Histopathological Assessment Research Articles

Histopathological biomarkers for predicting the tumour accumulation of nanomedicines.

The clinical prospects of cancer nanomedicines depend on effective patient stratification. Here we report the identification of predictive biomarkers of the accumulation of nanomedicines in tumour tissue. By using supervised machine learning on data of the accumulation of nanomedicines in tumour models in mice, we identified the densities of blood vessels and of tumour-associated macrophages as key predictive features. On the basis of these two features, we derived a biomarker score correlating with the concentration of liposomal doxorubicin in tumours and validated it in three syngeneic tumour models in immunocompetent mice and in four cell-line-derived and six patient-derived tumour xenografts in mice. The score effectively discriminated tumours according to the accumulation of nanomedicines (high versus low), with an area under the receiver operating characteristic curve of 0.91. Histopathological assessment of 30 tumour specimens from patients and of 28 corresponding primary tumour biopsies confirmed the score's effectiveness in predicting the tumour accumulation of liposomal doxorubicin. Biomarkers of the tumour accumulation of nanomedicines may aid the stratification of patients in clinical trials of cancer nanomedicines.

Cartilage protective and anti-edema effects of JTF in osteoarthritis via inhibiting NCOA4-HMGB1-driven ferroptosis and aquaporin dysregulation

BackgroundPreventing joint edema is crucial in halting osteoarthritis (OA) progression. Growing clinical evidence indicate that Jianpi-Tongluo Formula (JTF) may have a promising anti-edema effect. However, the therapeutic properties of JTF and the underlying mechanisms remains unclear. Materials and methodsAn OA rat model was established and employed to evaluate pharmacological effects of JTF in vivo based on dynamic histopathologic assessments and micro-CT observations. Then, OA-related genes and potential targets of JTF were identified through clinical transcriptomic data analysis and "disease gene-drug target" network analysis, which were verified by a series of in vivo experiments. ResultsJTF administration effectively reduced pain and joint edema, inhibited matrix degradation, chondrocyte apoptosis, and aquaporin expression in OA rats. Notably, JTF dose-dependently reversed damage-associated molecular patterns and inflammatory factor upregulation. Mechanically, our "disease gene-drug target" network analysis indicated that the NCOA4-HMGB1-GSK3B-AQPs axis, implicated in ferroptosis and aquaporin dysregulation, may be potentially served as a target of JTF against OA. Accordingly, JTF mitigated NCOA4, HMGB1, and GSK3B expression, oxidative stress, and iron metabolism aberrations in OA rats. Furthermore, JTF treatment significantly attenuated the aberrant upregulation of AQP1, AQP3, and AQP4 proteins observed in cartilage tissues of OA rats. ConclusionOur data reveal for the first time that JTF may exert cartilage protective and anti-edema effects in osteoarthritis therapy by inhibiting NCOA4-HMGB1-driven ferroptosis and aquaporin dysregulation.

التقييم النسيجي المرضي للتأثيرات التحسينية المحتملة للخلايا الجذعية والروتن ضد التسمم الكلوي الحاد الناجم عن الأسيتامينوفين في ذكور الجرذان.

The present investigation aims at a histopathological assessment of the potential ameliorating effects of stem cells and rutin against acute renal toxicity by acetaminophen in male rats. Two main experiments were conducted using seventy rats. Twenty immature rats were used in the primary investigation as a source of bone marrow. In the second investigation, fifty mature rats were split into two groups: G (1) served as the control group, and G (2) received 750 mg/kg b.w./72 hours of oral acetaminophen (APAP) for three weeks. This group was divided into four subgroups: (A) rats receiving APAP for three weeks, then left for two months without treatment; (B) rats receiving APAP for three weeks, followed by treatment with rutin (RUT) (25 mg/kg b.w./d) for two months; (C) rats receiving APAP for three weeks, then the rats were injected in their tail vein by mesenchymal cells (MS) (1.5x 106 cells in 0.5 PBS) for two months; and (D) rats received APAP for three weeks, then MS injected in the tail vein, and received RUT for two months. After taking tissue sections of the kidneys: it was found that the rats receiving APAP alone had perivascular edema with blood vessel congestion, tubular deterioration, glomerulus deteriorating lesions, and inflammatory cell penetration in their renal tissues. Whereas the APAP RUT and APAP-MS-RUT groups showed few tubular deteriorations. Moreover, APAP MS displayed the typical kidney histological structure. The results of the investigation showed that MS significantly lowers acute renal toxicity. Keywords: kidney; rutin; histopathology; mesenchymal cell; acetaminophen.

