Potential of Edaravone Dexborneol in the treatment of cerebral ischemia: focus on cell death-related signaling pathways.

Cerebral ischemia has the highest global rate of morbidity and mortality. It occurs when a sudden occlusion develops in the arterial system, and consequently some parts of the brain are deprived from glucose and oxygen due to the cessation of blood flow. The ensuing reperfusion of the ischemic area results in a cascade of pathological alternations like neuronal apoptosis by producing excessive reactive oxygen species (ROS), oxidative stress and neuroinflammation. Edaravone Dexborneol is a novel agent, comprised of Edaravone and Dexborneol in a 4:1 ratio. It has documented neuroprotective effects against cerebral ischemia injury. Edaravone Dexborneol improves neurobehavioral and sensorimotor function, cognitive function, brain edema, and blood-brain barrier (BBB) integrity in experimental models. It at dosages ranging between 0.375 and 15 mg/kg (from immediately after ischemia until the 28th post-ischemic days) has shown neuroprotective effects in experimental models of cerebral ischemia by inhibiting cell death-signaling pathways. For example, it inhibits apoptosis by increasing Bcl2, and reducing Bax and caspase-3 expression. Edaravone Dexborneol also inhibits pyroptosis by attenuating NF-κB/NLRP3/GSDMD signaling, as well as ferroptosis by activating the Nrf-2/HO-1/GPX4 signaling pathway. It also inhibits autophagy by targeting PI3K/Akt/mTOR signaling pathway. Here, we provide a review on the impacts of Edaravone Dexborneol on cerebral ischemia.

Can infliximab serve as a new therapy for neuropsychiatric symptoms?

Neuropsychiatric disorders present a global challenge to public health. Mechanisms associated with neuropsychiatric disorders etiology include apoptosis, oxidative stress, and neuroinflammation. Tumor necrosis factor alpha, an inflammatory cytokine, mediates pathophysiology of neuropsychiatric disorders. Therefore, its inhibition by infliximab might afford a valuable target for intervention. Infliximab is commonly used to treat inflammatory diseases, including ulcerative colitis, Crohn's disease, and rheumatoid arthritis. Recently, it has been shown that infliximab improves cognitive dysfunction, depression, anxiety, and life quality. Here, we review contemporary knowledge supporting the need to further characterize infliximab as a potential treatment for neuropsychiatric disorders.

Cross-cultural adaptation and measurement properties of the Persian version of the modified Cincinnati knee rating system.

Purpose: To validate and assess the cross-sectional adaptation of the modified Cincinnati knee rating system (MCRKS) Persian translation. Methods: To assess test-pretest reliability, 102 participants were asked to fill out the MCRKS (Per) scale after anterior cruciate ligament (ACL) reconstruction surgery. Internal consistency (Cronbach's α), reliability (intraclass correlation coefficients), construct validity (Pearson's r) and sensitivity (floor/ceiling effect) were determined. In addition, patients completed other relevant measures as the ACL return to sports after injury (ACL-RSI) survey, hospital for special surgery ACL satisfaction survey (HSS ACL-SS), visual analogue scale (VAS) of pain and patient's satisfaction, Tegner activity score (TAS), single assessment numeric evaluation, and Lysholm score. Results: Using MCRKS (Per), the internal consistency (Cronbach's α) was 0.9 (if item deleted: 0.81-0.86); the construct validity (Pearson's r) varied between -0.50 (for VAS pain scale) and 0.79 (for Lysholm score); the reliability (ICC value) varied between 0.82 and 0.97; furthermore, no ceiling or floor effect was present. Conclusion: The MCRKS (Per) has adequate measurement properties and is considered a valid, reliable and sensitive instrument which can identify clinical outcomes after ACLR surgery. Level of Evidence: Level IV.

Effect of a single versus serial platelet-rich plasma injection on the healing of acute patellar tendon defect: an experimental study.

