Phytofabricated gold nanoparticles as modulators of salt stress responses in spinach: implications for redox homeostasis, biochemical and physiological adaptation.

Introduction: The utilization of plant material for synthesizing nanoparticles effectively triggers physiological and biochemical responses in plants to combat abiotic stresses. Salt stress, particularly caused by NaCl, significantly affects plant morphology and physiology, leading to reduced crop yields. Understanding the mechanisms of salt tolerance is crucial for maintaining crop productivity. Methods: In this study, we examined the effects of 150 µM spinach-assisted gold nanoparticles (S-AuNPs) on various parameters related to seed germination, growth attributes, photosynthetic pigments, stomatal traits, ion concentrations, stress markers, antioxidants, metabolites, and nutritional contents of spinach plants irrigated with 50 mM NaCl. Results: Results showed that S-AuNPs enhanced chlorophyll levels, leading to improved light absorption, increased photosynthates production, higher sugar content, and stimulated plant growth under NaCl stress. Stomatal traits were improved, and partially closed stomata were reopened with S-AuNPs treatment, possibly due to K+/Na+ modulation, resulting in enhanced relative water content and stomatal conductance. ABA content decreased under S-AuNPs application, possibly due to K+ ion accumulation. S-AuNPs supplementation increased proline and flavonoid contents while reducing ROS accumulation and lipid peroxidation via activation of both non-enzymatic and enzymatic antioxidants. S-AuNPs also regulated the ionic ratio of K+/Na+, leading to decreased Na+ accumulation and increased levels of essential ions in spinach plants under NaCl irrigation. Discussion: Overall, these findings suggest that S-AuNPs significantly contribute to salt stress endurance in spinach plants by modulating various physiological attributes.

Isotretinoin as a promising option in the treatment of facial papules of frontal fibrosing alopecia.

Frontal fibrosing alopecia (FFA) is a primary cicatricial alopecia characterized by hairline recession, pruritus, and facial papules (FP). Various therapies are used to stabilize disease activity and induce remission. However, FP of FFA is resistant to treatment in many cases. In this review, we searched the PubMed and Google Scholar databases to screen the published literature on treatment options for FP in the context of FFA. Overall, 12 studies were included in this review. Available literature suggests a noticeable improvement in resistant-to-treatment FP in FFA patients with oral isotretinoin. The available evidence is limited and is derived from retrospective studies and case reports/series. Systemic isotretinoin can be considered a promising therapeutic regimen for treating resistant-to-treatment FP of FFA patients. However, more extensive, well-designed studies are necessary for confirmatory evidence.

Mycobacterium tuberculosis and host interactions in the manifestation of tuberculosis.

The final step of epigenetic processes is changing the gene expression in a new microenvironment in the body, such as neuroendocrine changes, active infections, oncogenes, or chemical agents. The case of tuberculosis (TB) is an outcome of Mycobacterium tuberculosis (M.tb) and host interaction in the manifestation of active and latent TB or clearance. This comprehensive review explains and interprets the epigenetics findings regarding gene expressions on the host-pathogen interactions in the development and progression of tuberculosis. This review introduces novel insights into the complicated host-pathogen interactions, discusses the challengeable results, and shows the gaps in the clear understanding of M.tb behavior. Focusing on the biological phenomena of host-pathogen interactions, the epigenetic changes, and their outcomes provides a promising future for developing effective TB immunotherapies when converting gene expression toward appropriate host immune responses gradually becomes attainable. Overall, this review may shed light on the dark sides of TB pathogenesis as a life-threatening disease. Therefore, it may support effective planning and implementation of epigenetics approaches for introducing proper therapies or effective vaccines.

Analyzing the effects of streetscape and land use on urban accidents and predicting future accidents by using machine learning algorithms (case study: Mashhad).