Abstract NG01: Germline-mediated immunoediting sculpts breast cancer subtypes and metastatic proclivity

Abstract NG01: Germline-mediated immunoediting sculpts breast cancer subtypes and metastatic proclivity

Pre-Transplant Cytokine Levels as Signatures of Microvascular Inflammation in Kidney Allograft Biopsies.

The presence of microvascular inflammation (MVI) characterized by leukocyte margination in the glomeruli (glomerulitis, Banff score 'g') and peritubular capillaries (peritubular capillaritis, Banff score 'ptc') is a hallmark histological feature of antibody-mediated rejection (AMR), even in the absence of circumferential C4d positivity. In this study, we assessed the efficacy of pre-transplant plasma cytokines as an ancillary screening tool to identify MVI in kidney allograft indication biopsies to facilitate better graft survival. This single-center prospective analytical study comprises 38 kidney transplant recipients whose peripheral blood was collected before transplant and assessed for the plasma cytokine concentrations of FOXP3, IL-6, TGF beta, and IL-17 using enzyme-linked immunosorbent assays (ELISA). Histopathological assessment was done in post-transplant indication biopsies, and Banff scores of 'g+ ptc' were calculated to categorize recipients into three MVI groups. The correlational, regression, and ROC curve analyses were used to assess the association and predictive ability of the cytokines with respect to MVI. In our study cohort, 27 recipients had MVI=0, five had MVI=1, and six had MVI≥2. A significant difference in plasma cytokines was observed between these groups, and we found a strong negative correlation of FOXP3 with MVI, whereas a strong positive correlation of IL-6, TGF beta, and IL-17 was recorded with MVI. We have also assessed the predictive ability of these cytokines, FOXP3, IL-6, TGF-beta, and IL-17, through the ROC curve, which showed an AUC of 0.70, 0.76, 0.84, and 0.72, respectively. Our findings suggest that the pre-transplant levels of cytokines FOXP3, IL-6, TGF-beta, and IL-17 could be measured to identify recipients at risk of post-transplant MVI, which could further serve as an additional tool for effective management of the kidney allograft.

Laser-irradiating infrared attenuated total reflection spectroscopy of articular cartilage: Potential and challenges for diagnosing osteoarthritis

ObjectiveA prototype infrared attenuated total reflection (IR-ATR) laser spectroscopic system designed for in vivo classification of human cartilage tissue according to its histological health status during arthroscopic surgery is presented. Prior to real-world in vivo applications, this so-called osteoarthritis (OA) scanner has been tested at in vitro conditions revealing the challenges associated with complex sample matrices and the accordingly obtained sparse spectral datasets. MethodsIn vitro studies on human knee cartilage samples at different contact pressures (i.e., 0.2–0.5 ​MPa) allowed recording cartilage degeneration characteristic IR signatures comparable to in vivo conditions with high temporal resolution. Afterwards, the cartilage samples were assessed based on the clinically acknowledged osteoarthritis cartilage histopathology assessment (OARSI) system and correlated with the obtained sparse IR data. ResultsAmide and carbohydrate signal behavior was observed to be almost identical between the obtained sparse IR data and previously measured FTIR data used for sparse partial least squares discriminant analysis (SPLSDA) to identify the spectral regions relevant to cartilage condition. Contact pressures between 0.3 and 0.4 ​MPa seem to provide the best sparse IR spectra for cylindrical (d ​= ​3 ​mm) probe tips. ConclusionLaser-irradiating IR-ATR spectroscopy is a promising analytical technique for future arthroscopic applications to differentiate healthy and osteoarthritic cartilage tissue. However, this study also revealed that the flexible connection between the laser-based analyzer and the arthroscopic ATR-probe via IR-transparent fiberoptic cables may affect the robustness of the obtained IR data and requires further improvements.

