Administration of silymarin in NAFLD/NASH: A systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease with a high prevalence worldwide and poses serious harm to human health. There is growing evidence suggesting that the administration of specific supplements or nutrients may slow NAFLD progression. Silymarin is a hepatoprotective extract of milk thistle, but its efficacy in NAFLD remains unclear. MATERIALS AND METHODS: Relevant studies were searched in PubMed, Embase, the Cochrane Library, Web of Science, clinicaltrails.gov, and China National Knowledge Infrastructure and were screened according to the eligibility criteria. Data were analyzed using Revman 5.3. Continuous values and dichotomous values were pooled using the standard mean difference (SMD) and odds ratio (OR). Heterogeneity was evaluated using the Cochran's Q test (I2 statistic). A P<0.05 was considered statistically significant. RESULTS: A total of 26 randomized controlled trials involving 2,375 patients were included in this study. Administration of silymarin significantly reduced the levels of TC (SMD[95%CI]=-0.85[-1.23, -0.47]), TG (SMD[95%CI]=-0.62[-1.14, -0.10]), LDL-C (SMD[95%CI]=-0.81[-1.31, -0.31]), FI (SMD[95%CI]=-0.59[-0.91, -0.28]) and HOMA-IR (SMD[95%CI]=-0.37[-0.77, 0.04]), and increased the level of HDL-C (SMD[95%CI]=0.46[0.03, 0.89]). In addition, silymarin attenuated liver injury as indicated by the decreased levels of ALT (SMD[95%CI]=-12.39[-19.69, -5.08]) and AST (SMD[95% CI]=-10.97[-15.51, -6.43]). The levels of fatty liver index (SMD[95%CI]=-6.64[-10.59, -2.69]) and fatty liver score (SMD[95%CI]=-0.51[-0.69, -0.33]) were also decreased. Liver histology of the intervention group revealed significantly improved hepatic steatosis (OR[95%CI]=3.25[1.80, 5.87]). CONCLUSIONS: Silymarin can regulate energy metabolism, attenuate liver damage, and improve liver histology in NAFLD patients. However, the effects of silymarin will need to be confirmed by further research.

Antihypertensive Potential of Japanese Quail (Couturnix Couturnix Japonica) Egg Yolk Oil (QEYO) in Sprague Dawley Rats.

Oils from animal sources have been used for centuries in the management of diseases. This research was conducted to screen the ex vivo and in vivo toxicity of quail egg yolk oil (QEYO) extracts and assess their effects on the management of hypertension in rats. QEYO was extracted using gentle heating (GH) and n-hexane (NHN). The extracts were subjected to toxicity testing using the hen's egg test on chorioallantoic membrane (HET-CAM) and bovine corneal histology test. Acute and sub-chronic toxicity (28 days) were evaluated in rats. Hypertension was induced in rats by administering 80 mg/kg of Nω-L-Arginine Methyl Ester (L-NAME) per day for 28 days. Treatments commenced on the 14th day; Nifedipine at 30 mg/kg and 1 mL of distilled water were administered as positive and negative controls. Blood pressure (BP), lipid profiles, and oxidative stress markers were quantified. No irritation was observed using the HET-CAM test in the egg treated with both extracts. Bovine corneal histology showed no lesions in all treated groups. No signs of toxicity were observed in either acute or sub-chronic toxicity studies. A significant reduction in blood pressure was observed in rats treated with the extracts (p < 0.05). Changes in total cholesterol (TC), triglycerides (TGs), low-density lipoproteins (LDLPs), and high-density lipoproteins (HDLPs) were not significant compared to the control (p > 0.05). Oxidative stress markers (SOD and CAT) increased significantly in the treated groups compared to the control, while the malondialdehyde levels decreased (p < 0.05). QEYO was safe in both ex vivo and in vivo studies and can be said to have the potential to lower blood pressure as well as cardio-protective effects in hypertensive rats. This research provides evidence based on which QEYO could be used safely as an adjuvant therapy in eye drops and cosmetics and can be considered an effective choice for preventing hypertension.

Histological Changes in Adrenal Glands in Suicidal and Sudden Death Cases: A Postmortem Study.

