Microplastics - A Growing Concern as Carcinogens in Cancer Etiology: Emphasis on Biochemical and Molecular Mechanisms.

In today's world, the widespread presence of microplastics is undeniable, with concentrations found in various environments, including up to 1000 particles per liter in seawater and up to 10 particles per cubic meter in the atmosphere. Originating from diverse sources, both intentional and unintentional, these minuscule fragments, measuring less than 5 mm, pose significant threats to environmental and human health. Recent research has uncovered a concerning link between microplastics and cancer, prompting urgent investigation. Studies demonstrate microplastics can infiltrate cells, disrupt biological processes, and potentially foster carcinogenic environments. From inducing DNA damage and oxidative stress to triggering inflammatory responses and dysregulating cellular pathways, microplastics exhibit a multifaceted capability in contributing to cancer development. Furthermore, microplastics act as carriers for a range of contaminants, compounding their impact on human health. Their accumulation within tissues and organs raises concerns for short and long-term health consequences, including chronic diseases, reproductive issues, and developmental abnormalities. This review explores the biochemical and molecular mechanisms underlying the interaction between microplastics and cellular systems, providing insights into routes of exposure and health effects, with a focus on lung, skin, and digestive system cancers. As we confront this pressing environmental and public health challenge, a deeper understanding of the microplastic-cancer relationship is crucial to safeguarding the well-being of present and future generations.

H-Deep-Net: A deep hybrid network with stationary wavelet packet transforms for Retinal detachment classification through fundus images.

Nowadays, automated disease diagnosis has become a vital role in the medical field due to the significant population expansion. An automated disease diagnostic approach assists clinicians in the diagnosis of disease by giving exact, consistent, and prompt results, along with minimizing the mortality rate. Retinal detachment has recently emerged as one of the most severe and acute ocular illnesses, spreading worldwide. Therefore, an automated and quickest diagnostic model should be implemented to diagnose retinal detachment at an early stage. This paper introduces a new hybrid approach of best basis stationary wavelet packet transform and modified VGG19-Bidirectional long short-term memory to detect retinal detachment using retinal fundus images automatically. In this paper, the best basis stationary wavelet packet transform is utilized for image analysis, modified VGG19-Bidirectional long short-term memory is employed as the deep feature extractors, and then obtained features are classified through the Adaptive boosting technique. The experimental outcomes demonstrate that our proposed method obtained 99.67% sensitivity, 95.95% specificity, 98.21% accuracy, 97.43% precision, 98.54% F1-score, and 0.9985 AUC. The model obtained the intended results on the presently accessible database, which may be enhanced further when additional RD images become accessible. The proposed approach aids ophthalmologists in identifying and easily treating RD patients.

Inflammatory responses during trichomoniasis: The role of Toll-like receptors and inflammasomes.

Toll-like receptors (TLRs) and inflammasomes belong to the pattern recognition receptors (PRRs) of innate immunity identifying conserved compounds produced by pathogens or discharged by injured cells. Different cell subsets in the human urogenital system, such as epithelial cells and infiltrating leukocytes, express different kinds of TLRs (such as TLR2, TLR3, TLR4, TLR5 and TLR9) as well as inflammasomes (such as NLRP3, NLRC4 and AIM2). Various types of the Trichomonas vaginalis-derived components such as glycosyl-phosphatidylinositol (GPI), T. vaginalis virus (TVV), Lipophosphoglycan (LPG) and flagellin can be recognized by TLR2, TLR3, TLR4 and TLR5, respectively, leading to the production of proinflammatory cytokines and chemokines in the cervicovaginal mucosa. The T. vaginalis-induced inflammasomes can lead to pyroptosis as well as the release of IL-1ß and IL-18 promoting innate and adaptive immune responses. The PRR-mediated responses to T. vaginalis may contribute to the induction of protective immune responses, local inflammation, promotion of co-infections, or even the development of malignancies, for example, prostate cancer. The protective or pathogenic roles of the TLRs and inflammasomes during trichomoniasis are highlighted in this review. A better understanding of PRR-mediated responses provides invaluable insights to develop effective immunotherapeutic strategies against T. vaginalis infection.

