Interstitial Inflammatory Infiltration Research Articles

Ultrasound viscoelastic imaging in the noninvasive quantitative assessment of chronic kidney disease

Background This study aims to evaluate the clinical application value of ultrasound viscoelastic imaging in noninvasive quantitative assessment of chronic kidney disease (CKD). Methods A total of 332 patients with CKD and 190 healthy adults as a control group were prospectively enrolled. Before kidney biopsy, ultrasound viscoelastic imaging was performed to measure the mean stiffness value (Emean), mean viscosity coefficient (Vmean), and mean dispersion coefficient (Dmean) of the renal. CKD patients were divided into three groups based on estimated glomerular filtration rate. The differences in clinic, pathology, ultrasound image parameters between the control and patient groups, or among different CKD groups were compared. The correlation between viscoelastic parameters and pathology were analyzed. Results Emean, Vmean, and Dmean in the control group were less than the CKD group (p < 0.05). In the identification of CKD from control groups, the area under curve of Vmean, Dmean, Emean, and combining the three parameters is 0.90, 0.79, 0.69, 0.91, respectively. Dmean and Vmean were increased with the decline of renal function (p < 0.05). Vmean and Dmean were positively correlated with white blood cell, urea, serum creatinine, and uric acid (p < 0.05). Vmean is positively correlated with interstitial fibrosis and inflammatory cell infiltration grades (p < 0.001). Conclusions Ultrasound viscoelastic imaging has advantages in noninvasive quantitative identification and evaluating renal function of CKD. Emean > 6.61 kPa, Vmean > 1.86 Pa·s, or Dmean > 7.51 m/s/kHz may suggest renal dysfunction. Combining Vmean, Dmean, and Emean can improve the efficiency of identifying CKD.

HMGB1 derived from lung epithelial cells after cobalt nanoparticle exposure promotes the activation of lung fibroblasts

We have previously demonstrated that exposure to cobalt nanoparticles (Nano-Co) caused extensive interstitial fibrosis and inflammatory cell infiltration in mouse lungs. However, the underlying mechanisms of Nano-Co-induced pulmonary fibrosis remain unclear. In this study, we investigated the role of high-mobility group box 1 (HMGB1) in the epithelial cell-fibroblast crosstalk in Nano-Co-induced pulmonary fibrosis. Our results showed that Nano-Co exposure caused remarkable production and release of HMGB1, as well as nuclear accumulation of HIF-1α in human bronchial epithelial cells (BEAS-2B) in a dose- and a time-dependent manner. Pretreatment with CAY10585, an inhibitor against HIF-1α, significantly blocked the overexpression of HMGB1 in cell lysate and the release of HMGB1 in the supernatant of BEAS-2B cells induced by Nano-Co exposure, indicating that Nano-Co exposure induces HIF-1α-dependent HMGB1 overexpression and release. In addition, treatment of lung fibroblasts (MRC-5) with conditioned media from Nano-Co-exposed BEAS-2B cells caused increased RAGE expression, MAPK signaling activation, and enhanced expression of fibrosis-associated proteins, such as fibronectin, collagen 1, and α-SMA. However, conditioned media from Nano-Co-exposed BEAS-2B cells with HMGB1 knockdown had no effects on the activation of MRC-5 fibroblasts. Finally, inhibition of ERK1/2, p38, and JNK all abolished MRC-5 activation induced by conditioned media from Nano-Co-exposed BEAS-2B cells, suggesting that MAPK signaling might be a key downstream signal of HMGB1/RAGE to promote MRC-5 fibroblast activation. These findings have important implications for understanding the pro-fibrotic potential of Nano-Co.

Prophylactic and curative activity of Withania somnifera on experimentally induced calcium oxalate nephrolithiasis

Withania somnifera an ayurvedic herb was utilized to assess the antilithic properties of calcium oxalate (CaOx) Nephrolithiasis in rats fed ethylene glycol (EG) in an experimental setting. There were 5 groups of animals (n = 6). The control group was given normal saline, Lithiatic control was given ethylene glycol 1% (v/v) with ammonium chloride 1% (w/v) for 4 days (received stone inducing treatment till 28th day ), follow by 1% ethylene glycol alone in water, Standard group received antiurolithiatic drug (Cystone) (500 mg/Kg) from 15th day till 28th day, treatment group received Withania somnifera methanolic extract (200 mg/Kg) from 15th day till 28th day (Curative regimen) and received Withania somnifera methanolic extract (WS-200 mg/Kg) from 1st day till 28th day (prophylactic regimen) in wistar rats. Blood and kidney tissue were collected after the 28th day of urine. Ca2-, Mg2+, K+ and PO4- levels were estimated in urine, creatinine and urea level were estimated in serum whereas all oxidative stress was measured in kidney tissue. Additionally, Urinary microscopy and kidney histopathology were estimated. Lithiatic control group showed significant elevation (P&lt;0.0001 vs. control) in serum creatinine, blood urea and antioxidants levels. Due to crystal deposits, the histopathology of Lithiatic group showed tubule dilatation with interstitial inflammatory infiltrate, whereas the therapy group showed less tubule dilatation with interstitial inflammatory infiltrate. It can be concluded that at 200 mg/kg the herbal drug possessed significant potential in the management of nephrolithiasis.