BACKGROUND: There is no consensus on the frequency and timing of platelet-rich plasma (PRP) injection in tendon healing. We aimed to evaluate the effectiveness of single versus multiple PRP injections in the healing of patellar tendon defects in the experimental model, through histological and biomechanical investigation. METHODS: Forty-four male skeletally mature Dutch rabbits were randomly divided into the five study groups ( A, B,C, D,E). After creating a longitudinal acute patellar tendon defect on both knees (One-third the width of the patella tendon), the right legs of the rabbits were used as the intervention group and the left legs as the control groups. Animals in groups A, B, and C were euthanized on days 7, 14, and 28, respectively, after the first PRP injection. Animals in group D received the second PRP injection on day 10 and was euthanized on day 14. Animals in group D received the second and third PRP injections on days 10 and 20, respectively, and were euthanized on day 28. The outcomes were evaluated histologically (modification of Movin's Grading) and biomechanically. RESULTS: The inflammatory condition was exaggerated in groups D and E. Load at failure was higher in the non-injected side of groups D and E, while there was no significant difference between the right and left legs of the three groups A, B and C. In other word, groups with a single PRP injection were more resistant to the increasing load compared to the groups with multiple PRP injections. CONCLUSIONS: PRP improves tendon healing if injected early after injury, while its injection after the initial phase of injury hampers tendon healing. In addition, a single PRP injection seems to be more effective than multiple PRP injection. Therefore, in cases where PRP injection is indicated for tendon repair, such as acute tendon injury, we recommend using a single PRP injection during tendon repair surgery.

Semantic similarity is not enough: A novel NLP-based semantic similarity measure in geospatial context.

In this study, we addressed two primary challenges: firstly, the issue of domain shift, which pertains to changes in data characteristics or context that can impact model performance, and secondly, the discrepancy between semantic similarity and geographical distance. We employed topic modeling in conjunction with the BERT architecture. Our model was crafted to enhance similarity computations applied to geospatial text, aiming to integrate both semantic similarity and geographical proximity. We tested the model on two datasets, Persian Wikipedia articles and rental property advertisements. The findings demonstrate that the model effectively improved the correlation between semantic similarity and geographical distance. Furthermore, evaluation by real-world users within a recommender system context revealed a notable increase in user satisfaction by approximately 22% for Wikipedia articles and 56% for advertisements.

Anterior cruciate ligament-Return to sport after injury scale brief version after ACL reconstruction: Persian translation, cross-cultural adaptation and validation.

Purpose: The purpose of this study is to analyze the short anterior cruciate ligament return to sport after injury (ACL-RSI) (Persian) version's cultural adaption and validity. Methods: To assess test-retest reliability, 102 participants were filled out the short ACL-RSI(Per) scale 6 months or more after ACLR surgery. Internal consistency (Cronbach's alpha), test-retest reliability (intraclass correlation coefficients), construct validity (Pearson's r) and sensitivity (floor/ceiling effect) were determined. In addition, patient completed other relevant measures such as Lysholm scores, the hospital for special surgery ACL satisfaction survey (HSS ACL-SS), the visual analogue scale (VAS) of pain and patient's satisfaction, the Tegner activity score (TAS), the single assessment numeric evaluation (SANE) and the Cincinnati Knee Rating System (CKRS). Results: The short ACL-RSI(Per) scale showed high internal consistency (Cronbach's alpha = 0.91) and test-retest reliability (ICC = 0.923). Significant correlations between short ACL-RSI(Per) and other scales supported validity. There was a statistically significant connection between the short ACL-RSI(Per) and the following outcomes: HSS ACL-SS (r = 0.698, p < 0.001), VAS pain (r = 0.356, p < 0.001), CKRS (r = 0.644, p < 0.001), TAS (r = 0414, p < 0.001), Lysholm score (r = 0.467, p < 0.001) and SANE score (r = 0.536; p < 0.001). In addition to a satisfactory ceiling impact (15%), a sizeable floor effect (16.7%) was also seen. Conclusion: The short ACL-RSI(Per) scale is a reliable and valid tool for assessing psychological readiness for return to sport after ACL reconstruction in Persian. Level of Evidence: III.

Therapeutic potential of Phycocyanin in gastrointestinal cancers and related disorders.