Introduction Various studies have linked suicidal behavior, stress, affective disorders, and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis resulting from chronic stress. Chronic stress has been shown to cause enlargement of the adrenal glands, altering their function and potentially leading to suicidal behaviors in individuals with depression. This study aimed to compare the histological changes in the adrenal glands of individuals who died by suicide with those who experienced sudden death. Suicide victims are exposed to chronic stress, while individuals with sudden deaths face acute stress related to the act of dying. Methods This analytical study, approved by the Institutional Ethics Committee (IEC), was conducted in the Department of Forensic Medicine and Toxicology at Gandhi Medical College, Bhopal. The study included 100 confirmed cases of suicide, irrespective of gender, aged 15-60 years, with notable autopsy findings, relevant history, no signs of decomposition, and varying survival periods (including immediate deaths within 24 hours). Additionally, 20 controls were selected, involving individuals who died suddenly from causes other than suicide within 24 hours of the incident. Informed consent was obtained using a prescribed proforma from relatives and the police. Histological examination slides of the adrenals were prepared and analyzed. Data were collected and statistically analyzed using GraphPad software and Epi Info 7. Results Capsular hemorrhage was observed in 98% of suicide cases and 40% of controls. Nodulation was present in 48% of suicidal cases and 20% of controls. Zonal extension of zona fasciculata was specific to chronic stress in suicidal cases. In 25% of suicidal cases, a prominent extension of the medulla was noted. Irregular thinning of zona glomerulosa with shrunken cells and increased nuclear density in 88% of cases were considered specific to chronic stress conditions and suicide, not observed in controls. Lipid depletion was observed in all suicidal cases, with diffuse depletion in 47% and focal depletion in 53% of cases. In contrast, 45% of those exposed to the acute stress of dying showed focal depletion, with none exhibiting diffuse depletion. Suicidal cases displayed dilated prominent sinusoids in all three zones and the adrenal medulla (98-99%), absent in controls. Adrenal hemorrhage and necrosis were specific to chronic stress conditions, with 7%, 8%, 32%, and 16% of cases showing hemorrhage in all three zones and adrenal medulla, respectively, and none in controls. Conclusion Histological changes observed in acute stress conditions included focal lipid depletion, capsular hemorrhage, nodular hyperplasia, and hemorrhage and necrosis with edema. However, the proportion and severity of these changes were lower than those observed in the suicidal group, suggesting that these findings may be considered non-specific for differentiating between acute and chronic stress.

Evaluation of starvation status in the early developmental stages of black rockfish (Sebastes schlegelii) based on morphological and histological characteristics.

Assessing the nutritional status and identifying major causes of mortality in larvae experiencing varying degrees of starvation are crucial for establishing appropriate feeding protocols and enhancing the welfare of hatchery-reared fish. The black rockfish Sebastes schlegelii is an important species in aquaculture and stock enhancement efforts in China, Japan, and Korea. This study aimed to identify optimal diagnostic morphometric indicators of starvation in newly hatched (0-6 days post-hatch, DPH) and postlarval stages (27-37 DPH) of this valuable fish species through histological analyses. Our findings revealed that certain morphometric parameters, including body length, the ratios of eye diameter to head height, body height to body length, and abdomen height to body height, exhibit sensitivity to starvation during both larval and postlarval stages. Particularly, the ratios of body height to body length and abdomen height to body height emerged as the most sensitive morphometric indicators of starvation. Histological examinations of the digestive system revealed rapid alterations in the morphology of hepatic parenchymal cells, accompanied by a significant decrease in the number of lipid cells in the liver during episodes of food deprivation. Starvation induced cellular degeneration in the digestive organs, manifested by reduced heights of epithelial cells and mucosal layers in the intestine, oesophagus, and stomach, along with degeneration and separation of muscle fibers. Among these variables, the height of the intestinal submucosa and muscle layer emerged as the most sensitive indicators reflecting nutritional conditions in newly hatched larvae. In contrast, the height of intestinal striated borders and mucosal folds proved to be the most sensitive indicators in the postlarval stage. Furthermore, the height of intestinal epithelial cells and the number of lipid vacuoles in enterocytes exhibited high sensitivity to food deprivation in both newly hatched larvae and postlarvae. These findings underscore the varying resilience of fish to starvation during different developmental phases and highlight the utility of morphological sensitivity characteristics as reliable diagnostic indices for assessing nutritional status in relation to starvation or suboptimal feeding during the early developmental stages of black rockfish in hatchery-reared processes.

Environmentally relevant concentrations of tris (2-chloroethyl) phosphate (TCEP) induce hepatotoxicity in zebrafish (Danio rerio): a whole life-cycle assessment.