Predictive Role of Hematological Markers on Pediatric Appendicitis: Still a Mystery

Aim: The diagnosis of appendicitis may be challenging in the pediatric population. It can be very difficult to examine a child or to take a medical history. The role of laboratory findings is still unclear. Therefore, we aimed to evaluate the diagnostic value of hematological parameters such as white blood cell, neutrophil to eosinophil ratio, and neutrophil to lymphocyte ratio. Material and Methods: We retrospectively analyzed patients who underwent surgery with suspected appendicitis between February 2018 and February 2020. Preoperative data were gathered from patient records. Histopathological assessment was accepted as the gold standard in the diagnosis of appendicitis. Results: The study population consists of 368 patients with a mean age of 11.95±3.68 years, 56.25% (n=207) of whom were male. The pathological examination revealed that 63.6% (n=234) of the patients were acute appendicitis, 18.5% (n=68) phlegmonous, and 8.7% (n=32) perforated. White blood cells, neutrophil-eosinophil ratio, and neutrophil-lymphocyte ratio were not diagnostic in acute appendicitis. On the other hand, the same parameters are useful markers in differentiating phlegmonous and perforated appendicitis. Conclusion: There is no established biomarker for acute appendicitis. Although the white blood cell count is a well-known parameter in scoring systems, it is not capable of guiding the surgeon. The neutrophil to eosinophil ratio may be a novel diagnostic index for phlegmonous and perforated appendicitis. Understanding whether a child is experiencing appendicitis is still a diagnostic challenge for the clinician. Although clinical symptoms, scoring systems, and imaging methods and laboratory tests are important in the diagnosis of appendicitis, there are not any specific markers helping the surgeon.

The effect of human recombinant epidermal growth factor on neovascularization and pedicle division time in a rat interpolation flap model.

In practice, waiting 2-3 weeks for interpolation flaps pedicle division result in certain morbidities and discomfort for patient. The division time of flap pedicle depends on neovascularization from the recipient bed and includes wound healing stages. We aimed to investigate the effect of recombinant human epidermal growth factor (rhEGF) on the flap viability during early pedicle division. Thirty-six rats were allocated to two main groups as control and study. A cranial based flap measuring 5 × 5 cm was elevated from the back, including all layers of the skin. While the cranial half of the defect was primarily closed, the flap was inset into the distal half. In the study group, a single dose of 20 μg EGF was injected into the recipient site and wound edges before the flap inset. The control group received no treatment. Each main group was divided into three subgroups based on pedicle division time of 8, 11 and 14 days. After pedicle division, each flap was monitored and photographed for 7 days, and histopathological samples were collected. Viable and necrotic areas were compared, and flaps were examined histopathologically. The necrosis area in the study group on the 11th day was significantly lower than that in the control group. The fibroblastic activity, granulation tissue and neovascularization on the 8th day, the granulation tissue level on the 11th day, and the neovascularization level on the 14th day were significantly higher in the study groups. Following the application of EGF, the necrosis area decreased within the study group. Histopathological assessments revealed a statistically significant increase in parameters related to granulation tissue and fibroblastic activity, notably neovascularization, across all subgroups within the study. It was concluded that the use of EGF positively affected the neovascularization, and flaps could be divided earlier.