Local cytokine/chemokine profiles in BALB/c and C57BL/6 mice in response to T. vaginalis infection.

Trichomonas vaginalis is the causative agent of Trichomoniasis (a sexually transmitted infection). Recent reports have shown that stimulation of cellular immunity can reduce trichomoniasis infection. Animal studies are essential to understanding the pathogenesis of infection and developing new potential drugs and vaccines to treat the infection. Therefore, we have tried to understand the pathogenesis of T. vaginalis infection by investigating the differences in the expression of chemokine/cytokine levels in vaginal and cervical tissues of BALB/c and C57BL/6 mice. Different pathological symptoms, like desquamation, neutrophil infiltration, and hemorrhage, were recorded in BALB/c and C57BL/6 in response to T. vaginalis infection. Vaginal and cervical tissues of BALB/c showed these symptoms on 2nd dpi, which became severe on 7th dpi and turned to mild or normal till 14th dpi compared to C57BL/6 strain. Immunohistochemistry in the vagina and cervical tissues of BALB/c and C57BL/6 mice was done to assess cytokines at different time intervals post-infection. Significant expression of Interleukin-1ß (IL-1ß) (a pro-inflammatory cytokine) was found in BALB/c compared to the C57BL/6 mice, on 7th dpi and 2nd dpi in vaginal and cervical tissues, respectively. Higher expression of MIP-2 (neutrophil chemoattractant) was observed in the vaginal tissues of BALB/c mice on 7th dpi compared to the C57BL/6 group. In addition, higher expression of TGF-ß (immune-suppressor) was observed on 7th dpi in the vaginal tissue of BALB/c mice. The present study demonstrates that more pathological signs of T. vaginalis infection developed in BALB/c mice than C57BL/6 mice. Also, significant levels of IL-1ß and MIP-2 were measured in BALB/c mice in response to T. vaginalis compared to C57BL/6.

α7nAChR activation protects against oxidative stress, neuroinflammation and central insulin resistance in ICV-STZ induced sporadic Alzheimer's disease.

Central insulin resistance is considered as one of the pathological hallmarks of Alzheimer's disease (AD), similar to formation of amyloid plaques and neurofibrillary tangles (NFT). Activation of α7nAChR by GTS-21 has been indicated to reverse peripheral insulin resistance and exert neuroprotection. Therefore, the aim of the present study was to determine the effect of α7nAChR agonist (GTS-21) on intracerebroventricular administration of streptozotocin (ICV-STZ)-induced oxidative stress, neuroinflammation, cholinergic dysfunction, central insulin resistance and cognitive deficits. GTS-21 (1, 4 and 8 mg/kg; i.p.) was administered for 21 days following bilateral ICV-STZ administration (3 mg/kg) in C57BL/6 mice. Neurobehavioral assessments were performed using Morris water maze (MWM) and novel object recognition (NOR). Inflammatory markers (TNF-α, IL-6 and IL-1ß) were determined using ELISA. Oxido-nitrosative stress (GSH, MDA and nitrite) and cholinergic activity (acetylcholine esterase and choline acetyltransferase) were estimated in the cortex and hippocampus through biochemical methods. Gene expression of insulin receptor (IR), IRS1, IRS2, BACE1, APP, PI3-K, AKT and GSK3ß were determined by q-RT-PCR. ICV-STZ administration induced memory impairment, increased oxidative stress and neuroinflammation, and caused cholinergic dysfunction. Our results demonstrated that activation of α7nAChR by GTS-21 treatment improved memory in MWM and NOR test. Moreover, GTS-21 treatment significantly decreased oxido-nitrosative stress, inflammatory markers and cholinergic dysfunction in cortex and hippocampus. Finally, GTS-21 treatment restored ICV-STZ induced downregulation of IR, IRS1, IRS2, PI3-k, Akt and attenuated GSK3ß, APP and BACE-1 indicating improved insulin signalling. Therefore, activation of α7nAChR through GTS-21 might be the potential target for the amelioration of central insulin resistance induced AD.

