Nicotine exacerbates liver damage in a mice model of Ehrlich ascites carcinoma through shifting SOD/NF-κB/caspase-3 pathways: ameliorating role of Chlorella vulgaris.

Nicotine, a pervasive global environmental pollutant, is released throughout every phase of the tobacco's life cycle. This study examined the probable ameliorative role of Chlorella vulgaris (ChV) extract against nicotine (NIC)-induced hepatic injury in Ehrlich ascites carcinoma (EAC) bearing female Swiss mice. Sixty female Swiss mice were assigned to four equal groups orally gavaged 2% saccharin 0.2 mL/mouse (control group), orally intubated 100 mg ChV /kg (ChV group), orally intubated 100 µg/mL NIC in 2% saccharin (NIC group), and orally intubated NIC + ChV as in group 3 and 2 (NIC+ChV group). The dosing was daily for 4 weeks. Mice from all experimental groups were then inoculated intraperitoneally with viable tumor cells 2.5 × 106 (0.2 mL/mouse) in the fourth week, and the treatments were extended for another 2 weeks. The results have shown that NIC exposure significantly altered the serum levels of liver function indices, lipid profile, LDH, and ALP in the NIC-exposed group. NIC administration significantly increased hepatic inflammation, lipid peroxidation, and DNA damage-related biomarkers but reduced antioxidant enzyme activities. NIC exposure downregulated SOD1, SOD2, CAT, GPX1, and GPX2 but upregulated NF-κB hepatic gene expression. Notably, the presence of the EAC cells outside the liver was common in all mice groups. Liver tissue of the NIC-exposed group showed multifocal expansion of hepatic sinusoids by neoplastic cells. However, with no evidence of considerable infiltration of EAC cells inside the sinusoids or in periportal areas in the NIC + ChV groups. NIC significantly altered caspase-3, Bax, and BcL2 hepatic immune expression. Interestingly, ChV administration significantly mitigates NIC-induced alterations in hepatic function indices, lipid profile, and the mRNA expression of antioxidant and NF-κB genes and regulates the caspase-3, Bax, and BcL2 immunostaining. Finally, the in vivo protective outcomes of ChV against NIC-induced hepatic injury combined with EAC in female Swiss mice could suggest their helpful role for cancer patients who are directly or indirectly exposed to NIC daily.

Delphi consensus on stereotactic ablative radiotherapy for oligometastatic and oligoprogressive renal cell carcinoma-a European Society for Radiotherapy and Oncology study endorsed by the European Association of Urology.

The purpose of this European Society for Radiotherapy and Oncology (ESTRO) project, endorsed by the European Association of Urology, is to explore expert opinion on the management of patients with oligometastatic and oligoprogressive renal cell carcinoma by means of stereotactic ablative radiotherapy (SABR) on extracranial metastases, with the aim of developing consensus recommendations for patient selection, treatment doses, and concurrent systemic therapy. A questionnaire on SABR in oligometastatic renal cell carcinoma was prepared by a core group and reviewed by a panel of ten prominent experts in the field. The Delphi consensus methodology was applied, sending three rounds of questionnaires to clinicians identified as key opinion leaders in the field. At the end of the third round, participants were able to find consensus on eight of the 37 questions. Specifically, panellists agreed to apply no restrictions regarding age (25 [100%) of 25) and primary renal cell carcinoma histology (23 [92%] of 25) for SABR candidates, on the upper threshold of three lesions to offer ablative treatment in patients with oligoprogression, and on the concomitant administration of immune checkpoint inhibitor. SABR was indicated as the treatment modality of choice for renal cell carcinoma bone oligometatasis (20 [80%] of 25) and for adrenal oligometastases 22 (88%). No consensus or major agreement was reached regarding the appropriate schedule, but the majority of the poll (54%-58%) retained the every-other-day schedule as the optimal choice for all the investigated sites. The current ESTRO Delphi consensus might provide useful direction for the application of SABR in oligometastatic renal cell carcinoma and highlight the key areas of ongoing debate, perhaps directing future research efforts to close knowledge gaps.

Dietary Curcumin Modulating Effect on Performance, Antioxidant Status, and Immune-Related Response of Broiler Chickens Exposed to Imidacloprid Insecticide.