4-methylimidazole can promote oxidative stress, inflammation and histopathological assessment following sub-chronic exposure in rats: mechanistic approaches

4-methylimidazole (4-MEI) as the main by-product of many foods like drink colas, beverages, soy sauce, meats, candy, vinegar and caramel color which is formed in a high temperature following millard reaction. Other data revealed that 4-MEI is a neurotoxic and carcinogenic agent in animals but the obscure mechanistic pathway on the liver of wistar rats after two month administration. Therefore, sub-chronic effects of 4-MEI (32 µg kg−1–64 mg kg−1) were conducted on the cytotoxicity and inflammatory biomarkers in the liver and then histopathological changes were evaluated following oral administration. Our data revealed that 4-MEI exposure enhanced protein and lipid oxidation, and decreased reduced glutathione and total antioxidant level (FRAP) with histopathological changes in rats in higher doses of 320 µg kg−1. Our data explored the potentially toxic role of 4-MEI on the liver via induction of oxidative stress, mitochondrial dysfunction with negative impacts on glutathione and Frap level, and a raise in protein carbonylation and lipid peroxidation in the different doses of 4-MEI which leads to cell death signaling in the liver. Increased nitric oxide (NO) levels suggested the involvement of inflammation in 4-MEI mechanistic toxicity. Our data explored the potential hepatotoxic of 4-MEI by considering its possible role in oxidative stress, inflammation, and mitochondrial dysfunction.

MMP-7, RANKL mRNA expression in the gingival tissue correlates with periodontitis: An in vivo study

Introduction MMP-7 supports the immune response and can have both beneficial and destructive effects. As part of the innate host defense, MMP-7 is connected to the mucosal antimicrobial defense. Even though research on other Matrix metalloproteinase (MMPs) is well-established, understanding MMP-7 expression is required to establish an improved diagnostic strategy. This research investigates the mRNA expression of MMP-7 and RANKL by RT-qPCR assay. Methods and material Twelve male Sprague Dawley rats were allocated into three groups, no treatment, experimental (7 and 14 days). Periodontitis is induced by sterile wire insertion (0.2 mm) and Enterococcus faecalis inoculation within the gingival sulcus situated between the maxillary right 1st and 2nd molar tooth regions. Following euthanasia, tissue samples from the maxillary gingiva and maxillary jaw were extracted for quantitative real-time PCR assay and histopathological assessment. Results Results showed that at 7 days, there was significant upregulation of MMP-7, which was downregulated in 14 days, as well as migration of the junctional epithelium, attachment loss, inflammatory cells, and fibroblasts, as observed by histological analysis. Conclusions Thus, the study suggests that MMP-7 is associated with the progression of periodontitis.

Anti-inflammatory effects of sericin and swimming exercise in treating experimental Achilles tendinopathy in rat.

The aim of this study was to assess the effectiveness of combining sericin with swimming exercise as a treatment for type-I collagenase-induced Achilles tendinopathy (AT) in rats, with a focus on inflammatory cytokines. An experimental AT model was established using type-I collagenase in male Sprague-Dawley rats, categorized into five groups: Group 1 (Control+Saline), Group 2 (AT), Group 3 (AT+exercise), Group 4 (AT+sericin), and Group 5 (AT+sericin+exercise). Intratendinous sericin administration (0.8g/kg/mL) took place from days 3 to 6, coupled with 30 min daily swimming exercise sessions (5 days/week, 4 weeks). Serum samples were analyzed using ELISA for tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), interleukin-10 (IL-10), and total antioxidant-oxidant status (TAS-TOS), alongside histopathological and immunohistochemical assessments of Achilles tendon samples. Elevated TNF-α and IL-1β and decreased IL-10 levels were evident in Group 2; Of these, TNF-α and IL-1β were effectively reduced and IL-10 increased across all treatment groups, particularly groups 4 and 5. Serum TAS was notably lower in Group 2 and significantly increased in Group 5 compared to Group 2. Histopathologically, Group 2 displayed severe degeneration, irregular fibers, and round cell nuclei, while Group 5 exhibited decreased degeneration and spindle-shaped fibers. The Bonar score increased in Group 2 and decreased in groups 4 and 5. Collagen type-I alpha-1 (Col1A1) expression was notably lower in Group 2 (P=0.001) and significantly increased in groups 4 and 5 compared to Group 2 (P=0.011 and 0.028, respectively). This study underscores the potential of sericin and swimming exercises in mitigating inflammation and oxidative stress linked to AT pathogenesis, presenting a promising combined therapeutic strategy.

