Histopathological Investigation Research Articles

Chondrosarcoma evaluation using hematein-based x-ray staining and high-resolution 3D micro-CT: a feasibility study

BackgroundChondrosarcomas are rare malignant bone tumors diagnosed by analyzing radiological images and histology of tissue biopsies and evaluating features such as matrix calcification, cortical destruction, trabecular penetration, and tumor cell entrapment.MethodsWe retrospectively analyzed 16 cartilaginous tumor tissue samples from three patients (51-, 54-, and 70-year-old) diagnosed with a dedifferentiated chondrosarcoma at the femur, a moderately differentiated chondrosarcoma in the pelvis, and a predominantly moderately differentiated chondrosarcoma at the scapula, respectively. We combined a hematein-based x-ray staining with high-resolution three-dimensional (3D) microscopic x-ray computed tomography (micro-CT) for nondestructive 3D tumor assessment and tumor margin evaluation.ResultsWe detected trabecular entrapment on 3D micro-CT images and followed bone destruction throughout the volume. In addition to staining cell nuclei, hematein-based staining also improved the visualization of the tumor matrix, allowing for the distinction between the tumor and the bone marrow cavity. The hematein-based staining did not interfere with further conventional histology. There was a 5.97 ± 7.17% difference between the relative tumor area measured using micro-CT and histopathology (p = 0.806) (Pearson correlation coefficient r = 0.92, p = 0.009). Signal intensity in the tumor matrix (4.85 ± 2.94) was significantly higher in the stained samples compared to the unstained counterparts (1.92 ± 0.11, p = 0.002).ConclusionsUsing nondestructive 3D micro-CT, the simultaneous visualization of radiological and histopathological features is feasible.Relevance statement3D micro-CT data supports modern radiological and histopathological investigations of human bone tumor specimens. It has the potential for being an integrative part of clinical preoperative diagnostics.Key points• Matrix calcifications are a relevant diagnostic feature of bone tumors.• Micro-CT detects all clinically diagnostic relevant features of x-ray-stained chondrosarcoma.• Micro-CT has the potential to be an integrative part of clinical diagnostics.Graphical

Stabilized oral lichen planus does not compromise dental implants survival: A systematic review and meta-analysis.

This study aimed to evaluate the incidence of implant failure in patients with oral lichen planus (OLP) and investigate the potential association between OLP and peri-implant diseases. Embase, Web of Science, PubMed, and Scopus databases were searched for studies with no time restrictions. Meta-analysis was performed calculating pooled proportion of peri-implantitis (PI), peri-implant mucositis (PIM), and bleeding on probing (BOP) prevalence using fixed-effects model. Odds ratio and corresponding 95% CI were calculated to assess the potential risk of PI, PIM, and BOP in dental implant patients with OLP compared to healthy controls. Implant failure rate was 4.38% at the patient level and 4.37% at the implant level. Six patients (3.92%) from five studies were diagnosed with oral cancer after receiving implant. The prevalence of PI, PIM, and BOP at the implant level were 14.00%, 20.00%, and 40.00%, respectively. There was no significant difference in the occurrence of PI and PIM between OLP patients and healthy controls. Stabilized OLP is not considered a significant risk factor for peri-implant diseases. It is advised against placing implants or prostheses during the acute phase of the disease. Histopathological investigation to differentiate OLP from oral lichenoid dysplasia is crucial.

A Preliminary Evaluation of the Prognostic Role of HER-2 and HER-3 Immunohistochemical Expression in Canine Melanomas

Canine melanoma is a malignant and aggressive neoplasm showing clinical, histological, and molecular features similar to the human counterpart. In human medicine, epidermal growth factor receptors (EGFRs) have already been suggested as prognostic markers and potential therapeutic targets in cutaneous melanoma. The aim of this study was to evaluate the expression of HER-2 and HER-3 in canine melanomas by immunohistochemistry and correlate their expression to the clinicopathological parameters of the examined tumors. Thirty-seven canine melanoma samples were recruited. Data regarding signalment and clinical parameters were also collected. The population was composed of 18 cutaneous, 16 oral/mucosal, and three digital/foot pad melanomas. Histopathological investigations were carried out to analyze histological type, ulceration, and mitotic count. On each sample, immunohistochemistry was performed using an anti-Melan-A or anti-Melanoma antigen, i.e., anti-HER-2 and anti-HER-3 antibodies. HER-2 and HER-3 positivity were classified using already established scoring criteria and a statistical analysis was carried out. The results highlighted that HER-2 expression was observed in 48.6% of the samples and HER-3 expression in 18.9%. The highest HER 2 score (3+) was recorded in 16.2% of the samples, while the coexpression of the two receptors was detected in 13.5% of the samples. A statistically significant association (p < 0.05) was observed between the expression of HER-2 and HER-3 and the presence of ulceration in oromucosal tumors. This work confirms the expression of HER-2 and HER-3 in canine melanomas and suggests a putative association with negative prognostic parameters. Further studies are necessary to strengthen these data by increasing the samples size and combining pathological examinations with molecular biology in the investigation of EGFR family receptors.

