Automatic classification of acute lymphoblastic leukemia cells and lymphocyte subtypes based on a novel convolutional neural network.

Acute lymphoblastic leukemia (ALL) is a life-threatening disease that commonly affects children and is classified into three subtypes: L1, L2, and L3. Traditionally, ALL is diagnosed through morphological analysis, involving the examination of blood and bone marrow smears by pathologists. However, this manual process is time-consuming, laborious, and prone to errors. Moreover, the significant morphological similarity between ALL and various lymphocyte subtypes, such as normal, atypic, and reactive lymphocytes, further complicates the feature extraction and detection process. The aim of this study is to develop an accurate and efficient automatic system to distinguish ALL cells from these similar lymphocyte subtypes without the need for direct feature extraction. First, the contrast of microscopic images is enhanced using histogram equalization, which improves the visibility of important features. Next, a fuzzy C-means clustering algorithm is employed to segment cell nuclei, as they play a crucial role in ALL diagnosis. Finally, a novel convolutional neural network (CNN) with three convolutional layers is utilized to classify the segmented nuclei into six distinct classes. The CNN is trained on a labeled dataset, allowing it to learn the distinguishing features of each class. To evaluate the performance of the proposed model, quantitative metrics are employed, and a comparison is made with three well-known deep networks: VGG-16, DenseNet, and Xception. The results demonstrate that the proposed model outperforms these networks, achieving an approximate accuracy of 97%. Moreover, the model's performance surpasses that of other studies focused on 6-class classification in the context of ALL diagnosis. RESEARCH HIGHLIGHTS: Deep neural networks eliminate the requirement for feature extraction in ALL classification The proposed convolutional neural network achieves an impressive accuracy of approximately 97% in classifying six ALL and lymphocyte subtypes.

Inhalation exposure to crude oil vapor induces behavioural deficits by increasing oxidative stress and histopathological changes in rat hippocampus: Quercetin therapeutic approach.

OBJECTIVE: Inhalation exposure to crude oil vapor (COV) and petroleum products is considered responsible for neurobehavioral toxicity in human and animal models. The antioxidant activity of quercetin (Que) and its derivatives are promising for protecting the hippocampus. This study aimed to evaluate the neuroprotective role of Que against COV-induced behavioral alterations and hippocampus damage. METHODS: Eighteen adult male Wistar rats were randomly divided into the following three groups (n = 6): the control, the COV, and the COV + Que group. The inhalation method was used to expose the rats to crude oil vapors for 5 h daily, and Que (50 mg/kg) was administered orally. After 30 days of treatment, the spatial working memory and anxiety levels were evaluated using the cross-arm maze and elevated plus maze (EPM), respectively. TUNEL assay and hematoxylin-eosin (H&E) staining were used to identify the necrosis, normal and apoptotic cells in the hippocampus. Moreover, the levels of oxidative stress biomarkers including malondialdehyde (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (TAC) were investigated in the hippocampus tissue. RESULTS: The results indicated that exposure to COV was associated with a significant decrease in spatial working memory and activity of CAT, TAC, SOD, and GPx enzymes compared to the control (P < 0.05). Moreover, COV significantly increased the level of anxiety, MDA, and hippocampal apoptosis (P < 0.05). The simultaneous administration of quercetin along with exposure to COV improved the behavioral alterations, activity of antioxidant enzymes, and hippocampal apoptosis. CONCLUSIONS: These findings suggest that quercetin prevents COV-induced hippocampal damage by enhancing the antioxidant system and preventing cell apoptosis.

Involvement of dopaminergic system in the dentate gyrus of the hippocampus in modulating the orofacial pain-related behaviors in the rats.