Inflammatory Giant Cell Carcinoma of the Lung: Clinicopathologic, Immunohistochemical, and Next-generation Sequencing Study of 14 Cases.

A distinctive histological variant of poorly differentiated, sarcomatoid, non-small cell lung carcinoma characterized by a discohesive population of giant tumor cells associated with prominent interstitial inflammatory cell infiltrates is described. The tumors occurred in 7 women and 7 men, 42 to 72 years of age (mean: 56y). They predominantly affected the upper lobes and measured 1.3 to 9cm in greatest diameter (mean: 4.6cm). The tumor cells were characterized by large pleomorphic nuclei with prominent nucleoli, ample cytoplasm, and frequent abnormal mitoses, and were surrounded by a dense inflammatory cell infiltrate, often associated with emperipolesis. Immunohistochemical stains were positive in the tumor cells for cytokeratin AE1/AE3 and CK8/18 and negative for TTF1, napsin A, p40, and CK5/6. Next-generation sequencing was performed in all cases using the Oncomine Precision Assay; the most common abnormalities found included TP53 mutations (9 cases) and AKT1 amplification (8 cases), followed by KRAS mutations (4 cases) and MAP2K1/2 mutations (4 cases). Clinical follow-up was available in 13 patients. Three patients presented with metastases as the initial manifestation of disease; 8 patients died of their tumors from 6 months to 8 years (mean: 2.7y); 3 patients were alive and well from 4 to 6 years; and 2 patients had metastases when last seen but were lost to follow-up thereafter. The importance of recognizing this distinctive and aggressive variant of non-small cell lung carcinoma lies in avoiding confusion with a sarcoma or other types of malignancy.

Effect of electroacupuncture on myocardial transient receptor potential channels in mice with myocardial hypertrophy.

To observe the effect of electroacupuncture (EA) at "Neiguan"(PC6) on cardiac function, cardiac morphology and transient receptor potential channel (TRPC) protein expressions in myocardial tissue of mice with myocardial hypertrophy, so as to explore its mechanisms underlying improvement of myocardial hypertrophy. Forty-five male C57BL/6 mice were randomly divided into control, model and EA groups (15 mice/group). The myocardial hypertrophy model was established by subcutaneous injection of isoproterenol hydrochloride (15 mg·kg-1·d-1) for 14 days. The mice of the control group received subcutaneous injection of same amount of normal saline. The mice of the EA group received EA stimulation (frequency of 2 Hz, intensity of 1 mA) of bilateral PC6 for 20 min each time, once a day for 14 consecutive days. After the intervention, the body weight, tibia length and heart weight were measured. The left ventricular ejection fraction (EF), fractional shortening index (FS), left ventricular end-systolic volume (LVEV), left ventricular end-systolic internal diameter (LVID) and left ventricular posterior wall thickness (LVPW) were measured by using echocardiography for evaluating the cardiac function. The mean number and surface area of myocardial cells was detected by wheat germ agglutinin (WGA) staining, and changes of the cardiac morphology were observed under light microscopy after HE staining. The expression levels of TRPC1, TRPC3, TRPC4 and TRPC6 (TRPC1/3/4/6) in the myocardial tissue were detected by real-time quantitative PCR (qPCR) and Western blot, separately. Compared with the control group, the heart-body weight ratio(P<0.05) and heart-weight-to-tibia-length ratio (P<0.01), LVEV and LVID levels, the relative surface area, left ventricular area ratio, and the expression levels of cardiac TRPC1/3/4/6 were significantly increased (P<0.01, P<0.05), while the EF, FS, LVPW, number of cardiomyocytes, and the left ventricular posterior wall ratio were obviously decreased (P<0.01, P<0.05) in the model group. In comparison with the model group, the heart/body weight ratio, heart-weight-to-tibia-length ratio, LVEV and LVID levels, relative surface area, left ventricular area ratio, and the expression levels of cardiac TRPC1/3/4/6 were significantly decreased (P<0.01, P<0.05), while the EF, FS, LVPW, number of cardiomyocytes and left ventricular posterior wall ratio were significantly increased (P<0.01, P<0.05) in the EA group. H.E. staining showed disordered arrangement of cardiomyocytes and obvious myocardial interstitial inflammatory cell infiltration in the model group, and evident reduction of degree of cardiac fibrosis and interstitial edema in the EA group. EA of PC6 can improve the cardiac function and cardiac morphology in mice with myocardial hypertrophy, which may be related to its functions in down-regulating the expression of transient receptor potential channels.