In general, land use and layout of streets can have a significant impact on the behavior of drivers and pedestrians. In particular, streetscape has often been overlooked that recognizing the role of streetscape on street accident in urban areas is important. The aim of this research is to investigate the influence of streetscape and land use on urban accidents that occurred in Mashhad between the years 2017 and 2021. To achieve this objective, the study focused on analyzing accidents in three different urban zones. It also considered the land use types adjacent to both closed and open streets, including residential, commercial, and mixed land uses. The research employed various surveys to gather the necessary data and insights related to the targeted areas. Statistics on accident in three zones show that among the mentioned land uses, commercial areas have experienced the highest number of accidents, with their share being approximately three times that of accidents in residential areas. Additionally, 75 % of all accidents took place in areas with open streetscape, whereas accidents in areas with enclosed view accounted for one third of the number of accidents in open streetscape areas. In this research, analysis and modeling were conducted using machine learning algorithms implemented in the Python programming language. Several models were employed, and the best models were selected based on their performance and accuracy, which include Random Forest Regression (RFR), Multilayer Neural Network Perceptron Regression (MLP) and Extreme Boost Gradient Regression (XGBoost). The accuracy of the machine learning models which successfully predicted future outcomes was as follows: Random Forest Regression (RFR) achieved 85 % accuracy, Extreme Boost Gradient Regression (XGBoost) achieved 81 % accuracy, and finally, Neural Network Multilayer Perceptron Regression (MLP) achieved 75 % accuracy.

Pre and perinatal predictors on autism spectrum disorders: a case-control study in the west of Iran.

INTRODUCTION: The constellation of pre and perinatal predictors are introduced as predictor for autism spectrum disorders (ASD), however, the information about the direction and strength of these predictors are lacking in Western, Iran. The current study aimed to determine the pre and perinatal predictors of ASD among children in this region. METHODS: This case-control study was conducted in Hamadan, Western Iran during January to March 2022. The study included 100 children with ASD who referred to the autism center as case group. Hundred children without ASD from registration system of health service centers were selected as control group and were matched (1:1) to cases by age and place of residency. A structured questionnaire about pre and perinatal predictors of ASD was developed by an expert panel. The questionnaire was administered by interviewing the mothers of children. RESULTS: Boy gender (OR: 3.51, 95% CI: 1.74-7.10, p-value < 0.001), small for gestational age (SGA) (3.92, 1.64-9.39, 0.002), maternal diabetes (3.51, 1.03-24.95, 0.04) and family history of mental disorders (3.64, 1.18-11.27, 0.04) were identified as significant predictors in a multivariable analysis. CONCLUSION: Our study emphasizes on the importance of screening and monitoring for ASD in the boys, those with history of SGA, from mothers with history of diabetes and with family history of mental disorders. Proposing the replication of findings emphasizes the necessity of conducting studies with larger sample sizes.

Endoscopic pilonidal sinus treatment (EPSiT) for sacrococcygeal pilonidal sinus disease: A prospective long-term study.

Objectives: To assess short-term and long-term outcomes of endoscopic pilonidal sinus treatment for pilonidal sinus disease. METHODS: The prospective study was conducted at Shifa International Hospital, Islamabad, Pakistan, from July 2015 to July 2021, and comprised all pilonidal sinus cases undergoing minimal invasive endoscopic pilonidal sinus treatment who were treated by a single surgical team. The primary outcomes were duration of healing, post-operative morbidities, persistence of discharge and recurrence at 1-7 years. The secondary outcomes were operative time, return to work, cosmetic results and patient satisfaction. The patients were observed for wound healing and discharge on follow-up in the out-patient department at 1, 3, 6 and 24 weeks. They were further followed up every year through telephonic survey for persistence or recurrence of symptoms. Patient satisfaction was assessed using the 36-item Short Form Survey questionnaire filled at admission and then at 6 weeks post-surgery. Data was analysed using SPSS 23. RESULTS: Of the 67 patients, 55(82%) were males and 12(18%) were females. The overall mean age was 25.69±8.305 years. There were 13(19.4%) patients with a history of recurrent disease and previous procedures for pilonidal sinus, while 54(80.6%) had no previous surgery. The median operative time was 35 minutes (interquartile range: 20-45 minutes). Complete wound healing was achieved in 60(89.6%) patients, while recurrence was seen in 7(10.4%). The median time off work was 2.5 days (interquartile range: 1-3 days). Patient satisfaction with the procedure was significantly high (p<0.05). CONCLUSIONS: Endoscopic pilonidal sinus treatment appeared to be a good minimally invasive surgical technique for the treatment of pilonidal sinus disease in terms of both short-term and long-term outcomes.

