Assessment of sedative activity of fraxin: In vivo approach along with receptor binding affinity and molecular interaction with GABAergic system.

Insomnia is a sleep disorder in which you have trouble falling and/or staying asleep. This research aims to evaluate the sedative effects of fraxin (FX) on sleeping mice induced by thiopental sodium (TS). In addition, a molecular docking study was conducted to investigate the molecular processes underlying these effects. The study used adult male Swiss albino mice and administered FX (10 and 20 mg/kg, i.p.) and diazepam (DZP) (2 mg/kg) either separately or in combination within the different groups to examine their modulatory effects. After a period of 30 min, the mice that had been treated were administered (TS: 20 mg/kg, i.p.) to induce sleep. The onset of sleep for the mice and the length of their sleep were manually recorded. Additionally, a computational analysis was conducted to predict the role of gamma-aminobutyric acid (GABA) receptors in the sleep process and evaluate their pharmacokinetics and toxicity. The outcomes indicated that FX extended the length of sleep and reduced the time it took to fall asleep. When the combined treatment of FX and DZP showed synergistic sedative action. Also, FX had a binding affinity of -7.2 kcal/mol, while DZP showed -8.4 kcal/mol. The pharmacokinetic investigation of FX demonstrated favorable drug-likeness and strong pharmacokinetic characteristics. Ultimately, FX demonstrated a strong sedative impact in the mouse model, likely via interacting with the GABAA receptor pathways.

MicroRNA mediated suppression of airway lactoperoxidase by TGF-ß1 and cigarette smoke promotes airway inflammation.

Transforming Growth Factor Beta1 (TGF-ß1) signaling is upregulated in Chronic Obstructive Pulmonary disease (COPD), smokers, and people living with HIV. Cigarette smoking and HIV are also independent risk factors for COPD. Chronic inflammation is a hallmark of COPD. However, the underlying mechanisms remain unknown. Previous research has suggested that TGF-ß1 alters the airway epithelial microRNAome and transcriptome, potentially contributing to lung inflammation. The Lactoperoxidase (LPO) system is an integral component of innate immunity within the airway. LPO plays a crucial role in host defense by catalyzing the oxidation of thiocyanate to hypothiocyanite in the presence of hydrogen peroxide (H2O2), generating a potent antibacterial and antiviral agent. Additionally, the LPO system potentially aids in maintaining cellular redox balance by reducing the levels of H2O2, thus mitigating oxidative stress within the airway epithelium. LPO dysfunction can impair immune responses and exacerbate inflammatory processes in respiratory diseases.In this study, primary bronchial epithelial cells and bronchial cell lines were treated with TGF-ß1 and exposed to cigarette smoke to characterize the effect of these factors on LPO and their downstream effects. RT-qPCR and Western Blot were applied to quantify mRNA and proteins' expression. The levels of H2O2 were detected using the Amplex Red Assay. Magnetofection and transfection were applied to probe the effect of miR-449b-5p. Staining procedures using the MitoTracker Green and C12FDG dyes were used to establish mitochondria mass and senescence. The levels of pro-inflammatory cytokines were measured via Luminex assays.We found that TGF-ß1 and cigarette smoke suppressed airway LPO expression, increasing H2O2 levels. This increase in H2O2 had downstream effects on mitochondrial homeostasis, epithelial cellular senescence, and the pro-inflammatory cytokine response. We demonstrate for the first time that airway LPO is regulated by TGF-ß1-induced miRNA-mediated post-transcriptional silencing through miR-449b-5p in the lungs. Further, we identify and validate miR-449-5p as the candidate miRNA upregulated by TGF-ß1, which is involved in LPO suppression. This paper demonstrates a new mechanism by which TGF-ß1 can lead to altered redox status in the airway.

Adulthood cosmetic and sexual outcomes of the patients who underwent hypospadias repair in childhood.