A sketch of microbiological remediation of explosives-contaminated soil focused on state of art and the impact of technological advancement on hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) degradation.

When high-energy explosives such as hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), 2,4,6-trinitrotoluene (TNT) are discharged into the surrounding soil and water during production, testing, open dumping, military, or civil activities, they leave a toxic footprint. The US Environmental Protection Agency has labeled RDX as a potential human carcinogen that must be degraded from contaminated sites quickly. Bioremediation of RDX is an exciting prospect that has received much attention in recent years. However, a lack of understanding of RDX biodegradation and the limitations of current approaches have hampered the widespread use of biodegradation-based strategies for RDX remediation at contamination sites. Consequently, new bioremediation technologies are required to enhance performance. In this review, we explore the requirements for in-silico analysis for producing biological models of microbial remediation of RDX in soil. On the other hand, potential gene editing methods for getting the host with target gene sequences responsible for the breakdown of RDX are also reported. Microbial formulations and biosensors for detection and bioremediation are also briefly described. The biodegradation of RDX offers an alternative remediation method that is both cost-effective and ecologically acceptable. It has the potential to be used in conjunction with other cutting-edge technologies to further increase the efficiency of RDX degradation.

Latent Upregulation of Nlrp3, Nlrc4 and Aim2 Differentiates between Asymptomatic and Symptomatic Trichomonas vaginalis Infection.

Trichomonas vaginalis is a parasitic protozoan that causes trichomoniasis. The involvement of NLRP3 inflammasome in trichomoniasis has been discussed in recent studies. The present study aimed to find out the involvement of Nlrp3, Nlrc4, and Aim2 in the BALB/c mouse model infected with symptomatic and asymptomatic isolates of T. vaginalis by quantitative real-time PCR and immunohistochemistry. Our results showed a significantly increased expression of Nlrp3 in the vaginal tissue of the symptomatic group on the 2nd dpi and 14th dpi in the asymptomatic group, respectively. The cervical tissue of asymptomatic groups expressed higher Nlrp3 on 14th dpi than the symptomatic group. The Nlrc4 was expressed on 14th dpi in the vaginal and cervical tissues of mice infected with asymptomatic group as compared to the symptomatic group. Aim2 expression in vaginal tissue was highest at early time points in both the infected groups as compared to controls. However, in cervical tissues, a significant increase of Aim2 expression was observed on 14th dpi in asymptomatic as compared to the symptomatic group. The significantly higher expression of caspase-1 and caspase-4 was observed in cervical tissues of the asymptomatic group on 14th dpi as compared to the symptomatic group, respectively. All NLRs together resulted in higher IL-1ß expression in the vaginal tissues of the symptomatic and asymptomatic groups. We conclude from this study that early expression of Nlrp3, Nlrc4, and Aim2 was seen in the symptomatic group as compared to the late-onset asymptomatic in the vaginal and cervical tissues.

Comparative Evaluation of Fluoride Release from Glass Ionomer, Compomer, and Giomer Sealants Following Exposure to Fluoride Toothpaste and Fluoride Varnish: An In Vitro Study.

