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There are several interactions between thyroid hormones (THs) and kidney and heart function. Consequently, THs deficit results in profound changes in renal and cardiac function regulation. Interestingly, emerging evidence suggests that vitamin D (Vit D) may benefit to fibrotic lesions in various tissues. Herein, this study was designed to investigate the potential impact of Vit D on renal and cardiac fibrosis in hypothyroid rats. Forty male Wistar rats were divided into four groups as follow: control, hypothyroid (0.05% PTU in drinking water), and hypothyroid + Vit D (PTU and doses of 100 or 500 IU/kg/day, by gavage) groups. After 6 weeks, biochemical parameters such as creatinine and urea in serum samples, and oxidative stress markers including malondialdehyde (MDA), total thiol groups, and superoxide dismutase (SOD) in renal and cardiac tissues homogenate were measured. Also, renal and cardiac fibrosis was evaluated histologically using Masson's trichrome staining. Hypothyroidism significantly increased creatinine and urea. Also, in hypothyroid group renal and cardiac fibrosis as well as MDA were increased, while anti-oxidative markers including total thiol group and SOD were decreased. Administration of Vit D significantly improved these alterations in oxidative stress markers and fibrosis in renal and cardiac tissues. In conclusion, this study highlighted that Vit D supplementation reduced renal and cardiac fibrosis and improved oxidative stress. These results support the emerging experimental findings linking Vit D being introduced as a potential therapeutic agent., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The prevalence of cardiovascular events, stroke, and diabetes worldwide underscores the urgent need for effective and minimally invasive treatments. With nearly 20 million annual casualties attributed to cardiovascular diseases and an estimated 463 million people living with diabetes in 2022. Identifying promising therapeutic candidates is paramount. MicroRNAs, short nucleic acids involved in regulating gene expression, emerge as potential game-changers. Among these, microRNA-24 (miR-24), a hypoxia-sensitive player in endothelial vessels, has protective roles against diverse vascular complications. Following heart infarction and stroke, elevating miR-24 expression proves beneficial by mitigating oxidative stress, inflammation, and apoptosis while enhancing cell survival. It reduces cardiac fibrosis in heart disease, regulates aberrant angiogenesis in cerebral hemorrhagic strokes, and enhances the functionality of cardiomyocytes and brain neurons. In diabetic conditions, augmenting miR-24 expression mitigates complications. Further, being miR-24 also expressed by the skeletal muscle (i.e., myo-miR) in response to exercise, this miRNA may participate in the complex molecular network that systemically spreads the beneficial effects of physical exercise. This review provides a comprehensive vision of the molecular mechanisms underpinning the miR-24 protective effects, offering new insights into its therapeutic potential and proposing a novel avenue for medical intervention., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Glioblastoma multiforme (GBM) is a malignant tumor of the brain that is considered to be incurable. Currently, surgical removal of tumors, chemotherapy with temozolomide, and radiation treatment remain established options for treatment. Nevertheless, the prognosis of those with GBM continues to be poor owing to the inherent characteristics of tumor growth and spread, as well as the resistance to treatment. To effectively deal with the present circumstances, it is vital to do extensive study to understand GBM thoroughly. The following piece provides a concise overview of the most recent advancements in using valproic acid, an antiseizure medication licensed by the FDA, for treating GBM. In this review, we outline the most recent developments of valproic acid in treating GBM, as well as its fundamental mechanisms and practical consequences. Our goal is to provide a greater understanding of the clinical use of valproic acid as a potential therapeutic agent for GBM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Silicon dioxide nanoparticles (SiO 2 -NPs) can be found in many products, such as composites, paints, ceramics, consumer products, and food additives. We recently demonstrated that via breastfeeding, SiO 2 -NPs transfer to the offspring's brain, interfering negatively with hippocampus development. In this work, we evaluated the protective effect of grape seed extract (GSE) against the adverse effects of SiO 2 -NPs. After delivery, animals were administered 25 mg/kg SiO 2 -NPs with/without GSE (300 mg/kg) for 20 days (from 2nd to 21st days post-delivery) by gavage. SiO 2 -NPs increased malondialdehyde concentration and decreased antioxidant activity in the offspring's hippocampi. The mean number of dark neurons (DNs) was significantly higher in the hippocampi of the SiO 2 -NPs group, whereas the mean number of DCX + cells was significantly lower than in the control group. The offspring in the SiO 2 -NPs groups had a weak cognitive performance in adulthood. Interestingly, these adverse effects of SiO 2 -NPs were alleviated in the GSE-treated groups. Therefore, GSE can attenuate the damaging effects of maternal exposure to SiO 2 -NPs during lactation., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Evidence declared lipopolysaccharide (LPS) initiates inflammatory responses by stimulating the abandon of cytokines, which may perturb organ function. On the other side, it has been suggested Cedrol has potential properties, including anti-inflammatory and anti-oxidative activities. Herein, this study was done to assess the protective effect of Cedrol against LPS-associated heart damage., Methods: Thirty-five rats (200-250 g) were sorted into five groups, including control, LPS, LPS-Cedrol 7.5 mg/kg, LPS-Cedrol 15 mg/kg, and LPS-Cedrol 30 mg/kg groups. Cedrol was administrated through injected intra-peritoneally for two weeks. The heart tissues were removed and malondialdehyde (MDA) as a lipid peroxidation marker, superoxide dismutase (SOD), and catalase (CAT) as antioxidant markers were assessed. Furthermore, the interleukin (IL)-6 level in cardiac tissue was measured and Masson's trichrome methods were employed to appraise cardiac inflammation and fibrosis, respectively., Results: Inflammation induced by LPS was significantly accompanied by myocardial fibrosis which was shown by Masson's trichrome staining ( P <0.001). In addition, LPS administration enhanced the MDA level while it diminished the activity of anti-oxidant markers such as CAT and SOD ( P <0.001 for all cases). In the histological results, Cedrol improved LPS-induced inflammation and cardiac fibrosis ( P <0.01 to P <0.001). Cedrol also enhanced CAT and SOD activities, whereas declined MDA level in the cardiac tissue ( P <0.01 to P <0.001)., Conclusion: The current findings proposed that the administration of Cedrol exerted a protective role in LPS-associated heart damage by reducing inflammation, cardiac fibrosis, and oxidative stress., Competing Interests: The authors asserted no conflicts of interest relating to the research and/or publication of this work., (© 2024 The Author(s).)

