Cellular Infiltration Research Articles

Gestational exposure to air pollutants perturbs metabolic and placenta-fetal phenotype

Air pollution (AP) is detrimental to pregnancies including increasing risk factors of gestational diabetes mellitus. We hypothesized that exposure to AP causes cardiovascular and metabolic disruption thereby altering placental gene expression, which in turn affects the placental phenotype and thereby embryonic/fetal development. To test this hypothesis, we investigated the impact of intra-nasal instilled AP upon gestational day 16–19 maternal mouse cardiovascular and metabolic status, placental nutrient transporters, and placental-fetal size and morphology. To further unravel mechanisms, we also examined placental total DNA 5’-hydroxymethylation and bulk RNA sequenced gene expression profiles. AP exposed pregnant mice and fetuses were tachycardic with a reduction in maternal left ventricular fractional shortening and increased uterine artery with decreased umbilical artery systolic peak velocities. In addition, they were hyperglycemic, glucose intolerant and insulin resistant, with changes in placental glucose (Glut3) and fatty acid (Fatp1 & Cd36) transporters, and a spatial disruption of cells expressing Glut10 that imports L-dehydroascorbic acid in protecting against oxidative stress. Placentas revealed inflammatory cellular infiltration with associated cellular edema and necrosis, with dilated vascular spaces and hemorrhage. Placental and fetal body weights decreased in mid-gestation with a reduction in brain cortical thickness emerging in late gestation. Placental total DNA 5’-hydroxymethylation was 2.5-fold higher, with perturbed gene expression profiles involving key metabolic, inflammatory, transcriptional, cellular polarizing and processing genes and pathways. We conclude that gestational exposure to AP incites a maternal inflammatory response resulting in features mimicking maternal gestational diabetes mellitus with altered placental DNA 5’-hydroxymethylation, gene expression, and associated injury.

Development of an Injectable, ECM-Derivative Embolic for the Treatment of Cerebral Saccular Aneurysms.

Cerebral aneurysms are a source of neurological morbidity and mortality, most often as a result of rupture. The most common approach for treating aneurysms involves endovascular embolization using nonbiodegradable medical devices, such as platinum coils. However, the need for retreatment due to the recanalization of coil-treated aneurysms highlights the importance of exploring alternative solutions. In this study, we propose an injectable extracellular matrix-derived embolic formed in situ by Michael addition of gelatin-thiol (Gel-SH) and hyaluronic acid vinyl sulfone (HA-VS) that may be delivered with a therapeutic agent (here, RADA-SP) to fill and remodel aneurysmal tissue without leaving behind permanent foreign bodies. The injectable embolic material demonstrated rapid gelation under physiological conditions, forming a highly porous structure and allowing for cellular infiltration. The injectable embolic exhibited thrombogenic behavior in vitro that was comparable to that of alginate injectables. Furthermore, in vivo studies in a murine carotid aneurysm model demonstrated the successful embolization of a saccular aneurysm and extensive cellular infiltration both with and without RADA-SP at 3 weeks, with some evidence of increased vascular or fibrosis markers with RADA-SP incorporation. The results indicate that the developed embolic has inherent potential for acutely filling cerebrovascular aneurysms and encouraging the cellular infiltration that would be necessary for stable, chronic remodeling.

Intensity of subarachnoid space inflammation corresponds to the evolution of vessel wall remodeling during the acute and chronic phases of bacterial meningitis

AbstractCerebrovascular alterations in acute bacterial meningitis significantly contribute to adverse patient outcomes, with reported complication rates ranging from 10% to 29%. Focal alterations in arterial lumens, leading to vasoconstriction, are common in cerebral ischemic and inflammatory conditions, such as bacterial meningitis, presenting neurological complications, such as seizures, brain swelling, hydrocephalus, hearing loss and ischemic or hemorrhagic brain damage. The observed arterial narrowing during meningitis is attributed to diverse factors, including direct encroachment by inflammatory exudate, vascular wall edema, vasospasm, and vasculitis due to cellular infiltration and vessel remodeling. Early‐stage constriction might result from a watery exudate's encroachment, whereas persistent inflammation leads to thicker exudates, attracting inflammatory cells and inducing arteriopathic growth factor synthesis. This process promotes structural modifications in the vessel wall, progressing from subintimal infiltration to organic intimal thickening, culminating in vasculitis and the risk of cerebral ischemia. Accordingly, this review seeks to more clearly delineate the intricate relationship between subarachnoid space inflammation and acute and chronic vessel wall remodeling during bacterial meningitis. Conceivably, understanding this pathological process holds promise in unveiling potential treatment avenues to improve patient outcomes, and reduced morbidity and mortality associated with cerebrovascular complications during bacterial meningitis.