Transcriptomic Revealed That Selenium-Rich Lactobacillus plantarum Alleviated Cadmium-Induced Immune Responses in Bulatmai barbel Luciobarbus capito Kidneys

Cadmium (Cd) is a common environmental pollutant that accumulates mainly in the kidneys and thus endangers the physiological health of aquatic animals. Selenium (Se) is a natural antidote to heavy metals that antagonises heavy metal toxicity and enhances the antioxidant capacity of organisms. Lactobacillus plantarum (L. plantarum) can reduce the toxicity of heavy metals through adsorption, reduction and metabolism. Studies have confirmed that the biological synthesis of Se nanoparticles (Bio-SeNPs) using bacterial microorganisms is simple, safe and less toxic than the synthesis of inorganic and organic Se, but the effect on Cd-induced immunosuppression is un-known. One hundred and eighty Bulatmai barbel (Luciobarbus capito: L. capito) plants were randomly divided into control (C), Cd and Cd + Se-enriched L. plantarum groups (S1L1-Cd) and fed for 28 days. The analysis methods included histopathology, test kits, transcriptomics and real-time quantitative PCR. The addition of selenium-enriched L. plantarum significantly attenuated cadmium-induced pathological changes such as glomerular atrophy, detachment of renal tubular epithelial cells, mild swelling, and interstitial inflammatory cell infiltration. Cd stress can lead to significant decreases in RBC, HCT, WBC, LZM, C3, and IgM levels, and the addition of Se-enriched L. plantarum can significantly reverse the changes in these indicators. Transcriptomic analysis revealed 488 DEGs in the Cd groups, 301 of which were upregulated and 187 of which were downregulated. There were 1474 DEGs in the S1L1-Cd group, of which 720 were upregulated and 754 were downregulated. In addition, GO enrichment analysis revealed that the biological regulation of the most differentially expressed genes involved metal ion binding, ATP binding and nucleotide inclusion. KEGG enrichment analysis revealed six of the most enriched pathways: oxidative phosphorylation, Huntington disease, retrograde endocannabinoid signalling, natural killer cell-mediated cyto-toxicity, the IL-17 signalling pathway, and leukocyte transient migration. Moreover, we selected 12 DEGs for qRT-PCR, which showed that the qRT-PCR results were consistent with our RNA-Seq results. Our results suggest that Se-enriched L. plantarum can enhance immunity and alleviate Cd exposure-mediated immunosuppression in L. capito.

Protective effect of quercetin on carp cardiac damage caused by difenoconazole via alleviating oxidative damage, inflammatory responses, and apoptosis

Pollution of aquatic environment by difenoconazole (DFZ) significantly affects survival and safety of freshwater aquaculture. Due to its anti-inflammatory and antioxidant properties, plant-derived quercetin (QUE) is often used as a dietary supplement. The main purpose of this study was to explore the protective effect of QUE on heart damage caused by exposure to pesticide DFZ and the potential mechanisms of these effects. This study found that QUE could effectively reduce the myocardial enzyme spectrum index of carp after exposure to DFZ, increase the levels of total antioxidant capacity (T-AOC), glutathione (GSH), and catalase (CAT), inhibit the content of malondialdehyde (MDA), and increase the transcription levels of superoxide dismutase (sod), glutathione peroxidase (gsh-px), and cat. By reducing the expression of keap1, QUE increased the transcription levels of nrf2 and nqo-1, reduced the production of reactive oxygen species (ROS) in the heart after exposure to DFZ, and restored the redox homeostasis of the heart. QUE upregulated the expression of anti-inflammatory cytokines il-10 and tgf-β1 levels, downregulated the transcription levels of pro-inflammatory factor inos, il-1β, il-6 and tnf-α, and alleviated the in vivo redox imbalance caused by exposure to DFZ, leading to myocardial interstitial inflammatory cell infiltration. The results showed that QUE inhibited the apoptosis after exposure to DFZ by affecting the expression of apoptotic factors in the mitochondrial apoptotic pathway. In summary, QUE can effectively decrease myocardial injury caused by exposure to DFZ in aquatic environment.