Tert-butylhydroquinone prevents cyclophosphamide induce lung toxicity in rats via inhibiting oxidative stress and apoptosis: in vivo and in silico study

BackgroundCyclophosphamide (CP) is a chemotherapeutic and immunosuppressive agent that induces oxidative stress, causing lung tissue damage.AimThe study aims to explore the antioxidant role of tert-butylhydroquinone (TBHQ) in ameliorating CP-induced lung toxicity exhibited as oxidative stress and programmed cell death.MethodsThirty-two adult male rats were allocated randomly into four groups: group 1 (control), group 2 TBHQ 50 mg/kg orally for 14 days, and group 3 single dose of (200 mg/kg, CP, i.p.) on the 9th day. In group 4, TBHQ (50 mg/kg, orally) was provided for 14 days, and (200 mg/kg, CP, i.p.) was administrated on the 9th day. Rats’ body and lung weight were measured. Oxidative stress marker malondialdehyde (MDA) and pulmonary tissue enzymatic antioxidant levels were assessed: glutathione S transferase, catalase, superoxide dismutase, and glutathione peroxidase. Additionally, glutathione level was measured. Assessment of the levels of TNF-α, IL-1β, and IL-6 were done as well as histopathological and immunohistochemistry investigations. Molecular docking studies of the protein structures of p53-MDM2, IL-6, and IL-1β were performed.ResultsCP-intoxicated rats demonstrated a significant decline (CAT, GPx, SOD, GST, and GSH) levels and a significant increase in MDA levels. The proinflammatory parameters (TNF-α, IL-6, IL-1ß) were significantly elevated in group 3. The noted biochemical changes, accompanied by histopathological destruction, indicate CP-induced pulmonary tissue injury. TBHQ played a protective role by attenuating most of the aforementioned biochemical alterations and histopathological distortions in rats’ lungs.ConclusionsTBHQ might be utilized as a potential ameliorative agent to inhibit CP-induced pulmonary toxicity via TBHQ’s antioxidant and anti-inflammatory effects.

Coenzyme Q10 mitigates cadmium cardiotoxicity by downregulating NF-κB/NLRP3 inflammasome axis and attenuating oxidative stress in mice

Coenzyme Q10 (CoQ10) occurs naturally in the body and possesses antioxidant and cardioprotective effects. Cardiotoxicity has emerged as a serious effect of the exposure to cadmium (Cd). This study investigated the curative potential of CoQ10 on Cd cardiotoxicity in mice, emphasizing the involvement of oxidative stress (OS) and NF-κB/NLRP3 inflammasome axis. Mice received a single intraperitoneal dose of CdCl2 (6.5 mg/kg) and a week after, CoQ10 (100 mg/kg) was supplemented daily for 14 days. Mice that received Cd exhibited cardiac injury manifested by the elevated circulating cardiac troponin T (cTnT), CK-MB, LDH and AST. The histopathological and ultrastructural investigations supported the biochemical findings of cardiotoxicity in Cd-exposed mice. Cd administration increased cardiac MDA, NO and 8-oxodG while suppressed GSH and antioxidant enzymes. CoQ10 decreased serum CK-MB, LDH, AST and cTnT, ameliorated histopathological and ultrastructural changes in the heart of mice, decreased cardiac MDA, NO, and 8-OHdG and improved antioxidants. CoQ10 downregulated NF-κB p65, NLRP3 inflammasome, IL-1β, MCP-1, JNK1, and TGF-β in the heart of Cd-administered mice. Moreover, in silico molecular docking revealed the binding potential between CoQ10 and NF-κB, ASC1 PYD domain, NLRP3 PYD domain, MCP-1, and JNK. In conclusion, CoQ10 ameliorated Cd cardiotoxicity by preventing OS and inflammation and modulating NF-κB/NLRP3 inflammasome axis in mice. Therefore, CoQ10 exhibits potent therapeutic benefits in safeguarding cardiac tissue from the harmful consequences of exposure to Cd.