The effect of radiation synovectomy with phosphorus-32 on the pain and swelling in 31 RA patients with resistant monoarthritis of the knee.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by symmetric polyarthritis. RA is routinely treated by various systemic drugs; on the other hand, administration of intra-articular corticosteroids or different types of synovectomies can be used in case of systemic medication's failure. Chemical, radio isotopic, and surgical synovectomies are being used as therapeutic options for chronic synovitis to improve joint function. Chemical synovectomy is not well tolerated, and the long-term response is relatively low. Surgical synovectomy has a better success rate, but it recommends higher expenses. In radiation synovectomy, radioactive labeled particles are applied directly in the articular cavity, followed by homogeneous distribution in joint. Next, the radioactive particles are transported in the depth of synovia and phagocytized by inflammatory cells. Finally, the radiation leads to fibrosis and sclerosis of formerly inflamed synovial membrane; thus, it stops the inflammation and reduces the symptoms. It has a success rate of 40-100% and its effect can be similar to surgical synovectomy. MATERIALS AND METHODS: Thirty-one patients with resistant monoarthritis of the knee were enrolled in this study. One millicurie of phosphorus-32 was injected into patients' knee via US guide. Saline was injected afterwards to prevent leakage. Direct pressure was performed after removing the needle and the knee was flexed slowly to ensure homogenous distribution and fixed with a splint for 1 to 2 weeks. Patients were followed up after 2 weeks, 1 month, 2 months, and 6 months. The following variables were assessed by the treating rheumatologist: patients' pain, joint tenderness, effusion, and ROM. At the time of injection and after the first week, patients were investigated for any complication including infection, necrosis, pain, and swelling. The effect of clinical characteristics and demographic data on existing complications and the changes of pain, joint tenderness, effusion, and ROM was assessed. RESULTS: Thirty-one patients with the mean age of 54.5 ± 12.2 years and the mean disease duration of 12 ± 6.5 years were enrolled in this study. Mean DAS-28 ESR score for our patients was 4 ± 0.7. The pain, effusion, and reduced ROM were decreased significantly after all follow-up intervals. Knee tenderness was not affected in the first 2 weeks, but it was reduced significantly after 1, 2, and 6 months. No serious complications like infection and necrosis were reported through our study. 51.6% and 54.8% of our patients reported pain and swelling in the administration site. Furthermore, 19.4% and 16.1% of patients reported deterioration of pain and effusion in the first week of injection. CONCLUSION: In our study, we demonstrated that pain, tenderness, effusion, and ROM are improved after radiation synovectomy with phosphorus-32. We also showed that there was no serious adverse effect like infection and necrosis. However, more than half of our patients experienced pain and swelling of injection site at the time of administration. Key points • We demonstrated the efficacy of radiation synovectomy as a medication for monoarthritis. • The results of our study can lead to a bigger clinical trial to assess the benefits and adverse effects of radiation synovectomy in comparison to treatment with local or systemic corticosteroids.

Genetic change investigation in DOCK1 gene in an Iranian family with sign and symptoms of temporomandibular joint disorder (TMD).