A Comparative Histological Study Between the Protective and the Therapeutic Effect of Probiotic on Cisplatin Induced Nephrotoxicity in Adult Male Albino Rat

Abstract Introduction Although cisplatin (CP) is one of the most effective chemotherapies, it is associated with significant nephrotoxicity (Acute kidney injury). Lactobacillus plantarum is often used as a probiotic on its own for its beneficial properties and anti-inflammatory activity. Aim to compare the protective and therapeutic role of probiotics on the microscopic structure of the kidney in a model of cisplatin-induced nephrotoxicity. Material and Methods thirty-five adult male albino rats weighing (200-220gm) were divided into 4 groups. Group I (control group), Group II (Cisplatin group): rats received intraperitoneal injection of CP (7.5 mg/kg) for 3 days. Group III (protective group): Rats received 1 mL of probiotic orally for 7 days. From the fifth day, the rats received intraperitoneal injections of CP (7.5mg/kg) for 3 days. Group IV (Therapeutic group): Rats received intraperitoneal injection of CP for 3 days. From the fourth day, the rats received probiotic L. plantarum orally at a dose of (1 mL/day) for 14 days. The concentration of probiotics in group III and group IV was 109 Colony forming units (CFU)/mL/100 g of body weight. Kidney specimens were proceeded for light microscopic examination, as well as Morphometrical and statistical analyses. Results H&E-stained sections of Group II showed marked renal affection in which most glomeruli showed atrophy. Renal tubules were mostly distorted, necrotic, and degenerative with interstitial hemorrhage, congestion, and cellular infiltration. PAS-stained sections showed marked increased reaction in glomerular and tubular Basement membranes with an apparent loss of Brush borders of most of the PCTs. Masson`s trichrome-stained sections showed a marked increase in collagen fibers in renal interstitia mostly around blood vessels. Immunohistochemically stained sections showed a marked increase in positive cytoplasmic reaction to caspase -3 antibodies mostly in renal tubules. On the other hand, the renal structure of The protective group showed marked improvement which appeared nearly comparable to that of the control group while the therapeutic group showed minimal improvement. Conclusion The protective effect of probiotics on cisplatin-induced Acute Kidney Injury (Nephrotoxicity) was markedly better than the therapeutic effect as detected by microscopic, morphometric, and statistical studies.

Effect of Consumption of Caffeinated Energy Drinks on the Myocardium of the Adult Male Albino Rat (A Histological and Morphometric Study)

Abstract Background Energy drinks are non-alcoholic beverages containing mainly caffeine. Chronic consumption of energy drinks may be associated with increased blood pressure, and cardiac work load, as well as, increased heart rate. Energy drinks consumption has been related to myocardial infarction in healthy young adult. Aim of the Work The aim of the present work was to study the harmful effect of energy drinks histologically and morphometrically, on the myocardium of the adult male albino rats. Material and Methods 20 Adult male albino rats aging 4-6 moths were divided randomly into two groups; Group I (Control group) which consisted of 10 male albino rats with free access to food (rat chew) and water and Group II (Experimental group): 10 male albino rats which received 3.75 ml/kg body weight red bull through oral gavage daily for 4 weeks with free access to food (rat chew) and water. At the end of experiment, rats werescarificed, and cardiac muscle was extracted and processed into paraffin blocks for light microscopic examination. Morphometric study and statistical analysis were done. Results The present work demonstrated that Red Bull induced several histopathological changes of the cardiac muscle. The results showed the cardiac muscle of rats with irregularities in the arrangement of fibers and wide spaces in between. Some cardiomyocytes showed areas of pale stained sarcoplasm, partial loss of the cross striations and ill-defined intercalated discs. Localized areas of hyaline degeneration and areas of tissue disruption were also noticed with less frequently localized coalesced cytoplasmic vacuoles. The nuclei of the cardiomyocytes appeared small, darkly stained, and pyknotic. Others were flattened and deeply stained. Congested, and thick walled blood vessels were also observed, with mononuclear cellular infiltrations. In Masson’s Trichrome sections, relative increase in collagen deposition between the cardiac muscle fibers was observed which was associated with focal fibrous degeneration. Examination of the semithin sections showed partial disruption of the cardiomyocytes. The nuclei of the cardiomyocytes were small, darkly stained with perinuclear degeneration. Some nuclei were eccentric, or with an irregular outline, and peripheral chromatin condensation. The characteristic finding was the presence of longitudinal wavy cardiac muscle fibers with relatively wide spaces in between and localized areas of partially lost cross striations and intercalated discs. Dilated, thick walled blood vessels was noticed between the bundles of cardiac muscle. Mononuclear inflammatory cellular infiltrations were also detected. Conclusion The present study demonstrated the degenerative and cardiotoxic effects of Red Bull as an example of energy drinks on the histological structure of the cardiac muscle.