Tris (2-chloroethyl) phosphate (TCEP), a typical organophosphate flame retardant, is of increasingly great concern considering their ubiquitous presence in aquatic environments and potential ecotoxicity. The present work was aimed to investigate the potential growth inhibition and hepatic stress induced by whole life-cycle exposure to TCEP (0.8, 4, 20 and 100 µg/L) in zebrafish. The results revealed that the body length, body mass and hepatic-somatic index (HSI) of zebrafish were significantly declined after exposure to TCEP for 120 days. GPx activity and GSH content were increased in the liver of zebrafish treated with low concentrations (0.8 and 4 µg/L) of TCEP, while exposure to high concentrations (20 and 100 µg/L) of TCEP reduced antioxidative capacity and elevated lipid peroxidation (LPO) levels. Gene transcription analysis demonstrated that the mRNA levels of nrf2 were altered in a similar manner to the transcription of the downstream genes nqo1 and hmox1, suggesting that Nrf2-Keap1 pathway mediated TCEP-induced oxidative stress in zebrafish liver. In addition, TCEP exposure might alleviate inflammatory response through down-regulating transcription of inflammatory cytokines (il-1ß, il-6 and inos), and induce apoptosis via activating the p53-Bax pathway. Moreover, whole life-cycle exposure to TCEP caused a series of histopathological anomalies in zebrafish liver. Overall, our results revealed that lifetime exposure to environmentally relevant concentrations of TCEP could result in growth retardation and induce significant hepatotoxicity in zebrafish.

Life-cycle exposure to tris (2-chloroethyl) phosphate (TCEP) causes alterations in antioxidative status, ion regulation and histology of zebrafish gills.

Tris (2-chloroethyl) phosphate (TCEP) has been receiving great concerns owing to its ubiquitous occurrence in various environmental compartments and potential risks to wildlife and humans. Gill is structural basis for ion regulation and homeostasis in fish and susceptible to xenobiotics. However, current knowledge on the impacts of long-term exposure to TCEP on the structure and physiological function of fish gills are insufficient. In this work, zebrafish were exposed to environmental realistic concentrations (0.8, 4, 20 and 100 µg/L) of TCEP from 3 h post ferterlization (hpf) till 120 days post ferterlization (dpf). Our results demonstrated that life-cycle exposure to TCEP significantly decreased the activity of glutathione S-transferase (GST), but elevated the activities of antioxidative enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and increased malondialdehyde (MDA) content in zebrafish gills. Gene transcription analysis implied that the mRNA expressions of antioxidant-related genes (nrf2, cat and nqo1) were induced, while the transcription of gstα1, hmox1, keap1 were down-regulated, indicating that Nrf2-Keap1 pathway might be activated to defend the oxidative stress induced by TCEP. Additionally, the ion homeostasis was disrupted by TCEP exposure, evidenced by reduced activities of Na+/K+-ATPase (NKA), Ca2+-ATPase and Mg2+-ATPase and downregulated transcription levels of ncc, nkcc, cftr and clc-3. Besides, whole-life exposure to TCEP resulted in a series of structural damages to gills, including epithelial lifting, epithelial rupture, telangiectasis, vacuolation, edema and shortened gill lamellae. Overall, our results demonstrated that long-term TCEP exposure could induce oxidative stress, affect ion regulation and cause histological changes in zebrafish gills.

Changes in Pulp and Roots of Deciduous Teeth during Different Stages of Physiologic Resorption: A Histologic Study.

Background: Resorption of primary teeth and eruption of permanent teeth involves a complex series of changes. The cellular and histological changes occurring during the process of resorption vary stagewise. The knowledge of the changes occurring in the pulp of deciduous teeth would provide information about the resorptive process. Aim: To evaluate the histologic changes of the pulp of deciduous teeth related to different stages of physiologic root resorption. Study setting and design: To establish the cause and effect relationship, a contrived histologic study design was planned. Materials and methods: A total of 60 extracted deciduous incisors, canines, and molars were included in the study. The remaining root length (RRL) was determined based on the standardized photographs. The teeth were then grouped into three based on the percentage of RRL. The teeth were subjected to decalcification with 5% nitric acid, following which histological processing was performed. Statistical analysis: The present study being a qualitative study design, descriptively explains the histologic findings, and no statistical tests have been applied. Results: During the initial stages of resorption, there were no histological alterations noted in the pulp, particularly in the cervical 3rd, with the cellular structure relatively maintained. As the resorption progresses, reversal lines were evident, indicating a process of repair occurring simultaneously during the process of resorption. With further advancement, the repair is overtaken by the resorption indicated by the presence of resorptive cells. Neovascularization and an increase in immune cells are also evident in advanced stages. Conclusion: The pulp exhibits progressive changes as the resorption continues from stage I to stage III. The changes vary from a smaller number of immune cells and odontoclasts in stage I to increasing number of the same as resorption progresses. How to cite this article: Murthy P, Bhojraj N, Hegde U. Changes in Pulp and Roots of Deciduous Teeth during Different Stages of Physiologic Resorption: A Histologic Study. Int J Clin Pediatr Dent 2023;16(3):437-443.