Gastrointestinal cancer is the most fatal cancer worldwide. The etiology of gastrointestinal cancer has yet to be fully characterized. Alcohol consumption, obesity, tobacco, Helicobacter pylori and gastrointestinal disorders, including gastroesophageal reflux disease, gastric ulcer, colon polyps and non-alcoholic fatty liver disease are among the several risks factors for gastrointestinal cancers. Phycocyanin which is abundant in Spirulina. Phycocyanin, a member of phycobiliprotein family with intense blue color, is an anti-diabetic, neuroprotective, anti-oxidative, anti-inflammatory, and anticancer compound. Evidence exists supporting that phycocyanin has antitumor effects, exerting its pharmacological effects by targeting a variety of cellular and molecular processes, i.e., apoptosis, cell-cycle arrest, migration and Wnt/ß-catenin signaling. Phycocyanin has also been applied in treatment of several gastrointestinal disorders such as, gastric ulcer, ulcerative colitis and fatty liver that is known as a risk factor for progression to cancer. Herein, we summarize various cellular and molecular pathways that are affected by phycocyanin, its efficacy upon combined drug treatment, and the potential for nanotechnology in its gastrointestinal cancer therapy.

Therapeutic Potential of Fingolimod on Psychological Symptoms and Cognitive Function in Neuropsychiatric and Neurological Disorders.

Neuropsychiatric and neurological disorders pose a significant global health burden, highlighting the need for innovative therapeutic approaches. Fingolimod (FTY720), a common drug to treat multiple sclerosis, has shown promising efficacy against various neuropsychiatric and neurological disorders. Fingolimod exerts its neuroprotective effects by targeting multiple cellular and molecular processes, such as apoptosis, oxidative stress, neuroinflammation, and autophagy. By modulating Sphingosine-1-Phosphate Receptor activity, a key regulator of immune cell trafficking and neuronal function, it also affects synaptic activity and strengthens memory formation. In the hippocampus, fingolimod decreases glutamate levels and increases GABA levels, suggesting a potential role in modulating synaptic transmission and neuronal excitability. Taken together, fingolimod has emerged as a promising neuroprotective agent for neuropsychiatric and neurological disorders. Its broad spectrum of cellular and molecular effects, including the modulation of apoptosis, oxidative stress, neuroinflammation, autophagy, and synaptic plasticity, provides a comprehensive therapeutic approach for these debilitating conditions. Further research is warranted to fully elucidate the mechanisms of action of fingolimod and optimize its use in the treatment of neuropsychiatric and neurological disorders.

Upregulation of Oxidative Phosphorylation Genes in Cumulus Cells of The Polycystic Ovary Syndrome Patients with or without Insulin Resistance.

OBJECTIVE: The relationship between oxidative stress (OS), insulin resistance (IR), and polycystic ovary syndrome (PCOS) is an important medical issue in human reproduction. Some of the oxidative phosphorylation (OXPHOS) genes have been previously studied in granulosa and muscle cells of PCOS patients. Cumulus cells (CCs) remain close to the oocyte even after ovulation. This research has been designed to compare the expression of OXPHOS genes in CCs of PCOS, with or without insulin resistance. MATERIALS AND METHODS: In this experimental study, patients were included in PCOS insulin-resistant, PCOS insulinsensitive (IS), and control (fertile women with male infertility history) groups. The expression of NCF2, TXNIP, UCP2, NDUFB6, ATP5H, COX7C, NDUFA3, SDHA, and SDHB was studied by real-time polymerase chain reaction (PCR), and normalization was performed considering HPRT1 and CYC1 as reference genes. One-way ANOVA and Tukey test were used for data analysis. RESULTS: The results showed that the expression of NCF2, TXNIP, UCP2, and ATP5H was significantly higher in the IR group than IS and control groups (P<0.01). NDUFB6 showed the highest expression in the IS group, which was significantly different from other groups (P<0.01). The other genes of interest, except COX7C, were observed with the most transcriptional levels in the IS group, although there was no significant difference for those genes. CONCLUSION: Altered expression of genes involved in mitochondrial function compared to the control group in CCs of both IR and IS categories of the PCOS patients suggests that alteration in OXPHOS genes can contribute to the pathophysiology of PCOS.

Abnormal frequency of the memory B cell subsets and plasmablasts in patients with congenital severe hemophilia A: correlation with "Inhibitor" formation.