Study of the Effect of Tumor Necrosis Factor Alpha (TNF-α) Antagonist (Adalimumab) on Giardiasis in Mice

Abstract Giardia lamblia (G. lamblia) is the most common worldwide intestinal protozoal. Serum TNF-α contributes to the recovery from Giardia lamblia infection especially in the first and second week of infection. TNF-α antagonists are biologics used to treat many inflammatory diseases as rheumatoid arthritis. The present study aimed to study the effect of TNF-α antagonist (Adalimumab) on experimental giardiasis in mice by parasitological and histopathological examination. A total of 45 parasite-free laboratory-bred Swiss albino mice included into 2 main groups: test group and control group were used. Test group included mice infected with G. lamblia and receiving three intraperitoneal Adalimumab injections from days 9 till 15 post infection (pi). This group was further subdivided into 3 subgroups (Ia, Ib, Ic) according to Adalimumab doses which were 1.5, 3 and 6 mg/kg BW, received, respectively. Control group (non-Adalimumab-treated group) included a non-infected healthy group and Giardia -infected group. Monitoring the serum TNF-α level in all mice was done on two occasions (day 16 and 28 pi) by ELISA to follow variation in its level with and without administration of the drug. Infection outcome was assessed by following cyst shedding in stools of infected mice on intermittent days, counting trophozoites in intestinal wash, registering weight of animals, and recording pathological changes occurring in histopathological sections from small intestine. Highly significant increase in serum TNF-α was recorded in infected control mice on day 16 post-infection than in normal control group. Similarly, a significant increase in TNF-α level in the 3 test subgroups but attaining significant lower levels. On day 28 post infection, serum TNF- α level decreased in all infected mice with no significant differences being higher in infected control group than in non-infected control group. On assessing the effect of decreased serum TNF-α by the drug on infection outcome, highly significant increases in cyst shedding were recorded in the test group specifically group receiving 3 mg/kg BW than in control infected group on day 16 pi, and in trophozoite counts on day 28 pi. Mice weight gain was highly significant being more in control non-infected group than in control infected group. It was significantly lower in test group than normal infection control. The intestinal sections of test subgroups showed moderate to severe inflammatory reaction with more inflammatory cellular infiltration in the lamina propria causing villous shortening and blunting more than that observed in infection control group. Furthermore, lymphoid follicles and sloughing of the epithelium were only observed in test subgroups on day 16 p.i. It was concluded that TNF-α antagonist (Adalimumab) led to increased parasitic load as evidenced by cyst shedding, trophozoite count, less weight gains with moderate to severe histopathological damage in test subgroups.

The Potential Role of Bone Marrow Mesenchymal Stem Cells Derived Exosomes on Experimentally Induced Osteoarthritis of Knee Joint in Male Albino Rats. Histological and Immunohistochemical Study