This study aimed to assess the cosmetic and sexual outcomes of childhood hypospadias repair after puberty. Among 672 patients who underwent hypospadias repair between 2001 and 2017, 243 sexually active patients were included in the study. At their last visit, cosmetic and sexual evaluation were done through the Penile Perception Score, the Hypospadias Objective Scoring Evaluation, IIEF, MSHQ-EjD. The levels of erectile dysfunction(ED) severity were determined according to erectile function domain of IIEF. The median follow-up after the last surgery was 16 [IQR (13-18)] years, and median patient age at the time of study was 19.67 [IQR(18-22)] years. Patients were divided into two subgroups as follows: Group I; Repairs using grafts (n = 120, 49.4%) and Group II; Graft-free repairs (n = 123, 50.6%). The rate of dissatisfaction with penile appearance was higher in Group I (16.7% vs. 4.9%, p = 0.003). Mild ED was more frequent in Group I (14.2% vs. 3.3%, p = 0.007); while none of the patients had either moderate or severe ED. Other domains of sexual function were observed to be similar in both groups. The need for unwanted interventions due to complications, and surgeries requiring grafts were found to be risk factors for ED development and dissatisfaction with penile appearance in adulthood. Those who underwent graft-free hypospadias repair experience better cosmetic and sexual outcomes when compared to grafted repairs, yet, satisfactory results were achieved in almost 90% of the grafted repairs.

In vitro and in vivo modulatory effects of fluoxetine on gene expression and antioxidant enzymes in CFA-induced chronic inflammatory model: drug repurposing for arthritis.

Fluoxetine, being a selective serotonin uptake inhibitor, has been broadly used to modulate the neurotransmission of serotonin in the central nervous system. Fluoxetine performs a number of crucial central nervous system-related tasks, including neuroprotective effects against microglial neurotoxicity and protecting oxidative cell damage produced by stress in a variety of stress-related unfavourable health disorders. Studies have shown that the drug (fluoxetine) also has analgesic and anti-inflammatory characteristics in addition to its other basic benefits. Furthermore, existing treatment approaches (NSAIDs, DMARDs, corticosteroids and other immunosuppressants) for RA have limited effects on chronic immunological models. These facts served as the basis for carrying out a study on fluoxetine to explore its therapeutics in a chronic inflammatory rat model called Freund's complete adjuvant (FCA)-induced arthritis. The therapeutic effect of the fluoxetine in FCA-induced arthritic rats was assessed by paw volume, paw diameter, arthritic index and body weight at specific days through the experiment of 28 days. These findings were further co-investigated by haematological, biochemical parameters and radiographic imaging at the end of experiment. Furthermore, the modulatory effects on gene expression (NF-κB, PGE2, COX2, INF-γ, IL-4 and IL-10) and antioxidant properties were gritty using qRT-PCR and ELISA kits, respectively, in experimental arthritic rats. Fluoxetine at 10, 20 and 40 mg/kg doses reduced (p < 0.001) the serum concentration of C-reactive protein and rheumatoid factor as well as suppressed the expression of PGE2, NF-kB, COX2 and INF-γ when compared to arthritic control. Moreover, fluoxetine (at higher doses) caused significant rise of IL-4 and IL-10. These findings supported the anti-inflammatory and antioxidant potential of fluoxetine in chronic inflammatory model and endorsed it for clinical trials.

Evidence for ~12-h ultradian gene programs in humans.

Mice and many marine organisms exhibit ~12-h ultradian rhythms, however, direct evidence of ~12-h ultradian rhythms in humans is lacking. Here, we performed prospective, temporal transcriptome profiling of peripheral white blood cells from three healthy humans. All three participants independently exhibited robust ~12-h transcriptional rhythms in molecular programs involved in RNA and protein metabolism, with strong homology to circatidal gene programs previously identified in Cnidarian marine species.

ß-Hydroxybutyrate dehydrogenase functionalized two-dimensional photonic crystals for quantitative and visual sensing of ketone bodies.