BACKGROUND: Development of antibodies against infused Factor VIII (FVIII) or "inhibitors" represents a major challenge following FVIII replacement therapy in patients with hemophilia A (HA). Recent studies have shown that certain cellular compartments of the immune system contribute to the production of such antibodies. Herein, we determined the frequency of class-switched CD19+IgD-CD27+/non-class-switched CD19+IgD+CD27+ memory B cell subsets and CD19+CD27hiCD38hi plasmablasts in patients with severe HA and their association with the development of inhibitors in these patients. METHODS: This cross-sectional case-control study enrolled 32 patients with severe HA, including 8 with and 24 without inhibitors, and 24 healthy individuals. The frequencies of the memory B cell subsets and plasmablasts were determined using flow cytometry. RESULTS: The frequency of CD19+IgD+CD27+ non-class-switched memory B cells was significantly lower in patients with HA (including both patients with and without inhibitors) than in healthy controls. The percentages of both CD19+IgD-CD27+ class-switched and CD19+IgD+CD27+ non-class-switched memory B cells did not differ significantly between patients with and without inhibitors. HA patients with inhibitors had significantly higher proportions of CD19+CD27hiCD38hi plasmablasts than the control group as well as the inhibitor (-) ones. No significant correlation was observed between the inhibitor levels with the percentages of memory B cell subsets and plasmablasts. CONCLUSION: This study is the first to demonstrate a dysregulated proportion of CD19+IgD+CD27+ non-class-switched memory B cells and CD19+CD27hiCD38hi plasmablasts in patients with severe HA. Therefore, strategies targeting memory B-cell/plasmablast differentiation may have promising outcomes in the management of inhibitor formation in patients with severe HA.

The Potential of Targeting Autophagy-Related Non-coding RNAs in the Treatment of Alzheimer's and Parkinson's Diseases.

Clearance of accumulated protein aggregates is one of the functions of autophagy. Recently, a clearer understanding of non-coding RNAs (ncRNAs) functions documented that ncRNAs have important roles in several biological processes associated with the development and progression of neurodegenerative disorders. Subtypes of ncRNA, including microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA), are commonly dysregulated in neurodegenerative disorders such as Alzheimer and Parkinson diseases. Dysregulation of these non-coding RNAs has been associated with inhibition or stimulation of autophagy. Decreased miR-124 led to decreased/increased autophagy in experimental model of Alzheimer and Parkinson diseases. Increased BACE1-AS showed enhanced autophagy in Alzheimer disease by targeting miR-214-3p, Beclin-1, LC3-I/LC3-II, p62, and ATG5. A significant increase in NEAT1led to stimulated autophagy in experimental model of PD by targeting PINK1, LC3-I, LC3-II, p62 and miR-374c-5p. In addition, increased BDNF-AS and SNHG1 decreased autophagy in MPTP-induced PD by targeting miR-125b-5p and miR-221/222, respectively. The upregulation of circNF1-419 and circSAMD4A resulted in an increased autophagy by regulating Dynamin-1 and miR-29c 3p, respectively. A detailed discussion of miRNAs, circRNAs, and lncRNAs in relation to their autophagy-related signaling pathways is presented in this study.

Evaluation of Staphylococcus Aureus and Pseudomonas Aeruginosa in Saliva of Patients with Acute Myeloid Leukemia.