Clinicopathologic Manifestations of Immunoglobulin A Nephropathy in a Northern Indian Cohort: A Mute Assassin with Delayed Diagnosis.

Introduction: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide, but there is a marked geographic difference in its prevalence and prognosis. IgAN is known to have an aggressive course in Asians. However, its exact prevalence and clinicopathologic spectrum in North India are not well documented. Materials and Methods: The study included all patients aged above 12 years with primary IgAN on kidney biopsy from January 2007 to December 2018. Clinical and pathological parameters were noted. Two histopathologists independently reviewed all kidney biopsies, and MEST-C score was assigned as per the Oxford classification. Results: IgAN was diagnosed in 681 (11.85%) out of 5751 native kidney biopsies. The mean age was 32 ± 12.3 years, and the male to female ratio was 2.5:1. At presentation, 69.8% had hypertension, 68% had an estimated glomerular filtration rate (eGFR) of less than 60 ml/min, 63.2% had microscopic hematuria, and 4.6% had gross hematuria. The mean proteinuria was 3.61 ± 2.26 g/day, with 46.8% showing nephrotic range proteinuria and 15.2% showing nephrotic syndrome manifestation. Histopathologically, 34.4% of patients had diffuse global glomerulosclerosis. Oxford MEST-C scoring revealed M1 in 67%, E1 in 23.9%, S1 in 46.9%, T1/T2 in 33%, and crescents in 19.6% of biopsies. The mean serum creatinine was significantly higher in cases with E1, T1/2, and C1/2 scores (P < 0.05). Hematuria and proteinuria were significantly higher (P < 0.05) with E1 and C1/2 scores. Coexisting C3 was associated with higher serum creatinine at presentation (P < 0.05). Conclusion: IgAN patients with late presentation and advanced disease became less amenable to immunomodulation in our cohort. The implementation of point-of-care screening strategies, early diagnosis, and retarding disease progression should be prioritized in the Indian strategy.

Biochemical, Histological Changes, Protein Electrophoretic Pattern, and Field Application of CuPb-Ferrite/TiO2 Nanocomposites for Controlling Terrestrial Gastropod Eobania vermiculata (Müller).

Eobania vermiculata is a hazardous snail that can damage ornamental plants and cause significant harm to plant sections in Egyptian areas. Herein, the molluscicidal activity of CuPb-Ferrite/TiO2 and TiO2 nanoparticles (NPs) against E. vermiculata was evaluated using the poisonous bait method. LC50 values were determined using the leaf dipping and contact methods, with values of 631.23 and 1703.49 ppm for CuPb-Ferrite/TiO2 and 193.67 and 574.97 ppm for TiO2. Exposure to both NPs resulted in a significant increase in the biochemical parameters of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP), as well as a decrease in total protein (TP) percentage of E. vermiculata. Histological examinations revealed that many digestive cells had ruptured, and their contents had been lost, while the foot's epithelial layer became ruptured. The average reduction was 66.36% for CuPb-Ferrite/TiO2 NPs compared to the recommended molluscicide, Neomyl, with a 70.23% reduction in the field application. Electrophoretic separation of total protein using sodium dodecyl sulfate-polyacrylamide gel electrophoresis after treatment with LC50 concentrations of TiO2 and CuPb-Ferrite/TiO2 demonstrated the potency of these synthetic compounds as molluscicidal agents. Therefore, we recommend the use of CuPb-Ferrite/TiO2 NPs as a novel land snail molluscicide because it is safe to use, and the baits are arranged to not affect irrigation water, with a high molluscicidal effect.

Does L-carnitine prevent cadmium-induced damage in gastrointestinal contractility and histological changes in prepubertal rat / ¿La L-carnitina previene el daño inducido por cadmio en la contractilidad gastrointestinal y los cambios histológicos en ratas prepúberes?