There is a complex correlation between thyroid hormones (THs) and liver function. Hypothyroidism as a failure of the thyroid gland to produce adequate thyroid hormones to fulfill the metabolic requirements of the body, may perturb liver structure and function. Emerging evidence suggests the protective effects of vitamin D against liver damage. Herein, this study aimed to investigate the role of vitamin D in hypothyroidism-associated liver injury. Forty male Wistar rats were classified into 4 groups: control, hypothyroid (Hypo) group received 0.05% PTU, Hypo- Vitamin D groups were given 100 and 500 IU/kg vitamin D orally via gavage for 6 weeks. Serum level of liver function including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were measured. Malondialdehyde (MDA) level, superoxide dismutase (SOD) enzyme activity, and total thiol content were measured as oxidative stress indicators in the liver tissue. Furthermore, to estimate liver tissue fibrosis, Masson's trichrome staining was done. Our findings showed that hypothyroidism-induced liver fibrosis was associated with increased levels of ALT, AST and ALP. Though, vitamin D administration could significantly reduce the ALT, AST and ALP in the serum and suppress the accumulation of collagen fibers. Moreover, the activity of SOD and total thiol content was notably reduced, while the MDA content was significantly increased in the PTU- induced hypothyroid rats compared to the control group. Nonetheless, treatment with vitamin D improved mentioned oxidative stress markers in the Hypo-vitamin D groups. In conclusion, vitamin D due to its potential antioxidant and anti-fibrotic properties could be effective in the decrease of hypothyroidism-associated liver injury., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Stroke is a leading cause of death and disability worldwide. It is among the most common neurological disorders with an 8-10% lifetime risk. Ischemic stroke accounts for about 85% of all strokes and damages the brain tissue via various damaging mechanisms. Following cerebral ischemia, the disrupted blood-brain barrier (BBB) leads to cerebral edema formation caused by activation of oxidative stress, inflammation, and apoptosis, targeting primarily endothelial cells. Activation of the protective mechanisms might favor fewer damages to the neural tissue. MicroRNA (miR)-126 is an endothelial cell-specific miR involved in angiogenesis. MiR-126 orchestrates endothelial progenitor cell functions under hypoxic conditions and could inhibit ischemia-induced oxidative stress and inflammation. It alleviates the BBB disruption by preventing an augment in matrix metalloproteinase level and halting the decrease in the junctional proteins, including zonula occludens-1 (ZO-1), claudin-5, and occludin levels. Moreover, miR-126 enhances post-stroke angiogenesis and neurogenesis. This work provides a therapeutic perspective for miR-126 as a new approach to treating cerebral ischemia., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neuroinflammation plays a crucial role in the development and progression of neurological disorders. MicroRNA-155 (miR-155), a miR is known to play in inflammatory responses, is associated with susceptibility to inflammatory neurological disorders and neurodegeneration, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis as well as epilepsy, stroke, and brain malignancies. MiR-155 damages the central nervous system (CNS) by enhancing the expression of pro-inflammatory cytokines, like IL-1β, IL-6, TNF-α, and IRF3. It also disturbs the blood-brain barrier by decreasing junctional complex molecules such as claudin-1, annexin-2, syntenin-1, and dedicator of cytokinesis 1 (DOCK-1), a hallmark of many neurological disorders. This review discusses the molecular pathways which involve miR-155 as a critical component in the progression of neurological disorders, representing miR-155 as a viable therapeutic target., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Numerous studies in humans and animals hypothesize that gut microbiota dysbiosis is involved in the development of behavioral and neurological diseases such as depression, autism spectrum disorder, Parkinson disease, multiple sclerosis, stroke and Alzheimer's disease. Some of the most salient works so far regarding the brain-gut axis are mentioned below. The current knowledge on the impact of gut microbiota on nervous system diseases is far from being directly used for pharmacologic or nutritional advice toward restoration of normal bodily functions. It seems that a more comprehensive approach should be followed so that the individual effect of each kind of intervention on the patient's somatic or psychological status is determined. Future research must address global need for regimens which could reestablish normal composition of gut microorganisms after each neuropsychological disorder., Competing Interests: Conflict of interest The authors declared no conflict of interest., (Copyright© 2023 Iranian Neuroscience Society.)