Certolizumab has favorable efficacy on preventing pancreas and target organs damage in acute pancreatitis

Abstract Objective It was targeted to assess the efficacy of certolizumab on pancreas and target organs via biochemical parameters and histopathologic scores in experimental acute pancreatitis (AP) model in rats. Methods 40 male Sprague Dawley rats were divided into 5 equal groups: Group 1 (sham group), Group 2 (AP group), Group 3 (AP + low-dose certolizumab group), Group 4 (AP + high-dose certolizumab group), and Group 5 (placebo group). Rats in all groups were sacrificed 24 hours after the last injection and amylase, TNF-alpha, TGF-β, IL-1 β, MDA, SOD, and GPx levels were studied in blood samples. Histopathological investigation of both the pancreas and target organs (lungs, liver, heart, kidneys) were performed by a pathologist blind to the groups. In silico analysis were also accomplished. Results The biochemical results in the certolizumab treatment groups were identified to be significantly favorable compared to the AP group (p < 0.001). The difference between the high-dose group (Group 4) and low-dose treatment group (Group 3) was found to be significant in terms of biochemical parameters and histopathological scores (p < 0.001). In terms of the effect of certolizumab treatment on the target organs (especially on lung tissue), the differences between the low-dose treatment group (Group 3) and high-dose treatment group (Group 4) with the AP group (Group 2) were found to be significant. Conclusion Certolizumab has favorable protective effects on pancreas and target organs in AP. It may be a beneficial agent for AP treatment and may prevent target organ damage.

Effect of ethanolic leaves extract of Myrianthus arboreus on lipid profile of Wistar rats

This study investigated the effect of ethanolic leaves extract of Myrianthus arboreus on lipid profile of Wistar rats. A total of 24 albino Wistar rats divided into 8 groups of three rats each, were orally administered with DMSO as control and varying doses of 1500 mg/KgBw, 1000 mg/KgBw and 500 mg/KgBw for 7days and 14 days respectively. After 7 and 14 days groups 1-4 and 5-8 were sacrificed respectively. Blood samples and hearts of rats were collected for biochemical and histopathology investigations respectively. The result showed non-significant differences (p>0.05) in the mean values of total-cholesterol (T-Chol) and Low density lipoprotein-cholesterol (LDL-Chol.) in all the extract treated groups for 7 and 14 days when compared to mean control values. Mean values of triglyceride (Tg) and very low density lipoprotein-cholesterol (VLDL-Chol) significantly increased (p<0.05) in 1500 and 1000 mg/kgbw extract treated groups for 7days and decreased significantly (p<0.05) in 500 mg/kgbw for 14 days when compared with mean control values. The results also reveal a significant decrease (p<0.05) in the level of high density lipoprotein-cholesterolHDL-Chol) for groups treated 1500 1000 and 500 mg/kgbws for 14 days when compared with control. Phytochemical screening of the plant revealed the presence of alkaloids, flavonoids, glycosides, phenols, saponins and tannins with phenols and tannins having the highest and lowest concentrations of 1185.04 and 16.75 mg/100g respectively. The histopathology results showed normal histology of the heart tissues of animals in groups 1,3-8 while that of group 2 showed inflammation of the heart tissues. In conclusion, oral administration of ethanol leaves extract of Myrianthus arboreus is safe for the heart.

A Research Study on Histopathological Changes that are Seen in Lungs of Victims Who Died of Drowning

Drowning is considered to be the leading cause of death in water and the third most common cause of accidental death worldwide, with the highest drowning rates in developing countries. The WHO defines drowning as the process of experiencing respiratory impairment from submersion/immersion in liquid. For forensic experts, death in water is a multifaceted issue presenting a challenge to them. Since all the circumstances from natural death to homicide are possible in the water, critical examination and interpretation of all abnormal findings found during autopsy are of great importance.Drowning is a diagnosis of exclusion, based on ruling out all other causes of death via complete autopsy and toxicology. Drowning causes hypoxemia, loss of consciousness, apnea and ultimately cardiac arrest. Fluid aspiration results in lung injury and acute respiratory distress syndrome. Acute Respiratory Failure is the main component of drowning pathophysiology. Near drowning results in multiple complications including aspiration pneumonia which is often life-threatening. Hence the histopathological changes in the lungs provide good corroborative evidence of death due to drowning. Nevertheless, for the examined drowning signs, no high diagnostic certainty could be observed. However, these findings can increase their diagnostic value if forensic doctors take influencing factors into consideration.From the central record section of the Department of Forensic Medicine, Siddhartha Medical College, Vijayawada, Andhra Pradesh, about 80 medicolegal postmortem reports of death due to drowning in undecomposed bodies were selected in which one whole lung was sent for histopathological examination during the past two years i.e, 2020 - 2022. Parameters like Age, Sex and Marital Status were also studied. Histopathological examination of drowned lungs showed that congestion was seen in 92% of cases, oedema in 96% cases, dilatation of alveoli in 86% of cases, thinning of septa was seen in 84% of cases rupture of alveoli seen in 64% of cases and hemorrhage is seen in 46% of cases. Mostly males are affected and drowning deaths are seen more in 26 – 40 years age group. The histopathological investigations must be performed on all the organs of non-putrefied bodies with the aim of making the difference between death by drowning and other causes of death. The lung examinations can show over-distension of the alveoli, thinning of the alveolar septa and compression with narrowing of the capillary network.

