Sinapic acid-pullulan based inflammation responsive nanomicelles for the local treatment of experimental inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disorder of joints. It is one of the major causes of disability and morbidity worldwide. Administration of conventional drugs through the systemic route restricts the bioavailability of drugs, systemic toxicity, and reduced efficacy. We have introduced Rebamipide (Reb)-loaded Sinapic acid (SA)-Pullulan (PL) nanomicelles (Reb@SA-PL NMs), a nanotechnology based drug delivery system for the treatment of inflammatory arthritis. PL is a polysaccharide obtained from the fungus Aureobasidium pullulans, and SA is a bioactive polyphenol found in various plants. Both are classified by US-FDA Generally Recognised as Safe (GRAS) materials. Reb@SA-PL NMs found to be cytocompatible. Subsequently, intra-articular administration of Reb@SA-PL NMs enhances the anti-arthritic potential compared to free Reb drug in collagen-induced experimental inflammatory arthritis rat model. Reb@SA-PL NMs reduced the expression of RANKL receptor and Nf-κB. Reb@SA-PL NMs reverses the breakdown of type II collagen, MMP-13, and inhibits the pro-inflammatory markers. Reb@SA-PL NMs prevented bone erosion, cartilage degradation, joint oedema, and synovial inflammation. The results of the study demonstrated that Reb@SA-PL NMs, an enzyme-responsive drug delivery system, has excellent potential for alleviating inflammatory arthritis by blocking MMP-13 and RANKL.

Pathophysiological role of histamine signaling and its implications in glioblastoma.

Glioblastoma (GBM), an extremely aggressive and prevalent malignant brain tumor, remains a challenge to treat. Despite a multimodality treatment approach, GBM recurrence remains inevitable, particularly with the emergence of temozolomide (TMZ) resistance and limited treatment options. Surprisingly, previous studies show that a history of allergies, atopy, or asthma is inversely associated with GBM risk. Further, the electronic medical record at the University Hospital of Lausanne showed that the GBM patients taking antihistamine during treatment had better survival. Histamine is an essential neurotransmitter in the brain and plays a significant role in regulating sleep, hormonal balance, and cognitive functions. Elevated levels of histamine and increased histamine receptor expression have been found in different tumors and their microenvironments, including GBM. High histamine 1 receptor (HRH1) expression is inversely related to overall and progression-free survival in GBM patients, further emphasizing the role of histamine in disease progression. This review aims to provide insights into the challenges of GBM treatment, the role of histamine in GBM progression, and the rationale for considering antihistamines as targeted therapy. The review concludes by encouraging further investigation into antihistamine mechanisms and their impact on the tumor microenvironment.

Computational and experimental small field dosimetry using a commercial plastic scintillator detector for the 0.35 T MR-linac.

PURPOSE: Although plastic scintillator detectors (PSDs) are considered ideal dosimeters for small field dosimetry in conventional linear accelerators (linacs), the impact of the magnetic field strength on the response of the PSD must be investigated. METHODS: A linac Monte Carlo (MC) head model for a low-field MR-linac was validated for small field dosimetry and utilized to calculate field output factors (OFs). The MC-calculated OFs were compared with the treatment planning system (TPS)-calculated OFs and measured OFs using a Blue Physics (BP) Model 10 commercial PSD and a synthetic diamond detector. The field-specific correction factors, [Formula: see text] , were calculated for the PSD in the presence of a 0.35 T and magnetic field. The impact of the source focal spot size and initial electron energy on the MC-calculated OFs was investigated. RESULTS: Good agreement to within 2 % was found between the MC-calculated OFs and BP PSD OFs except for the 0.415 × 0.415 cm2 field size. The BP PSD [Formula: see text] correction factors were calculated to be within 1 % of unity. For field sizes ≥1.66 × 1.66 cm2, the MC-calculated OFs were relatively insensitive to the focal spot size and initial electron energy to within 2.5 %. However, for smaller field sizes, the MC-calculated OFs were found to differ up to 9.50 % and 7.00 % when the focal spot size and initial electron energy was varied, respectively. CONCLUSIONS: The BP PSD was deemed suitable for small field dosimetry in MR-linacs without requiring any [Formula: see text] correction factors.

Phytochemical Screening and Antidiabetic Efficacy of Balanites aegyptiaca Seed Extract and Their Silver Nanoparticles on Muscle and Pancreatic Cell Lines.