SUMMARY: Cadmium (Cd) is the industrial and environmental toxic heavy metal which is found in air, water and soil. Cd, adversely affects many organs in humans such as kidney, intestine, liver, testis and lungs. L-carnitine (LC) is an important agent that plays essential role in energy metabolism. In our study, we aimed to work out whether LC application has any protective effect on intestinal contractility and morphologic damage of prepubertal rat duodenum on Cd-induced toxicity. Twenty eight prepubertal female Wistar rats were divided into four groups. The first group is control (C), second group; Cd group; Cadmium chloride was given 2 mg/kg 28 days with a one-day break by i.p. The third group; Cd+LC, which cadmium chloride was given 2 mg/kg i.p. and LC was given orally by gastric lavage. The LC dose was given as 75 mg/kg. The fourth group; LC, which only LC was given orally. The intestinal segments were isolated and suspended in tissue bath. Contractile responses were induced by acetylcholine (ACh) and relaxation was achieved with phenylephrine. Also the segments were examined for histological changes by light microscopy. Ach-induced contractions were higher in Cd+LC, LC, and control group compared to the Cd group in duodenal segments. The phenylephrine-induced relaxations were lower in Cd groups as compared with Control, Cd+LC and LC group in duodenal segments. In Cd group intestinal morphology was observed to be severely damaged whereas in Cd+LC group the damage was noticeably lower. Cd administration caused severe cellular damage and decreased gastrointestinal motility. Treatment with the LC has affected the gastrointestinal contractility and reduced the damage in intestinal morphology, which occured after Cd application.

El cadmio (Cd) es el metal pesado tóxico industrial y ambiental que se encuentra en el aire, el agua y el suelo. El Cd afecta negativamente a muchos órganos humanos, como los riñones, los intestinos, el hígado, los testículos y los pulmones. La L-carnitina (LC) es un agente importante que juega un rol esencial en el metabolismo energético. El objetivo de este estudio fue determinar si la aplicación de LC tiene algún efecto protector sobre la contractilidad intestinal y el daño morfológico del duodeno de rata prepuberal sobre la toxicidad inducida por Cd. Veintiocho ratas Wistar hembras prepúberes se dividieron en cuatro grupos. El primer grupo control (C), segundo grupo; grupo cd; Se administró cloruro de cadmio 2 mg/kg durante 28 días con un descanso de un día por vía i.p. El tercer grupo; Cd+LC, al que se administró cloruro de cadmio 2 mg/kg i.p. y LC se administró por vía oral mediante lavado gástrico. La dosis de LC se administró como 75 mg/kg. El cuarto grupo; LC, al cual solo LC se administraba por vía oral. Los segmentos intestinales fueron aislados y suspendieron en baño de tejido. Las respuestas contráctiles fueron inducidas por acetilcolina (ACh) y la relajación se logró con fenilefrina. También se examinaron los segmentos en busca de cambios histológicos mediante microscopía óptica. Las contracciones inducidas por Ach fueron mayores en Cd+LC, LC y el grupo control en comparación con el grupo Cd en los segmentos duodenales. Las relajaciones inducidas por fenilefrina fueron menores en los grupos Cd en comparación con el grupo Control, Cd+LC y LC en los segmentos duodenales. En el grupo Cd se observó que la morfología intestinal estaba severamente dañada mientras que en el grupo Cd+LC el daño fue notablemente menor. La administración de Cd causó daño celular severo y disminución de la motilidad gastrointestinal. El tratamiento con LC afectó la contractilidad gastrointestinal y redujo el daño en la morfología intestinal, que ocurría después de la aplicación de Cd.

Effects of the water-soluble fraction of diesel oil on the sera biochemical indicators, histological changes, and immune responses of black rockfish Sebastes schlegelii.