Histopathological investigation of some facial cosmetic products mixture exposed to fingerlings of mud catfish <i>(Clarias gariepinus</i>)

Cosmetics are one of the major pollutants in the aquatic ecosystem due to the quantum of production to meet the astronomical demand  of users that eventually becomes harmful to organisms. Changes in physic-chemical parameters such as potential of hydrogen (pH),  Electrical conductivity (EC), Temperature (T oC) Dissolved oxygen (DO) were investigated at the beginning and after 96 hours of cosmetic  exposure. This study also investigated the effects of four facial cosmetic products (Powder, foundation, concealer, and primer) histopathologically in fingerlings of Clarias gariepinus (gills) exposed to binary, trinary, and quaternary mixtures in o laboratory bioassays  for 48 hours and 96 hours. The results of pH, T C, EC and DO ranged from 6.21 - 6.64, o 25.40 - 26.70 oC, 0.04 - 0.14 mS/cm, and  10.00 -12.00 mg/l respectively. The joint action toxicity evaluation of the binary, trinary, and quaternary mixtures of the cosmetics  prepared based on an equitoxic ratio against the test organism was in concordance with the model of synergism. Results showed the  prevalence of severe lamellar necrosis in the gills of C. gariepinus which was observed across all combinations except in the combinations  of Powder + Primer as well as Powder + Foundation + Concealer + Primer. Moderate lamellar necrosis and hypertrophied  epithelium were observed in fish exposed to a mixture of Powder + Foundation + Concealer. The results obtained in this study suggested  that the presence of facial cosmetics in the aquatic ecosystem could be dangerous to fish and subsequently human health via  biomagnification. Therefore, there is an urgent need for environmental regulators to enforce safety standards for the emission of these  selected cosmetics wastes into the waterways to prevent damage to aquatic organisms and public health issues.  

Betaine ameliorates doxorubicin-induced cardiomyopathy by inhibiting oxidative stress, inflammation, and fibrosis through the modulation of AMPK/Nrf2/TGF-β expression.

Doxorubicin (DOX) is a broad-spectrum antibiotic with potent anti-cancer activity. Nevertheless, despite having effective anti-neoplasm activity, its use has been clinically restricted due to its life-threatening side effects, such as cardiotoxicity. It is evident that betaine has anti-oxidant, and anti-inflammatory activity and has several beneficial effects, such as decreasing the amyloid-β generation, reducing obesity, improving steatosis and fibrosis, and activating AMP-activated protein kinase (AMPK). However, whether betaine could mitigate DOX-induced cardiomyopathy is still unexplored. Cardiomyopathy was induced in male Sprague Dawley rats using DOX (4 mg/kg dose with a cumulative dose of 20 mg/kg, i.p.). Further, betaine (200 and 400 mg/kg) was co-treated with DOX through oral gavage for 28 days. After the completion of the study, several biochemical, oxidative stress parameters, histopathology, western blotting, and qRT-PCR were performed. Betaine treatment significantly reduced CK-MB, LDH, SGOT, and triglyceride levels, which are associated with cardiotoxicity. DOX-induced increased oxidative stress was also mitigated by betaine intervention as the SOD, catalase, MDA, and nitrite levels were restored. The histopathological investigation also confirmed the cardioprotective effect of betaine against DOX-induced cardiomyopathy as the tissue injury was reversed. Further, molecular analysis revealed that betaine suppressed the DOX-induced increased expression of phospho-p53, phospho-p38 MAPK, NF-kB p65, and PINK 1 with an upregulation of AMPK and downregulation of Nrf2 expression. Interestingly, qRT-PCR experiments show that betaine treatment alleviates the DOX-induced increase in inflammatory (TNF-α, NLRP3, and IL-6) and fibrosis (TGF-β and Acta2) related gene expression, halting the cardiac injury. Interestingly, betaine also improves the mRNA expression of Nrf2, thus modulating the expression of antioxidant proteins and preventing oxidative damage. Here, we provide the first evidence that betaine treatment prevents DOX-induced cardiomyopathy by inhibiting oxidative stress, inflammation, and fibrosis by regulating AMPK/Nrf2/TGF-β expression. We believe that betaine can be utilized as a potential novel therapeutic strategy for preventing DOX-induced cardiotoxicity.