#1495 5 and 10 year kidney outcomes in acute interstitial nephritis: a retrospective single-centre cohort study

Abstract Background and Aims Acute interstitial nephritis (AIN) is a common cause of acute kidney injury (AKI), histologically characterized by an interstitial inflammatory cell infiltrate. Data regarding long term kidney outcomes is lacking. We performed a retrospective cohort study to evaluate the long-term kidney and mortality outcomes in patients with biopsy-proven AIN between 2011-2018. Method We serve as a tertiary referral centre and sole nephrology provider for a population of over 650,000 people. We identified biopsy-proven AIN cases from the years 2011-2018 from our pathology database. Demographic data, creatinine, eGFR (calculated using CKD-EPI 2021 formula), dialysis and mortality data were collected from our electronic medical record. Ethical approval was obtained. Results Between 2011 – 2018, 576 native kidney biopsies were performed in our centre. 66 (11.5%) cases had pathologically confirmed AIN as the primary kidney diagnosis. Long-term outcome data was available for 90.9% (60). The median age at time of biopsy was 52.5 years (IQR 41.5 - 68.3). 68% of patients were male. The aetiology of AIN was medication in 42%, autoimmune in 15% and infection-associated in 3%. Of the cases of drug-induced AIN the predominant culprits agents were non-steroidal anti-inflammatories 28%, proton pump inhibitors in 24%, antibiotics 20%, with other medications in 8%. The median eGFR at the time of biopsy was 13.6 (IQR 7.9 -25.4) mls/min/1.73 m2. The median eGFR at year 1 was 47.8 (IQR 30.7 - 72.7) mls/min/1.73 m2, 54.4 (IQR 31.2 -79.6) mls/min/1.73 m2 at year 5 and 69.4 (IQR 19.9 - 86.1) mls/min/1.73 m2 at year 10. See Table 1 for results. At one year 64.3% of cases had eGFR &amp;lt; 60 mls/min/1.73 m2 (CKD III or higher). Interestingly the rate of CKD was lower at years 5 and 10 (54.7% and 50% respectively). GFR &amp;lt;30 mls/min (CKD IV or higher) were present in 25% at year 1, 26% at year 5 and 37% at year 10. 23% (14/60) people had dialysis-requiring AKI at the time of biopsy. Of these 21.4% (3) remained dialysis dependent at one year. In this group, no additional cases of ESKD were seen between years 1 through 5, one additional case of ESKD occurred by year 10. A composite outcome of kidney failure (GFR &amp;lt;15, dialysis or kidney transplantation) occurred in 48.2% at year 1, 54.7% at year 5 and 56.2% at year 10. Mortality data was available on 58 patients. 18.9% (11) people had died at 10 years follow-up. 8 out of the 11 deaths were within 5 years, 2 of which were within 1 year of diagnosis. Conclusion In this single centre study, kidney failure occurred in 48% of people at 10 years of follow up. 78% of dialysis-requiring cases recover independent renal function.

MYOCARDITIS: VIRUS OR DESMOSOME?

Abstract Patient Profile Female, 56 yo, arterial hypertension, FH of autoimmune diseases, no history of sudden death. Medical History: • At the age of 46: Hospitalized for chest pain. Coronary angiography: negative. Diagnosis: myocardial ischemia with normal coronary arteries. • 2018: Hospitalized again for angina. ECG showed low voltages, flat T–waves in the inf–lat. leads. Coronary angiography: negative. Biopsy Mild hypertrophy and cytoplasmic vacuolization, minimal increase in interstitial fibrosis, no necrosis or inflammatory infiltrates. Mild nonspecific cardiomyopathy. Viral DNA test positive for HHV–6. Serology: HHV–6 in blood (neg), IgG HHV–6 (pos), IgM (neg). Diagnosis: myocarditis due to HHV–6. • San Camillo Cardiomyopathy Center: Echocardiogram: basal ant–lat. hypokinesia, EF 60%. Therapy: Bisoprolol 3.75 mg, Ramipril 5 mg, Ranolazine 1000 mg. MRI: basal transmural ant–lat. and subepicardial lateral LGE. Oedema and hypokinesia coexists. Subacute myocarditis. MRI at 1 year: mild left ventricular dilation, EF 60%, meso–subepicardial LGE in the ant–lat and inf mid–basal regions without oedema. Serial Holter ECGs: frequent polymorphic ventricular ectopics, couplets, and runs. CPET: normal exercise capacity, pVO2 19.4 (ml/min)/kg (90%). Genetic testing VUS in DSC, probably pathogenic, and VUS in ABCC9, PKP2, DSP (2 mutations) with uncertain clinical significance. • In 2022: Readmitted for angina. Elevated Troponin levels. Coro CT angiography: negative. MRI: EF 45%, akinesia of the apex and apical lat. wall; diffuse LGE and edema. Pericardial effusion. Patient refused biopsy. Discharged after recovery (EF 52%) with the diagnosis of recurrent myocarditis. Empagliflozin added. • Follow up. ECG: progression of repolarization abnormalities (TWI in V1–V3 + inf.–lat. leads). Biopsy: fibroadipose replacement, no necrosis or inflammatory infiltrates. Chronic myocarditis and sequels. Viral tests: negative. CPET and stress echo: VO2peak 20.7 (ml/kg)/min (88%), normal work capacity. Very rare monomorphic PVCs. EF 50%, preserved contractile reserve. Conclusions Diagnosis of left dominant arrhythmogenic cardiomyopathy with a typical pattern for hot phases of myocardial inflammation. The first episode could have been triggered by a viral infection on a predisposing genetic substrate. Nadolol 40 mg x2 was introduced. The possibility of ICD implantation was discussed, and patient refused. A six–month follow–up was planned. Family screening results were negative.