Balanites aegyptiaca (L.) Delile, a member of the Zygophyllaceae family, is commonly known as the desert date. This tree is famous for yielding edible fruits and is esteemed for its nutritional richness and diverse health advantages. The primary aim of this research was to assess the potential antidiabetic and cytotoxic effects of seed extracts from B. aegyptiaca and its AgNPs for the first time on C2C12 and MIN6 cells, focusing on glucose uptake and insulin secretion, respectively. Additionally, the seed extracts underwent column chromatography through different solvent systems, resulting in the isolation of five distinct fractions with a mixture of methanol and water as an eluting solvent in different ratios. Comprehensive characterization of the aqueous seed extract was carried out using GC-MS and UPLC-MS. The study determined that the aqueous seed extract exhibited no toxicity at any tested concentration (6.25-100 µg/mL) on both cell types. The calculated IC50 values were 206.00 and 140.44 µg/mL for C2C12 and MIN6 cells, respectively, for seeds of AgNPs. Additionally, the aqueous seed extract and their AgNPs significantly increased glucose uptake by 150.45% and 156.00% of the control in C2C12 cells at a concentration of 100 µg/mL. Insulin secretion was also notably enhanced by 3.47- and 3.92-fold of the control after administering seed extracts and AgNPs, respectively, at 100 µg/mL. GC-MS and UPLC-MS analyses identified various compounds across different categories. Notably, the F2 fraction (methanol and water in ratio of 80:20 as eluting solvent) exhibited the highest glucose uptake activity (156.81% of control), while the F3 fraction (methanol and water in ratio of 70:30 as eluting solvent) fraction demonstrated the highest insulin secretion activity (3.70 folds of the control) among all fractions at 100 µg/mL. GC-MS analysis was employed to characterize both fractions, aiming to identify the compounds contributing to their antidiabetic potential. The study's findings concluded that both seed extracts and their AgNPs possess significant antidiabetic properties, with elevated activity observed in the case of AgNPs in both assays. Various compounds, including diosgenin, oleic acid, linoleic acid and palmitic acid esters were detected in the seed extracts, known for their reported antidiabetic and hypoglycemic effects.

Corrections to "Phytochemical Screening and Antidiabetic Efficacy of Balanites aegyptiaca Seed Extract and Their Silver Nanoparticles on Muscle and Pancreatic Cell Lines".

[This corrects the article DOI: 10.1021/acsomega.4c00327.].

The Neuroimmune Axis and Its Therapeutic Potential for Primary Liver Cancer.

The autonomic nervous system plays an integral role in motion and sensation as well as the physiologic function of visceral organs. The nervous system additionally plays a key role in primary liver diseases. Until recently, however, the impact of nerves on cancer development, progression, and metastasis has been unappreciated. This review highlights recent advances in understanding neuroanatomical networks within solid organs and their mechanistic influence on organ function, specifically in the liver and liver cancer. We discuss the interaction between the autonomic nervous system, including sympathetic and parasympathetic nerves, and the liver. We also examine how sympathetic innervation affects metabolic functions and diseases like nonalcoholic fatty liver disease (NAFLD). We also delve into the neurobiology of the liver, the interplay between cancer and nerves, and the neural regulation of the immune response. We emphasize the influence of the neuroimmune axis in cancer progression and the potential of targeted interventions like neurolysis to improve cancer treatment outcomes, especially for hepatocellular carcinoma (HCC).

Engineered nanomicelles targeting proliferation and angiogenesis inhibit tumour progression by impairing the synthesis of ceramide-1-phosphate.

Tumour cells secrete various proangiogenic factors like VEGF, PDGF, and EGF that result in the formation of highly vascularized tumours with an immunosuppressive tumour microenvironment. As tumour growth and metastasis are highly dependent on angiogenesis, targeting tumour vasculature along with rapidly dividing tumour cells is a potential approach for cancer treatment. Here, we specifically engineered sub-100 sized nanomicelles (DTX-CA4 NMs) targeting proliferation and angiogenesis using an esterase-sensitive phosphocholine-tethered docetaxel conjugate of lithocholic acid (LCA) (PC-LCA-DTX) and a poly(ethylene glycol) (PEG) derivative of an LCA-combretastatin A4 conjugate (PEG-LCA-CA4). DTX-CA4 NMs effectively inhibit the tumour growth in syngeneic (CT26) and xenograft (HCT116) colorectal cancer models, inhibit tumour recurrence, and enhance the percentage survival in comparison with individual drug-loaded NMs. DTX-CA4 NMs enhance the T cell-mediated anti-tumour immune response and DTX-CA4 NMs in combination with an immune checkpoint inhibitor, anti-PDL1 antibody, enhance the anti-tumour response. We additionally showed that DTX-CA4 NMs effectively attenuate the production of ceramide-1-phosphate, a key metabolite of the sphingolipid pathway, by downregulating the expression of ceramide kinase at both transcriptional and translational levels. Therefore, this study presents the engineering of effective DTX-CA4 NMs for targeting the tumour microenvironment that can be explored further for clinical applications.