Processing methodology for histopathological assessment of black soldier fly (Hermetia illucens) larvae gut

Processing methodology for histopathological assessment of black soldier fly (Hermetia illucens) larvae gut

Hepatoprotective Activity of Ezetimibe Against Risperidone-Induced Liver Injury in Rats

Abstract Background: Drug-induced hepatic injury is an unfavorable reaction to medications and/or their byproducts, which can result in ongoing harm to liver function and even death. Risperidone, the second most prescribed antipsychotic drug, has been linked to weight gain, abnormal hepatic enzyme levels, and further damage to liver cells. On the other hand, ezetimibe is an antihyperlipidemic agent that reduces serum cholesterol levels by inhibiting its absorption in the gastrointestinal tract. Additionally, it possesses antioxidant, hepatoprotective, and nephroprotective properties. Objectives: The purpose of this study is to evaluate the hepatoprotective and hypolipidemic effects of ezetimibe in mitigating liver damage induced by risperidone. Materials and Methods: A total of 24 adult male Swiss albino rats aged 6–7 weeks and weighing 170–180 g each were randomly divided into four groups, with 6 rats in each group. The first group served as a control and received vehicles only (0.5 mL of corn oil). Rats in the second group were administered risperidone alone at a dose of 2 mg/kg. In the last two groups, rats received a combination of risperidone (2 mg/kg) and ezetimibe at doses of 3 and 5 mg/kg, respectively. After sacrificing the rats, serum samples were collected to measure parameters related to lipid profile and liver enzymes. Additionally, liver tissue was immediately gathered for histopathological assessment using the NAS scoring system. Results: Ezetimibe exhibited marked hepatoprotective effects in rats exposed to risperidone-induced hepatic injury. This was achieved by significantly (P < 0.05) lowering adverse lipid profile components (TCHO, TG, LDL, and VLDL) and liver enzymes (ALT and AST), while at the same time significantly (P < 0.05) elevating the beneficial lipid profile (HDL). Moreover, Ezetimibe demonstrated remarkable liver protection by mitigating hepatic lobule destruction, inflammatory cell infiltration, and the presence of steatotic cells. Conclusion: Ezetimibe exhibited notable hepatoprotective and hypolipidemic properties in countering hepatic injury induced by risperidone.

Nanoliposome enabled topical gel-based drug delivery system of ivermectin: Fabrication, characterization, in vivo and in vitro investigation

Nanoliposomes loaded with ivermectin possess the ability to deliver the drug to an intended area, ensuring optimal stability and eventual release at that precise location. The nanoliposome's size range results in an expanded surface area, which enables the delivery of the maximum amount of medication to the designed location. This investigation shows that the thin film lipid hydration technique can be employed to formulate nanoliposomes. For the formulation, the amount of cholesterol and phosphatidylcholine was chosen applying response surface methodology (RSM). With a range of zeta potentials from −13.4 ​± ​0.14 ​mV to −34.5 ​± ​0.11 ​mV, average dimension of the particles in the different formulation tested in this study is between 93.2 ​nm and 156.4 ​nm. The factorial design optimization demonstrates that the entrapment efficiency (Y3) has a p-value of 0.0160, the percentage of medicament release rate 8 ​h (Y1) has a p-value of 0.0414, and the percentage of medicament release rate 12 ​h (Y2) has a p-value of 0.0119. Therefore, all the models and responses were significant. After the thorough assessment from the present investigation, it was found that F7 batch has the highest R2 value and n exponent, the release kinetics of the ivermectin-loaded nanoliposome accompanied zero-order release model as well as korsmeyer–peppas model. Additionally, the current study demonstrated the histopathological assessments in the course of wound healing in animal model. Investigated results showcased that the ivermectin loaded nanoliposomes has substantial possibility as a nano conveyor for the targeted drug delivery system.