Urinary liver-type fatty acid-binding protein level as a prognostic indicator of acute kidney injury secondary to severe falciparum malaria.

Acute kidney injury (AKI) secondary to severe falciparum malaria possesses a high mortality rate; however, a prognostic marker of renal dysfunction has not yet been identified. Thus, we reported a case of a patient with AKI secondary to falciparum malaria who underwent hemodialysis and a renal biopsy due to prolonged renal dysfunction. The male patient, in his 50s, presented to our hospital with vomiting, diarrhea, fever, and decreased level of consciousness. The Giemsa-stained peripheral blood film revealed approximately 5% parasitemia, and a rapid diagnostic test was positive for Plasmodium falciparum. He was diagnosed with severe falciparum malaria and was started on quinine hydrochloride. Hemodialysis was initiated due to the decreased urine output and fluid retention. Subsequently, he was weaned off hemodialysis. The histopathological analysis of a renal biopsy revealed interstitial fibrosis, tubular atrophy, and chronic inflammatory cell infiltration; thus, malarial nephropathy was diagnosed. Thereafter, his renal function stabilized, and he was discharged from the hospital. The urinary liver-type fatty acid-binding protein (L-FABP) level decreased before renal function improved. Our report highlighted that long-term follow-up is essential for severe AKI secondary to malaria. The urinary L-FABP level may be a useful prognostic indicator of AKI secondary to severe falciparum malaria.

Functional MRI assessment of microstructural and perfusion changes in the kidneys of rats with intrauterine growth restriction

To explore the value of functional magnetic resonance imaging (MRI) techniques, including intravoxel incoherent motion (IVIM), T1 mapping, and T2 mapping, in assessing the microstructural and perfusion changes in the kidneys of rats with intrauterine growth restriction (IUGR). An IUGR rat model was established through a low-protein diet during pregnancy. Offspring from pregnant rats on a low-protein diet were randomly divided into an IUGR 8-week group and an IUGR 12-week group, while offspring from pregnant rats on a normal diet were divided into a normal 8-week group and a normal 12-week group (n=8 for each group). The apparent diffusion coefficient (ADC), true diffusion coefficient (Dt), pseudo-diffusion coefficient (D*), perfusion fraction (f), T1 value, and T2 value of the renal cortex and medulla were compared, along with serum creatinine and blood urea nitrogen levels among the groups. The Dt value in the renal medulla was higher in the IUGR 12-week group than in the IUGR 8-week group, and the D* value in the renal medulla was lower in the IUGR 12-week group than in both the normal 12-week group and the IUGR 8-week group (P<0.05). The T1 value in the renal medulla was higher than in the cortex in the IUGR 8-week group, and the T1 value in the renal medulla was higher in the IUGR 12-week group than in both the IUGR 8-week group and the normal 12-week group, with the cortical T1 value in the IUGR 12-week group also being higher than that in the normal 12-week group (P<0.05). The T2 values in the renal medulla were higher than those in the cortex across all groups (P<0.05). There were no significant differences in the T2 values of either the cortex or medulla among the groups (P>0.05). There were no significant differences in serum creatinine and blood urea nitrogen levels among the groups (P>0.05). Glomerular hyperplasia and hypertrophy without significant fibrotic changes were observed in the IUGR 8-week group, whereas glomerular atrophy, cystic stenosis, and interstitial inflammatory infiltration and fibrosis were seen in the IUGR 12-week group. IVIM MRI can be used to assess and dynamically observe the microstructural and perfusion damage in the kidneys of IUGR rats. MRI T1 mapping can be used to evaluate kidney damage in IUGR rats, and the combination of MRI T1 mapping and T2 mapping can further differentiate renal fibrosis in IUGR rats.

Isolation, identification and characterization of Aeromonas jandaei from diseased Chinese soft-shell turtles.