The current study was designed to investigate the protective effects of Vitamin D (VD) on hippocampal neurogenesis, apoptosis, and subsequent hippocampal-dependent learning and memory performance in hypothyroid juvenile rats. Twenty eight male Wistar rats were randomly divided into four groups as; control, Hypothyroid (Hypo), Hypo-VD100 and Hypo-VD500. Hypothyroidism was induced by giving 0.05 % propylthiouracil (PTU), and VD (100 or 500 IU/kg) treatment was performed daily by gavage. At the end of treatment, Morris water maze (MWM) was carried out and evaluated hippocampal neurogenesis, apoptosis, and dark neurons (DNs). Our results revealed that the escape latency and the traveled distance to find the platform in the Hypo group were significantly longer but the time spent and distance traveled in the target area in probe trial was lower than the control group. Hypothyroidism was accompanied by a marked decrease in hippocampal neurogenesis, and a significant increase in the number of apoptotic neurons and DNs compared to the control group. VD decreased escape latency and the traveled distance to find the platform but increased the time spent and distance traveled in the target area in probe trial than the Hypo group. VD also increased neurogenesis, reduced apoptosis and DNs production compared to the Hypo group. In conclusion, these results support a role for VD in the restoring hippocampal neurogenesis impairment, reducing neuronal apoptosis, and DNs in hypothyroid rats as well as raise the possibility that VD may contribute as a therapeutic approach to improve the learning and memory deficits associated with hypothyroidism., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Spinal cord injury (SCI) is a devastating neurological state causing physical disability, psychological stress and financial burden. SCI global rate is estimated between 250,000 and 500,000 individuals every year, of which 60% of victims are young, healthy males between 15 and 35 years. A variety of pathological conditions such as neuroinflammation, mitochondrial dysfunction, apoptosis, glial scar formation, blood-spinal cord barrier disruption, and angiogenesis disruption occur after SCI leading to a limitation in recovery. MicroRNAs (miRs) are endogenous and non-coding RNAs consisting of 22 nucleotides that regulate 60% of all human genes and involve several normal physiological processes and pathological conditions. miR-21 is among the most highly expressed miRs and its expression has been shown to increase one day after SCI and this elevation is sustained up to 28 days after injury. Overexpression of miR-21 exerts many protective effects against SCI by inhibiting neuroinflammation, improving blood-spinal cord barrier function, regulating angiogenesis, and controlling glial scar formation. It also exhibits anti-apoptotic effects in SCI by down-regulating the expression of PTEN, Spry2, and PDCD4. This review provides a novel therapeutic perspective for miR-21 in SCI., (© 2022. The Author(s).)