In order to understand the physiological and immune responses of Sebastes schlegelii to the water-soluble fraction of diesel oil (WSD), S. schlegelii were used as the experimental objects to study the effect of WSD on the sera biochemical indicators, histological changes, and immune responses. Significant differences in sera biochemical indicators were observed in S. schlegelii after WSD exposure. The alkaline phosphatase (ALP), glucose (GLU), and globulin (GLB) were reduced by 3.51-fold, 3.12- fold, and 1.58-fold, respectively; however, K+ was increased by 3.55-fold. The results of HE staining showed that interstitial congestion was observed in the liver; the secondary lamellae deformity and hyperplasia, epithelial lifting, the primary lamellae hyperplasia, and aneurism were observed in the gill. Epidermis thickness increased, and epidermal hyperplasia in the skin was shown. The length of the secondary lamellae shortened significantly after WSD exposure. The results of AB-PAS staining showed that three different types of mucous cells were observed in the gill, and a significant increase in the number of all three types of mucous cells was observed after WSD exposure (P < 0.05). In addition, the results of the relative mRNA expressions in the liver of eleven immune-related genes showed that the relative expression levels of IL-1ß, IL-8, TNF receptor, BAFF, C1s, C1r, and MyD88 in the WSD group were substantially higher than those in the LPS group (P < 0.05), and the relative expression of caspase 10 was significantly lower than that in the LPS group (P < 0.05). At the same time, no significant differences were observed in the relative expression levels of IL-1, TNFα, and C1inh between the two groups (P > 0.05). This study was expected to provide essential data for health assessments of S. schlegelii and establish the foundation for the immune-related researches of S. schlegelii after WSD exposure.

Non-Diabetic Kidney Disease in Type 2 Diabetes Mellitus: A Changing Spectrum with Therapeutic Ascendancy.

BACKGROUND AND OBJECTIVES: Owing to changing epidemiology and therapeutic practices, a change in the spectrum of renal involvement in Type-2 diabetes mellitus (T2DM) has also been noted. The treatment of non-diabetic kidney disease (NDKD) differs from diabetic kidney disease (DKD) and the reversibility of NDKD in many cases to normal, prompts biopsy for rapid and accurate diagnosis. Data are scarce on kidney biopsy findings in T2DM. STUDY DESIGN & SETTING: In this observational study, we prospectively collected the data of kidney biopsies of patients aged ≥ 18 years with T2DM admitted between 1 August 2005 and 31 July 2022. The clinical, demographic and histopathological data were evaluated. The spectrum of kidney involvement in the form of DKD and/or NDKD was studied. The impact of these findings with the use of drugs retarding disease progression was also analyzed. RESULTS: A total of 5485 biopsies were performed during the study period and of these 538 patients had T2DM. The mean age of the study population was 56.9 ± 11.5 years and 81% were males. The mean duration of DM was 6.4 ± 6.1 years. Diabetic retinopathy (DR) was noted in 29.7%. The most common indication for biopsy was an acute rise in creatinine (147, 27.3%). Amongst the 538 diabetic patients who underwent biopsy, histological features only of DKD were noted in 166 patients (33%), NDKD alone in 262 (49%) and NDKD with DKD lesions in 110 (20%). On multivariate analysis, duration of DM less than 5 years, absence of CAD, absence of DR, oliguria at presentation, an acute rise in creatinine and low C3 were associated with NDKD. CONCLUSIONS: The prevalence of NDKD among diabetics and ATIN in particular might be on an increasing trend in the current era of changing T2DM epidemiological patterns. The use of anti-pro-teinuric agents was associated with lesser degrees of histopathological chronicity in T2DM.

Pharmaco-Toxicological Effects of Atypical Synthetic Cathinone Mephtetramine (MTTA) in Mice: Possible Reasons for Its Brief Appearance over NPSs Scene.

Over the last year, NPSs have been steadily on the rise in the illicit drug market. Among these, synthetic cathinones seem to become increasingly popular among young adults, mainly because of their ability to replicate the effects of traditional psychostimulant drugs, such as cocaine, MDMA and amphetamines. However, scarce data are available about the in vivo pharmaco-toxicology of these new substances. To this end, this study focused on evaluation of effects induced by repeated administration of mephtetramine (MTTA 0.1-30 mg/kg i.p.) in mice. This atypical cathinone highlighted a sensorial (inhibition of visual and acoustic reflexes) and transient physiological parameter (decrease in breath rate and temperature) change in mice. Regarding motor activity, both a dose-dependent increase (accelerod test) and biphasic effect (drag and mobility time test) have been shown. In addition, blood and urine samples have been analysed to enrich the experimental featuring of the present study with reference to evaluation of potential toxicity related to consumption of MTTA. The latter analysis has particularly revealed important changes in blood cells count and blood and urine physicochemical profile after repeated treatment with this atypical cathinone. Moreover, MTTA induced histological changes in heart, kidney and liver samples, emphasizing its potential toxicity.

Comparative assessment of acute toxicity and histological changes in liver of African catfish Clarias gariepinus exposed to cotton insecticides.