Birds appear to be especially vulnerable to adverse impacts from insecticides. This is especially true for imidacloprid (IMI), which is considered the most toxic to avian species. Recently, prospective studies aimed at including natural alternative products to alleviate the toxic impact that comes from insecticides have been increased. Focusing on herbal growth promoters and antioxidative medicament for the poultry industry, this ongoing experiment was conducted to examine the curcumin role (CUR) in mitigating IMI-prompted detrimental effects on broilers' performance, immunity, and antioxidant status. A total number of one hundred and fifty commercial meat-type Ross 308 broilers chicks (one-day-old) were randomly allocated into equal five groups (30 chicks/group and 10 birds/replicate). The first group (C) was the control; the second group (CUR) was fed a diet containing CUR at the level of 450 mg/kg; the third group (IMI) was fed control diet for 14 days and then was fed a diet containing IMI at the level of 50 mg/kg; the fourth group (CUR+IMI co-treated) was fed a diet containing CUR+IMI; and the fifth group (CUR+IMI pro/co-treated) was fed a diet containing CUR for 14 days as protective and then a diet containing CUR+IMI for the rest of the trial. CUR supplementation either in the (CUR pro/co-treated) or (CUR co-treated) groups significantly (p < 0.05) improved final body weight and total body weight gain while decreasing the total feed intake and feed conversion ratio when compared to the IMI-exposed and non-treated birds. CUR induced a significant (p < 0.05) enhancement in hematological indices, phagocytosis %, phagocytic index, intracellular killing capacity, total proteins, globulin, liver function enzymes, lysozyme activity, and immunoglobulin-G levels compared to IMI-exposed and non-treated birds. In addition, dietary supplementation of CUR significantly (p < 0.05) modulated oxidative stress-related biomarkers in splenic tissues (total antioxidant capacity, superoxide dismutase, catalase, and glutathione peroxidase) and decreased malondialdehyde levels (p < 0.05) when compared to IMI-exposed and non-treated birds. CUR significantly down-regulated mRNA levels expression of IL-1ß, TNF-α, and TLR4 and up-regulated IL-10 mRNA expression levels in spleens of birds when compared to those exposed to IMI-and non-treated. Finally, our results provided new insight into IMI-induced immuno-toxicity in broiler chickens. Furthermore, for the first time, our study informed that CUR can cause an in vivo protective effect against IMI toxicity, principally as a protective and/or as concurrent supplementation during the exposure to IMI toxicity.

Development and in vivo evaluation of therapeutic phytosomes for alleviation of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with progressive articular damage, functional loss and comorbidity. Conventional RA therapy requires frequent dosing and prolonged use, and usually results in poor efficacy and severe toxicity. In the current study, for the first time, we describe a combination strategy using phytosomes co-loaded with curcumin (CUR) and leflunomide (LEF) to improve the clinical outcomes of RA therapy. Exploiting 23 factorial design, various compositions of CUR and LEF co-loaded phytosomes (CUR/LEF-phytosomes) were successfully prepared and were extensively characterized (e.g., particle size, zeta potential, drugs encapsulation efficiency, morphology, DSC, FTIR and release kinetics). The optimal CUR/LEF-loaded phytosomes (F2) demonstrated high stability and spherical morphology with a particle size of ca. 760 nm and negative zeta potential value of - 55.7, high entrapment for both drugs, and sustained release profile of the entrapped medications. In vivo, oral administration of the CUR/LEF-phytosomes (F2) in arthritic rats resulted in significant reduction of paw swelling and inflammatory markers, compared to the free drugs and their physical mixture. Histopathological examination revealed significant improvement in phytosomes-treated animal group with no signs of arthritis. CUR/LEF-loaded phytosomes provide an auspicious strategy for alleviation of RA.

Ab initio study of structural, mechanical and electronic properties of 3d transitional metal carbide in cubic rocksalt (rs), zincblende (zb), and cesium chloride (cc) structures by using LDA and GGA Approximation.

CONTEXT: This study rigorously investigates three 3d transition metal carbide (TMC) structures via LDA and GGA approximations. It examines cohesive energy (Ecoh), Vickers hardness (Hv), mechanical stability, and electronic properties. Notably, most 3d TMCs exhibit higher cohesive energy than nitrides, and rs-TiC demonstrates a Vickers hardness of 25.66 GPa, outperforming its nitride counterpart. The study employs theoretical calculations to expedite research, revealing mechanical stability in CrC and MnC (GGA) and CrC (LDA in cc structure), while all 3d TMCs in rs and seven in zb structures show stability. Charge transfer and bonding analysis reveal enhanced covalency along the series, influenced by the interplay between p orbitals of carbon and d orbitals of the metal. Most 3d TMCs exhibit metallic properties, excluding zb-TiC and zb-FeC in all phases. An inverse correlation between elastic constant C44 and electronic states near the Fermi level (EF) emerges, guiding applications and design. This study efficiently uncovers 3d TMC properties, offering insights for applications and design. METHODS: We employed the Vienna ab initio Simulation software (VASP) to perform computations based on density functional theory (DFT). Our approach incorporated both the projector augmented wave (PAW) and PW91 general gradient approximation (GGA) methods within the local density approximation (LDA).