Background: During the elderly, hippocampal neurogenesis and synaptogenesis reduce and dark neurons (DNs) increase, leading to cognitive impairment. It is believed that natural products can protect the neural cells and system by protecting from damages or promoting regeneration. Therefore, the effects of grape seed extract (GSE) on the hippocampus of aged mice were investigated in this study., Methods: twelve old mice were divided into two groups of control and GSE. Animals in the GSE group received 300 mg/kg of GSE for eight weeks via gavage. At the end of treatment, cognition performance was evaluated by Morris water maze (MWM) and passive avoidance tests. Hippocampal neurogenesis, synaptogenesis and DNs production were evaluated with immunohistochemistry and histological evaluations on 5-micron coronal tissue sections., Results: The hippocampal mean number of double cortin positive cells (DCX + ) per unit area, as well as synaptophysin expression in the GSE group, were significantly higher than the control group ( p  < 0.01). The frequency of DNs in the GSE group was lower than the control group ( p  < 0.05). Behavioral tests showed that GSE improves memory and learning performance., Conclusion: Consuming GSE in the elderly can potentially alleviate the age-related reduction of hippocampal neurogenesis and synaptogenesis. It is also able to decrease hippocampal DNs production and increase memory and learning.

MicroRNAs (miRs) are regulatory RNAs with 18-25 nucleotides lengths involved in various biological processes. Some miRs, including miR-22, play an essential role in regulating neurological disorders. MiR-22 is a brain-enriched regulatory element involved in angiogenesis, energy supply, adjustment of ionic channels, and suppression of malignant cell proliferation, migration, and invasion. This article discusses the protective and therapeutic effects of miR-22 on neurological diseases and injuries, including cerebral ischemia, neurodegenerative diseases, epilepsy, and brain malignancies. We also correlated miR-22 with amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), panic disorders, schizophrenia, neural tube defect (anencephaly), and traumatic brain injury. This work provides a therapeutic perspective for miR-22 as a new approach in treating neurological disorders., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Nano selenium (Nano Sel) has many therapeutic properties including antioxidant, anticancer, and anti-inflammatory actions., Objective: Impacts of Nano Sel administration against cardiac fibrosis and heart and aorta tissue oxidative damage observed in hypothyroid rats were explored., Methods: The animals were randomly grouped and treated as: 1) Control; 2) Propylthiouracil (PTU) in which PTU was added to the drinking water (0.05%) to induce hypothyroidism; 3-5) PTU-Nano Sel 50, PTU-Nano Sel 100, and PTU-Nano Sel 150 groups, which received daily PTU plus 50,100 or 150 µg/kg of Nano Sel for 6 weeks intraperitoneally. The heart and aorta tissues were removed under deep anesthesia and then biochemical parameters including malondialdehyde (MDA), total thiol groups, catalase (CAT), and superoxide dismutase (SOD), as well as cardiac fibrosis were assessed., Results: Hypothyroidism induced by PTU was remarkably associated with myocardial hypertrophy and perivascular fibrosis in Masson's trichrome staining. Moreover, hypothyroidism increased MDA level, while it subtracted total thiol group content and activity of SOD and CAT. Treatment with Nano Sel recovered hypothyroidism-induced cardiac fibrosis in the histological assessment. Nano Sel also promoted CAT and SOD activity and thiol content, whereas alleviated MDA levels in the heart and aorta tissues., Conclusion: Results propose that administration of Nano Sel exerts a protective role in the cardio vascular system via preventing cardiac fibrosis and inhibiting oxidative stress.