Abstract Introduction Osteoarthritis (OA) is the most common joint disorder worldwide characterized by progressive loss of articular cartilage. This study was conducted to evaluate the role of bone marrow mesenchymal stem cells (BMSCs) derived Exosomes as a promising therapy for treating osteoarthritis. Aim of the Work to study the healing potential of BMSCs derived exosomes on experimentally induced knee osteoarthritis. Materials and Methods Forty adult male albino rats, weighing 200-250 gm, were used in this study, five rats used as a source of BM-MSCs derived exosomes. The other thirty-five rats were randomly divided into three main groups Group I: The control group (20 rats) in which rats were subdivided into four subgroups. Subgroups IA and IB were sacrificed 2 and 6 weeks after the beginning of the experiment. Subgroup IC left for 2 weeks then were received intra-articular injection of 0.1ml Phosphate buffer saline (PBS) in right knee joint once weekly for 4 weeks Subgroup ID: left for 2 weeks then given intra-articular injection of purified exosome concentrate in the right knee joint once weekly for 4 weeks then the animals were sacrificed Group II:(15 rats) in which OA was induced by intra-articular injection of 2% formaldehyde solution in the right knee joints. The rats of group II were subdivided into two subgroups. Subgroups IIA and IIB were sacrificed 2 and 6 weeks after induction of OA respectively. Group III (5 rats), Osteoarthritis induced, as in group II and animals left for 2 weeks then treated by intra-articular injection of purified exosome concentrate in right knee joint once weekly for 4 weeks. The right joints from all groups were collected, decalcified and processed for histological studies. Morphometric and statistical measurements were done. Results Histological examination of the right knee joints of OA group (subgroups IIA and IIB) showed surface erosions, decrease cartilage thickness, chondrocytes with pyknotic nuclei and areas of chondrocytes loss with longitudinal clefts reaching the deep zone. Synovial membrane of group II showed increased thickness of the intima, mononuclear cellular infiltration with abundant collagen fibres deposition and dilated congested blood vessels in subintima, apparent increase in the number of iNOS positive intimal synovial cells. Meanwhile, group III showed smooth articular surface, with multiple colonies of chondrocytes and multiple cell nests, significant increase in the mean area percentage of PCNA positive chondrocytes in animals of group Ш when compared to all the other groups. Conclusion BMSCs derived exosomes improved OA induced damage of articular cartilage and synovial membrane. Therefore, it offers a cell-free treatment of OA and joint damage.

The Possible Effect of Platelet Rich Plasma on Liver and Small intestine in Adult and Aged Male Rats. A Histological and Immunohistochemical Study

Abstract Introduction There is a general modest decline in the function of different organs in the body with aging. In the small intestine, there may be alterations in the intestinal morphology, as well as a decline in the absorption of fatty acids and sugars. The aging process decreases regenerative ability which significantly delays the restoration of liver function. Platelet-rich plasma (PRP) has recently attracted interest in many medical fields. PRP might has benefit effect on aged male rats. Aim of the Work This study aims to investigate the structural changes that might occur during normal aging and the possible effect of PRP intraperitoneal injection on adult and aged male albino rats. Materias and Methods Forty-two male albino rats were classified according to age into adult group and old aged groups. Adult male rats (300 -350 g), their age range between 6-8 months. Aged male rats (570-660 g), their age range between 12-24 months. They were divided randomly into four groups: Group I (Control adult): Included 14 rats that further subdivided into 2 equal subgroups: subgroup IA: untreated rats and subgroup Ib: rats were injected by sterile saline intraperitoneally (0.5 mL/kg by intraperitoneal injection 3 times/week). Group II (Control Aged): Included 14 rat that further subdivided into 2 similar subgroups as group I, Group III (Adult treated): Included 7 rats that received intraperitoneal injection of PRP (0.5 mL/kg by intraperitoneal injection 3 times/week), Group IV (Aged treated): Included 7 rats that received intraperitoneal injection of PRP as group III. Animals were kept under observation and the treated groups received intraperitoneal injections for 21 days. At the end of the experiment, Liver and small intestine specimens were processed for histological and immunohistochemical examination. Morphometric and statistical analysis was also done. Results Group II showed decrease in height of intestinal villi with disruption of their epithelium surface, increase spacing between enterocytes and abundant mononuclear cellular infiltration. Changes in the liver comprised nuclear and cytoplasmic changes that included an increase in nuclei number in hepatocytes with droplets fat infiltration. Treated Groups showed decreasing mononuclear cellular infiltration with decreasing collagen fibres and congested blood vessels. Conclusion Aging process enhanced the vulnerability to injury and inflammation in both the liver and small intestine. PRP had ameliorating effects on these changes.

Investigation of Possible Positive Effects of Arbutin Application in Experimental Colitis Model.