Combined effect of pantoprazole and mesenchymal stem cells on experimentally induced gastric ulcer: implication of oxidative stress, inflammation and apoptosis pathways.

Gastric ulcer (GU) is one of the most common diseases of the upper gastrointestinal tract that affects millions of people worldwide. This study aimed to investigate the possible alleviating effect of a combined treatment of pantoprazole (PANTO) and adipose tissue-derived mesenchymal stem cells (ADSCs) in comparison with each treatment alone on the healing process of the experimentally induced GU in rats, and to uncover the involved pathways. Rats were divided into five groups: (1) Control, (2) GU, (3) PANTO, (4) ADSCs and (5) ADSCs + PANTO. Markers of oxidative stress, inflammation and apoptosis were assessed. The current data indicated that PANTO-, ADSCs- and ADSCs + PANTO-treated groups showed significant drop (p < 0.05) in serum advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEPs) along with significant elevation (p < 0.05) in serum TAC versus the untreated GU group. Moreover, the treated groups (PANTO, ADSCs and ADSCs + PANTO) displayed significant down-regulation (p < 0.05) in gastric nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), tumor necrosis factor alpha (TNF-α), cyclooxygenase-2 (COX-2), intercellular adhesion molecule-1 (ICAM-1), matrix metallopeptidase 9 (MMP-9) and caspase-3 along with significant up-regulation (p < 0.05) in vascular endothelial growth factor (VEGF) and peroxisome proliferator-activated receptor gamma (PPARγ) genes expression compared to the untreated GU group. Immunohistochemical examination of gastric tissue for transforming growth factor β1 (TGF-β1), epidermal growth factor (EGF) and proliferating cell nuclear antigen (PCNA) showed moderate to mild and weak immune reactions, respectively in the PANTO-, ADSCs- and ADSCs + PANTO-treated rat. Histopathological investigation of gastric tissue revealed moderate to slight histopathological alterations and almost normal histological features of the epithelial cells, gastric mucosal layer, muscularis mucosa and submucosa in PANTO-, ADSCs- and ADSCs + PANTO-treated rats, respectively. Conclusively, the co-treatment with ADSCs and PANTO evidenced sententious physiological protection against GU by suppressing oxidative stress, inhibiting inflammation and reducing apoptosis with consequent acceleration of gastric tissue healing process.

Immunopathological investigation and genetic evolution of Avian leukosis virus Subgroup-J associated with myelocytomatosis in broiler flocks in Egypt

BackgroundAvian leukosis virus Subgroup-J (ALV-J) is a rapidly oncogenic evolving retrovirus infecting a variety of avian species; causing severe economic losses to the local poultry industry.MethodsTo investigate ALV-J, a total of 117 blood samples and 57 tissue specimens of different organs were collected for virological, and pathological identification, serological examinations, molecular characterization, and sequencing analysis. To the best of our knowledge, this is the first detailed report recorded in broiler flocks in Egypt. The present study targets the prevalence of a viral tumor disease circulating in broiler flocks in the El-Sharqia, El-Dakahliya, and Al-Qalyubiyya Egyptian governorates from 2021 to 2023 using different diagnostic techniques besides ALV-J gp85 genetic diversity determination.ResultWe first isolated ALV-J on chicken embryo rough cell culture; showing aggregation, rounding, and degeneration. Concerning egg inoculation, embryonic death, stunting, and curling were observed. Only 79 serum samples were positive for ALV-J (67.52%) based on the ELISA test. Histopathological investigation showed tumors consist of uniform masses, usually well-differentiated myelocytes, lymphoid cells, or both in the liver, spleen, and kidneys. Immunohistochemical examination showed that the myelocytomatosis-positive signals were in the spleen, liver, and kidney. The PCR assay of ALV-J gp85 confirmed 545 base pairs with only 43 positive samples (75.4%). Two positive samples were sequenced and submitted to the Genbank with accession numbers (OR509852–OR509853). Phylogenetic analysis based on the gp85 gene showed that the ALV-J Dakahlia-2 isolate is genetically related to ALV-EGY/YA 2021.3, ALV-EGY/YA 2021.4, ALV-EGY/YA 2021.14, and ALV-EGY/YA 2021.9 with amino acid identity percentage 96%, 97%; 96%, 96%; respectively. Furthermore, ALV-J Sharqia-1 isolate is highly genetically correlated to ALV-EGY/YA 2021.14, and ALV-EGY/YA 2021.9, ALV-J isolate QL1, ALV-J isolate QL4, ALV-J isolate QL3, ALV-EGY/YA 2021.4 with amino acid identity percentage 97%, 97%; 98%, 97%, 97%, 95%; respectively.ConclusionsThis study confirmed that ALV-J infection had still been prevalent in broilers in Egypt, and the genetic characteristics of the isolates are diverse.