Apart from a role as a key regulator of calcium/phosphate homeostasis, vitamin D (Vit D) is suggested to be a potential player in nervous system growth and function. This study aimed to assess the impacts of Vit D administration on memory impairment, oxidative damage, and acetylcholinesterase (AchE) overactivity in hypothyroid juvenile rats. The animals were randomly grouped as (1) Control; (2) Hypothyroid; (3) Hypothyroid-Vit D100, and (4) Hypothyroid-Vit D 500. Propylthiouracil (PTU) was added to their drinking water (0.05%) for 6 weeks, and Vit D (100 or 500 IU/kg) treatment was performed daily by gavage. Morris water maze (MWM) and passive avoidance (PA) tests were performed. The brains were removed under deep anesthesia, then the hippocampal and cortical tissues were separated to assess biochemical parameters. Hypothyroidism was significantly associated with learning and memory impairment in MWM and PA tests. Hypothyroidism was also accompanied by an elevation in AChE activity and malondialdehyde (MDA) content and a reduced level of thiol content and superoxide dismutase (SOD) activity in the brain. Treatment with Vit D recovered hypothyroidism-induced cognitive impairment and improved memory performance in MWM and PA tasks. On the other hand, Vit D alleviated AChE activity and MDA level, whereas increased SOD activity and thiol content in the hippocampal and cortical tissues. In conclusion, these outcomes suggest an association between the oral administrations of Vit D and learning and memory improvement of hypothyroid rats, which was accompanied by decreasing AChE activity and brain tissue oxidative damage., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Implicit (unconscious) and explicit (strategy) processes have been shown to contribute to visuomotor adaptation. Current methods, such as the Process Dissociation Procedure (PDP) and the Verbal Report Framework (VRF), simultaneously evaluate both implicit and explicit contributions to visuomotor adaptation. It is unclear whether the act of assessing explicit adaptation leads to variations in the magnitude of implicit adaptation observed. To address this question, four groups of participants adapted their reaches to a 40° clockwise visuomotor rotation. Implicit and explicit adaptation were assessed in a PDP-IE group and a VRF-IE group following 3 blocks of rotated reach training trials. In contrast, only implicit adaptation was assessed at the same time points for a PDP-I group and VRF-I group. Results indicated a similar magnitude of implicit adaptation regardless of whether explicit adaptation was assessed or not. Thus, assessing explicit adaptation simultaneously with implicit adaptation following reach adaptation does not influence the magnitude of implicit adaptation established via the PDP and VRF methods., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Silicon dioxide nanoparticles (SiO 2 -NPs) are among the most widely used nanoparticles because of their chemical-physical properties. Since most brain maturation occurs in the neonatal period in humans and many mammals, it is important to understand how NPs may affect this process. This study tested the hypothesis that SiO2-NPs from treated dams could affect the hippocampus of neonatal rats during lactation. Twenty-four pregnant rats, after delivery, were divided into three groups of control, SiO 2 -NPs (25 mg/kg) and SiO 2 -NPs (100 mg/kg). The rats were treated from 2 nd to 21 st days post-delivery by gavage and the effects of these NPs were evaluated in the offspring's hippocampi to reveal the effects of maternal exposure to SiO 2 -NPs during lactation on the offspring's hippocampi. The offspring in the SiO 2 -NPs groups had higher malondialdehyde concentration and lower antioxidant activity in the hippocampi than the non-treated control group. The mean number of doublecortin positive (DCX + ) cells and synaptophysin expression in the hippocampi of the SiO 2 -NPs groups were significantly lower than the control group, whereas the mean number of dark neurons was significantly higher. Also, animals in the SiO 2 -NPs groups had a weak cognitive performance in adulthood. In conclusion, maternal exposure to SiO 2 -NPs via breastfeeding could affect offspring's hippocampal neurogenesis and synaptogenesis, leading to impaired cognitive performance.

Lanthanum nanoparticles are widely used in industry, agriculture, and biomedicine. Over 900 kg of lanthanum is annually released into the environment only in Europe, 50 times higher than the metals, mercury, and cadmium's environmental spread. Human health risk associated with long-term exposure to the abundant lanthanum nanoparticles is a concerning environmental issue. Due to lanthanum's ability to disrupt the main biological barriers and interrupt various cells' hemostasis, they seem to cause severe disruptions to various tissues. This review opens a new perspective regarding the cellular and molecular interaction of nanosized and ionic lanthanum with the possible toxicity on the nervous system and other tissues that would show lanthanum nanoparticles' potential danger to follow in toxicological science.

Purpose: To determine whether rectal displacement devices (RDDs) have a prostate-stabilizing effect during prostate external beam radiotherapy (EBRT)., Methods: A systematic literature search using the PubMed database from January 1, 2000 to December 30th, 2019 was conducted. The effect of RDDs on inter- and intra-fractional prostate displacements was extracted., Results: From 356 articles identified via the PubMed database and hand search, 21 articles were included in the systematic review. There was no randomized study. Twelve studies evaluated the role of the endorectal balloon (ERB) in managing prostate motion. Four studies reported the effect of hydrogel spacer on prostate motion. Four studies examined the effect of the rectal retractor (RR) on intra-fractional prostate motion, and only one study assessed the impact of ProSpare (Nottinghamshire, UK) in reducing prostate motion., Conclusion: Using an ERB significantly reduces intra-fractional prostate motion. This prostate-stabilizing effect of the ERB can translate into reduced planning target volume (PTV) margins and additional rectal dose sparing. Even with an ERB in place, inter-fractional prostate displacements are seen. As a consequence, ERB application does not obviate daily verification; however, this is not a crucial topic because pretreatment imaging is always done nowadays. As compared with ERB, the hydrogel spacer significantly reduces rectal dose and toxicity without influencing prostate immobilization. The RR can increase prostate and rectal inter- and intra-fractional stability without a clear influence on the reduction of rectal toxicity. Finally, it is unclear whether ProSpare is a suitable device reducing prostate motion. Further study will be required to clarify whether the prostate-stabilizing effects of the ERB and RR can result in a safe reduction of PTV margins and further sparing of organs at risks, especially the rectum.

Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are elucidated as cells that can perpetuate themselves via autorestoration. These cells are highly resistant to current therapeutic approaches and are the main reason for cancer recurrence. Radiotherapy has made a lot of contributions to cancer treatment. However, despite continuous achievements, therapy resistance and tumor recurrence are still prevalent in most patients. This resistance might be partly related to the existence of CSCs. In the present study, recent advances in the investigation of different biological properties of CSCs, such as their origin, markers, characteristics, and targeting have been reviewed. We have also focused our discussion on radioresistance and adaptive responses of CSCs and their related extrinsic and intrinsic influential factors. In summary, we suggest CSCs as the prime therapeutic target for cancer treatment., (© 2019 Wiley Periodicals, Inc.)

Purpose: Radiomic features, clinical and dosimetric factors have the potential to predict radiation-induced toxicity. The aim of this study was to develop prediction models of radiotherapy-induced toxicities in prostate cancer patients based on computed tomography (CT) radiomics, clinical and dosimetric parameters., Methods: In this prospective study, prostate cancer patients were included, and radiotherapy-induced urinary and gastrointestinal (GI) toxicities were assessed by Common Terminology Criteria for adverse events. For each patient, clinical and dose volume parameters were obtained. Imaging features were extracted from pre-treatment rectal and bladder wall CT scan of patients. Stacking algorithm and elastic net penalized logistic regression were used in order to feature selection and prediction, simultaneously. The models were fitted by imaging (radiomics model) and clinical/dosimetric (clinical model) features alone and in combinations (clinical-radiomics model). Goodness of fit of the models and performance of classifications were assessed using Hosmer and Lemeshow test, - 2log (likelihood) and area under curve (AUC) of the receiver operator characteristic., Results: Sixty-four prostate cancer patients were studied, and 33 and 52 patients developed ≥ grade 1 GI and urinary toxicities, respectively. In GI modeling, the AUC for clinical, radiomics and clinical-radiomics models was 0.66, 0.71 and 0.65, respectively. To predict urinary toxicity, the AUC for radiomics, clinical and clinical-radiomics models was 0.71, 0.67 and 0.77, respectively., Conclusions: We have shown that CT imaging features could predict radiation toxicities and combination of imaging and clinical/dosimetric features may enhance the predictive performance of radiotoxicity modeling.

The objective of this study was to estimate heritability as well as genetic and environmental relationships between days to first heat (DFH), days to first service (DFS), interval from calving to conception (ICC), calving interval (CI) and number of inseminations per conception (NIS) with mastitis (Mast), number of mastitis occurrence (NumMast), different measures of somatic cell count (SCC) and fat to protein ratio (F:P) in the first lactation of Holstein cows in Iran using linear and threshold animal and sire models. The 33851 first lactation records of Holstein cows from five large dairy herds with calving dates from March 2002 to September 2014 were analyzed with univariate and bivariate linear and threshold animal and sire models using Gibbs sampling methodology. Data from parity one to nine comprising 62483 records were used to conduct repeatability model analysis for reproductive traits. Heritabilities of the reproduction traits varied from 0.067 (for ICC) to 0.105 (for DFH) using linear animal models. Also, the heritabilities of udder health traits varied from 0.005 to 0.102 using different models. The repeatabilities of reproductive traits ranged from 0.110 to 0.307. In general, the genetic correlations (r g ) between reproduction traits were positive and high (with the exception of r g between DFH-NIS). The r g between reproduction traits with udder health traits ranged from -0.029 to 0.359 and 0.151 to 0.584 using linear-linear and threshold-linear animal models, respectively. Generally, there was favorable r g between reproduction traits with udder health traits; therefore, selection for one set of these traits would improve the correlated traits. However, due to different (co)variance components and economic weights in each country/region, it can be recommended to investigate inclusion of both sets of these traits in breeding objectives., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The objective of this study was to establish different single or multiple trait selection indices to calculate genetic and economic gains by combining some production, reproduction and udder health traits in a population similar to the overall practical situation in Iran, with and without imposing restrictions on genetic change for some traits. The SelAction software was used to perform the analyses based on selection index theory through a deterministic model. Results indicated that among established indices, the index that showed the highest genetic gain for milk yield did not maximize the total genetic and economic gains. Rather, the index that included all production, reproduction and udder health traits yielded the highest genetic and economic gains. When we placed restriction on the selection indices, the economic gain decreased and the amount of reduction depended on the heritability and the correlation of restricted trait(s) with other traits. Generally, regarding the economic genetic gain per generation, the indices based on records of 200 offspring were 4.819% more efficient than those that used information of 100 offspring.