Introduction: Applying sealants to the deep pit and fissure area will be an excellent way to stop and slow down tooth caries from developing. Dental sealants that include fluoride are more successful at lowering dental cavities. It is anticipated that exposure to fluoride from dental sealants of various origins may enhance the fluoride release from dental sealants. Therefore, this study's objective was to investigate the amount of fluoride released after using fluoride toothpaste and fluoride varnish from different sealants. Materials and methods: Using only a fluoride ion selective electrode, the initial release of fluoride was detected every 24 hours for 15 days. After every measurement, the saliva was refreshed. The samples were split into three identical subgroups and given the respective regimes on the 15th day-subgroup A was given fluoride toothpaste every morning and evening, subgroup B was provided fluoride varnish once, and subgroup C was not given any fluoride regime at all. After another 15 days of fluoride exposure, the fluoride release was monitored. Results: With notable variations across groups over the initial 15 days, glass ionomer sealants (GIS) released more amount of fluoride, second by giomer sealant, and third by resin sealant (p = 0.00). All dental sealants that have been tested released more fluoride when using fluoride toothpaste, with giomer sealants surpassing GIS, followed by resin sealants (p = 0.00). Giomer and resin sealants, fluoride varnish treatment dramatically improves fluoride release in GIS (p = 0.00). Conclusion: The release of fluoride among all dental sealants is improved by using fluoride toothpaste daily and fluoride varnish just once. How to cite this article: Senthilkumar A, Chhabra C, Trehan M, et al. Comparative Evaluation of Fluoride Release from Glass Ionomer, Compomer, and Giomer Sealants Following Exposure to Fluoride Toothpaste and Fluoride Varnish: An In Vitro Study. Int J Clin Pediatr Dent 2022;15(6):736-738.

A cellular expression map of epidermal and subepidermal cell layer-enriched transcription factor genes integrated with the regulatory network in Arabidopsis shoot apical meristem.

Transcriptional control of gene expression is an exquisitely regulated process in both animals and plants. Transcription factors (TFs) and the regulatory networks that drive the expression of TF genes in epidermal and subepidermal cell layers in Arabidopsis are unexplored. Here, we identified 65 TF genes enriched in the epidermal and subepidermal cell layers of the shoot apical meristem (SAM). To determine the cell type specificity in different stages of Arabidopsis development, we made YFP based transcriptional fusion constructs by taking a 3-kb upstream noncoding region above the translation start site. Here, we report that for ~52% (22/42) TF genes, we detected transcription activity. TF genes derived from epidermis show uniform expression in early embryo development; however, in the late globular stage, their transcription activity is suppressed in the inner cell layers. Expression patterns linked to subepidermal cell layer identity were apparent in the postembryonic development. Potential upstream regulators that could modulate the activity of epidermal and subepidermal cell layer-enriched TF genes were identified using enhanced yeast-one-hybrid (eY1H) assay and validated. This study describes the activation of TF genes in epidermal and subepidermal cell layers in embryonic and postembryonic development of Arabidopsis shoot apex.

Potential of formulated Dyadobacter jiangsuensis strain 12851 for enhanced bioremediation of chlorpyrifos contaminated soil.

Chlorpyrifos (O, O-diethyl O-3, 5, 6-trichloropyridin-2-yl phosphorothioate) is a toxic and chlorinated organic contaminant in soils across the globe. The present study examines the chlorpyrifos (CP) degrading potential of gram-negative bacterium Dyadobacter jiangsuensis (MTCC 12851), to be a promising and sustainable remedial approach. The proliferation of D. jiangsuensis in the chlorpyrifos spiked minimal salt media indicated the ability of this strain to utilize CP as a sole carbon source and also confirmed the utilization of 3,5,6- trichloro-2-pyridinyl (TCP) through silver nitrate assay. The strain 12851 degraded 80.36% and 76.93% chlorpyrifos (CP) in aqueous medium and soil environment, respectively. The water dispersible granules (WDG) of 45% (v/w) inoculum (bacterial suspension) were developed using talcum powder, acacia gum and alginic acid as key ingredients. The formulated strain (12851) achieved 21.13% enhanced CP degradation in soil under microcosm condition as compared to the unformulated one on 15th day of the treatment. The intermediate metabolites namely 3,5,6-trichloro-2-pyridinol (TCP), tetrahydropyridine, thiophosphate and phenol, 1, 3-bis (1,1-dimethylethyl) were detected during the CP degradation. The current investigation reveals D. jiangsuensis as a potential microbe for CP degradation and opens up the possibility of exploiting its formulations to remediate the CP polluted soils.

AdCOFE: Advanced Contextual Feature Extraction in conversations for emotion classification.