OBJECTIVES: Temporomandibular joint disorder (TMD) is a complex condition with pain and dysfunction in the temporomandibular joint and related muscles. Scientific evidence indicates both genetic and environmental factors play a crucial role in TMD. In this study, we aimed to discover the genetic changes in individuals from 4 generations of an Iranian family with signs and symptoms of TMD and malocclusion Class III. MATERIALS AND METHODS: Whole Exome Sequencing (WES) was performed in 4 patients (IV-8, IV-9, V-4, and V-6) with TMD according to (DC/TMD), along with skeletal Class III malocclusion. Then, PCR sequencing was performed on 23 family members to confirm the WES. RESULTS: In the present study, WES results analysis detected 6 heterozygous non-synonymous Single Nucleotide Variants (SNVs) in 5 genes, including CRLF3, DNAH17, DOCK1, SEPT9, and VWDE. A heterozygous variant, c.2012T > A (p.F671Y), in Exon 20 of the DOCK1 (NM_001290223.2) gene was identified. Then, this variant was investigated in 19 other members of the same family. PCR-Sequencing results showed that 7/19 had heterozygous TA genotype, all of whom were accompanied by malocclusion and TMD symptoms and 12/19 individuals had homozygous TT genotype, 9 of whom had no temporomandibular joint problems or malocclusion. The remaining 3 showed mild TMD clinical symptoms. The 5 other non-synonymous SNVs of CRLF3, DNAH17, SEPT9, and VWDE were not considered plausible candidates for TMD. CONCLUSIONS: The present study identified a heterozygous nonsynonymous c.2012T > A (p.F671Y) variant of the DOCK1 gene is significantly associated with skeletal class III malocclusion, TMD, and its severity in affected individuals in the Iranian pedigree. CLINICAL RELEVANCE: The role of genetic factors in the development of TMD has been described. The present study identified a nonsynonymous variant of the DOCK1 gene as a candidate for TMD and skeletal class III malocclusion in affected individuals in the Iranian pedigree.

Morphological characterization of Iris hymenospatha and Iris histrio populations in Iran: implications for conservation and breeding.

The native populations of Iris hymenospatha and Iris histrio, two endangered bulbous species within the large Iris genus in Iridaceae, are threatened with extinction due to mining and other industrial activities in their natural habitats in Central Asia, including Iran. These species not only have a significant economic impact on the global horticultural industry due to their versatility and attractive phenotypic traits, but also have significant ecological value that necessitates their conservation. In this study, we examined the morphological and functional diversity between individuals within these two species, which exhibit high tolerance to environmental stresses. Our study examined 10 populations of I. hymenospatha and two populations of I. histrio based on bulb, flower, and leaf characteristics throughout Iran. We recognized a gradation of five different leaf shapes among I. hymenospatha populations with significant differences between some populations, including "Arak-Khomain" and "Arak-Gerdo". The "Jaro", "Natanz-Karkas", "Ardestan-Taleghan", "Arak-Rahjerd", "Arak-Gerdo", "Ganjnameh", and "Abas-Abad" populations of I. hymenospatha displayed maximal values in leaf width, stem diameter under flower, crown diameter, flower number, leaf number, and bulb diameter. The I. histrio "Velian" population had a significantly larger flower size, a longer stem length, a larger style width, a longer flowering date, and a higher plant height compared to the "Ganjnameh" population of I. histrio. Such characteristics of both species make them remarkable ornamental plants. Our study also revealed that I. hymenospatha populations grow on different soils and elevations and have the ability to adapt to different growing conditions. Given the threats they face, conservation through horticultural selection and propagation offers a viable conservation strategy for both species. This approach not only preserves the genetic diversity of these species, but also enables their further contribution to the horticultural industry.

New molecular and macroscopic understandings of novel green chemicals based on Xanthan Gum and bio-surfactants for enhanced oil recovery.