Heat shock proteins (HSPs), well-known in respond to various kinds of stress situations, have been widely studied in Drosophila. However, a few reports related to silkworm bombyx mori. Genetic and non-genetic factors affecting on the expression of some HSPs in heat-treated silkworm were studied at the present paper. The mRNA levels of HSPs were quantified by real-time quantitative RT-PCR method and compared with their expression in the proteome profiles. The results showed up-regulation of two small heat shock proteins (sHSPs), HSP19.9 and HSP20.4 and down-regulation of HSP70 in the fat body, testis and ovary of heat exposed larvae. Higher variation of the sHSPs than HSP70 was observed in the different conditions such as heat exposures and genetic backgrounds. Significant difference in the HSP19.9 expression between two breeds was observed which implied the importance of this gene in the genetic differences. There was significant difference between responses of severe and mild heat shocks after 4 h heat recovery. The HSPs expression in male was significantly higher than that in female silkworm larva for all transcript measurements (P < 0.001). Comparison of two methods of quantification showed a fair similarity between HSPs expression in the transcriptome and proteome levels. Nistari breed as a naturally thermo-tolerant breed was expressed lower HSPs than a thermo-sensitive breed.

Insect head is comprised of important sensory systems to communicate with internal and external environment and endocrine organs such as brain and corpus allatum to regulate insect growth and development. To comprehensively understand how all these components act and interact within the head, it is necessary to investigate their molecular basis at protein level. Here, the spectra of peptides digested from silkworm larval heads were obtained from liquid chromatography tandem mass spectrometry (LC-MS/MS) and were analyzed by bioinformatics methods. Totally, 539 proteins with a low false discovery rate (FDR) were identified by searching against an in-house database with SEQUEST and X!Tandem algorithms followed by trans-proteomic pipeline (TPP) validation. Forty-three proteins had the theoretical isoelectric point (pI) greater than 10 which were too difficult to separate by two-dimensional gel electrophoresis (2-DE). Four chemosensory proteins, one odorant-binding protein, two diapause-related proteins, and a lot of cuticle proteins, interestingly including pupal cuticle proteins were identified. The proteins involved in nervous system development, stress response, apoptosis and so forth were related to the physiological status of head. Pathway analysis revealed that many proteins were highly homologous with the human proteins which involved in human neurodegenerative disease pathways, probably implying a symptom of the forthcoming metamorphosis of silkworm. These data and the analysis methods were expected to be of benefit to the proteomics research of silkworm and other insects.

Embryonic development of silkworm, Bombyx mori is a process of systematical expression of genes and proteins which is dominated by complex regulatory networks. To gain comprehensive insight into the molecular basis of embryonic development and its regulation mechanisms, the proteome profile of the B. mori embryos at the end of organogenesis (tubercle appearance stage, TA) was characterized using LTQ-Orbitrap mass spectrometer. Totally 963 proteins were identified with a false discovery rate (FDR) of 0.12%. They were involved in embryonic development, chemoreception, and stimuli response and so forth. The proteins with the largest number of identified unique peptides, implying their possibly higher abundance, were involved in heat shock response, lipid transport and metabolism, and apoptosis. It was consistent with the physiological status of embryo at the end of organogenesis. Many functionally important proteins were identified for the first time in B. mori embryo such as the progesterone receptor membrane component 2, antennal binding protein, sericotropin, and molting fluid carboxypeptidase A (MF-CPA). 253 (26.27%) specific proteins in TA versus labrum appearance stage (LA, four days before TA) embryos were identified, which were mainly associated with musculature, nervous system, and chemoreception system. They disclosed the differential temporal and spatial expression of proteins in the process of organogenesis. The relative mRNA levels of fifteen identified proteins in the two experimented stages were also compared using quantitative reverse transcription PCR (qRT-PCR) and showed some inconsistencies with protein expression. Gene Ontology (GO) annotation of the identified proteins showed that the most proteome representations were in the categories of "binding" and "catalytic" in molecular function, and "cellular process" and "metabolic process" in biological process., (Copyright (c) 2010 Elsevier Ltd. All rights reserved.)