This study investigated the acute toxicity in Clarias gariepinus to insecticides currently used in Benin cotton fields, including Thalis 112 EC (Emamectin benzoate 48 g L-1, Acetamiprid 64 g L-1), Vizir C 92 EC (Cypermethrin 72 g L-1, Abamectin 20 g L-1), Pyrinex Quick 212 EC (Deltamethrin 12 g L-1, Chlorpyrifos 200 g L-1) and Pyro FTE 472 EC (Cypermethrin 72 g L-1, Chlorpyrifos 400 g L-1) with emphasis on liver histopathological effects. A set of 180 juveniles of C. gariepinus (5.21 ± 3.22 g) was exposed for 96 h to increasing concentrations of each pesticide. The values of 96-hLC50 were 4.778, 0.002, 0.004, and 0.012 µL L-1 for Thalis, Vizir, Pyrinex, and Pyro, respectively, indicating that Vizir, Pyrinex, and Pyro were very highly toxic to C. gariepinus juveniles. During the experiments, the morphological and behavioral responses (discoloration, hyperactivity, lethargy, etc.) were observed in exposed fish, hypothesizing the neurotoxicity of these pesticides. Histopathological alterations observed in liver of contaminated fish were regressive changes, such as necrosis, vacuolation, bleeding, nuclear degeneration, hepatocytes degeneration, sinusoids dilatation, etc. Vizir induced the highest histological alteration indices while the lowest were induced by Thalis, confirming the highest toxicity of Vizir. These results indicate that acute concentrations of these insecticidal molecules have destructive effects on the liver of C. gariepinus.

Assessment of hindlimb motor recovery after severe thoracic spinal cord injury in rats: classification of CatWalk XT® gait analysis parameters.

Assessment of locomotion recovery in preclinical studies of experimental spinal cord injury remains challenging. We studied the CatWalk XT® gait analysis for evaluating hindlimb functional recovery in a widely used and clinically relevant thoracic contusion/compression spinal cord injury model in rats. Rats were randomly assigned to either a T9 spinal cord injury or sham laminectomy. Locomotion recovery was assessed using the Basso, Beattie, and Bresnahan open field rating scale and the CatWalk XT® gait analysis. To determine the potential bias from weight changes, corrected hindlimb (H) values (divided by the unaffected forelimb (F) values) were calculated. Six weeks after injury, cyst formation, astrogliosis, and the deposition of chondroitin sulfate glycosaminoglycans were assessed by immunohistochemistry staining. Compared with the baseline, a significant spontaneous recovery could be observed in the CatWalk XT® parameters max intensity, mean intensity, max intensity at%, and max contact mean intensity from 4 weeks after injury onwards. Of note, corrected values (H/F) of CatWalk XT® parameters showed a significantly less vulnerability to the weight changes than absolute values, specifically in static parameters. The corrected CatWalk XT® parameters were positively correlated with the Basso, Beattie, and Bresnahan rating scale scores, cyst formation, the immunointensity of astrogliosis and chondroitin sulfate glycosaminoglycan deposition. The CatWalk XT® gait analysis and especially its static parameters, therefore, seem to be highly useful in assessing spontaneous recovery of hindlimb function after severe thoracic spinal cord injury. Because many CatWalk XT® parameters of the hindlimbs seem to be affected by body weight changes, using their corrected values might be a valuable option to improve this dependency.

Evaluation of acute toxicity and histology effect on liver of glyphosate and atrazine in the African catfish Clarias gariepinus (Burchell 1822).

Aquatic organisms are exposed to chemical pesticides including glyphosate (Sharp 480 SL) and atrazine (Atraforce), two phytocidal molecules used for agriculture purposes in Benin. In this study, we assessed the acute toxicity of these two herbicides with emphasis on their histopathological effects on the liver of catfish Clarias gariepinus. One hundred and eighty juveniles of C. gariepinus (mean length 7.26 ± 0.59 cm and mean weight 5.21 ± 3.22 g) were exposed over 96 h to increasing concentrations of each phytocide. The values of 96 h-LC50 were 6.175 × 103 and 3.165 ppm, respectively for Sharp 480 SL and Atraforce. This indicates that Sharp 480 SL was nontoxic, while Atraforce displayed a moderate toxicity to C. gariepinus juveniles. During the tests, the behavioral responses (hyperexcitation, lethargy, loss of balance, discoloration of skin, etc.) that usually precede death were observed in exposed fishes, confirming the neurotoxicity of these phytocides. Histological alterations observed in liver of contaminated fishes were regressive changes, such as necrosis, hepatocyte vacuolation, nuclear degeneration, hepatocytes degeneration, sinusoids dilatation, etc. These results indicate that exposure to these herbicides had destructive effects on the liver of C. gariepinus.