The dosimetric impact of titanium implants in spinal SBRT using four commercial treatment planning algorithms.

To evaluate the dosimetric impact of titanium implants in spine SBRT using four dose calculation algorithms. Twenty patients with titanium implants in the spine treated with SBRT without density override (DO) were selected. The clinical plan for each patient was created in Pinnacle and subsequently imported into Eclipse (AAA and AcurosXB) and Raystation (CC) for dose evaluation with and without DO to the titanium implant. We renormalized all plans such that 90% of the tumor volume received the prescription dose and subsequently evaluated the following dose metrics: (1) the maximum dose to 0.03 cc (Dmax), dose to 99% (D99%) and 90% (D90%) of the tumor volume; (2) Dmax and volumetric metrics of the spinal cord. For the same algorithm, plans with and without DO had similar dose distributions. Differences in Dmax, D99% and D90% of the tumor were on average <2% with slightly larger variations up to 5.58% in Dmax using AcurosXB. Dmax of the spinal cord for plans calculated with DO increased but the differences were clinically insignificant for all algorithms (mean: 0.36% ± 0.7%). Comparing to the clinical plans, the relative differences for all algorithms had an average of 1.73% (-10.36%-13.21%) for the tumor metrics and -0.93% (-9.87%-10.95%) for Dmax of the spinal cord. A few cases with small tumor and spinal cord volumes, dose differences of >10% in both D99% and Dmax of the tumor, and Dmax of the spinal cord were observed. For all algorithms, the presence of titanium implants in the spine for most patients had minimal impact on dose distributions with and without DO. For the same plan calculated with different algorithms, larger differences in volumetric metrics of >10% could be observed, impacted by dose gradient at the plan normalization volume, tumor volumes, plan complexity, and partial voxel volume interpolation.

Apitoxin alleviates methyl mercury-induced peripheral neurotoxicity in male rats by regulating dorsal root ganglia neuronal degeneration and oxidative stress.

Methylmercury (MeHg) toxicity is associated with extensive neuronal degeneration of dorsal root ganglia (DRG). This study aimed to assess the ameliorative effect of bee venom (BV) on methyl mercury chloride (MeHgCl)-induced peripheral neurotoxicity using DRGs in rats. Forty-eight adult male Sprague Dawley rats were allocated into four equal groups: G I: control (gavaged MilliQ water 1 ml/rat), G II: subcutaneously injected with BV (0.5 mg/kg b.wt), G III: gavaged MeHgCl (6.7 mg/kg b.wt), and G IV: received MeHgCl+BV. Dosing was done five times/week for 2 weeks. Ataxic behavior and visual impairments were significantly increased, whereas the movement behavior and motility gait were suppressed in the MeHgCl group. MeHgCl significantly decreased total antioxidant capacity (TAC) in DRG and significantly decreased the serum levels of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Tumor necrosis factor-alpha (TNF-α) and interleukin 1ß (IL-1ß) levels were significantly elevated, whereas interleukin 10 (IL-10) levels were significantly decreased in the MeHgCl group compared with the control group. DRGs of the MeHgCl-exposed rats showed pyknotic shrunken neurons with perineural vacuolations, demyelination of nerve axons, and proliferation of the satellite cells. MeHgCl significantly induced a higher positive index ratio of Iba-1, SOX10, neurofilament, pan-neuron, and vimentin immunostaining in the DRG. BV administration significantly mitigated the MeHgCl-induced alterations in oxidative stress-related indices. BV modified the immunostaining of Iba-1, SOX10, neurofilament, pan-neuron, and vimentin-positive index ratio in the DRG of the MeHgCl group. Our findings acknowledged that BV could enhance in vivo neuroprotective effects against MeHgCl-induced DRGs damage in male rats.

Colorectal Cancer Risk and Recommendations for Colorectal Cancer Surveillance in Adult Survivors of Childhood Cancer.