Histopathological Assessment of the intestinal barrier in broilers treated with a phytogenic oregano-rich essential oil and challenged with Eimeria spp

histopathological Assessment of the intestinal barrier in broilers treated with a phytogenic oregano-rich essential oil and challenged with Eimeria spp

INTRA-ORAL LINGUAL SCHWANNOMA - A RARE CASE REPORT FROM AN INDIAN TERTIARY CARE HOSPITAL

Schwannomas are most noted in the head and neck region, and their occurrence in the oral cavity is rare. Due to the rarity of intraoral schwannomas, are typically excluded from the differential diagnosis of tongue masses. Here we present such a case report describing the rare occurrence of an intra-oral lingual schwannoma in a young, male patient. The diagnosis was noted after histopathological assessment of the lesion, highlighting the importance of histopathology. Complete surgical excision of the lesion was effective without recurrence.

Silent Threats Unveiled: Navigating the Landscape Endometrial Cancer in Women Over 50 - A Comprehensive Analysis of Post-Menopausal Bleeding as a Crucial Diagnostic Indicator

Background: Endometrial cancer, with a global incidence of 9 per 100,000 women and a 1% lifetime risk, predominantly affects women aged >50 years and commonly manifests as post-menopausal bleeding (PMB). Timely referral for further investigation is imperative in cases of PMB. Objective: This study aimed to determine the frequency of endometrial cancer in females with abnormal uterine bleeding (AUB) and compare this frequency between premenopausal and postmenopausal women presenting with AUB. Study Design: Descriptive cross-sectional study. Settings: Department of Obstetrics & Gynecology, Independent University Hospital, Faisalabad Pakistan. Duration: Six months from December 15, 2022 to June 15, 2023. Methods: This study aimed to assess endometrial samples from 415 females over. Participants meeting inclusion criteria were enrolled from the Department's outpatient department, providing informed consent and demographic details. Endometrial sampling using Pipelle or D&C under general anesthesia was performed, and subsequent histopathology assessments in the hospital's pathology laboratory categorized findings into premenopausal and postmenopausal groups for comparative analysis. The study, initiated after ERC approval, spanned. Results: Out of 415 cases, 61.45% (n=255) were aged 30-50 years, while 38.55% (n=160) were aged 51-70 years, with a mean age of 48.52±7.02 years. The frequency of endometrial cancer in females with AUB was 6.51% (n=27). Comparing premenopausal (4.46%, n=10) to postmenopausal (8.90%, n=17) females with endometrial cancer, the p value was 0.06. Conclusion: While the overall frequency of endometrial cancer in females with AUB requires attention, this study emphasizes that the frequency is significantly lower in premenopausal compared to postmenopausal females presenting with AUB.

Feasibility of an MR-based digital specimen for tongue cancer resection specimens: a novel approach for margin evaluation.

This study explores the feasibility of ex-vivo high-field magnetic resonance (MR) imaging to create digital a three-dimensional (3D) representations of tongue cancer specimens, referred to as the "MR-based digital specimen" (MR-DS). The aim was to create a method to assist surgeons in identifying and localizing inadequate resection margins during surgery, a critical factor in achieving locoregional control. Fresh resection specimens of nine tongue cancer patients were imaged in a 7 Tesla small-bore MR, using a high-resolution multislice and 3D T2-weighted Turbo Spin Echo. Two independent radiologists (R1 and R2) outlined the tumor and mucosa on the MR-images whereafter the outlines were configured to an MR-DS. A color map was projected on the MR-DS, mapping the inadequate margins according to R1 and R2. We compared the hematoxylin-eosin-based digital specimen (HE-DS), which is a histopathological 3D representation derived from HE stained sections, with its corresponding MR-images. In line with conventional histopathological assessment, all digital specimens were divided into five anatomical regions (anterior, posterior, craniomedial, caudolateral and deep central). Over- and underestimation 95th-percentile Hausdorff-distances were calculated between the radiologist- and histopathologist-determined tumor outlines. The MR-DS' diagnostic accuracy for inadequate margin detection (i.e. sensitivity and specificity) was determined in two ways: with conventional histopathology and HE-DS as reference. Using conventional histopathology as a reference, R1 achieved 77% sensitivity and 50% specificity, while R2 achieved 65% sensitivity and 57% specificity. When referencing to the HE-DS, R1 achieved 94% sensitivity and 61% specificity, while R2 achieved 88% sensitivity and 71% specificity. Range of over- and underestimation 95HD was 0.9mm - 11.8mm and 0.0mm - 5.3mm, respectively. This proof of concept for volumetric assessment of resection margins using MR-DSs, demonstrates promising potential for further development. Overall, sensitivity is higher than specificity for inadequate margin detection, because of the radiologist's tendency to overestimate tumor size.

