the characteristics of the patients with heart failure who had chest infection and the potential risk factors. Methods: A retrospective, descriptive cross-sectional study was carried out at internal medicine department, Al-Wahdah Teaching Hospital, Dhamar, Yemen over six months (June – December 2022). A total of 100 patients were enrolled in our study. A semi-structured questionnaire was designed and used for data collection. Results: A total of 100 heart failure patients including 53 (53%) males, and 47 (47%) females were successfully enrolled in this study. The majority of participated patients were of age group 40 – 60 years (55%), and were of rural residence (83%). Chest infection was documented in approximately two-thirds of included patients (63%). Chest infection was documented in majority of patients who were smokers, Qat chewer, shamma intakes, being obese, had cardiomyopathy, as well as those patients who had dyspnea of NYHA class III &amp; IV, orthopnea, PND, productive cough, high sputum amount, whitish sputum color, peripheral chest pain, fatigue, sweating, fever and high WBC count, such associations were significant statistically. Conclusion: This study revealed that, chest infection in heart failure patients was common with overall prevalence of (63%) among included patients this study was. Based on this, an early prevention and intervention measures should be taken to reduce pulmonary infections in patients with heart failure.

Musclin attenuates lipid deposition in hepatocytes through SIRT7/autophagy-mediated suppression of ER stress

Musclin, an exercise-responsive myokine, has the ability to attenuate inflammation, oxidative stress, and apoptosis in cardiomyocytes under pathogenic conditions. While the potential benefits of musclin in the cardiovascular system have been well documented, its effects on hepatic endoplasmic reticulum (ER) stress and lipid metabolism are not fully understood. The present study showed that musclin treatment reduced lipid accumulation and lipogenic protein expression in primary hepatocytes exposed to palmitate. Palmitate treatment led to an increase in markers of ER stress, which was reversed by musclin treatment. Musclin treatment increased SIRT7 expression and markers of autophagy in a dose-dependent manner. Small interfering (si) RNA of SIRT7 or 3-methyladenine (3 MA) reduced the effects of musclin on lipogenic lipid deposition in hepatocytes under hyperlipidemic conditions. These findings suggest that musclin can suppress palmitate-induced ER stress by upregulating SIRT7 and autophagy signaling, thereby alleviating lipid accumulation in primary hepatocytes. The current study provides a potential therapeutic strategy for the treatment of liver diseases characterized by lipid accumulation and ER stress, such as nonalcoholic fatty liver disease (NAFLD).

Reactive oxygen species-specific characteristics of transient receptor potential ankyrin 1 receptor and its pain modulation

Transient receptor potential ankyrin 1 (TRPA1) receptors are major polymodal nociceptors that generate primary pain responses in the peripheral nerve endings of the dorsal root ganglion neurons. Recently, we reported that the activation of TRPA1 receptors by reactive oxygen species (ROS) signaling, which is triggered by Ca&lt;sup&gt;2+&lt;/sup&gt; influx through T-type Ca&lt;sup&gt;2+&lt;/sup&gt; channels, contributes to prolonged pain responses induced by jellyfish toxin. In this review, we focus on the characteristics of the TRPA1 receptor involved in intracellular signaling as a secondary pain modulator. Unlike other transient receptor potential receptors, TRPA1 receptors can induce membrane depolarization by ROS without exogenous stimuli in peripheral and central sensory neurons. Therefore, it is important to identify the functional characteristics of TRPA1 receptors to understand pain modulation under several pathogenic conditions such as neuropathic pain syndromes and autoimmune diseases, which are mediated by oxidative signaling to cause chronic pain in the sensory system.

Periodontal Disease Pathogens, Pathogenesis, and Therapeutics: The CRISPR-Cas Effect.

Periodontal disease (PD) is an immune-inflammatory disease affecting the supporting structures of the teeth, which results in progressive destruction of the hard and soft tissues surrounding teeth, ultimately resulting in tooth loss. The primary etiological factor for this disease is the presence of pathogenic microorganisms. Pathogenic bacteria face antagonistic conditions and foreign DNA components during the infection stage and depend on defense mechanisms such as clustered regularly interspaced short palindromic repeats (CRISPR)-Cas to counter them. Virulence genes regulated by the CRISPR-Cas system are often expressed by bacteria as part of the stress response to the presence of stress conditions and foreign elements. There is ever-growing evidence regarding the role of CRISPR-Cas in virulence of periodontal pathogens. The same CRISPR-Cas system may also be targeted to reduce bacterial virulence and it may also be utilized to develop diagnostic and therapeutic strategies for prevention and control of PD progression. This review article describes the CRISPR-Cas systems in the periodontal dysbiotic microbial communities, their role in the virulence of periodontal pathogens, and their potential role in understanding the pathogenesis of periodontitis and treatment of PD.

Regulation of Cell Plasticity by Bromodomain and Extraterminal Domain (BET) Proteins: A New Perspective in Glioblastoma Therapy.

BET proteins are a family of multifunctional epigenetic readers, mainly involved in transcriptional regulation through chromatin modelling. Transcriptome handling ability of BET proteins suggests a key role in the modulation of cell plasticity, both in fate decision and in lineage commitment during embryonic development and in pathogenic conditions, including cancerogenesis. Glioblastoma is the most aggressive form of glioma, characterized by a very poor prognosis despite the application of a multimodal therapy. Recently, new insights are emerging about the glioblastoma cellular origin, leading to the hypothesis that several putative mechanisms occur during gliomagenesis. Interestingly, epigenome dysregulation associated with loss of cellular identity and functions are emerging as crucial features of glioblastoma pathogenesis. Therefore, the emerging roles of BET protein in glioblastoma onco-biology and the compelling demand for more effective therapeutic strategies suggest that BET family members could be promising targets for translational breakthroughs in glioblastoma treatment. Primarily, "Reprogramming Therapy", which is aimed at reverting the malignant phenotype, is now considered a promising strategy for GBM therapy.