While many organizations have published guidance on the approach to colorectal cancer (CRC) screening in average-risk and certain high-risk groups, adult survivors of childhood cancer (ASCC) who have a heightened risk of CRC are rarely included as a target group for enhanced CRC surveillance. The population of ASCC continues to grow due to increasingly effective cancer therapies and improved survival. With this increased survival comes an increased risk for subsequent malignant neoplasms, including CRC. Since there is little published guidance for CRC surveillance in ASCC and limited awareness of increased CRC risk among both physicians and patients, the objectives of our paper are to review the incidence of and risk factors for colorectal neoplasia in ASCC, describe the clinical phenotypes of colorectal neoplasia in ASCC, review published surveillance strategies based on consensus-based survivorship guidelines, and outline areas for future research to optimize surveillance strategies.

Kinetically driven island morphology in growth on strained Cu(100).

We study the effects of strain on the monomer and dimer diffusion mechanisms and island morphology during the growth of Cu on a biaxially strained Cu(100) substrate. We find an approximately linear dependence of the activation barriers on strain. In particular, while hopping is favored for compressive and/or small (<2%) tensile strain, for greater than 2% tensile strain, the exchange mechanism is favored. We then present the results of temperature-accelerated dynamics simulations of submonolayer growth at 200 K. For the case of 2% compressive strain we find that, as in previous kinetic Monte Carlo simulations of Cu/Ni(100) growth, the competition between island growth and multi-atom relaxation ("pop-out") events leads to an island morphology with a mixture of open and closed steps. At slightly higher coverage, island coalescence then leads to elongated islands. However, annealing leads to a significant decrease in the number of open steps. In contrast, for the case of 8% tensile strain, only one large strongly anisotropic island is formed. Surprisingly, we find that despite the large strain, the island anisotropy is not due to energetics but is instead due to anisotropic attachment barriers that favor the exchange-mediated attachment of monomers to corners over close-packed step-edges. An explanation for the asymmetry in attachment barriers is provided. Our results provide a new general kinetic mechanism for the formation of anisotropic islands in the presence of isotropic diffusion and tensile strain.

A Volumetric Dosimetry Analysis of Vertebral Body Fracture Risk After Single Fraction Spine Stereotactic Body Radiation Therapy.

PURPOSE: Vertebral compression fractures (VCF) are a common and severe complication of spine stereotactic body radiation therapy (SBRT). We sought to analyze how volumetric dosimetry and clinical factors were associated with the risk of VCF. METHODS AND MATERIALS: We evaluated 173 spinal segments that underwent single fraction SBRT in 85 patients from a retrospective database. Vertebral bodies were contoured and dosimetric values were calculated. Competing risk models were used to evaluate the effect of clinical and dosimetry variables on the risk of VCF. RESULTS: Our primary endpoint was development of a post-SBRT VCF. New or progressive fractures were noted in 21/173 vertebrae (12.1%); the median time to fracture was 322 days. Median follow-up time was 426 days. Upon multivariable analysis, the percentages of vertebral body volume receiving >20 Gy and >24 Gy were significantly associated with increased risk of VCF (hazard ratio, 1.036, 1.104; P = .029, .044, respectively). No other patient or treatment factors were found to be significant on multivariable analysis. Sensitivity analysis revealed that the percentages of vertebral body volume receiving >20 Gy and >24 Gy required to obtain 90% sensitivity for predicting vertebral body fracture were 24% and 0%, respectively. CONCLUSIONS: VCF is a common complication after SBRT, with a crude incidence of 12.1%. Treatment plans that permit higher volumes receiving doses >20 Gy and >24 Gy to the vertebral body are associated with increased risk of VCF. To achieve 90% sensitivity for predicting VCF post-SBRT, the percentage of vertebral volume receiving >20 Gy should be <24% and maximum point dose should be <24 Gy. These results may help guide clinicians when evaluating spine SBRT treatment plans to minimize the risk of developing posttreatment VCF.

Protective prospects of eco-friendly synthesized selenium nanoparticles using Moringa oleifera or Moringa oleifera leaf extract against melamine induced nephrotoxicity in male rats.