Assessment of patho-physiological responses, gill histopathology and SEM analysis in common carp (Cyprinus carpio) exposed to varied doses of chloramine-T: A potent chemotherapeutic agent

Chloramine-T (Cl-T) is a chemo-therapeutant used at aquafarms to control fish mortalities associated with bacterial and parasitic infections in freshwater aquaculture. It is also effective as a disinfectant against a wide range of viruses known to cause disease in fish. However, a very little information is available on the patho-physiological alterations in common carp (Cyprinus carpio) exposed to different doses of Cl-T. Herein, the present study aimed to assess the patho-physiological changes in common carp exposed to different doses of Cl-T (20 mg/L, 100 mg/L, and 200 mg/L) for 15 days followed by a post-exposure assessment for another 15 days. The results indicated a significant decrease in haematological indices viz., Total Erythrocyte Count (TEC), Total Leucocyte Count (TLC), Total Platelet Count (TPC), Haemoglobin (Hb), Haematocrit (Hct), and Mean Corpuscular Haemoglobin Concentration (MCHC) at higher Cl-T concentrations. Whereas, a decrease in some of the immune-biochemical parameters was also noted viz., lysozyme, NBT, Total Ig, phagocytic activity, protein, albumin and globulin in a dose-dependent manner. However, a significant increase in Mean Corpuscular Volume (MCV) and glucose levels was observed during exposure period. Histopathological analysis revealed gill hypertrophy, fusion of secondary lamellae, sloughing of lamellar epithelium and gill necrosis which were more pronounced with increasing concentration of Cl-T. The maximum damage to the gill was noted at a concentration of 200 mg/L. Whereas, scanning electron microscopic (SEM) analysis of gill revealed sloughing of lamellar epithelium, reduced interlamellar space and hypertrophy of secondary lamellae in Cl-T exposed fishes. Together, these results suggest that Cl-T exposure in common carp at 20 mg/L has a mild and acceptable effect on gill and physiology of fish, 100 mg/L has moderate effect, and 200 mg/L causes extensive damage to gills and physiology of fish.

Targeted Redox Balancing through Pulmonary Nanomedicine Delivery Reverses Oxidative Stress Induced Lung Inflammation.

Non-invasive delivery of drugs is important for the reversal of respiratory diseases essentially by-passing metabolic pathways and targeting large surface area of drug absorption. Here, we study the inhalation of a redox nano medicine namely citrate functionalized Mn3O4 (C-Mn3O4) duly encapsulated in droplet evaporated aerosols for the balancing of oxidative stress generated by the exposure of Chromium (VI) ion, a potential lung carcinogenic agent. Our optical spectroscopic in-vitro experiments demonstrates the efficacy of redox balancing of the encapsulated nanoparticles (NP) for the maintenance of a homeostatic condition. The formation of Cr-NP complex as an excretion of the heavy metal is also demonstrated through optical spectroscopic and high resolution transmission optical microscopy (HRTEM). Our studies confirm the oxidative stress mitigation activity of the Cr-NP complex. A detailed immunological assay followed by histopathological studies and assessment of mitochondrial parameters in pre-clinical mice model with chromium (Cr) induced lung inflammation establishes the mechanism of drug action to be redox-buffering. Thus, localised delivery of C-Mn3O4 NPs in the respiratory tract via aerosols can act as an effective nanotherapeutic agent against oxidative stress induced lung inflammation.