Aeromonas jandaei is a gram-negative bacterium commonly found in aquatic environments and can induce illnesses in amphibians, reptiles and aquatic animals. In this study, a strain of bacteria was isolated from the diseased Chinese soft-shell turtle (Pelodiscus sinensis), then named strain JDP-FX. This isolate was identified as A. jandaei after analysis of morphological, physiological and biochemical characteristics, as well as 16S rRNA and gyrB gene sequences. Virulence genetic testing further detected temperature-sensitive protease (eprCAI), type III secretion system (TTSS) (ascv), nuclease (nuc), cytotonic enterotoxin (alt) and serine proteinase (ser) in JDP-FX. Compared with healthy Chinese soft-shell turtle, the serum levels of total protein (TP), albumin (ALB) and globulin (GLB) were significantly decreased in the diseased Chinese soft-shell turtle, while, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were significantly increased. Histopathological observations showed that multiple tissues, including intestinal mucosa, liver and kidney, were severely damaged in the diseased Chinese soft-shell turtle. Moreover, the diseased Chinese soft-shell turtle had significant cell degeneration, necrosis, sloughing and interstitial inflammatory cell infiltration. The pathogenicity of JDP-FX was tested via artificial infection. The median lethal dosage (LD50 ) of the strain was 1.05 × 105 colony forming units (CFU/g) per weight of Chinese soft-shell turtle. Drug susceptibility analysis revealed that JDP-FX was susceptible to ceftazidime, minocycline, cefoperazone, ceftriaxone and piperacillin. In addition, JDP-FX was resistant to doxycycline, florfenicol, sulfonamides, gentamicin, ampicillin and neomycin. Therefore, this study may provide guidance for further research into the diagnosis, prevention and treatment of JDP-FX infection.

15-Lipoxygenase promotes resolution of inflammation in lymphedema by controlling Treg cell function through IFN-β

Lymphedema (LD) is characterized by the accumulation of interstitial fluid, lipids and inflammatory cell infiltrate in the limb. Here, we find that LD tissues from women who developed LD after breast cancer exhibit an inflamed gene expression profile. Lipidomic analysis reveals decrease in specialized pro-resolving mediators (SPM) generated by the 15-lipoxygenase (15-LO) in LD. In mice, the loss of SPM is associated with an increase in apoptotic regulatory T (Treg) cell number. In addition, the selective depletion of 15-LO in the lymphatic endothelium induces an aggravation of LD that can be rescued by Treg cell adoptive transfer or ALOX15-expressing lentivector injections. Mechanistically, exogenous injections of the pro-resolving cytokine IFN−β restores both 15-LO expression and Treg cell number in a mouse model of LD. These results provide evidence that lymphatic 15-LO may represent a therapeutic target for LD by serving as a mediator of Treg cell populations to resolve inflammation.

Granulomatous lobular mastitis co-existing with ductal carcinoma in situ: Report of three cases and review of the literature

Granulomatous lobular mastitis (GLM) is a benign and infrequent chronic breast ailment. Although this lesion can be clinically and radiographically mistaken for early-onset breast cancer, it is a rare occurrence for the two to coexist. This report describes three such cases. In all three patients, the primary signs and symptoms were related to the formation of diffuse breast masses or abscesses. Breast ultrasound and MRI revealed glandular edema and dilated breast ducts. The biopsies of all lesions exhibited both granulomatous inflammation confined to the lobules of the breast, abundant interstitial inflammatory cell infiltrates, and apparently cancerous cells located in dilated ducts with intact basement membranes. The surgically excised specimens confirmed the diagnosis of GLM and ductal carcinoma in situ (DCIS) in all three patients who underwent breast mass resection. By clinical imaging and clinical manifestations, GLM may obscure a concurrent DCIS, as highlighted by the cases reported herein.

Proteomic analysis of acute radiation-induced rectal injury in rats

ObjectiveTo comprehensively elucidate overall protein alterations associated with acute radiation-induced rectal injury in rats. MethodsA rat model of acute radiation-induced rectal injury was established by irradiating rectal segments with a single dose of 17.5 ​Gy X-rays. These segments were then collected at 7 d and 10 ​d post-irradiation. Tandem mass tag-based quantitative proteomic analysis was then performed. Results65,526 peptides were identified, corresponding to 8,088 proteins. Hematoxylin-eosin staining revealed characteristic epithelial cell degeneration and necrosis, intestinal gland atrophy and dilatation, and interstitial inflammatory cell infiltration. Inflammation was more pronounced in the 10 d irradiation group than in the 7 d irradiation group. Overall, 127 up- and 108 downregulated proteins were identified at 7 d post-irradiation, and 122 up- and 44 downregulated proteins were identified at 10 d post-irradiation. Notably, 17 up- and 6 downregulated proteins were consistently co-expressed at both time points. The expression of three of these proteins was validated via real-time quantitative PCR: polypeptide YY (Pyy), thymidylate synthase (Tyms), and tetraspanin (CD9). Tyms transcript levels were significantly higher in irradiated rectal tissues (P ​< ​0.05). Pyy transcript levels were significantly higher at both time points (P ​< ​0.05). Finally, CD9 mRNA expression was significantly lower in both the 7 d and 10 d irradiation groups (P ​< ​0.05). ConclusionsThe potential targets were found to prevent and treat acute radiation-induced rectal injury in clinical practice.