ß-Hydroxybutyrate (BHB) is a substantial physiological ketone body. Its elevated concentration causes ketoacidosis, which is a disorder with a high mortality rate. Therefore, there is an urgent need to develop a simple method for the in-situ monitoring of BHB in urine. In this study, a photonic crystal hydrogel (PCH) sensing material for the detection of urinary ketones was prepared by embedding a two-dimensional polystyrene photonic crystal array (PCA) in a hydrogel functionalized with ß-hydroxybutyrate dehydrogenase (BHBDH). BHBDH catalyzes the interconversion between ß-hydroxybutyrate and acetoacetic acid and relies on the cofactor nicotinamide adenine dinucleotide (NAD+) to participate in the reaction process. The catalytic cycle of converting ß-hydroxybutyrate to acetoacetate generates H+, which reduces the electrostatic repulsion between the carboxyl groups in the hydrogel network, ultimately leading to the shrinkage of the hydrogel volume. The hydrogel volume change was detected by measuring the diameter of the Debye diffraction ring, thus reflecting the concentration of BHB. When the concentration of BHB was increased from 0 to 10 mM, the reflection spectrum of PCH shifted for 117 nm within 60 min, consequently, the structural color of PCH changed from red to green and finally to blue. The material was used for quantitative detection of BHB with a detection limit of 48.94 µM. Then it was used for detection in artificial urine samples. While, this smart and reusable sensing material could provide a more convenient and efficient strategy for the ketone body detection in clinical diagnosis and point-of-care monitoring.

Evaluating the impact of testosterone replacement therapy on carotid atherosclerosis: a systematic review and meta-analysis.

Aim: This meta-analysis investigates the association between testosterone replacement therapy [TRT] and carotid artery atherosclerosis. Methods: 3 databases were searched for studies up to June 2023 per the PRISMA guidelines. The eligibility criteria comprised RCTs and observational studies involving hypogonadal males receiving exogenous testosterone, in which CIMT was assessed. CAA was the primary outcome, whereas secondary outcomes included HDL, LDL, CRP, total cholesterol and total testosterone. The statistical analysis was performed using Review Manager. Results: Statistical analysis revealed no association between TRT and assessed outcomes. There was a significant increase in total testosterone levels, depicting indirect anti-atherosclerotic effects of TRT. Conclusion: Meta-analysis shows no relation between TRT and CIMT or other markers, allowing its safe usage for hypogonadal males.

[Box: see text].

Clinical Outcome of Pipeline Embolization Device with and without Coil to Treat Intracranial Aneurysm: A Systematic Review and Meta-Analysis.

BACKGROUND: The use of a Pipeline Embolization Device (PED) in combination with coils (PEDC) to treat intracranial aneurysms remains unclear as to whether it offers significant benefits for the patients since the results have varied. PURPOSE: This study aimed to investigate the clinical outcome of PEDC compared to PED in treating intracranial aneurysms. DATA SOURCES: We systematically searched the articles from PubMed, Web of Science, and the Cochrane Library databases published before January 25, 2024. STUDY SELECTION: We selected studies comparing PEDC vs. PED to treat intracranial aneurysms. Patients treated with PEDC but using dense coiling were excluded from the study. DATA ANALYSIS: The clinical outcomes observed in this meta-analysis were intraprocedural complications, postoperative complications (stenosis, stroke, hemorrhage, mortality), favorable outcome (mRS ≤ 2), complete occlusion rate, and retreatment rate. Forest plot was used to analyze pooled Odds Ratio (OR) of clinical outcomes. DATA SYNTHESIS: A total of 3001 subjects from nine observational studies were included. PEDC was mainly used to treat larger aneurysms. PEDC has a significantly higher complete occlusion rate at 6 months [OR= 2.66, 95% CI(1.26, 5.59), p= 0.01], a lower retreatment rate [OR= 0.18, 95% CI(0.05, 0.07), p= 0.010], higher stroke-related complications [OR= 1.66, 95% CI(1.16, 2.37), p= 0.005], and higher hemorrhage-related complications [OR= 1.98, 95% CI(1.22, 3.21), p = 0.005]. There was no significant difference in intraprocedural complications, stenosis-related complications, mortality, favorable outcomes, and complete occlusion at the end of the study. LIMITATIONS: No randomized controlled trials have been performed comparing PEDC and PED. Considering that all the included studies were observational, the patients' baseline characteristics were not completely balanced. CONCLUSIONS: This meta-analysis study showed that PEDC in large intracranial aneurysms induces a faster complete occlusion rate at 6 months and a lower retreatment rate. However, it increases the risk of stroke-related postoperative complications, and the faster complete aneurysm occlusion rate found in this study did not correlate with a reduction in long-term aneurysm or distal artery ruptures. Thus, this study suggests the need to find a better strategy to improve long-term hemorrhage-related complications in large intracranial aneurysms. ABBREVIATIONS: F = female; FDDs = flow-diverter devices; M = male; NOS = Newcastle-Ottawa Scale; PED = pipeline embolization device; PEDC = pipeline embolization device in combination with coils.