Non-clinical Safety Evaluation of Camelina Oil: Acute and 12-Week Oral Toxicities

: This study assessed the acute and sub-chronic toxicity of Camelina oil, a well-known oil rich in polyunsaturated fatty acids that enhance cellular immunity and human health, in Wistar rats. Wistar rats, 5 per sex per group, were randomly assigned to three groups for acute (14 days) toxicity studies and five groups for sub-chronic (90 days) toxicity studies. In the acute study, Camelina sativa oil was administered orally at a single dose of 5000 mg/kg of body weight (BW). The positive control group received a single dose of 5 000 mg/kg BW Canola oil by gavage. In the sub-chronic study, Groups III-V received 250, 500, and 1 000 mg/kg BW of Camelina oil, while Groups I and II received ultra-pure water and Canola oil at a dose of 500 mg/kg BW, respectively. Throughout the experiment, clinical signs, mortality, and body weight were monitored. At the end of the sub-chronic study, hematological, biochemical, and histopathological investigations were conducted. Administration of Camelina oil and Canola had no significant effect on daily weight gain (P &gt; 0.05) of the test rats. Serum calcium levels decreased while phosphorous levels increased in male rats treated with Camelina oil. Other hematological and biochemical parameters showed no significant differences or dose-response effects between control and seed oil groups in both sexes (P &lt; 0.05). Moreover, in animal necropsy, there were no apparent lesions in the liver, heart, and kidney organs in any of the doses administered. In conclusion, the results suggest that oral administration of Camelina oil is unlikely to be toxic. Therefore, the possibility for the development of future human nutrition should be considered.

Neuroprotective Assessment of Betaine against Copper Oxide Nanoparticle-Induced Neurotoxicity in the Brains of Albino Rats: A Histopathological, Neurochemical, and Molecular Investigation.

Copper oxide nanoparticles (CuO-NPs) are commonly used metal oxides. Betaine possesses antioxidant and neuroprotective activities. The current study aimed to investigate the neurotoxic effect of CuO-NPs on rats and the capability of betaine to mitigate neurotoxicity. Forty rats; 4 groups: group I a control, group II intraperitoneally CuO-NPs (0.5 mg/kg/day), group III orally betaine (250 mg/kg/day) and CuO-NPs, group IV orally betaine for 28 days. Rats were subjected to neurobehavioral assessments. Brain samples were processed for biochemical, molecular, histopathological, and immunohistochemical analyses. Behavioral performance of betaine demonstrated increasing locomotion and cognitive abilities. Group II exhibited significantly elevated malondialdehyde (MDA), overexpression of interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α). Significant decrease in glutathione (GSH), and downregulation of acetylcholine esterase (AChE), nuclear factor erythroid 2-like protein 2 (Nrf-2), and superoxide dismutase (SOD). Histopathological alterations; neuronal degeneration, pericellular spaces, and neuropillar vacuolation. Immunohistochemically, an intense immunoreactivity is observed against IL-1β and glial fibrillary acidic protein (GFAP). Betaine partially neuroprotected against CuO-NPs associated alterations. A significant decrease at MDA, downregulation of IL-1β, and TNF-α, a significant increase at GSH, and upregulation of AChE, Nrf-2, and SOD. Histopathological alterations partially ameliorated. Immunohistochemical intensity of IL-1β and GFAP reduced. It is concluded that betaine neuroprotected against most of CuO-NP neurotoxic effects through antioxidant and cell redox system stimulating efficacy.