Proteomic profiling of Arabidopsis G-protein ß subunit AGB1 mutant under salt stress.

Salt stress is a limiting environmental factor that inhibits plant growth in most ecological environments. The functioning of G-proteins and activated downstream signaling during salt stress is well established and different G-protein subunits and a few downstream effectors have been identified. Arabidopsis G-protein ß-subunit (AGB1) regulates the movement of Na+ from roots to shoots along with a significant role in controlling Na+ fluxes in roots, however, the molecular mechanism of AGB1 mediated salt stress regulation is not well understood. Here, we report the comparative proteome profiles of Arabidopsis AGB1 null mutant agb1-2 to investigate how the absence of AGB1 modulates the protein repertoire in response to salt stress. High-resolution two-dimensional gel electrophoresis (2-DE) showed 27 protein spots that were differentially modulated between the control and NaCl treated agb1-2 seedlings of which seven were identified by mass spectrometry. Functional annotation and interactome analysis indicated that the salt-responsive proteins were majorly associated with cellulose synthesis, structural maintenance of chromosomes, DNA replication/repair, organellar RNA editing and indole glucosinolate biosynthesis. Further exploration of the functioning of these proteins could serve as a potential stepping stone for dissection of molecular mechanism of AGB1 functions during salt stress and in long run could be extrapolated to crop plants for salinity stress management.

Emerging concern of nano-pollution in agro-ecosystem: Flip side of nanotechnology.

Nanomaterials (NMs) have proven to be a game-changer in agriculture, showcasing their potential to boost plant growth and safeguarding crops. The agricultural sector has widely adopted NMs, benefiting from their small size, high surface area, and optical properties to augment crop productivity and provide protection against various stressors. This is attributed to their unique characteristics, contributing to their widespread use in agriculture. Human exposure from various components of agro-environmental sectors (soil, crops) NMs residues are likely to upsurge with exposure paths may stimulates bioaccumulation in food chain. With the aim to achieve sustainability, nanotechnology (NTs) do exhibit its potentials in various domains of agriculture also have its flip side too. In this review article we have opted a fusion approach using bibliometric based analysis of global research trend followed by a holistic assessment of pros and cons i.e. toxicological aspect too. Moreover, we have also tried to analyse the current scenario of policy associated with the application of NMs in agro-environment.

Therapeutic potential and pharmacological mechanism of visnagin.

Visnagin is a furanochromone and one of the most important compound in the Ammi visnaga (L.) Lam (a synonym of Visnaga daucoides Gaertn.) plant, which is used to cure various ailments. Many investigations into the bioactive properties of visnagin have been studied to date. The literature on visnagin demonstrates its biological properties, including anti-inflammatory, anti-diabetic, and beneficial effects in cardiovascular and renal diseases. Moreover, visnagin improves sperm quality parameters, stimulates steroidogenesis, and increases serum gonadotropins and testosterone levels, while decreasing pro-inflammatory cytokines, oxidative damage, genomic instability, and it modulates apoptosis. Thus, visnagin has emerged as an exciting lead for further research, owing to its potential in various unmet clinical needs. The current review summarized its basic structure, pharmacokinetics, and pharmacological effects, focusing on its mechanisms of action. The review will help to understand the potential of visnagin as an alternative treatment strategy for several diseases and provide insight into research topics that need further exploration for visnagin's safe clinical use. Please cite this article as: Yadav P, Singh SK, Datta S, Verma S, Verma A, Rakshit A, Bali A, Bhatti JS, Khurana A, Navik U. Therapeutic potential and pharmacological mechanism of visnagin. J Integr Med. 2024; 22(4): 399-412.