Emotion recognition in conversations is an important step in various virtual chatbots which require opinion-based feedback, like in social media threads, online support, and many more applications. Current emotion recognition in conversations models face issues like: (a) loss of contextual information in between two dialogues of a conversation, (b) failure to give appropriate importance to significant tokens in each utterance, (c) inability to pass on the emotional information from previous utterances. The proposed model of Advanced Contextual Feature Extraction (AdCOFE) addresses these issues by performing unique feature extraction using knowledge graphs, sentiment lexicons and phrases of natural language at all levels (word and position embedding) of the utterances. Experiments on emotion recognition in conversations datasets show that AdCOFE is beneficial in capturing emotions in conversations.

Insights into the toll-like receptors in sexually transmitted infections.

Toll-like receptors (TLRs) are like soldiers of an innate immune system, which protects vital biological processes against invading pathogens. TLR signalling pathways help in the removal of pathogens and mediate well-established inflammatory processes. However, these processes may also aid in the development or augmentation of an infection or an autoimmune disease. Recent studies have delineated TLR polymorphism's role in the loss of function, making hosts more resistant or vulnerable to the development of an infection. In this review, we have discussed the association of TLRs with sexually transmitted infections (STIs), especially to the pathogen-specific ligands. We have also assessed the impact on TLR downstream signalling and the maintenance of cellular homeostasis during immune responses. Besides, we have discussed the role of TLRs single nucleotide polymorphisms in various STIs. Since TLRs are known to play a part in defence mechanisms and in aiding infections therefore, a thorough understanding of TLRs structure and molecular mechanisms is required to explain how they can influence the outcome of an STI. Such a strategy may lead to the development of novel and useful immunotherapeutic approaches to control pathogen progression and prevent transmission.

Management of ocular surface squamous neoplasia extending up to a filtering trabeculectomy bleb.

A 73-year-old-gentleman was referred for ocular surface squamous neoplasia (OSSN) in his right eye (RE). He had history of combined cataract with trabeculectomy in RE and was maintaining his intraocular pressure (IOP). He showed a corneoscleral lesion measuring 11 × 8 mm in nasal quadrant wherein, the superior edge of the lesion was extending up to the filtering bleb. After ruling out intraocular invasion or regional spread, he underwent complete tumor excision with "no touch" technique along with cryotherapy and surface reconstruction and a perilesional injection of Interferon α2B. At 6-month visit, he shows no locoregional recurrence and has controlled IOP.

α-Hemolysin of uropathogenic E. coli regulates NLRP3 inflammasome activation and mitochondrial dysfunction in THP-1 macrophages.

Hemolysin expressing UPEC strains have been associated with severe advanced kidney pathologies, such as cystitis and pyelonephritis, which are associated with an inflammatory response. Macrophages play an important role in regulating an inflammatory response during a urinary tract infection. We have studied the role of purified recombinant α-hemolysin in inducing inflammatory responses and cell death in macrophages. Acylation at lysine residues through HlyC is known to activate proHlyA into a fully functional pore-forming toxin, HlyA. It was observed that active α-hemolysin (HlyA) induced cleavage of caspase-1 leading to the maturation of IL-1ß, while inactive α-hemolysin (proHlyA) failed to do so in THP-1 derived macrophages. HlyA also promotes deubiquitination, oligomerization, and activation of the NLRP3 inflammasome, which was found to be dependent on potassium efflux. We have also observed the co-localization of NLRP3 within mitochondria during HlyA stimulations. Moreover, blocking of potassium efflux improved the mitochondrial health in addition to a decreased inflammatory response. Our study demonstrates that HlyA stimulation caused perturbance in potassium homeostasis, which led to the mitochondrial dysfunction followed by an acute inflammatory response, resulting in cell death. However, the repletion of intracellular potassium stores could avoid HlyA induced macrophage cell death. The findings of this study will help to understand the mechanism of α-hemolysin induced inflammatory response and cell death.

Data showing differential expression of Monocyte chemoattractant protein-1 in response to symptomatic and asymptomatic T. vaginalis infection.