Future directions for early detection of fracture related infections

IntroductionFracture related infection (FRI) refers to pathogens infecting a fracture site and hence impeding fracture healing. It is a significant complication that carries substantial disease burden and socio-economic costs, but has had limited scientific development. Hence, this paper will review the existing strategies for early detection of FRI, in the form of serum markers, molecular diagnostics and imaging modalities, and further discuss potential future directions for improved detection of FRI. Existing Strategies for Diagnosis of FRIThe Anti-infection Global Expert Committee (AIGEC) developed a consensus definition for FRI in 2017, which includes confirmatory and suggestive criteria for diagnosis of FRI. Existing strategies for diagnosis include clinical, laboratory, histopathological, microbiological and radiological investigations. Future Directions for Early Detection of FRIWith increasing recognition of FRI, early detection is crucial for early treatment to be enforced. We have identified potential areas for future development in diagnostics for early detection of FRI, which are discussed in this manuscript. They include inflammatory cytokines, serum calcium levels, platelet count, improved management of histopathological and microbiological specimens, metagenomics, wound biomarkers, gut microbiota analysis, and novel imaging technologies.

Trichoscopic Features in Female Pattern Hair Loss: 1-Year Hospital-Based Cross-sectional Study

Introduction: Female pattern hair loss (FPHL) a nonscarring alopecia, is a common cause of hair loss in women. FPHL shows miniaturization of the hair follicles with thinning of hair. Scalp biopsy is diagnostic of FPHL but usually not needed. Trichoscopy a noninvasive higher magnification method (vs. scalp biopsy) for diagnosis of hair loss allows measurement of anisotrichosis characteristic of FPHL. Materials and methods: A total of 110 patients with clinically diagnosed FPHL of all grades were subjected to clinical and trichoscopic examination, and findings were looked for and compared with the occipital region serving as control. Results: Trichoscopic features apart from yellow dots and 2–3 hairs per unit follicle (HU) were statistically significant like hair diameter diversity, brown and white peripilar sign, one hair per follicular unit, white dots (WD), fine scaling, and honey-comb pigmentation (HCP). Focal atrichia, 2–3 hairs/HU, WD, HCP correlated with the grade of hair loss. Conclusion: Trichoscopy could be excellent tool for diagnosing FPHL in early stages and may aid in differentiating it from other conditions like chronic telogen effluvium and obviating the need of painful procedures like scalp biopsy. The study lacks histo-pathological and hormonal investigations however past studies done have already established correlation of trichoscopic and histo-pathological changes.

Clinical and Histopathological Investigation of Pediatric Melanonychia: A Single-Center Retrospective Case Series.

The natural history of pediatric melanonychia and the necessity of biopsy for ruling out melanoma are debated in the literature. We hypothesize that there is a low rate of malignant nail pathology among pediatric patients undergoing nail bed biopsy for melanonychia. We performed a retrospective chart review of 54 pediatric patients (age <18 years) at a single institution who presented with melanonychia and underwent nail bed biopsy from 2007 to 2022. Data points collected included patient demographics, medical history, physical exam findings, pathology reports, and clinical photos. Univariate and multivariate analyses were performed to assess for risk factors associated with high-risk pathology findings. The average age of melanonychia onset was 5.5 years (SD 4.4). The average age of first biopsy was 7.8 years (SD 4.3). On physical exam, 27 patients had at least four features concerning for melanoma (asymmetry, border irregularity, color heterogeneity, diameter > 1/3 of nail, evolving color, evolving diameter, Hutchinson's sign). The most common pathology diagnoses were melanocytic nevus (35%), atypical intraepidermal melanocytic proliferation (AIMP) with benign features (24%), subungual lentigo (22%), and AIMP with concerning features (17%). There were no cases of melanoma in situ or invasive malignant melanoma. On multivariate regression, the only significant risk factor associated with more concerning pathology (AIMP with concerning features) was the calendar year in which biopsy was performed (coefficient = -0.34, P = 0.016). There was no association between physical exam features and high-risk pathology. Twelve patients had surgical re-excision of the lesion, 6 of which were due to incomplete excision of AIMP with concerning features and 6 of which were due to recurrence. Our case series did not find any cases of melanoma in situ or malignant melanoma arising from pediatric melanonychia. Atypical intraepidermal melanocytic proliferation with concerning features was associated only with the year in which the biopsy was performed, which may reflect the improved understanding of pediatric melanonychia as often benign despite concerning features on pathology. The decision to perform a nail matrix biopsy in pediatric melanonychia should be based on a collaborative discussion between the patient's parents, dermatologist, and plastic surgeon.