Chemical stimulation of the lateral hypothalamus (LH) induces analgesia by forming neural circuitries with multiple brain regions. The involvement of hippocampal dopaminergic receptors in the LH stimulation-induced antinociception in specific pain models in animals has been documented. However, because the neural circuitries involved in the mediation of orofacial pain are not the same as those that mediate the other types of pain, the present study aims to detect the role of dopamine receptors within the dentate gyrus (DG) in the antinociceptive responses induced by LH stimulation in an animal model of orofacial pain. Male Wistar rats (220-250 g) were implanted with two separate cannulae into the LH and DG on the same side. D1- or D2-like dopamine receptor antagonist, SCH23390, or sulpiride (0.25, 1, and 4 µg) were microinjected into the DG, five minutes before intra-LH injection of carbachol (250 nM). The animals were then injected with formalin 1% (50 µL; sc) into the upper lip lateral to the nose and subjected to the orofacial formalin test. Intra-DG administration of SCH23390 or sulpiride attenuated the antinociceptive responses induced by intra-LH microinjection of carbachol during the orofacial formalin test. The findings of the current study suggest that chemical stimulation of the LH modulates orofacial pain, possibly through activation of the DG dopaminergic neurons. Due to the high incidence and prevalence of orofacial pain in the general population, understanding how such neuronal circuitry modulates nociceptive processing will advance the search for novel therapeutics.

A survey on the effect of adding aspirin to anti-migraine drugs on the severity of headache in patients with chronic migraine headaches with lateral venous sinus stenosis in MRV.

Introduction: One of the probable etiologies raised in patients with chronic migraine headaches is stenosis of the lateral venous sinuses of the brain, which is detectable using magnetic resonance venography (MRV). In this study, we decided to observe the effect of adding aspirin to anti-migraine medicines on the severity of headache in patients with chronic migraine headaches with lateral venous sinus stenosis in MRV. Methods: The study was a double-blind randomized clinical trial. Patients were included in the study in two groups including 30 people. The first group was treated with propranolol and nortriptyline, and the second group was treated with propranolol, nortriptyline, and aspirin. The severity of headache, number of headaches during one month, and duration of a headache before treatment and one, two, and three months after treatment were examined. Data were analyzed utilizing SPSS software version 19 and statistical tests like t-test, Chi-squared test, Paired t-test, and repeated measure. Results: The results showed that the mean severity of headache in the second group was significantly lower than the first group two months after treatment (P = 0.003) and three months after treatment (P = 0.002). Additionally, the number of headaches (P = 0.001) and duration of headache (P = 0.043) were significantly lower in the second group than the first group in the first three months after treatment. No statistically significant difference was observed between the frequency distribution of nausea/vomiting in the two groups. Conclusion: The addition of aspirin to anti-migraine medicines is effective in improving the severity of headache in patients with migraine with lateral venous sinus stenosis of the brain.

A multi-method and structure-based in silico vaccine designing against Echinococcus granulosus through investigating enolase protein.

Introduction: Hydatid disease is a ubiquitous parasitic zoonotic disease, which causes different medical, economic and serious public health problems in some parts of the world. The causal organism is a multi-stage parasite named Echinococcus granulosus whose life cycle is dependent on two types of mammalian hosts viz definitive and intermediate hosts. Methods: In this study, enolase, as a key functional enzyme in the metabolism of E. granulosus (EgEnolase), was targeted through a comprehensive in silico modeling analysis and designing a host-specific multi-epitope vaccine. Three-dimensional (3D) structure of enolase was modeled using MODELLER v9.18 software. The B-cell epitopes (BEs) were predicted based on the multi-method approach and via some authentic online predictors. ClusPro v2.0 server was used for docking-based T-helper epitope prediction. The 3D structure of the vaccine was modeled using the RaptorX server. The designed vaccine was evaluated for its immunogenicity, physicochemical properties, and allergenicity. The codon optimization of the vaccine sequence was performed based on the codon usage table of E. coli K12. Finally, the energy minimization and molecular docking were implemented for simulating the vaccine binding affinity to the TLR-2 and TLR-4 and the complex stability. Results: The designed multi-epitope vaccine was found to induce anti-EgEnolase immunity which may have the potential to prevent the survival and proliferation of E. granulosus into the definitive host. Conclusion: Based on the results, this step-by-step immunoinformatics approach could be considered as a rational platform for designing vaccines against such multi-stage parasites. Furthermore, it is proposed that this multi-epitope vaccine is served as a promising preventive anti-echinococcosis agent.