Trichomoniasis is caused by Trichomonas vaginalis (a protozoan parasite). About 80% of the infected cases remain asymptomatic [1]. The differential response of showing symptoms or no symptoms is not yet explored. However, some studies gave us some insights on the pathogenesis of trichomonas and also about host defense mechanism. Host secretes pro-inflammatory cytokines and chemokines to evade infection. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a strong chemoattractant of monocytes, NK-cells and T-lymphocytes. Many reports have shown high MCP-1 levels during trichomonas infection [2], [3], [4], [5] in human prostate stromal myofibroblast cells (WPMY-1), HeLa cells, vaginal epithelial cells (VECs) but levels in response to symptomatic and asymptomatic isolates is not yet reported. In this article, we have reported MCP-1 levels in the vaginal washes and serum samples of BALB/c mouse infected with symptomatic and asymptomatic T. vaginalis isolates for different time points. We found higher levels of MCP-1 in vaginal washes of symptomatic group on 2nd day post infection (dpi) than control uninfected group. While on 4th dpi and 14th dpi, higher levels of MCP-1 in vaginal washes was observed in asymptomatic group as compared to control group. However, significant level of MCP-1 was observed in asymptomatic group on 14th dpi as compared to symptomatic group in vaginal washes. We have also observed significantly higher levels of MCP-1 in the serum samples of symptomatic group on 2nd, 4th and 14th dpi as compared to control group. A higher level of MCP-1 was found at all the time points in serum samples of asymptomatic group as compared to control group. Interestingly, a significant higher level of MCP-1 was found in the serum samples of BALB/c mice in asymptomatic as compared to symptomatic group. The MCP-1 levels in both vaginal washes and serum were significantly higher in asymptomatic group at later time points.

Eyelid Lesion as a Presenting Sign of Pancreatic Adenocarcinoma.

Eyelid metastases are relatively rare, and they can occasionally lead the way to an unknown primary malignancy elsewhere. The authors report a case of 65-year-old diabetic gentleman with a right-sided eyelid lesion that was present for 1 month and turned out to be a presenting sign of a previously undiagnosed pancreatic adenocarcinoma. The eyelid mass had been treated elsewhere for 2 weeks for a presumed infectious lesion, using systemic antibiotics and was then referred to us in view of no response. The right-sided lesion involving the subbrow and eyelid area was tender and showed surface ulceration, as well as induration with scabbing. An incision biopsy of the mass was performed followed by computed tomography imaging. Histopathologic findings were suggestive of adenocarcinoma of a probable secondary origin. A whole-body positron emission tomography (PET) scan along with raised serum tumor markers (carcinoembryonic antigen 125 [CEA 125] and carbohydrate antigen 19-9 [CA-19-9]) was helpful in diagnosing a stage IV probable primary carcinoma of the pancreas, with metastasis to paraaortic nodes, liver, lungs, and eyelid. After a detailed systemic work-up, the patient was put on systemic chemotherapy with carboplatin and capacitabane. He responded well to the treatment. At a follow up of 12 months, upon clinical examination and PET imaging, he showed a complete resolution of eyelid, lung, and liver disease and a near-complete resolution of the pancreatic lesion. This case delineates the role of a prompt biopsy and histopathologic evaluation of an atypical eyelid mass in diagnosing asymptomatic primary malignancy.

Enhancing hexahydro-1, 3, 5-trinitro-1, 3, 5-triazine (RDX) remediation through water-dispersible Microbacterium esteraromaticum granules.

In the current manuscript, we explored the remediation potential of Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) by Gram-positive Microbacterium esteraromaticum 12849. The strain detoxified 70.9 and 63.93% RDX in minimal nutrient medium and soil, respectively. Subsequently, the strain 12849 was formulated in form of water-dispersible granules (WDG) using talcum powder and alginic acid as inert ingredients. During the microcosm study, WDG exhibited 8.98% enhanced RDX degradation in contrast to the unformulated Microbacterium esteraromaticum. The LC-MS analysis revealed the presence of two intermediates, namely N-methyl-N, N'-dinitromethanediamine, and methylenedintramine, during the RDX degradation by strain 12849 in soil. Interestingly, no significant difference was observed in the rate of RDX degradation by strain 12849 due to the formulation process. The first-order kinetics was seen in RDX degradation with a degradation coefficient of 0.04 and 0.0339 day-1 by formulated and unformulated strain, respectively. The current investigation implies M. esteraromaticum as a potential microbe for RDX degradation and opens up the possibility of exploiting it in its effective WDG form for explosive contaminated sites.