Nanotechnology is used in a wide range of applications, including medical therapies that precisely target disease prevention and treatment. The current study aimed firstly, to synthesize selenium nanoparticles (SeNPs) in an eco-friendly manner using Moringa oleifera leaf extract (MOLE). Secondly, to compare the protective effects of green-synthesized MOLE-SeNPs conjugate and MOLE ethanolic extract as remedies for melamine (MEL) induced nephrotoxicity in male rats. One hundred and five male Sprague Dawley rats were divided into seven groups (n = 15), including 1st control, 2nd MOLE (800 mg/kg BW), 3rd SeNPs (0.5 mg/kg BW), 4th MOLE-SeNPs (200 µg/kg BW), 5th MEL (700 mg/kg BW), 6th MEL+MOLE, and 7th MEL+MOLE SeNPs. All groups were orally gavaged day after day for 28 days. SeNPs and the colloidal SeNPs were characterized by TEM, SEM, and DLS particle size. SeNPs showed an absorption peak at a wavelength of 530 nm, spherical shape, and an average size between 3.2 and 20 nm. Colloidal SeNPs absorption spectra were recorded between 400 and 700 nm with an average size of 3.3-17 nm. MEL-induced nephropathic alterations represented by a significant increase in serum creatinine, urea, blood urea nitrogen (BUN), renal TNFα, oxidative stress-related indices, and altered the relative mRNA expression of apoptosis-related genes Bax, Caspase-3, Bcl2, Fas, and FasL. MEL-induced array of nephrotoxic morphological changes, and up-regulated immune-expression of proliferating cell nuclear antigen (PCNA) and proliferation-associated nuclear antigen Ki-67. Administration of MOLE or MOLE-SeNPs significantly reversed MEL-induced renal function impairments, oxidative stress, histological alterations, modulation in the relative mRNA expression of apoptosis-related genes, and the immune-expression of renal PCNA and Ki-67. Conclusively, the green-synthesized MOLE-SeNPs and MOLE display nephron-protective properties against MEL-induced murine nephropathy. This study is the first to report these effects which were more pronounced in the MOLE group than the green biosynthesized MOLE-SeNPs conjugate group.

Bee venom Apis mellifera lamarckii rescues blood brain barrier damage and neurobehavioral changes induced by methyl mercury via regulating tight junction proteins expression in rat cerebellum.

The objective of the current study is to investigate the protective effect of Egyptian bee venom (BV) against methyl mercury chloride (MMC) induced blood-brain barrier (BBB) damage and neurobehavioral changes. Eighty male Sprague-Dawley rats were randomly grouped into 1st control (C), 2nd BV (0.5 mg/kg S/C for14 days), 3rd MMC (6.7 mg/kg orally/14 days), and 4th MMC + BV group. MMC exposure significantly altered rat cognitive behavior, auditory startle habituation, and swimming performance, increased the exploratory, grooming, and stereotypic behavior. MMC significantly impaired BBB integrity via induction of inflammation, oxidative stress, and down-regulation of tight junction proteins genes (TJPs) mRNA expression levels: Occludin (OCC), Claudins-5 (CLDN5), Zonula occludens-1 (ZO-1), while up-regulated the transforming growth factor-beta (TGF-ß) mRNA expression levels. MMC revealed a significantly higher percentage of IgG positive area ratio, a higher index ratio of Iba1, Sox10, and ss-DNA, while index ratio of CD31, neurofilament, and pan neuron showed a significant reduction. Administration of BV significantly regulates the MMC altered behavioral responses, TJPs relative mRNA expression, and the immune-expression markers for specific neural cell types. It could be concluded for the first time that BV retains a promising in vivo protection against MMC-induced BBB dysfunction and neurobehavioral toxicity.

Stereotactic body radiotherapy for the treatment of oligometastatic gynecological malignancy in the abdomen and pelvis: A single-institution experience.

PURPOSE/OBJECTIVES: Metastasis-directed therapy with stereotactic body radiotherapy (SBRT) in the setting of oligometastatic disease is a rapidly evolving paradigm given ongoing improvements in systemic therapies and diagnostic modalities. However, SBRT to targets in the abdomen and pelvis is historically associated with concerns about toxicity. The purpose of this study was to evaluate the safety and efficacy of SBRT to the abdomen and pelvis for women with oligometastases from primary gynecological tumors. MATERIALS/METHODS: From our IRB-approved registry, all patients who were treated with SBRT between 2014 and 2020 were identified. Oligometastatic disease was defined as 1 to 5 discrete foci of clinical metastasis radiographically diagnosed by positron emission tomography (PET) and/or computerized tomography (CT) imaging. The primary endpoint was local control at 12 months. Local and distant control rates were estimated using the Kaplan-Meier method. Time intervals for development of local progression and distant progression were calculated based on follow up visits with re-staging imaging. Acute and late toxicity outcomes were determined based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. RESULTS: We identified 34 women with 43 treated lesions. Median age was 68 years (range 32-82), and median follow up time was 12 months (range 0.2-54.0). Most common primary tumor sites were ovarian (n=12), uterine (n=11), and cervical (n=7). Median number of previous lines of systemic therapy agents at time of SBRT was 2 (range 0-10). Overall, SBRT was delivered to 1 focus of oligometastasis in 29 cases, 2 foci in 2 cases, 3 foci in 2 cases, and 4 foci in 1 case. All patients were treated comprehensively with SBRT to all sites of oligometastasis. Median prescription dose was 24 Gy (range 18-54 Gy) in 3 fractions (range 3-6) to a median prescription isodose line of 83.5% (range 52-95). Local control by lesion at 12 and 24 months was 92.5% for both time points. Local failure was observed in three treated sites among two patients, two of which were at 11 months in one patient, and the other at 30 months. Systemic control rate was 60.2% at 12 months. Overall survival at 12 and 24 months was 85% and 70.2%, respectively. Acute grade 2 toxicities included nausea (n=3), and there were no grade > 3 acute toxicities. Late grade 1 toxicities included diarrhea (n=1) and fatigue (n=1), and there were no grade > 2 toxicities. CONCLUSION: SBRT to oligometastatic gynecologic malignancies in the abdomen and pelvis is feasible with encouraging preliminary safety and local control outcomes. This approach is associated with excellent local control and low rates of toxicity during our follow-up interval. Further investigations into technique, dose-escalation and utilization are warranted.