Betaine ameliorates doxorubicin-induced cardiomyopathy by inhibiting oxidative stress, inflammation, and fibrosis through the modulation of AMPK/Nrf2/TGF-ß 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-ß 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-ß 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-ß expression. We believe that betaine can be utilized as a potential novel therapeutic strategy for preventing DOX-induced cardiotoxicity.

Engineered nanomicelles inhibit the tumour progression via abrogating the prostaglandin-mediated immunosuppression.

Cancer treatment is challenged due to immunosuppressive inflammatory tumour microenvironment (TME) caused by infiltration of tumour-promoting and inhibition of tumour-inhibiting immune cells. Here, we report the engineering of chimeric nanomicelles (NMs) targeting the cell proliferation using docetaxel (DTX) and inflammation using dexamethasone (DEX) that alters the immunosuppressive TME. We show that a combination of phospholipid-DTX conjugate and PEGylated-lipid-DEX conjugate can self-assemble to form sub-100 nm chimeric NMs (DTX-DEX NMs). Anti-cancer activities against syngeneic and xenograft mouse models showed that the DTX-DEX NMs are more effective in tumour regression, enhance the survival of mice over other treatment modes, and alter the tumour stroma. DTX-DEX NMs cause a significant reduction in myeloid-derived suppressor cells, alter the polarization of macrophages, and enhance the accumulation of cytotoxic CD4+ and CD8+ T cells in tumour tissues, along with alterations in cytokine expression. We further demonstrated that these DTX-DEX NMs inhibit the synthesis of prostaglandins, especially PGE2, by targeting the cyclooxygenase 2 that is partly responsible for immunosuppressive TME. Therefore, this study presents, for the first time, the engineering of lithocholic acid-derived chimeric NMs that affect the prostaglandin pathway, alter the TME, and mitigate tumour progression with enhanced mice survival.

Radiomics-enhanced early regression index for predicting treatment response in rectal cancer: a multi-institutional 0.35 T MRI-guided radiotherapy study.

PURPOSE: The accurate prediction of treatment response in locally advanced rectal cancer (LARC) patients undergoing MRI-guided radiotherapy (MRIgRT) is essential for optimising treatment strategies. This multi-institutional study aimed to investigate the potential of radiomics in enhancing the predictive power of a known radiobiological parameter (Early Regression Index, ERITCP) to evaluate treatment response in LARC patients treated with MRIgRT. METHODS: Patients from three international sites were included and divided into training and validation sets. 0.35 T T2*/T1-weighted MR images were acquired during simulation and at each treatment fraction. The biologically effective dose (BED) conversion was used to account for different radiotherapy schemes: gross tumour volume was delineated on the MR images corresponding to specific BED levels and radiomic features were then extracted. Multiple logistic regression models were calculated, combining ERITCP with other radiomic features. The predictive performance of the different models was evaluated on both training and validation sets by calculating the receiver operating characteristic (ROC) curves. RESULTS: A total of 91 patients was enrolled: 58 were used as training, 33 as validation. Overall, pCR was observed in 25 cases. The model showing the highest performance was obtained combining ERITCP at BED = 26 Gy with a radiomic feature (10th percentile of grey level histogram, 10GLH) calculated at BED = 40 Gy. The area under ROC curve (AUC) of this combined model was 0.98 for training set and 0.92 for validation set, significantly higher (p = 0.04) than the AUC value obtained using ERITCP alone (0.94 in training and 0.89 in validation set). CONCLUSION: The integration of the radiomic analysis with ERITCP improves the pCR prediction in LARC patients, offering more precise predictive models to further personalise 0.35 T MRIgRT treatments of LARC patients.

Out of field scatter from electron applicator in modern linear accelerators.

BACKGROUND: Electron out-of-field scatter is generally not given importance mainly in electron fields. However, this is important when applicator down and boost treatments are given usually at an angle from the central axis. The electron scatter dose is found to be far away from the central axis which could be easily ignored. PURPOSE: This study aims to investigate the out-of-field radiation doses from electron applicators and their effects on clinical treatment. By identifying the parameters that contribute to out-of-field doses and to explore potential strategies for reducing these doses in order to improve patient outcomes from modern machines. METHODS: Measurements were performed in water phantom using electron diode for modern Elekta and Varian machines. Dose profiles were acquired at surface and dmax with 0° and 90° collimation angle. Various gantry angles were also studied for some data with IC Profiler. The profiles were normalized with respect to the central axis dose. RESULTS: The scatter dose peaks were found at a distance between 11 and 28 cm from the central axis on all machines. However, the peak shifts to 15 cm at 90° collimator when beam is tilted. The position and intensity of the dose varies with depth, collimator, and gantry angles for both Elekta and Varian machines. Due to clearance issues more gantry angles were studied for Elekta applicator compared to Varian. In general, Varian TrueBeam has a lower scatter that Elekta Infinity. The 90° collimator angle has a higher scatter compared to zero degree for both machines. CONCLUSIONS: There are clinically significant peripheral doses around 3% of the central axis dose from the electron applicator. Elekta has a slightly higher scatter (3%) than Varian (2%) that peaks at 25 cm which is clinically important but often overlooked.