Rifampicin induced acute interstitial nephritis in a patient with tuberculosis: A case report

Interstitial nephritis is a rare complication of anti-tuberculosis treatment, most commonly rifampicin. This case report describes a 65-year-old woman with diabetes who presented with loss of consciousness due to a major hypoglycemic episode precipitated by severe acute kidney injury, one month after initiating anti-tuberculous therapy. The presence of active urinary sediments, subnephrotic proteinuria and normal sized kidneys prompted performing a renal biopsy which showed interstitial inflammatory cell infiltration suggestive of acute interstitial nephritis, possibly drug induced. The reversal of renal impairment on cessation of rifampicin confirmed the diagnosis. As this is a reversible cause of acute kidney injury, awareness of this association and early identification is vital to prevent deterioration.

The Effect of Covid-19 on the Respiratory System

This study aims to assess the risk factors associated with COVID-19 patients at the General Basrah Hospital from June to October 2020. Since COVID-19 is related to acute respiratory distress syndrome, very few interstitial mononuclear inflammatory infiltrates were detected within the heart tissue samples during the research period [3]. The results of the study demonstrate that COVID-19 infections were more common in patients with cardiovascular diseases and acute respiratory. People aged &gt;51 years showed a higher COVID-19 infection rate. Conclusions: The study demonstrates that COVID-19 infection rates were higher in patients with cardiovascular and acute respiratory diseases. Covid 19 posed a similar risk to males and women.

Urinary Modified C-Reactive Protein is Closely Associated with Tubulointerstitial Lesions in Lupus Nephritis.

Modified C-reactive protein (mCRP) is known to be involved in the upregulation and amplification of the local inflammatory response. This study investigated the circulating and local levels of mCRP and their relevance to clinicopathological features in patients with lupus nephritis. Ninety-five patients with renal biopsy-proven lupus nephritis and 30 normal controls were enrolled in this study. Plasma and urinary mCRP were screened by enzyme-linked immunosorbent assay (ELISA). The renal deposition of mCRP was detected by immunohistochemistry and immunofluorescence staining. A human proximal tubular epithelial cell line (HK2 cells) was incubated with purified IgG from lupus nephritis, and the production of CRP by HK2 cells was further evaluated. Plasma and urinary levels of mCRP increased significantly in patients with lupus nephritis compared with normal controls (P = 0.013, P < 0.001, respectively). The urinary mCRP levels were associated with interstitial inflammatory cell infiltration (r = 0.514, P < 0.001) and interstitial fibrosis (r = 0.270, P = 0.008). The ROC-AUC of the urinary mCRP levels for diagnosing tubulointerstitial lesions was 0.766. The urinary mCRP levels were closely associated with poor outcomes (HR: 1.204, 95% CI: 1.029-1.409, P = 0.020). However, no correlations were found of the plasma mCRP levels with clinicopathological data or the prognosis of lupus nephritis. CRP was mostly deposited in the renal tubules in patients with lupus nephritis, and the expression of CRP was significantly correlated with tubulointerstitial lesion indices. Immunofluorescence staining showed that mCRP could colocalize with IgG in tubules. Lupus nephritis-derived IgG could induce CRP production by HK2 cells. Urinary mCRP levels were significantly increased, and urinary mCRP might be a biomarker for tubulointerstitial lesions in patients with lupus nephritis. Renal CRP could be produced by tubular epithelial cells after stimulation by lupus nephritis-derived IgG, and the local presence of mCRP might play a critical role in the development of tubulointerstitial lesions.

#6078 MODULATION OF TRYPTOPHAN METABOLISM IN SEPSIS-INDUCED ACUTE KIDNEY INJURY (AKI): A NEW THERAPEUTIC APPROACH TO PREVENT NEUROCOGNITIVE IMPAIRMENT