This study aimed to investigate the possible positive effects of arbutin in a trinitrobenzene sulfonic acid (TNBS)- induced experimental colitis model, to compare it with mesalazine, which is used in treating inflammatory bowel disease and to observe the effect of its concomitant use. Forty Wistar albino species male rats were randomized into 5 groups as control, colitis, colitis+arbutin (Arb), colitis+mesalazine (Mes), and colitis+mesalazine+arbutin (M+A). Proinflammatory cytokines [interleukin (IL)-6, IL-1β, tumor necrosis factor alpha (TNF-α)] and oxidant/antioxidant parameters [malondialdehyde (MDA), superoxide dismutase inhibition (SOD) inhibition, myeloperoxidase (MPO), and catalase, glutathione peroxidase (GPx)] were processed from the samples. Histopathological evaluation evaluated goblet cell reduction, cellular infiltration, and mucosal loss. When the treatment groups and the TNBS group were compared, statistical significance was achieved in MDA, MPO, SOD inhibition, GPx values, IL-6, IL-1β and TNF-α levels. Histopathological evaluation revealed a statistically significant decrease in the mucosal loss value in the group where mesalazine and arbutin were used together compared to the TNBS group. Our study's results elaborated that using arbutin alone or in combination with mesalazine produced positive effects in colitis-induced rats.

The potential therapeutic effects of exosomes derived from bone marrow mesenchymal stem cells on ileum injury of a rat sepsis model (histological and immunohistochemical study)

ABSTRACT Sepsis denotes a serious high mortality concern. The study was designed to evaluate the effect of mesenchymal stem cell exosomes (MSC-exosomes) on the evolution of the animal model of sepsis. In this study, 36 rats were distributed into three groups, (I) controls, (II) LPS-treated, and (III) LPS+MSC-EVs. Sepsis was simulated by administering E. coli-LPS to the laboratory animals. Group III was given MSC-exosomes four hours after the LPS injection. Forty-eight hours later rats were sacrificed. Ileum samples were excised, and processed for the histological assessment, immunohistochemical identification of CD44, and inducible nitric oxide synthase (iNOS). Ileum homogenate was used to estimate tumor necrosis factor α (TNF α) besides Cyclooxygenase-2 (COX 2). PCR was used for the detection of interleukin 1α (IL‑1α), and interleukin 17 (IL‑17). Statistical and morphometrical analysis was done. The LPS-treated group showed increased TNF-α, IL‑1α, IL‑17, and decreased COX 2. LPS administration led to cytoplasmic vacuolization of enterocytes, an increase in the vasculature, and cellular infiltrations invaded the lamina propria. There was a significant rise in goblet cells and the proportion of collagen fibers. Ultrastructurally, the enterocytes displayed nuclear irregularity, rough endoplasmic reticulum (rER) dilatation, and increased mitochondria number. Sepsis induces a significant increase in iNOS and a decrease in CD44 immune expressions. LPS+MSC-EVs group restored normal ileum structure and revealed a significant elevation in CD44 and a reduction in iNOS immunoreactions. LPS-sepsis induced an obvious ileum inflammatory deterioration ameliorated by MSC-exosomes, mostly through their antioxidant, anti-inflammatory, and anti-apoptotic properties.

Harnessing lipid metabolism modulation for improved immunotherapy outcomes in lung adenocarcinoma

BackgroundWhile anti-programmed cell death protein-1 (PD-1) monotherapy has shown effectiveness in treating lung cancer, its response rate is limited to approximately 20%. Recent research suggests that abnormal lipid metabolism in...

The effect of sleeve gastrectomy on pyloric mucosa of obese adult male albino rat: a histological study

Background Obesity is an excessive accumulation of fat tissue that threatens health. The number of sleeve gastrectomy (SG) has been increased greatly over the last 10 years, because it seems to be a safer and easier solution. Aim This work’s objective was to study the effect of SG on the pyloric gastric mucosa of obese adult male albino rats using light microscope (LM). Materials and methods The present study was carried out on fifty adult male albino rats, weighing between 190 and 260 gm. They were divided into four main groups; control GI, obese nonoperated GII, sham GIII, and operated GIV. Pyloric specimens were processed for LM study and statistical analysis. Results After 4 weeks of obesity induction, (GII, III, and IV) showed a statistically significant increase in their body weight compared with GI. After 4 weeks of the operation, statistically significant differences in the body weight were observed between all groups. GIII was running in between. LM examination of the pyloric mucosa of GIV revealed damage to the epithelial surface with abnormal pits. Distorted gastric glands with inflammatory cellular infiltration and congested blood vessels were evident in their lamina propria in association with altered muscularis mucosa. These results were confirmed statistically. Conclusion Microscopic changes in the pyloric mucosa of adult male albino rats take place after SG.