Sustainable water management in rice cultivation reduces arsenic contamination, increases productivity, microbial molecular response, and profitability.

Arsenic (As) and silicon (Si) are two structurally competitive natural elements where Si minimises As accumulation in rice plants, and based on this two-year field trial, the study proposes adopting alternating wetting and drying (AWD) irrigation as a sustainable water management strategy allowing greater Si availability. This field-based project is the first report on AWD's impact on As-Si distribution in fluvio-alluvial soils of the entire Ganga valley (24 study sites, six divisions), seasonal variance (pre-monsoon and monsoon), rice plant anatomy and productivity, soil microbial diversity, microbial gene ontology profiling and associated metabolic pathways. Under AWD to flooded and pre-monsoon to monsoon cultivations, respectively, greater Si availability was achieved and As-bioavailability was reduced by 8.7 ± 0.01-9.2 ± 0.02% and 25.7 ± 0.09-26.1 ± 0.01%. In the pre-monsoon and monsoon seasons, the physiological betterment of rice plants led to the high rice grain yield under AWD improved by 8.4 ± 0.07% and 10.0 ± 0.07%, proving the economic profitability. Compared to waterlogging, AWD evidences as an optimal soil condition for supporting soil microbial communities in rice fields, allowing diverse metabolic activities, including As-resistance, and active expression of As-responsive genes and gene products. Greater expressions of gene ontological terms and complex biochemical networking related to As metabolism under AWD proved better cellular, genetic and environmental responsiveness in microbial communities. Finally, by implementing AWD, groundwater usage can be reduced, lowering the cost of pumping and field management and generating an economic profit for farmers. These combined assessments prove the acceptability of AWD for the establishment of multiple sustainable development goals (SDGs).

Beam quality correction factors for ionization chambers in a 0.35 T magnetic resonance (MR)-linac - A Monte Carlo study.

PURPOSE: The purpose of this study was to directly calculate [Formula: see text] correction factors for four cylindrical ICs for a 0.35 T MR-linac using the Monte Carlo (MC) method. METHODS: A previously-validated TOPAS/GEANT4 MC head model of the 0.35 T MR-linac was employed. The MR-compatible Exradin A12, A1SL, A26, and A28 cylindrical ICs were modeled considering the dead volume in the air cavity. The [Formula: see text] correction factor was determined for initial electron energies of 5-7 MeV. The correction factor was calculated for all four angular orientations in the lateral plane. The impact of the 0.35 T magnetic field on the IC response was also investigated. RESULTS: The maximum beam quality dependence in the [Formula: see text] exhibited by the A12, A1SL, A26, and A28 ICs was 1.10 %, 2.17 %, 0.81 %, and 1.75 %, respectively, considering all angular orientations. The magnetic field dependence was < 1 % and the maximum [Formula: see text] correction was < 2 % when the detector was aligned along the direction of the magnetic field at 0° and 180° angles. The A12 IC over-responded up to 5.40 % for the orthogonal orientation. An asymmetry in the response of up to 8.30 % was noted for the A28 IC aligned at 90° and 270° angles. CONCLUSIONS: A parallel orientation for the IC, with respect to the magnetic field, is recommended for reference dosimetry in MRgRT. Both over and under-response in the IC signal was noted for the orthogonal orientations, which is highly dependent on the cavity diameter, cavity length, and the dead volume.

Role of buccal fat pad to reduce the chances of re-ankylosis-A systematic review of literature.