This research investigates the interactions between a novel environmentally friendly chemical fluid consisting of Xanthan gum and bio-based surfactants, and crude oil. The surfactants, derived from various leaves using the spray drying technique, were characterized using Fourier-transform infrared (FTIR) spectroscopy, zeta potential analysis, Dynamic light scattering, and evaluation of critical micelle concentration. Static emulsion tests were conducted to explore the emulsification between crude oil and the polymer-surfactant solution. Analysis of the bulk oil FTIR spectra revealed that saturated hydrocarbons and light aromatic hydrocarbons exhibited a higher tendency to adsorb onto the emulsion phase. Furthermore, the increased presence of polar hydrocarbons in emulsion phases generated by polar surfactants confirmed the activation of electrostatic forces in fluid-fluid interactions. Nuclear magnetic resonance spectroscopy showed that the xanthan solution without surfactants had a greater potential to adsorb asphaltenes with highly fused aromatic rings, while the presence of bio-based surfactants reduced the solution's ability to adsorb asphaltenes with larger cores. Microfluidic tests demonstrated that incorporating surfactants derived from Morus nigra and Aloevera leaves into the xanthan solution enhanced oil recovery. While injection of the xanthan solution resulted in a 49.8% recovery rate, the addition of Morus nigra and Aloevera leaf-derived surfactants to the xanthan solution increased oil recovery to 58.1% and 55.8%, respectively.

Synthetic Methods of Quinoxaline Derivatives and their Potential Anti-inflammatory Properties.

Quinoxaline molecule has gathered a great attention in medicinal chemistry due to its vide spectrum of biological activities and emerged as a versatile pharmacophore in drug discovery and development. Its structure comprises bicyclic ring of benzopyrazine and displays a range of pharmacological properties including antibacterial, antifungal, antiviral, anticancer and anti-inflammatory. This review summarizes the different strategies for the synthesis of quinoxalines and their anti-inflammatory properties acting through different mechanisms. Structure activity relationships have also been discussed in order to determine the effect of structural modifications on anti-inflammatory potential. These analyses illuminate critical structural features required for optimal activity, driving the design and synthesis of new quinoxaline analogues with better anti-inflammatory activities. The anti-inflammatory properties of quinoxalines are attributed to their inhibitory action on expression of several inflammatory modulators such as cyclooxygenase, cytokines, nuclear factor kappa-light-chain-enhancer of activated B cells (NFB) and p38 mitogen activated protein kinase (p38 MAPK). Activators of nuclear factor erythroid 2-related factor 2 (NRF2) and agonistic effect on opioid receptors have also been discussed. Hence, this review may provide a future template for the design and development of novel quinoxaline derivatives acting through different molecular targets as potential anti-inflammatory agents with better efficacy and safety profile.

Anti-Leukemic Effects of Small Molecule Inhibitor of c-Myc (10058-F4) on Chronic Myeloid Leukemia Cells.

BACKGROUND: As one of the main molecules in BCR-ABL signaling, c-Myc acts as a pivotal key in disease progression and disruption of long-term remission in patients with CML. OBJECTIVES: To clarify the effects of c-Myc inhibition in CML, we examined the anti-tumor property of a well-known small molecule inhibitor of c-Myc 10058-F4 on K562 cell line. METHODS: This experimental study was conducted in K562 cell line for evaluation of cytotoxic activity of 10058-F4 using Trypan blue and MTT assays. Flow cytometry and Quantitative RT-PCR analysis were also conducted to determine its mechanism of action. Additionally, Annexin/PI staining was performed for apoptosis assessment. RESULTS: The results of Trypan blue and MTT assay demonstrated that inhibition of c-Myc, as shown by suppression of c-Myc expression and its associated genes PP2A, CIP2A, and hTERT, could decrease viability and metabolic activity of K562 cells, respectively. Moreover, a robust elevation in cell population in G1-phase coupled with up-regulation of p21 and p27 expression shows that 10058-F4 could hamper cell proliferation, at least partly, through induction of G1 arrest. Accordingly, we found that 10058-F4 induced apoptosis via increasing Bax and Bad; In contrast, no significant alterations were observed NF-KB pathway-targeted anti-apoptotic genes in the mRNA levels. Notably, disruption of the NF-κB pathway with bortezomib as a common proteasome inhibitor sensitized K562 cells to the cytotoxic effect of 10058-F4, substantiating the fact that the NF-κB axis functions probably attenuate the K562 cells sensitivity to c-Myc inhibition. CONCLUSIONS: It can be concluded from the results of this study that inhibition of c-Myc induces anti-neoplastic effects on CML-derived K562 cells as well as increases the efficacy of imatinib. For further insight into the safety and effectiveness of 10058-F4 in CML, in vivo studies will be required.