RNA-seq gene expression profiling of the bladder in a mouse model of urogenital schistosomiasis.

Parasitic flatworms of the Schistosoma genus cause schistosomiasis, which affects over 230 million people. Schistosoma haematobium causes the urogenital form of schistosomiasis (UGS), which can lead to hematuria, fibrosis, and increased risk of secondary infections by bacteria or viruses. UGS is also linked to bladder cancer. To understand the bladder pathology during S. haematobium infection, our group previously developed a mouse model that involves the injection of S. haematobium eggs into the bladder wall. Using this model, we studied changes in epigenetics profile, as well as changes in gene and protein expression in the host bladder tissues. In the current study, we expand upon this work by examining the expression level of both host and parasite genes using RNA sequencing (RNA-seq) in the mouse bladder wall injection model of S. haematobium infection. We used a mouse model of S. haematobium infection in which parasite eggs or vehicle control were injected into the bladder walls of female BALB/c mice. RNA-seq was performed on the RNA isolated from the bladders four days after bladder wall injection. RNA-seq analysis of egg- and vehicle control-injected bladders revealed the differential expression of 1025 mouse genes in the egg-injected bladders, including genes associated with cellular infiltration, immune cell chemotaxis, cytokine signaling, and inflammation We also observed the upregulation of immune checkpoint-related genes, which suggests that while the infection causes an inflammatory response, it also dampens the response to avoid excessive inflammation-related damage to the host. Identifying these changes in host signaling and immune responses improves our understanding of the infection and how it may contribute to the development of bladder cancer. Analysis of the differential gene expression of the parasite eggs between bladder-injected versus uninjected eggs revealed 119 S. haematobium genes associated with transcription, intracellular signaling, and metabolism. The analysis of the parasite genes also revealed fewer transcript reads compared to that found in the analysis of mouse genes, highlighting the challenges of studying parasite egg biology in the mouse model of S. haematobium infection.

Occurrence of Microplastics in the Tissues of Nile Tilapia (Orechromis niloticus) from Zobe Dam, Katsina State, Nigeria

A study of the detection of microplastics on Oreochromis niloticus in Zobe Reservoir, Katsina State, Nigeria was carried out. Three fish sampling sites were used; the upstream (Tsawatsawa), midstream (Makera), and downstream (Garhi) were selected based on variation of anthropogenic activities. A total number of one hundred and forty-four (144) fish samples with a total weight (MTW) and total length (MTL) varied between 134.1 ±1.50 to 154.2± 3.41g and 17.5 ± 0.10– 22.1± 0.54 cm respectively, were collected and analysed for the presence of microplastics using standard protocols. Fourier Transform Infrared Spectrophotometer (FTIR) was used for the chemical characterization of microplastic composition examined in the fish species. The examination of microplastic occurrence in different sampled fish gills, liver, and kidney revealed the presence of Polystyrene, Polypropylene, Polyethylene terephthalate, Nylon, Polyester, and Polyvinyl chloride. Fish from all sampling sites revealed varying histopathological alterations ranging from lifting of epithelium thickening, distortion of the primary lamellae, and degeneration of secondary lamellae, blood congestion, and massive lamellae degeneration in the gill tissues. Liver tissues had hepatocyte hypertrophy, sinusoidal dilatation and cytoplasmic vacuolation, presence of lipid granules, cellular infiltration, cytoplasmic vacuolation, and haemorrhage. The kidney tissues were presented with Bowman’s capsules hyperplasia, tubular elongation, renal tubular epithelium shrinkage, hyperplasia, and cytoplasmic vacuolization of renal cells. The severity of the damage varies from site to site indicating that the water body is experiencing pollution at varying locations. Our findings provide important insights into the prevalence and distribution of microplastics in this particular environment.

Alterations in viscera histoarchitecture and organosomatic index as biomarkers of toxicity induced by Aba-Eku and Olusosun solid waste landfill leachates in Rattus norvegicus.