The role of buccal fat pad (BFP) as interpositional material in the temporomandibular joint ankylosis (TMJA) have been well documented. The purpose of the present systematic review is to reinforce the role of buccal fat pad as interpositional material in preventing re-ankylosis. A systematic search was conducted in PubMed, Google Scholar, Semantic scholar and Cochrane library database from 1980 to 2022 following the PRISMA guidelines. The studies using BFP as interpositional material in TMJA with more than 10 patients with atleast a follow-up of 6-months were included. All the human studies {prospective, retrospective, case reports/series (with more than 10 subjects), randomized or non-randomized trial) reporting the outcome of BFP as interpositional material were included. The present systematic review included 11 studies (prospective=7, Retrospective=3 and ambispective=1) using BFP as interpositional material. The total number of patients were 205. The number of unilateral TMJA and bilateral TMJA were 153 and 52 respectively, making a number of joint to 257. The distribution of gender was almost equal (few studies did not report the gender distribution). The minimum follow-up was 6-months and extended up to 5.3 years. Out of 205 patients, no re-ankylosis was reported in patients. The authors concluded that the BFP is nearly ideal and a preferred interpositional material to prevent re-ankylosis in temporomandibular joint ankylosis. Its vicinity to TMJ, ease of harvesting through the same surgical site and avoiding other scar makes it a preferred interpositional material in TMJA cases.

Betaine alleviates doxorubicin-induced nephrotoxicity by preventing oxidative insults, inflammation, and fibrosis through the modulation of Nrf2/HO-1/NLRP3 and TGF-ß expression.

Doxorubicin (Dox) is an anthracycline antibiotic used to treat various cancers and shows severe toxicity in multiple organ systems, including kidneys. Evidence shows that betaine's antioxidant and anti-inflammatory properties could prevent the onset of several disorders. Hence, the present study aims to investigate the therapeutic potential of betaine on Dox-induced nephrotoxicity (DIN). Nephrotoxicity was induced in male Sprague Dawley rats using Dox at a dose of 4 mg/kg (cumulative dose: 20 mg/kg) by the intraperitoneal route and cotreated with betaine through oral gavage (200 and 400 mg/kg) for 28 days. At the end of the experiment, biochemical, oxidative stress parameters, histopathology, and qRT-PCR were performed. DIN was indicated by elevated serum creatinine, urea, and decreased albumin levels representing kidney damage; the histopathological lesions (increased capsular space, renal tubule damage, and fibrosis) in renal tissues supported these biochemical findings. Interestingly, betaine treatment improves these alterations in Dox-treated rats. Further, betaine treatment decreases the lipid peroxidation and nitrite concentration and increases the superoxide dismutases and catalase enzyme concentration in Dox-treated rats. Fascinatingly, at the molecular level, DIN in rats shows upregulation of the Nrf2/HO-1 gene, while betaine treatment attenuated its expression along with the downregulation of inflammatory genes (NLRP3, TLR-4, TNF-α, and IL-6) and fibrosis-related genes (TGF-ß and Acta2) expression in Dox-treated rats. These results showed that betaine has reno-protective properties by reducing inflammatory and fibrotic mediators and enhancing antioxidant capacity in the renal tissue of rats treated with Dox. We believe betaine can be exploited as a dietary supplement to attenuate DIN.

Characteristics of a plastic scintillation detector in photon beam dosimetry.

BACKGROUND: Plastic scintillating detectors (PSD) have gained popularity due to small size and are ideally suited in small-field dosimetry due to no correction needed and hence detector reading can be compared to dose. Likewise, these detectors are active and water equivalent. A new PSD from Blue Physics is characterized in photon beam. PURPOSE: Innovation in small-field dosimetry detector has led us to examine Blue Physics PSD (BP-PSD) for use in photon beams from linear accelerator. METHODS: BP-PSD was acquired and its characteristics were evaluated in photon beams from a Varian TrueBeam. Data were collected in a 3D water tank. Standard parameters; dose, dose rate, energy, angular dependence and temperature dependence were studied. Depth dose, profiles and output in a reference condition as well as small fields were measured. RESULTS: BP-PSD is versatile and provides data very similar to an ion chamber when Cerenkov radiation is properly accounted. This device measures data pulse by pulse which very few detectors can perform. The differences between ion chamber data and PSD are < 2% in most cases. The angular dependence is a bit pronounces to 1.5% which is due to PSD housing. Depth dose and profiles are comparable within < 1% to an ion chamber. For small fields this detector provides suitable field output factor compared to other detectors and Monte Carlo (MC) simulated data without any added correction factor. CONCLUSIONS: The characteristics of Blue Physics PSD is uniquely suitable in photon beam and more so in small fields. The data are reproducible compared to ion chamber for most parameters and ideally suitable for small-field dosimetry without any correction factor.