Dietary exposure to methyl mercury chloride induces alterations in hematology, biochemical parameters, and mRNA expression of antioxidant enzymes and metallothionein in Nile tilapia.

Methyl mercury chloride "MMC" (CH3ClHg) is an ubiquitous environmental toxicant that causes a variety of adverse effects. In the present study, we investigated the effects of sub-chronic toxicity of MMC on Nile tilapia (Oreochromis niloticus) through the evaluation of growth performance and hematological, biochemical, and oxidative stress biomarkers. From 150 healthy fish, five equally sized treatment groups were created: a control (CT) group fed with a basal diet and four MMC treatment groups exposed to 0.5, 1, 1.5, and 2 mg of MMC per kg of basal diet for 60 days. MMC exposure significantly reduced the growth performance and survival of O. niloticus and decreased red blood cell count and hemoglobin concentration. Treated fish exhibited normocytic normochromic anemia in addition to leucopenia, lymphopenia, granulocytopenia, and monocytopenia. Moreover, MMC exposure significantly affected liver function, including a reduction in the total protein levels while increasing cholesterol and triglyceride levels. It also markedly increased the production of stress biomarkers such as glucose and cortisol levels. Furthermore, MMC significantly elevated the levels of hepatic enzymes, induced tissue damage, and caused inflammation, as indicated by the upregulation of mRNA expression of hepatic metallothionein. Finally, MMC exposure induced oxidative stress by altering the antioxidant status of the liver and downregulating the mRNA expression of superoxide dismutase, glutathione peroxidase, and glutathione S-reductase. In conclusion, MMC toxicity induced hematological and biochemical alterations, leading to an enhanced state of oxidative stress in O. niloticus.

Neurobehavioral and immune-toxic impairments induced by organic methyl mercury dietary exposure in Nile tilapia Oreochromis niloticus.

Although substantial knowledge of mercury toxicity in fish has been assembled; until now, studies investigating the toxic impacts in Nile tilapia (Oreochromis niloticus) following dietary exposure to organic methyl mercury (MeHg) are less prolific. Accordingly, the current study aimed to evaluate the impacts of MeHg on neurobehavioral and immune integrity in Nile tilapia after dietary exposure. Two hundred and twenty-five juvenile Nile tilapia (19.99 ± 0.33 g) were allocated into five groups in triplicates (15 fish/replicate). G1, G2, G3, G4, and G5. O. niloticus were fed corresponding basal diets containing 0, 0.5, 1, 1.5, and 2 mg/kg diet MeHg chloride (MeHgCl) daily for 30 days, zero value represented the control G1 group. The results showed that MeHg induced significant alterations in O. niloticus behavior, the swimming behavior was significantly decreased, while scratching, biting, and fin tugging behaviors were significantly augmented. Moreover; chasing, mouth pushing, and butting behaviors were significantly increased in all the exposed groups. MeHg significantly decreased brain acetylcholine esterase (AChE) and serum immunoglobulin M (IgM) levels in all the exposed groups. Meanwhile, serum levels of lysozyme (LYZ), nitric oxide (NO), superoxide dismutase (SOD) malondialdehyde (MDA), protein carbonyl (PCO), and 8 hydroxy 2 deoxyguanosine (8OH2dG) were significantly elevated in all the exposed groups except for serum reduced glutathione (GSH) content was significantly decreased implying oxidative stress (OS), lipid peroxidation (LPO), protein, DNA damage and impaired immune response of the exposed tilapia. MeHg significantly altered transcriptional expression of immune-related genes including (TNF-α, IL-1ß, and IL-8, and IL-10) in all the exposed groups. From the obtained outcomes, the present research is the premier to investigate that dietary MeHg exposure in O. niloticus significantly induced neurobehavioral and immune defense impairments in a dose-related manner. This study exhibits that dietary MeHg may pose a potential threat to the O. niloticus populations.