Solid waste disposal generates leachate, a mixture of deleterious chemical, physical and microbial contaminants, which poses risk to human and wildlife health. Leachate toxicity on relative organ weight and histopathology of important viscera in mammalian body is scarce. Leachate induced toxic effects on organosomatic indices and histopathology of vital mammalian organs were investigated. Wister rats were orally exposed to 1 - 25 % of raw and simulated leachates from Aba-Eku and Olusosun landfills for 30 days. At post-exposure, organosomatic index and histoarchitectural assessment of major viscera (heart, spleen, thymus and lungs) were conducted. The physico-chemical and organic compositions of the leachates were analysed using standard protocol. The tested leachates decreased weekly and terminal body weights, and altered organosomatic index of examined viscera in rats. The histoarchitecture of the investigated viscera revealed pathologies that ranged from mild to severe degeneration, cellular infiltration, haemorrhage, congestion, necrosis, disorganization of tissues and vacuolations. Others include increased histiocytes within the bronchial associated lymphoid, lymphoid depletions, haemosiderin deposits and apoptosis were observed in the examined viscera. Physico-chemical analysis of the leachates showed different concentrations of toxic metals, PAHs and PCBs that were higher than national and international permissible limits allowed in wastewaters. The physico-chemical compositions of the leachates are capable of eliciting the observed alterations in organosomatic indices and histopathological lesions in mammalian viscera. Xenobiotic components of the leachates possibly generated free radicals and/or directly disrupted the organ architectures. These findings suggest health risk to wildlife and human population exposed to emissions from waste landfills.

The true extent of eosinophil involvement in disease is unrecognized: the secret life of dead eosinophils.

Eosinophil-mediated pathophysiology is tissue destructive and tissue altering with proinflammatory, prothrombotic, and profibrotic effects. The distinctive morphology of an eosinophil reveals a cytoplasm chockfull of unique granules, and the granule proteins have numerous toxic effects on cells, tissues, and organs. Eosinophils are not found in most human tissues, and eosinophil involvement in diseased tissues generally is identified by cell infiltration on histopathologic examination. However, eosinophils characteristically lose their structural integrity and deposit granules and granule proteins at sites of inflammation. Hence, their participation in tissue damage may be underrecognized or entirely overlooked. The eosinophil major basic protein 1 is a toxic granule protein and, when deposited, persists in tissues. Major basic protein 1 deposition can be regarded as a footprint of eosinophil activity. Analyses of numerous eosinophil-related diseases have demonstrated clear-cut evidence of major basic protein 1 deposition in affected tissues where eosinophils were not recognized by hematoxylin and eosin tissue staining and light microscopy. Eosinophil granule protein deposition, as exemplified by localization of major basic protein 1, especially when disproportionately greater than cellular infiltration, emerges as a biomarker of hidden eosinophil-related pathophysiology. Consequently, current assessments of recognized eosinophils may vastly underestimate their role in disease.

Added value of postmortem mri in sudden unexpected infant death cases.

We aimed to investigate the potential added value of postmortem MRI (PMMRI) in sudden unexpected infant death (SUID) cases referred to our center between September 2020 and June 2023. Ultimately, 19 SUID cases underwent PMMRI alongside standard autopsy procedures, which included technical examinations such as postmortem CT (PMCT). Four radiologists, two with prior PMMRI experience, provided structured reports following consensus. For each case, the responsible forensic medicine specialist documented the cause of death before and after reviewing the PMMRI report. Additionally, they assessed the overall impact of the PMMRI report and had the opportunity to provide written comments. The results of our study indicate that none of the PMMRI reports altered the prior determined cause of death, which included cases of infection, asphyxia, and sudden infant death syndrome (SIDS). However, we observed a moderate impact in one case and a low impact in 10 cases. The moderate impact arose from the PMMRI report identifying hypoxic-ischemic changes, where histologic examination of the brain was perceived as normal. Conversely, in the 10 cases with a low impact, the PMMRI reports supported the autopsy findings, specifically indicating brain injury and intra-alveolar cellular infiltrates. In conclusion, our study suggests that while PMMRI may not be pivotal in determining the cause of death in SUID cases, it could aid in detecting hypoxic-ischemic changes and reinforcing brain and lung observations. However, distinguishing genuine lung pathology from postmortem changes using PMMRI remains challenging. Further research is warranted to clarify the role of PMMRI in forensic SUID investigations.