​Statement of the Problem: Patients with leukemia are prone to infectious and often life-threatening complications. Evidence suggests that a specific oral microbiota may contribute to septicemia, which can delay antineoplastic treatment, compromise treatment efficacy, or even endanger patients' lives. Purpose: This study investigated the prevalence of Staphylococcus aureus and Pseudomonas aeruginosa in the saliva of patients with acute myeloid leukemia who were candidates for bone marrow transplantation. Materials and Method: This cross-sectional study was conducted in 2019 in the Hematology-Oncology Department of Namazi Hospital, Shiraz University of Medical Sciences. The study included 28 patients with acute myeloid leukemia eligible for bone marrow transplantation as the case group and age- and sex-matched healthy individuals as the control group. Unstimulated saliva samples were collected to determine the frequency of Staphylococcus aureus and Pseudomonas aeruginosa. Data were analyzed using SPSS version 18, the chi-square test, and the independent t-test. Results: In the patients with acute myeloid leukemia, 26 (86%) were positive for Staph-ylococcus aureus and 18 (60%) were positive for Pseudomonas aeruginosa. In the healthy group, 11 (22.9%) were positive for Staphylococcus aureus and 3 (6.2%) were positive for Pseudomonas aeruginosa. The frequency of Pseudomonas aeruginosa and Staphylococcus aureus in the saliva samples of patients with acute myeloid leukemia was significantly higher than in the healthy control subjects (p value < 0.05). Chi-square test showed no significant association between age and the frequency of bacteria (p value= 0.27). Conclusion: In the current study, the frequency of Staphylococcus aureus and Pseudomonas aeruginosa in the saliva of patients with acute myeloid leukemia was higher than in the healthy control group.

Incorporating mesoporous SiO2-HA particles into chitosan/hydroxyapatite scaffolds: A comprehensive evaluation of bioactivity and biocompatibility.

In this work, composite scaffolds with various composition ratios of chitosan (CS), hydroxyapatite (HA), and mesoporous SiO2 particles co-synthesized with hydroxyapatite (SiO2-HA) were fabricated via the freeze-drying method for bone tissue engineering applications. Morphological studies showed that adding mesoporous particles resulted in a structure with a more uniformly porous geometry, subsequently leading to reduced biodegradation rates and water absorption in the scaffolds. The bioactivity results showed the introduction of mesoporous particles notably enhanced the coverage of the scaffold surface with apatite films. Moreover, biocompatibility assessments using sarcoma osteogenic cell line (SAOS-2) highlighted mesoporous particles' positive impact on cell adhesion and growth. The fluorescence images showed spindle-shaped cells with a greater number and normal cell nuclei for the scaffolds containing mesoporous SiO2-HA particles. The MTT cytotoxicity results indicated that the scaffolds containing mesoporous particles showed approximately 25 % higher cell survival more than single chitosan-based ones. What is more, the mesoporous-containing scaffolds occurred to have the best alkaline phosphatase test (ALP) activity among all scaffolds. It is important to add that CS/HA/mesoporous SiO2-HA scaffolds including SAOS-2 cells showed no sign of either early or late apoptosis. These findings affirm the potential of CS/HA/mesoporous SiO2-HA scaffolds as promising implants for bone tissue engineering.

Common Complication From Routine Shoulder Surgery: Postoperative Stiffness After Rotator Cuff Repair.

Rotator cuff repair is commonly performed, and stiffness represents one of the most common complications. Unique characteristics of postoperative stiffness, including its natural history and pathoanatomy, differentiate it from other etiologies of shoulder stiffness. Patient risk factors that have been associated with postoperative stiffness should be reviewed to better help clinicians tailor their presurgical risk assessment. Although stiffness in this setting has clinical consequences for patients' postoperative shoulder function, it is important to discuss the important implications of stiffness as it relates to rotator cuff healing. Multiple strategies have been proposed to decrease the incidence of postoperative stiffness. There is evidence to support these preventive strategies, and it has led to author recommendations for treatment of refractory cases and prevention.

Non-Coding RNAs and Neurodegenerative Diseases: Information of their Roles in Apoptosis.

Apoptosis can be known as a key factor in the pathogenesis of neurodegenerative disorders. In disease conditions, the rate of apoptosis expands and tissue damage may become apparent. Recently, the scientific studies of the non-coding RNAs (ncRNAs) has provided new information of the molecular mechanisms that contribute to neurodegenerative disorders. Numerous reports have documented that ncRNAs have important contributions to several biological processes associated with the increase of neurodegenerative disorders. In addition, microRNAs (miRNAs), circular RNAs (circRNAs), as well as, long ncRNAs (lncRNAs) represent ncRNAs subtypes with the usual dysregulation in neurodegenerative disorders. Dysregulating ncRNAs has been associated with inhibiting or stimulating apoptosis in neurodegenerative disorders. Therefore, this review highlighted several ncRNAs linked to apoptosis in neurodegenerative disorders. CircRNAs, lncRNAs, and miRNAs were also illustrated completely regarding the respective signaling pathways of apoptosis.