Grape seed extract protects rat offspring hippocampus from the silicon dioxide nanoparticles' neurotoxicity.

Silicon dioxide nanoparticles (SiO2-NPs) can be found in many products, such as composites, paints, ceramics, consumer products, and food additives. We recently demonstrated that via breastfeeding, SiO2-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 SiO2-NPs. After delivery, animals were administered 25 mg/kg SiO2-NPs with/without GSE (300 mg/kg) for 20 days (from 2nd to 21st days post-delivery) by gavage. SiO2-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 SiO2-NPs group, whereas the mean number of DCX + cells was significantly lower than in the control group. The offspring in the SiO2-NPs groups had a weak cognitive performance in adulthood. Interestingly, these adverse effects of SiO2-NPs were alleviated in the GSE-treated groups. Therefore, GSE can attenuate the damaging effects of maternal exposure to SiO2-NPs during lactation.

Nanobodies against the myelin enzyme CNPase as tools for structural and functional studies.

2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) is an abundant constituent of central nervous system non-compact myelin, frequently used as a marker antigen for myelinating cells. The catalytic activity of CNPase, the 3'-hydrolysis of 2',3'-cyclic nucleotides, is well characterised in vitro, but the in vivo function of CNPase remains unclear. CNPase interacts with the actin cytoskeleton to counteract the developmental closure of cytoplasmic channels that travel through compact myelin; its enzymatic activity may be involved in adenosine metabolism and RNA degradation. We developed a set of high-affinity nanobodies recognizing the phosphodiesterase domain of CNPase, and the crystal structures of each complex show that the five nanobodies have distinct epitopes. One of the nanobodies bound deep into the CNPase active site and acted as an inhibitor. Moreover, the nanobodies were characterised in imaging applications and as intrabodies, expressed in mammalian cells, such as primary oligodendrocytes. Fluorescently labelled nanobodies functioned in imaging of teased nerve fibers and whole brain tissue sections, as well as super-resolution microscopy. These anti-CNPase nanobodies provide new tools for structural and functional biology of myelination, including high-resolution imaging of nerve tissue.

Comparison of the effects of platelet-rich plasma and platelet-rich fibrin on the healing process of a rat's mucosal wound.

Due to the problems associated with the use of PRP, a platelet concentrates without coagulation factors, called platelet-rich fibrin (PRF), has been developed that, in addition to tissue regeneration and wound healing, contains more white blood cells (WBCs), which are important in the wound healing process. In this study, the effect of these two platelet-rich plasmas on the thickness of the epithelium, the number of blood vessels and fibroblasts, and wound area were measured in two groups of PRP and PRF and at different periods. We divided the rats into three groups: the control group, the group receiving PRP, and the group receiving PRF. The results showed a significant difference in the number of fibroblasts, wound area, thickness of epithelium, and number of vessels in all three groups. Based on the results, the use of PRP and PRF in wounds can accelerate the formation of epithelium, create better and more blood vessels, create a platform for the migration and formation of fibroblast cells, and facilitate faster wound closure. Also, comparing PRP and PRF, it can be concluded that, finally, PRF acts better than PRP in epithelialization.