Abstract Background and Aims Partial recovery following AKI could lead to long-term consequences that predispose to chronic dysfunction and may also accelerate progression of neurocognitive impairment. In this scenario, a tight crosstalk between kidney and brain named “kidney-brain axis” seems to play a pivotal role leading to detrimental outcome for AKI patients. Notably, many studies suggest a high relationship between kidney damage and brain dysfunction (cognitive impairment, taste and olfactory dysfunction, peripheral nerve dysfunction) even after the resolution of AKI. Furthermore, patients who suffered AKI may afterward show a disturbance of arousal, also called “brain fog”. Although major advances have been made in our understanding of the pathophysiology of AKI and brain dysfunction, there are no available preventive and therapeutic strategies in this field. Recent findings have revealed remarkable link existing between dyslipidemia/low High-density lipoprotein (HDL) levels and Kynurenine pathway (KP) alterations that lead to the production of neuroactive metabolites such as kynurenine (KYN) and quinolinic acid (QA) in AKI setting. Method Sepsis-induced AKI (SI-AKI) was induced in a porcine model by intravenous infusion of a saline solution containing 300 μg/kg of LPS. After LPS injection, 12 animals were treated with different doses of recombinant HDL (rHDL) (20–40 mg/kg) (rHDL group), while 6 animals did not receive treatment (LPS group). Animals were sacrificed after 24h from the start of experimental procedure. Results Endotoxemic pigs developed oliguric AKI with increased tubular and glomerular damage and interstitial inflammatory infiltrate. We found that rHDL treatment significantly decreased the inflammatory process and tubular damage, preventing AKI, especially in the rHDL 40 mg/kg group. Then, we evaluated the Indolamine-2,3-dioxygenase 1 (IDO1) enzyme activation, which is the first and rate-limiting step of KP, upregulated during inflammation in both sera and brain tissue, and has been linked to cognitive dysfunction. In our model, LPS induced an increased activation of the IDO-1 gene expression at brain level in endotoxemic animals, meanwhile it appears to be reduced in both treated arms (p&amp;lt;0.005). Furthermore, sera from the rHDL group showed a significant reduction in IDO1 activity (KYN/Trp ratio) (p&amp;lt;0.05) and QA levels (p&amp;lt;0.005) compared with the LPS group. Moreover, a significant decrease of both systemic and brain IL-6 levels was observed after rHDL treatments. Conclusion Our preliminary data indicated that HDL-enhancing therapies may decrease the inflammatory response, the retention of waste products and neuroactive compounds, improving renal and cognitive function in SI-AKI.

#2907 ASYMPTOMATIC NEPHROTIC SYNDROME: AN INTERESTING PRESENTATION OF ADULT ONSET MINIMAL CHANGE DISEASE

Abstract Background and Aims Minimal change disease (MCD), a predominantly pediatric disease, is less common in adults. Patients often present with florid hypervolemia, manifested by significant lower extremity edema, anasarca, pericardial effusion or pleural effusion. Herein, we present a case of newly diagnosed MCD in an elderly gentleman with an atypical presentation. Method A 69 year old male with hypertension and benign prostate hypertrophy presented to the emergency department (ED). He was noted to have abnormal labs at an outside clinic on routine testing and was directed to the ED. In the ED, he was found to have a serum creatinine (SCr) of 10.89 mg/dL. Initial urine studies also revealed proteinuria of 11g/g with 6.5 g/g of albuminuria. Other initial labs were significant for a potassium of 4.5 mEq/L, BUN 126 mg/dL and albumin 2.2 g/dL with normal liver enzymes. Renal ultrasound was unremarkable. Upon further discussion with the patient, he endorsed long term daily use of diclofenac for many months. He stated that he stopped diclofenac three weeks prior to presentation. He denied any proton pump inhibitor or recent antibiotic use. He denied any fevers, nights sweats or weight loss to suggest Type B symptoms. There was no personal kidney disease history nor family history of kidney disease. He was a non-alcoholic and non-smoker. We continued to hold further non-steroidal anti-inflammatory medications as well as other nephrotoxic medications. Although patient had elevated SCr and azotemia, he did not meet any acute indications for dialysis and we continued to manage the patient conservatively. Serologies were negative for ANA, ANCA, Anti-GBM, HIV, hepatitis B and C, as well as antiPLA2R. Serum protein electrophoresis, kappa to lambda ratio, complements 3 and 4 were all within normal values. A kidney biopsy was revealing for patchy interstitial inflammatory infiltrate containing mononuclear cells admixed with few eosinophils on light microscopy as well as diffuse foot process effacement on electron microscopy (Figure 2). The patient had a one-week hospital stay with improvement of SCr to 2.29 mg/dL without any prednisone or treatment for MCD. Spot urine protein improved to 7.4 g/g by time of discharge. At clinic follow up 2 weeks later his creatinine had improved to 1.1 mg/dL with UPCR of 0.4 g/g. Results MCD is a podocytopathy that can occur in up to 10% of adults with nephrotic syndrome [1]. Secondary MCD has been reported with NSAIDs. Steroids are the first line therapy for MCD and can lead to remission in the majority of the cases. In patients who do not respond to steroids, calcineurin inhibitors or mycophenolate can be used. Conclusion Our patient presented with biopsy proven-MCD that was presumed to be secondary to diclofenac. His clinical presentation was not characteristic of nephrotic syndrome with no edema. Few reports exist of spontaneous remission in these patients with most of the patient requiring steroids. While it is uncommon for patients with MCD to spontaneously resolve, not all patients with NSAID-induced MCD require treatment and these patients could be monitored conservatively.