Histopathological investigation and risk factors of Coccidiosis in camels (Camelus dromedarius), Algeria

Coccidiosis in dromedaries is an intestinal protozoan infection caused by apicomplexan parasites belonging to the genus Eimeria. A prospective examination was conducted at two slaughterhouses in southern Algeria. The primary objective of this investigation was to ascertain the prevalence of intestinal parasites in camels, elucidate the associated microscopic lesions, and identify the risk factors contributing to this infestation. In pursuit of this, we procured four segments of the intestines from 31 dromedarieas that appeared healthy and displayed no symptoms. Subsequently, these samples were collected, preserved, subjected to routine processing, and subsequently stained with haematoxylin and eosin (H&amp;E). Intestinal parasitic infection showed an incidence rate of 45.16% (14 out of 31). Specifically, two types of parasites were discerned in the intestinal specimens through microscopic examination, namely Eimeria (41.93%; 13 out of 31) (p-value = 0.046) and Taenia (3.22%; 1 out of 31) (p = 0.001). Eimeria cameli was observed in the ceacum (41.93%; 13 out of 31), jejunum (12.90%; 4 out of 31), and in one instance in the duodenum (3.22%; 1 out of 31). Furthermore, numerous development stages of coccidia were identified, including gamonts, schizonts and oocysts. Deep microscopic lesions attributed to Eimeria cameli were detected, such as enteritis, eosinophilic infiltration and inflammation. In addition, associated risk factors were identified. This study has furnished valuable insights into parasitic infestations affecting dromedaries, particularly Eimeria cameli. The molecular studies are needed to delineate the diverse variations within Eimeria strains. Effective parasite control strategies specific to dromedary camels need to be developed.

A study of scarless wound healing through programmed inflammation, proliferation and maturation using a redox balancing nanogel.

In the study, we have shown the efficacy of an indigenously developed redox balancing chitosan gel with impregnated citrate capped Mn3O4 nanoparticles (nanogel). Application of the nanogel on a wound of preclinical mice model shows role of various signaling molecules and growth factors, and involvement of reactive oxygen species (ROS) at every stage, namely hemostasis, inflammation, and proliferation leading to complete maturation for the scarless wound healing. While in vitro characterization of nanogel using SEM, EDAX, and optical spectroscopy reveals pH regulated redox buffering capacity, in vivo preclinical studies on Swiss albino involving IL-12, IFN-γ, and α-SMA signaling molecules and detailed histopathological investigation and angiogenesis on every stage elucidate role of redox buffering for the complete wound healing process.

Dual blockade of interleukin-17A and interleukin-17F as a therapeutic strategy for liver fibrosis: Investigating the potential effect and mechanism of brodalumab

Liver fibrosis is a terminal manifestation of various chronic liver diseases. There are no drugs that can reverse the condition. Recently, the importance of interleukin-17 (IL17) in the pathophysiology has been revealed and has attracted attention as a therapeutic target. We aimed to reveal the roles of IL17A and IL17F in liver fibrosis, and to validate the potential of their dual blockade as therapeutic strategy. First, we retrospectively reviewed the longitudinal change of FIB-4 index, a clinical indicator of liver fibrosis, among psoriasis patients treated by brodalumab, which blocks IL17 receptor A (IL17RA). Next, we examined anti-fibrotic efficacy of anti-IL17RA antibody (Ab) in two murine liver fibrosis models by histopathological investigation and real-time reverse transcription polymerase chain reaction (RT-PCR). Finally, we analyzed the effect of IL17A and IL17F upon human hepatic stellate cells with RNA sequencing, real-time RT-PCR, western blotting, chromatin immunoprecipitation, and flow cytometry. Clinical data showed that FIB-4 index significantly decreased among psoriasis patients treated by brodalumab. In vivo studies additionally demonstrated that anti-IL17RA Ab ameliorates liver fibrosis induced by tetrachloride and methionine-choline deficient diet. Furthermore, in vitro experiments revealed that both IL17A and IL17F enhance cell-surface expression of transforming growth factor-β receptor II and promote pro-fibrotic gene expression via the JUN pathway in human hepatic stellate cells. Our insights suggest that IL17A and IL17F share their pro-fibrotic function in the context of liver fibrosis, and moreover, dual blockade of IL17A and IL17F by anti-IL17RA Ab would be a promising strategy for the management of liver fibrosis.