Background and the Purpose of the Study: Aging is the major risk factor for neurodegenerative diseases and oxidative stress is involved in the pathophysiology of them. Oxidative stress can induce neuronal damages and modulate intracellular signaling, ultimately leading to neuronal death by apoptosis or necrosis. In this study, the possible antioxidant and neuroprotective properties of the natural polyphenolic antioxidant compound, curcumin against homocysteine (Hcy) neurotoxicity was investigated., Methods: Curcumin (5, 15, 45 mg/kg) was injected intraperitonealy (i.p.) once daily for a period of 10 days beginning 5 days prior to Hcy (0.2 µmol/µl) intracerebroventricular (i.c.v) injection in rats. Biochemical and behavioral studies, including passive avoidance learning and locomotor activity tests were studied 24 hrs after the last curcumin or its vehicle injection. The cell density of hippocampus layers and apoptosis in rats' hippocampi by immunohistochical methods were also studied., Results and Major Conclusion: Results indicated that Hcy could induce lipid peroxidation and increase Malondialdehyde (MDA) and Super Oxide Anion (SOA) levels in rat's brain. Additionally, Hcy impaired memory retention in passive avoidance learning test. However, curcumin decreased MDA and SOA levels significantly and improved learning and memory in rats. On the other hand Hcy could induce cell death and apoptosis in rats' hippocampi which was inhibited by curcumin. These results suggest that Hcy may induce lipid peroxidation in rat's brain. and polyphenol treatment (curcumin) improves learning and memory deficits by protecting the nervous system against Oxidative stress.

The shotgun approach has gained considerable acknowledgement in recent years as a dominant strategy in proteomics. We observed a dramatic increase of specific protein spots in two-dimensional electrophoresis (2-DE) gels of the silkworm (Bombyx mori) embryo at labrum appearance, a characteristic stage during embryonic development of silkworm which is involved with temperature increase by silkworm raiser. We employed shotgun liquid chromatography tandem mass spectrometry (LC-MS/MS) technology to analyse the proteome of B. mori embryos at this stage. A total of 2168 proteins were identified with an in-house database. Approximately 47% of them had isoelectric point (pI) values distributed theoretically in the range pI 5-7 and approximately 60% of them had molecular weights of 15-45 kDa. Furthermore, 111 proteins had an pI greater than 10 and were difficult to separate by 2-DE. Many important functional proteins related to embryonic development, stress response, DNA transcription/translation, cell growth, proliferation and differentiation, organogenesis and reproduction were identified. Among them proteins related to nervous system development were noticeable. All known heat shock proteins (HSPs) were detected in this developmental stage of B. mori embryo. In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed energetic metabolism at this stage. These results were expected to provide more information for proteomic monitoring of the insect embryo and better understanding of the spatiotemporal expression of genes during embryonic developmental processes.

Three organs of silkworm larva endocrine system, including brain (Br), subesophageal ganglion (SG) and prothoracic glands (PG), were studied employing shotgun LC-MS/MS combined with bioinformatic analysis to comprehensively understand their roles and relations. Totally, 3430, 2683, and 3395 proteins were identified including 1885 common and 652, 253, and 790 organ-specific ones in Br, SG, and PG, respectively. Identified common-expressed proteins indicated the existence of intrinsic complex interactions among these parts of endocrine system. Most of the reputed organs-specific proteins were identified by this approach. KEGG pathway analysis showed 162 same pathways among the 169, 164, and 171 relating Br, SG, and PG. This analysis revealed functional similarities with exceptional resemblance in their metabolism and signaling pathways of the three organs. On the other hand, 70, 57, and 114 organ-specific enzymes related pathways were detected for Br, SG, and PG confirming their functional differences. These results reveal a cooperative mechanism among the three endocrine organs in regulating various physiological and developmental events, and also suggest that the organ-specific proteins might be the fundamental factors responsible for the functional differentiation of these organs.

Background: Anti-thyroid peroxidase antibody (anti-TPO antibody) is a member of thyroid autoantibodies which are important in inducing and also diagnosing autoimmune thyroid diseases. Thyroid autoimmunity can cause several forms of thyroiditis and abnormal thyroid functions, ranging from hypothyroidism to hyperthyroidism., Objective: To evaluate the relationship between serum levels of anti-TPO antibody and thyroid function test parameters (T3, T4, and TSH) in patients with thyroid disease., Methods: In 2425 subjects suspected of having thyroid disease referred to Yazd central medical laboratory by physicians during a 2 year period, the concentrations of serum anti-TPO antibody (ELISA) and T3, T4, and TSH (RIA) were measured., Results: 53.53% of the patients were 20 to 39 years old. 2135 patients (88.04%) were female and 290 (11.96%) were male. The levels of T3, T4, and TSH in individuals with normal and raised anti-TPO antibody titers was significantly different (p<0.0001). A correlation between TSH and T4 levels and abnormal anti-TPO antibody was detected (p=0.002)., Conclusion: Our results confirm the correlation between thyroid function test and anti-TPO antibody values, indicating the clinical significance of this antibody and suggesting a through clinical examination and follow up of individuals with high anti-TPO antibody titer.