The palliative effect of camel milk on hepatic CYP1A1 gene expression and DNA damage induced by fenpropathrin oral intoxication in male rats.

The present study investigated the alleviating role of camel milk (CM) in the mitigation of fenpropathrin (FNP) type II pyrethroid induced oxidative stress, alterations of hepatic (CYP1A1) mRNA expression pattern, and DNA damage using the alkaline comet assay (SCGE) in male rats. Sixty male Sprague-Dawley rats were separated into six groups (n = 10): 1st control (C), 2nd corn oil (CO), 3rd (CM): gavaged CM 2ml/rat, 4th (FNP): gavaged FNP 7.09 mg/kg body weight (BW), 5th (FNP pro/co-treated): gavaged CM firstly for 15 days, then CM + FNP by the same mentioned doses and route, 6th (FNP + CM co-treated): gavaged FNP firstly followed by CM by the same mentioned doses and route. Rats were orally gavaged three times per week, day after day for 60 days. FNP exposure significantly reduced serum glutathione (GSH) levels, but significantly increased serum levels of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), protein carbonyl (PCO), and 8hydroxy2deoxyguanosine (8OH2dG). Additionally, FNP exposure significantly up-regulated the mRNA expression levels of hepatic CYP1A1 and increased the SCGE indices in whole blood, liver, and spleen tissues of exposed male rats. Administration of CM significantly regulated the FNP induced oxidative stress, reduced hepatic CYP1A1 mRNA expression levels and values of comet assay indices particularly in the (CM + FNP pro/co-treated) group compared to the (FNP + CM co-treated) group. In conclusion, our results indicate, for the first time, that FNP retains an in vivo genotoxic potential at a dose of (1/10 LD50) and up-regulated hepatic CYP1A1 mRNA expression in male rats. Additionally, CM supplements may improve the genotoxic outcomes, oxidative stress, and altered CYP1A1 mRNA expression induced by FNP particularly in the pro/concurrent-treatment compared to the concurrent treatment alone.

Ethanolic Extract of Moringa oleifera Leaves Influences NF-κB Signaling Pathway to Restore Kidney Tissue from Cobalt-Mediated Oxidative Injury and Inflammation in Rats.

This study aimed to describe the protective efficacy of Moringa oleifera ethanolic extract (MOEE) against the impact of cobalt chloride (CoCl2) exposure on the rat's kidney. Fifty male rats were assigned to five equal groups: a control group, a MOEE-administered group (400 mg/kg body weight (bw), daily via gastric tube), a CoCl2-intoxicated group (300 mg/L, daily in drinking water), a protective group, and a therapeutic co-administered group that received MOEE prior to or following and concurrently with CoCl2, respectively. The antioxidant status indices (superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)), oxidative stress markers (hydrogen peroxide (H2O2), 8-hydroxy-2-deoxyguanosine (8-OHdG), and malondialdehyde (MDA)), and inflammatory response markers (nitric oxide (NO), tumor necrosis factor (TNF-α), myeloperoxidase (MPO), and C-reactive protein (CRP)) were evaluated. The expression profiles of pro-inflammatory cytokines (nuclear factor-kappa B (NF-kB) and interleukin-6 (IL-6)) were also measured by real-time quantitative polymerase chain reaction (qRT-PCR). The results showed that CoCl2 exposure was associated with significant elevations of oxidative stress and inflammatory indices with reductions in the endogenous tissue antioxidants' concentrations. Moreover, CoCl2 enhanced the activity of the NF-κB inflammatory-signaling pathway that plays a role in the associated inflammation of the kidney. MOEE ameliorated CoCl2-induced renal oxidative damage and inflammatory injury with the suppression of the mRNA expression pattern of pro-inflammatory cytokine-encoding genes. MOEE is more effective when it is administered with CoCl2 exposure as a prophylactic regimen. In conclusion, MOEE administration exhibited protective effects in counteracting CoCl2-induced renal injury in rats.

Treatment planning of VMAT and step-and-shoot IMRT delivery techniques for single fraction spine SBRT: An intercomparative dosimetric analysis and phantom-based quality assurance measurements.