Iron Overload in Children With Leukemia; Identification of a Cutoff Value for Serum Ferritin Level.

OBJECTIVE: To determine the prevalence of iron overload in children with acute lymphoblastic leukemia (ALL) after treatment cessation and establish a cutoff value for serum ferritin level as an indicator of iron overload. BACKGROUND: Early detection and monitoring of iron overload in patients with leukemia is crucial. METHODS: In this prospective cohort study, 66 pediatric patients with ALL who were treated at a tertiary referral center affiliated with Shiraz University of Medical Sciences in Shiraz, Southern Iran, were investigated from July 2020 to December 2022. Serum ferritin levels were measured 6 months after treatment completion. T2* magnetic resonance imaging of the liver and heart was done for all patients. The receiver operating characteristic curve was used to illustrate the area under the receiver operating characteristic curve to assess the diagnostic value of serum ferritin level and total transfusion volume. RESULTS: A total of 24 patients (36.4%) had iron overload in the heart or liver based on T2 magnetic resonance imaging findings. Serum ferritin level was a highly accurate diagnostic marker for iron overload in pediatric patients with ALL, with a sensitivity of 95.8%, and specificity of 85.7% for a cutoff value of 238.5 ng/mL. Also, blood transfusion was a good predictor of iron overload a sensitivity of 75% and specificity of 81% for a cutoff value of 28.3 mL/kg. CONCLUSION: We identified specific cutoff values for serum ferritin and blood transfusion volume to predict iron overload with high sensitivity and specificity. These markers offer a cost-effective and accessible approach for periodic screening of iron deposition, particularly in resource-constrained settings.

Case Report: Gastrointestinal Basidiobolomycosis in a Young Girl with Cystic Fibrosis and Celiac Disease.

Basidiobolomycosis is an uncommon fungal infection that has been reported in the literature mainly as a cause of infection in the skin and subcutaneous tissue. Intraabdominal infections have been reported in tropical and subtropical areas in the Middle East, such as Iran and Saudi Arabia, and in the United States. Our patient was a 6-year-old girl with cystic fibrosis and celiac disease who was referred to our department with a history of chronic abdominal pain. In the imaging studies of the abdomen and pelvis, a large retroperitoneal mass was reported in the right upper part of the abdomen with involvement of the duodenum and the mesentery of the small and large intestines, as well as the superior mesenteric vessels, and was diagnosed as basidiobolomycosis through biopsy. Because of the large unresectable mass, the patient was first treated with antifungal drugs for 2 months and then surgical resection was performed. The main point in the management of these patients is a combination of antifungal therapy and surgical resection. In some patients, complex surgeries such as the Whipple procedure may be performed to appropriately manage intraabdominal infections.

Non-coding RNAs and Aquaporin 4: Their Role in the Pathogenesis of Neurological Disorders.

Neurological disorders are a major group of non-communicable diseases affecting quality of life. Non-Coding RNAs (ncRNAs) have an important role in the etiology of neurological disorders. In studies on the genesis of neurological diseases, aquaporin 4 (AQP4) expression and activity have both been linked to ncRNAs. The upregulation or downregulation of several ncRNAs leads to neurological disorder progression by targeting AQP4. The role of ncRNAs and AQP4 in neurological disorders is discussed in this review.

Development of a Green Single Drop Microextraction Based on Deep Eutectic Solvent and HPLC-UV for Trace Residue Analysis of Three Frequent-Used Pesticides.

Background: A green sample preparation method named deep eutectic solvent-based single drop microextraction (DES-SDME) was developed and optimized for determining trace metribuzin, dichlorvos, and fenthion. Methods: Two hundred seventy experimental runs were performed, and the optimal values of the five influential factors in the DES-SDME method were determined. The design of the study was based on one factor at a time and the peak area of high-performance liquid chromatography was used as a benchmark for comparing analysis results. Results: After optimizing the effective factors, the linearity range, detection limit and quantification limit of the method were determined by drawing calibration curves for the studied analytes. Conclusion: The results indicated the success of the developed method in obtaining acceptable figures of merit as a green preparation method with accuracy and precision.