Warfarin: A double-edged sword.

Warfarin is the commonest anticoagulant used in today's practice; it has a very narrow therapeutics window. Under and overdosing results in various life-threatening complications. Warfarin-related nephropathy (WRN) is a rare cause of acute kidney injury (AKI) in patients on long-term anticoagulation, as a result of supratherapeutic anticoagulation. Warfarin causes AKI by inducing glomerular hemorrhage with subsequent tubular obstruction by red blood cell (RBC) casts. WRN has been associated with irreversible kidney injury and increased risk of mortality. Despite a better understanding of pathophysiology and histopathology of WRN, its preventive measures and clinical outcome are not well known. We report here the case of a 62-year-old male, who was on a long-term warfarin therapy due to chronic atrial fibrillation with a history of old ischemic stroke and dilated cardiomyopathy. He was presented with AKI and his renal biopsy was suggestive of WRN. He was managed by withholding warfarin for a few days until the therapeutic range of international normalized ratio was achieved and steroids and N-acetylcysteine (NAC) recovered. WRN is a diagnosis of exclusion; other causes of AKI must be ruled out. Renal biopsy is the gold standard for diagnosis. Patients on chronic anticoagulant therapy should be monitored periodically for the therapeutic range of anticoagulants, deterioration of renal function, and hematuria.

Involvement of NLRP3 and NLRC4 Inflammasome in Uropathogenic E. coli Mediated Urinary Tract Infections.

BACKGROUND: Inflammatory response during urinary tract infection (UTI) is mediated by innate immune defense. Nod like receptors (NLRs) have been proposed to work simultaneously beside TLR pathways to mediate pro-inflammatory response and maintain tissue homeostasis. Some in vitro reports have showed the involvement of NLRP3 inflammasome during uropathogenic Escherichia coli (UPEC) mediated UTI. So we have sought to determine the status of various inflammasomes and their components in UPEC mediated UTI. METHODS: A total of 186 females experiencing the first episode of UTI were recruited for the study and forty were found to be positive for UPEC (≥105 CFU/ml) in their urine (N = 40). Further, we analyzed the expression of NLRP3, NLRC4, NAIP, AIM2, ASC, CASPASE-4, and CASPASE-1 gene at mRNA and protein level in the blood of UPEC confirmed study subjects through real time qPCR and immunoblotting. Healthy females (N = 40) visiting the OPD for health checkups, family planning advice and subjects undergoing routine medical examinations, were recruited as healthy control subjects. Pro-inflammatory cytokines (IL-6, IL-8, IFN-γ, TNF-α and MCP-1) were measured in the plasma of patients and controls through ELISA. For investigation of the involvement of NLRC4 and NLRP3 inflammasome, in vitro studies were performed using co-immunoprecipitation and confocal microscopy. RESULTS: Most of the inflammatory regulators studied (i.e., NLRP3, NAIP, NLRC4, ASC, and CASPASE-1) were found to be up-regulated at both mRNA and protein levels in the UPEC infected UTI patients. Also, pro-inflammatory cytokines (IL-6, IL-8, IFN-γ, TNF-α, and MCP-1) were found to be up-regulated in the patients group. However, no significant difference was observed in the expression of AIM2 and CASPASE-4 genes at both mRNA and protein levels. Further, in vitro studies have shown the involvement of NLRC4 inflammasome in UPEC infected THP1 derived macrophages. CONCLUSION: Involvement of NLRP3 and NLRC4 inflammasomes in UPEC infected UTI is evident from our findings. This is the first report showing levels of inflammasome and its components in UTI patients suggesting a possible role during UPEC mediated UTI. We have also reported the involvement of NLRC4 inflammasome for the first time during UTI infection.