PURPOSE: To retrospectively compare clinically treated step-and-shoot intensity modulated radiotherapy (ssIMRT) and volumetric modulated arc therapy (VMAT) spine stereotactic body radiotherapy (SBRT) plans in dosimetric endpoints and pretreatment quality assurance (QA) measurements. METHODS: Five single fraction spine SBRT (18 Gy) cases - including one cervical, two thoracic, and two lumbar spines - clinically treated with ssIMRT were replanned with VMAT, and all plans were delivered to a phantom for comparing plan quality and delivery accuracy. Furthermore, we analyzed 98 clinically treated plans (18 Gy single fraction), including 34 ssIMRT and 29 VMAT for cervical/thoracic spine, and 19 ssIMRT and 16 VMAT for lumbar spine. The conformality index (CI) and homogeneity index (HI) were calculated, and QA measurement records were compared. For the spinal cord/cauda equina, the maximum dose to 0.03 cc (D0.03cc ) and volume receiving 10 or 12 Gy (V10Gy /V12Gy ) were recorded. Statistical significance was tested with the Mann-Whitney U test. RESULTS: Compared to ssIMRT, replanned VMAT plans had lower V10Gy /V12Gy and D0.03cc to the spinal cord/cauda equina in all five cases, and better CI in three out of five cases. The VMAT replans were slightly less homogeneous than those of ssIMRT plans. Both modalities passed IMRT QA with >95% passing rate with (3%, 3 mm) gamma criteria. With the 98 clinical cases, for cervical/thoracic ssIMRT and VMAT plans, the median V10Gy of spinal cord was 4.15% and 1.85% (P = 0.004); the median D0.03cc of spinal cord was 10.85 Gy and 10.10 Gy (P = 0.032); the median CI was 1.28 and 1.08 (P = 0.009); the median HI were 1.34 and 1.33 (P = 0.697), respectively. For lumbar spine, no significant dosimetric endpoint differences were observed. The two modalities were comparable in delivery accuracy. CONCLUSION: From our clinically treated plans, we found that VMAT plans provided better dosimetric quality and comparable delivery accuracy when compared to ssIMRT for single fraction spine SBRT.

Malignant Transformation of Molecularly Classified Adult Low-Grade Glioma.

PURPOSE: Malignant transformation (MT) of adult grade 2 glioma (low-grade glioma [LGG]) is associated with adverse survival. We sought to describe the incidence, outcomes, and risk factors for MT of molecularly classified LGG. METHODS AND MATERIALS: We reviewed a single-institutional database of adults who received a diagnosis of LGG with data allowing for molecular classification from 1980 to 2018 to evaluate time to MT and its associated risk factors. MT was defined as pathologic confirmation of grade 3-4 glioma and/or imaging characteristics consistent with MT by multidisciplinary consensus. RESULTS: Among the included 486 adults with molecularly classified LGG, median age was 39 years (range, 18-78), median tumor size was 3.9 cm (range, 0.3-13.0), and 262 (54%) were male. Molecular classification was IDHmut1p/19qcodel in 169 (35%), IDHmut1p/19qintact in 125 (26%), and IDHwt in 192 (40%) patients. Adjuvant management was observation in 246 (51%) patients, temozolomide alone in 82 (16%), radiation therapy alone in 63 (13%), and radiation therapy concurrent with temozolomide in 81 (17%). Temozolomide monotherapy was more likely to be given to IDHmut1p/19qcodel patients (P < .001). Median follow-up was 5.3 years. MT occurred in 84 (17%) patients, with a 5-year freedom from MT of 86% (95% confidence interval [CI], 82%-90%). Median overall survival after MT was 2.4 years (95% CI, 1.5-3.3) and was associated with molecular classification (P = .03) and grade at MT (P < .001). Factors associated with MT were male sex (hazard ratio [HR], 2.1; 95% CI, 1.2-3.6; P = .009), tumor size ≥5 cm (HR, 3.5; 95% CI, 2.0-6.2; P < .001), IDHmut1p/19qintact (HR, 2.7; 95% CI, 1.3-5.6; P = .009) or IDHwt classification (HR, 5.5; 95% CI, 2.5-11.8; P < .001), and adjuvant temozolomide monotherapy (HR, 3.8; 95% CI, 1.4-10.3; P = .008). CONCLUSIONS: MT of LGG has a poor prognosis associated with unfavorable molecular groups. Analysis of our large cohort identified adjuvant temozolomide monotherapy as the only modifiable risk factor for MT and provides the first clinical evidence of temozolomide-associated MT among molecularly classified adult LGG. This novel finding supplements our understanding of temozolomide-induced hypermutation and informs precision management of LGG.