DbAQP-SNP: a database of missense single-nucleotide polymorphisms in human aquaporins.

Aquaporins and aquaglyceroporins belong to the superfamily of major intrinsic proteins (MIPs), and they transport water and other neutral solutes such as glycerol. These channel proteins are involved in vital physiological processes and are implicated in several human diseases. Experimentally determined structures of MIPs from diverse organisms reveal a unique hour-glass fold with six transmembrane helices and two half-helices. MIP channels have two constrictions formed by Asn-Pro-Ala (NPA) motifs and aromatic/arginine selectivity filters (Ar/R SFs). Several reports have found associations among single-nucleotide polymorphisms (SNPs) in human aquaporins (AQPs) with diseases in specific populations. In this study, we have compiled 2798 SNPs that give rise to missense mutations in 13 human AQPs. To understand the nature of missense substitutions, we have systematically analyzed the pattern of substitutions. We found several examples in which substitutions could be considered as non-conservative that include small to big or hydrophobic to charged residues. We also analyzed these substitutions in the context of structure. We have identified SNPs that occur in NPA motifs or Ar/R SFs, and they will most certainly disrupt the structure and/or transport properties of human AQPs. We found 22 examples in which missense SNP substitutions that are mostly non-conservative in nature have given rise to pathogenic conditions as found in the Online Mendelian Inheritance in Man database. It is most likely that not all missense SNPs in human AQPs will result in diseases. However, understanding the effect of missense SNPs on the structure and function of human AQPs is important. In this direction, we have developed a database dbAQP-SNP that contains information about all 2798 SNPs. This database has several features and search options that can help the user to find SNPs in specific positions of human AQPs including the functionally and/or structurally important regions. dbAQP-SNP (http://bioinfo.iitk.ac.in/dbAQP-SNP) is freely available to the academic community. Database URL http://bioinfo.iitk.ac.in/dbAQP-SNP.

Biocontrol of Foot and Root Rot Disease of Groundnut (Arachis hypogaea) by Dual Inoculation with Rhizobium and Arbuscular Mycorrhiza

The present study was carried out to investigate the potential of AM (Arbuscular mycorrhiza) fungi alone and in combination with bioinoculants i.e., Rhizobium to find out the best combination on dry biomass, nodulation, colonization, and yield, along with their biocontrol against groundnut foot and root rot caused by Sclerotium rolfsii. The study was carried out under pot culture conditions in the net house of the Soil Science Division, Bangladesh Agricultural Research Institute, Joydebpur, Gazipur in 2020 and 2021. The experiment was designed in RCBD with eight treatments and four replications. Peat-based rhizobial inoculum (BARI RAh-801) was used @ 1.5 kg ha-1 in this experiment. Soil-based AM inoculum containing approximately 252 spores and infected root pieces of the host plant was used in pot-1. The treatments were Arbuscular mycorrhiza (AM), Rhizobium, AM+Rhizobium, Sclerotium rolfsii, Sclerotium rolfsii+AM, Sclerotium rolfsii+Rhizobium, Sclerotium rolfsii+AM+Rhizobium and Control. Dual inoculation (AM+Rhizobium) significantly increased dry biomass, nodulation, colonization, yield, and yield attributes of groundnut compared to single inoculation or other treatments. The result showed that dual inoculation (AMF+Rhizobium) increased nut yield (59.61% in 2020 and 26.32% in 2021) and stover yield (23.21% in 2020 and 33.74% in 2021) compared to control. On the contrary, Sclerotium rolfsii+AMF+Rhizobium increased nut yield (65.50% in 2020 and 52.94% in 2021) and stover yield (36.45% in 2020 and 99.35% in 2021) compared to only Sclerotium rolfsii treatment. The plant dry biomass, nodulation, colonization, nutrient concentration and uptake were increased by dual inoculation under pathogenic and non-pathogenic conditions leading to an improved yield of groundnut. Therefore, AMF species and its combination with rhizobial inoculum were significant in the formation and effectiveness of AM fungi symbiosis. They also increased yield and reduced the incidence of foot and root rot disease in groundnut plants.

The emerging roles of leukocyte cell-derived chemotaxin-2 in immune diseases: From mechanisms to therapeutic potential.

Leukocyte cell-derived chemotaxin-2 (LECT2, also named ChM-II), initially identified as a chemokine mediating neutrophil migration, is a multifunctional secreted factor involved in diverse physiological and pathological processes. The high sequence similarity of LECT2 among different vertebrates makes it possible to explore its functions by using comparative biology. LECT2 is associated with many immune processes and immune-related diseases via its binding to cell surface receptors such as CD209a, Tie1, and Met in various cell types. In addition, the misfolding LECT2 leads to the amyloidosis of several crucial tissues (kidney, liver, and lung, etc.) by inducing the formation of insoluble fibrils. However, the mechanisms of LECT2-mediated diverse immune pathogenic conditions in various tissues remain to be fully elucidated due to the functional and signaling heterogeneity. Here, we provide a comprehensive summary of the structure, the "double-edged sword" function, and the extensive signaling pathways of LECT2 in immune diseases, as well as the potential applications of LECT2 in therapeutic interventions in preclinical or clinical trials. This review provides an integrated perspective on the current understanding of how LECT2 is associated with immune diseases, with the aim of facilitating the development of drugs or probes against LECT2 for the theranostics of immune-related diseases.