Identification of oxidative stress signatures of lung adenocarcinoma and prediction of patient prognosis or treatment response with single-cell RNA sequencing and bulk RNA sequencing data

Lung adenocarcinoma (LUAD), the most common subtype of lung cancer globally, has seen improved prognosis with advancements in diagnostic, surgical, radiotherapy, and molecular therapy techniques, while its 5-year survival rate remains low. Molecular biomarkers provide prognostic value. Oxidative stress factors, such as reactive nitrogen species and ROS, are crucial in various stages of tumor progression, influencing cell transformation, proliferation, angiogenesis, and metastasis. ROS demonstrate dual roles, affecting tumor cells, hypoxia sensitivity, and the microenvironment. Comprehensive analysis of oxidative stress in LUAD has not been conducted to date. Therefore, we systematically investigated the regulatory patterns of oxidative stress in LUAD based on oxidative stress-related genes and correlated these patterns with cellular infiltration characteristics of the tumor immune microenvironment. The model utilizes single-factor Cox analysis to screen key differential genes with prognostic value and employs least absolute shrinkage and selection operator (LASSO) penalized Cox regression analysis to construct a prognostic-related prediction model. Ten candidate genes were selected based on this model. The risk score was constructed using the coefficients and expression levels of these ten genes. Furthermore, the impact of this risk score on overall survival (OS) was determined. Two genes with the most significant differential expression, SFTPB and S100P, were selected through qRT-PCR. Cell experiments including CCK-8, Edu, transwell assays confirmed their effects on lung cancer cells growth, consistent with the results of bioinformatics analysis. These findings suggested that this model held potential clinical value for evaluating the prognosis of lung adenocarcinoma.

Correlation of CT-based radiomics analysis with pathological cellular infiltration in fibrosing interstitial lung diseases

PurposeWe aimed to identify computed tomography (CT) radiomics features that are associated with cellular infiltration and construct CT radiomics models predictive of cellular infiltration in patients with fibrotic ILD.Materials and methodsCT images of patients with ILD who underwent surgical lung biopsy (SLB) were analyzed. Radiomics features were extracted using artificial intelligence-based software and PyRadiomics. We constructed a model predicting cell counts in histological specimens, and another model predicting two classifications of higher or lower cellularity. We tested these models using external validation.ResultsOverall, 100 patients (mean age: 62 ± 8.9 [standard deviation] years; 61 men) were included. The CT radiomics model used to predict cell count in 140 histological specimens predicted the actual cell count in 59 external validation specimens (root-mean-square error: 0.797). The two-classification model’s accuracy was 70% and the F1 score was 0.73 in the external validation dataset including 30 patients.ConclusionThe CT radiomics-based model developed in this study provided useful information regarding the cellular infiltration in the ILD with good correlation with SLB specimens.

The crosstalk role of CDKN2A between tumor progression and cuproptosis resistance in colorectal cancer.

Cuproptosis is a type of cell death characterized by excessive copper-lipid reactions in the tricarboxylic acid cycle, resulting in protein toxicity stress and cell death. Although known as a cuproptosis inhibitor through CRISPR-Cas9 screening, the role of cyclin-dependent kinase inhibitor 2A (CDKN2A) in cuproptosis resistance and its connection to tumor development remains unclear. In this study, we combined single-cell sequencing, spatial transcriptomics, pathological image analysis, TCGA multi-omics analysis and in vitro experimental validation to comprehensively investigate CDKN2A distribution, expression, epigenetic modification, regulation and genomic features in colorectal cancer cells. We further explored the associations between CDKN2A and cellular pathway, immune infiltration and spatial signal communication. Our findings showed an increasing trend in cuproptosis in the trajectory of tumor progression, accompanied by an upward trend of CDKN2A. CDKN2A underwent transcriptional activation by MEF2D and via the SNHG7/miR-133b axis, upregulating glycolysis, copper metabolism and copper ion efflux. CDKN2A likely drives epithelial-mesenchymal transition (EMT) and progression by activating Wnt signaling. CDKN2A is associated with high genomic instability and sensitivity to radiation and chemotherapy. Tumor regions expressing CDKN2A exhibit distinctive SPP1+ tumor-associated macrophage (TAM) infiltration and MMP7 enrichment, along with unique signaling crosstalk with adjacent areas. CDKN2A mediates cuproptosis resistance through regulating glycolysis and copper homeostasis, accompanied by a malignant phenotype and pro-tumor niche. Radiation and chemotherapy are expected to potentially serve as therapeutic approaches for cuproptosis-resistant colorectal cancer with high CDKN2A expression.