The PI3K signaling pathway; from normal lymphopoiesis to lymphoid malignancies.

INTRODUCTION: As a vital mechanism of survival, lymphopoiesis requires the collaboration of different signaling molecules to orchestrate each step of cell development and maturation. The PI3K pathway is considerably involved in the maturation of lymphatic cells and therefore, its dysregulation can immensely affect human well-being and cause some of the most prevalent malignancies. As a result, studies that investigate this pathway could pave the way for a better understanding of the lymphopoiesis mechanisms, the undesired changes that lead to cancer progression, and how to design drugs to solve this issue. AREAS COVERED: The present review addresses the aforementioned aspects of the PI3K pathway and helps pave the way for future therapeutic approaches. In order to access the articles, databases such as Medicine Medline/PubMed, Scopus, Google Scholar, and Science Direct were utilized. The search formula was established by identifying main keywords including PI3K/Akt/mTOR pathway, Lymphopoiesis, Lymphoid malignancies, and inhibitors. EXPERT OPINION: The PI3K pathway is crucial for lymphocyte development and differentiation, making it a potential target for therapeutic intervention in lymphoid cancers. Studies are focused on developing PI3K inhibitors to impede the progression of hematologic malignancies, highlighting the pathway's significance in lymphoma and lymphoid leukemia.

Hippocampal D1-like dopamine receptor as a novel target for the effect of cannabidiol on extinction and reinstatement of methamphetamine-induced CPP.

Methamphetamine (METH) is a major health problem without effective pharmacological treatment. Cannabidiol (CBD), a component of the Cannabis sativa plant, is believed to have the potential to inhibit drug-related behavior. However, the neurobiological mechanisms responsible for the effects of CBD remain unclear. Several studies have proposed that the suppressing effects of CBD on drug-seeking behaviors could be through the modulation of the dopamine system. The hippocampus (HIP) D1-like dopamine receptor (D1R) is essential for forming and retrieving drug-associated memory. Therefore, the present study aimed to investigate the role of D1R in the hippocampal CA1 region on the effects of CBD on the extinction and reinstatement of METH-conditioned place preference (CPP). For this purpose, different groups of rats over a 10-day extinction period were administered different doses of intra-CA1 SCH23390 (0.25, 1, or 4 µg/0.5 µl, Saline) as a D1R antagonist before ICV injection of CBD (10 µg/5 µl, DMSO12%). In addition, a different set of animals received intra-CA1 SCH23390 (0.25, 1, or 4 µg/0.5 µl) before CBD injection (50 µg/5 µl) on the reinstatement day. The results revealed that the highest dose of SCH23390 (4 µg) significantly reduced the accelerating effects of CBD on the extinction of METH-CPP (P < 0.01). Furthermore, SCH23390 (1 and 4 µg) in the reinstatement phase notably reversed the preventive effects of CBD on the reinstatement of drug-seeking behavior (P < 0.05 and P < 0.001, respectively). In conclusion, the current study revealed that CBD made a shorter extinction period and suppressed METH reinstatement in part by interacting with D1-like dopamine receptors in the CA1 area of HIP.

The PI3K/Akt signaling axis and type 2 diabetes mellitus (T2DM): From mechanistic insights into possible therapeutic targets.

Type 2 diabetes mellitus (T2DM) is an immensely debilitating chronic disease that progressively undermines the well-being of various bodily organs and, indeed, most patients succumb to the disease due to post-T2DM complications. Although there is evidence supporting the activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway by insulin, which is essential in regulating glucose metabolism and insulin resistance, the significance of this pathway in T2DM has only been explored in a few studies. The current review aims to unravel the mechanisms by which different classes of PI3Ks control the metabolism of glucose; and also to discuss the original data obtained from international research laboratories on this topic. We also summarized the role of the PI3K/Akt signaling axis in target tissues spanning from the skeletal muscle to the adipose tissue and liver. Furthermore, inquiries regarding the impact of disrupting this axis on insulin function and the development of insulin resistance have been addressed. We also provide a general overview of the association of impaired PI3K/Akt signaling pathways in the pathogenesis of the most prevalent diabetes-related complications. The last section provides a special focus on the therapeutic potential of this axis by outlining the latest advances in active compounds that alleviate diabetes via modulation of the PI3K/Akt pathway. Finally, we comment on the future research aspects in which the field of T2DM therapies using PI3K modulators might be developed.