Effect of antifreeze protein on the quality and microstructure of frozen chicken breasts.

The cryo-protective effects of different concentrations of antifreeze protein (AFP, 0 %, 0.10 %, 0.15 %, 0.20 %, 0.25 %, w/v) on chicken frozen at -18 °C for different storage perispeeods were investigated by monitoring water holding capacity (WHC), water distribution, color, protein properties, microstructure and histological changes. The results showed that AFP significantly maintained the quality traits of frozen chicken. Treatment with 0.20 % AFP represented highest cryo-protective effect on the WHC and protein properties during frozen storage. The carbonyl content with 0.20 % AFP was significantly lower than that of without AFP (P < 0.05). Besides, the myofibrils of chicken supplemented with AFP, especially with 0.25 % AFP, had significantly tighter microstructure, smaller ice crystal area and equivalent diameter than those of without AFP treatment (P < 0.05) after 75 d freezing storage. Overall, AFP had a positive effect to improve the quality of frozen chicken, and it was a potential, safe and efficient cryo-protective agent.

Evaluation of the Histological Changes in the Structure of the Minor Salivary Glands in Patients With Oral Submucous Fibrosis (OSMF).

BACKGROUND: The minor salivary glands (MSGs) are critical components of the mouth's delicate environment. The pre-malignant changes of oral submucous fibrosis (OSMF) have been associated with a decline in the quality of life and an uptick in the prevalence of oral malignancies. AIM: The aim was to provide evidence of the histological alterations in minor salivary gland structure seen in individuals with OSMF. METHODS AND MATERIALS: A total of 106 confirmed cases of OSMF were enrolled in the study. In order to perform an incisional biopsy, we first collected the patient's complete demographic and clinical history. Using a Vernier calliper, the inter-incisal distance was used to evaluate the mouth opening of the patients. An incisional biopsy of the buccal mucosa was carried out using a 6 mm diameter punch and local anaesthesia. After the appropriate demographic and medical information had been gathered. Acinar cells and the surrounding stroma of tissue slices were observed under a light microscope for alterations. The cytoplasm, nucleus morphology, cellular shape, mucin pooling, and acinar outline of acinar cells were all examined by the researchers. It was taken into account to classify OSMF histologically based on variations in juxta epithelial hyalinization. RESULTS: Multiple aetiologies for the symptoms of OSMF were reflected in the patient's histological abnormalities in the minor salivary glands. On the measurement of the diameter of acini, we discover that the average area of salivary gland acini in OSMF patients is smaller than in the normal group indicative of a decrease in size. The number of functional acini in OSMF is fewer than compared in the control group. CONCLUSION:  Because of the findings of this study, we now have a better understanding of the factors that play a role in the incidence of dryness of the oral and pharyngeal mucosa (OSMF), although it has to be mentioned that no major impact of OSMF on minor salivary glands was observed in our study.

Adrenal histological and functional changes after hepatic encephalopathy: From mice model to an integrative bioinformatics analysis.

Hepatic encephalopathy (HE), which is caused by neurotoxin agents in the liver, is a complicated condition with a variety of neurological manifestations. Recently, endocrine alterations have been more paid attention to for neurological severity in the course of HE, e.g. adrenal gland. To identify the role of adrenal gland in the context of HE, we evaluated the functional changes of adrenal gland (i.e., plasma corticosterone concentrations and histopathological changes) in mice model of HE. To dig deep into the molecular and genetic underpinnings, a comprehensive enrichment analysis for shared genes between HE and adrenal insufficiency (AI) was also performed. Our results showed a significant reduction in the level of plasma corticosterone and severe cellular necrosis in zona fasciculate of adrenal cortex, possibly indicating adrenal insufficiency. Enrichment analysis indicated four common genes, besides predicted five novel genes and some significant MicroRNAs (miRNAs) and transcription factors for both HE and AI. Couples with, several biological processes, such as DNA damage, inflammatory responses, glycolytic processes, and insulin receptor signaling pathway were predicted in both HE and AI. To sum up, data from experimental tests and bioinformatics analyses suggest that AI play an important role in the pathogenesis and progression of HE.

Corrigendum: Biomarker responses, gene expression alterations, and histological changes in zebrafish (Danio rerio) after in vivo exposure to polychlorinated diphenyl ethers.

[This corrects the article DOI: 10.3389/fphys.2022.907906.].