Effect of interaction between acute administration of morphine and cannabinoid compounds on spontaneous excitatory and inhibitory postsynaptic currents of magnocellular neurons of supraoptic nucleus.

OBJECTIVES: Opioids and cannabinoids are two important compounds that have been shown to influence the activity of magnocellular neurons (MCNs) of supraoptic nucleus (SON). The interaction between opioidergic and cannabinoidergic systems in various structures of the brain and spinal cord is now well established, but not in the MCNs of SON. MATERIALS AND METHODS: In this study, whole cell patch clamp recording of neurons in rat brain slice was used to investigate the effect of acute morphine and cannabinoid administration on spontaneous inhibitory and excitatory spostsynaptic currents (sIPSCs and sEPSCs) in MCNs. RESULTS: Bath application of morphine produced an increase in sEPSCs frequency and a decrease in sIPSCs frequency. In contrast, bath application of URB597 (fatty acid amide hydrolase (FAAH) inhibitor) produced a decrease in sEPSCs frequency but an increase in sIPSCs frequency. WIN55212-2 (cannabinoid receptor agonist) decreased both sIPSCs and sEPSCs frequencies of MCNs. Co-application of morphine and URB597 attenuated the effect of morphine on MCNs. CONCLUSION: Taken together, these data indicated that at the cellular level, pharmacological augmentation of endocannabinoids could attenuate morphine effects on MCNs.

The comparison of the effects of acute and repeated morphine administration on fast synaptic transmission in magnocellular neurons of supraoptic nucleus, plasma vasopressin levels, and urine volume of male rats.

The activity of the magnocellular neurons (MCNs) of supraoptic nucleus (SON) is regulated by a variety of excitatory and inhibitory inputs. Opioids are one of the important compounds that affect these inputs at SON synapses. In this study, whole-cell patch clamp recording of SON neurons was used to investigate the effect of acute and repeated morphine administration on spontaneous inhibitory and excitatory post synaptic currents (sIPSCs and sEPSCs) in MCNs. While acute bath application of morphine to brain slice of intact rat produced an increase in sEPSCs frequency and a decrease in sIPSCs frequency, repeated in-vivo administration of morphine produced opposite effect. Moreover, repetitive i.c.v. administration of morphine for three consecutive days caused significant increase in urine volume, but had no significant alteration in water consumption compared to control group. The increase in urine volume was consistent with a significant decrease in plasma arginine vasopressin (AVP) levels after repetitive i.p. morphine administration. The results suggest that acute administration of morphine stimulates whereas repeated administration of morphine inhibits the MCNs. Morphine-induced MCN inhibition could result in diminished plasma AVP levels and eventually an increase in urine volume of rats.

The role of PI3/Akt pathway in the protective effect of insulin against corticosterone cell death induction in hippocampal cell culture.

Corticosterone induces neuroanatomical and neurochemical changes in the hippocampus that are associated with cognitive impairments. In the present study corticosterone induced cell death in primary hippocampal neurons cultured in Neurobasal + B27 medium. Insulin prevents neuronal cell death induced in a concentration dependent manner. The neuroprotective effect of insulin was reversed by LY294002, a phosphatidylinositol 3'-kinase (PI3 kinase) inhibitor, whereas the mitogen-activated protein kinase (MAPK) inhibitor PD98059, an upstream blocker of MAPK had no effect. Western blot analyses showed that insulin induced the activation of protein kinase B (Akt). These results suggest that insulin can prevent neuronal cell death induced by corticosterone in hippocampal neurons by modulating the activity of the PI3 kinase/Akt pathway.