Pattern of Traumatic Injuries in Patients with Tramadol Poisoning: A Cross-Sectional Study in a Tertiary Care Hospital.

Objective: This study aimed to investigate the incidence and pattern of tramadol-induced seizures and injuries in patients admitted to the hospital. Methods: The cross-sectional study included 300 patients with alleged tramadol intoxication. Demographic information, tramadol dosage and duration of abuse, co-existing illicit drug abuse, hospital stay length, and occurrence of seizures and trauma (type and site of injuries) were collected. Different statistical tests, including the Mann-Whitney U-test, Pearson's Chi-square test, and Student's t-test, were conducted to compare the patients with and without seizures, trauma, and co-ingestion of illicit drugs. The analysis was performed using SPSS software (version 21.0). A p value of less than 0.05 was considered statistically significant. Results: The average patient's age was 24.66±5.64 years, with males comprising 84.3% of the sample. The mean tramadol dose and duration of abuse were 1339.3±1310.2 mg and 2.43±1.35 years, respectively. Seizures were observed in 66% of patients, with men having a higher incidence (69.6% vs. 46.8%; p=0.004). Trauma was reported in 23% of patients, accounting for 35.4% of seizure cases. All trauma patients had experienced seizures, with the head and neck being the most prevalent injury sites (55.1%), typically presenting as abrasions (55.9%). Patients with seizures and trauma had an average hospital stay of 1.73±0.94 days, which was significantly longer. Conclusion: Trauma occurs in more than one-third of tramadol-induced seizures, highlighting the need to perform physical examinations to detect and localize injuries. Tramadol-associated traumas prolonged hospitalization times and thus required prompt attention to prevent further injuries during pre-hospital handling and transferring to hospitals.

Outcomes of Induction Chemotherapy Followed by Chemoradiotherapy Versus Chemoradiotherapy Alone in Esophageal Squamous Cell Carcinoma Induction chemotherapy in Esophageal Squamous Cell Carcinoma.

BACKGROUND: There is still no definite conclusion regarding the effect of Induction Chemotherapy (IC) combined with concurrent Chemoradiotherapy (CRT). Thus this study was aimed to assess outcomes of IC followed By CRT versus CRT alone in Esophageal Squamous Cell Carcinoma (ESCC). METHODS: This multicenter retrospective study performed on 105 patients who underwent CRT and 73 patients who underwent IC+CRT, between January 2016 and December 2018. The primary endpoints were OS (from the date of treatment to the date of death or 3- years follow-Up). The toxicities of CRT were graded according to the National Cancer Institute Common Toxicity Criteria (version 3.0). RESULTS: one-year (73.8% vs. 53.2%) and 2-year (53.4% vs. 38.5%) OS rate of the IC+CRT group was significantly higher than that of the CRT group (p < 0.05). No statistically significant differences were observed between the IC+CRT group and the CRT group (31.5% vs. 27.4%) in terms of the 3-year OS rate (p > 0.05). In multivariate logistic regression, age<60 (OR: 1.48; CI 95% 1.02-1.97), clinical staging II (OR: 1.36; CI 95% 1.11-1.88), and the addition of IC (OR: 1.66; CI 95% 1.07-2.19) were independent prognostic factors that affected survival positively. CONCLUSION: Our data demonstrated that a combination of IC and CRT might be a promising treatment strategy to further improve OS in ESCC patients.