Predictive Ability of Inflammatory Markers on In-Hospital Outcomes in Patients Admitted to Coronary Care Unit (MORCOR-TURK INFLAME).

We investigated the prognostic implications of the systemic immune-inflammatory index (SII), atherogenic index of plasma (AIP), C-reactive protein/albumin ratio (CAR), neutrophil-lymphocyte ratio (NLR), prognostic nutritional index (PNI), and triglyceride/glucose index (TGI) in the MORtality predictors in the CORonary Care Units in TURKey (MORCOR-TURK) population. This is the largest registry of coronary care unit (CCU) patients in Turkey (3157 patients admitted to CCU in 50 different centers). The study population was divided into two according to in-hospital survival status; 137 patients (4.3%) died in-hospital follow-up. A significant correlation was found between death and SII, CAR, NLR, and PNI but not for AIP and TGI in logistic regression. In Model 1 (combining parameters proven to be risk predictors), the -2 log-likelihood ratio was 888.439, Nagelkerke R2 was 0.235, and AUC (area under curve) was 0.814 (95% CI: 0.771-0.858). All other models were constructed by adding each inflammatory marker separately to Model 1. Only Model 3 (CAR + Model 1) had a significantly greater AUC than Model 1 (DeLong P = .01). Our study showed that CAR, but not other inflammatory index, is a significant predictor of in-hospital mortality in CCU patients when added to proven risk predictors.

Corrigendum: Methotrexate-conjugated zinc oxide nanoparticles exert substantially improved cytotoxic effect on lung cancer cells by inducing apoptosis.

[This corrects the article DOI: 10.3389/fphar.2023.1194578.].

Mirikizumab: A promising breakthrough in Crohn's disease treatment.

Introduction: Crohn's disease (CD) is a chronic, progressive inflammatory bowel disorder characterized by persistent inflammation and noncontiguous "skip lesions" throughout the gastrointestinal tract. With a prevalence of 100-300 cases per 100,000 individuals, CD is most common in Western Europe and North America. Symptoms include abdominal pain, diarrhea, fever, weight loss, and anemia, with severe cases leading to complications such as perianal abscesses and cutaneous fistulas. Treatment involves pharmaceutical interventions, bowel rest, and sometimes surgery, with biological therapies like ustekinumab and mirikizumab gaining prominence. Clinical Trials: The VIVID-1 trial assessed mirikizumab in patients with moderately to severely active CD. By Week 12, mirikizumab significantly outperformed placebo in clinical response (45.4% vs. 19.6%, p < 0.000001). By Week 52, it showed higher clinical remission rates (54.1% vs. 19.6%) and demonstrated non-inferiority to ustekinumab in clinical remission (p = 0.51). The SEQUENCE study compared risankizumab to ustekinumab, with risankizumab showing superior reductions in inflammatory markers and higher biologic remission rates at Weeks 8, 24, and 48. Both treatments had similar safety profiles, with common adverse events including COVID-19, anemia, and headache. Conclusion: Mirikizumab, based on the VIVID-1 trial outcomes, is a promising addition to CD therapy. It demonstrated significant clinical responses and remission rates, warranting further research on its long-term efficacy and safety. Updating professional guidelines and addressing affordability will ensure broader access and improved management of CD.

Lichenoid Drug Eruption Secondary to Adalimumab: A Case Report.

Adalimumab, an anti-tumor necrosis factor-α (TNF-α), is widely prescribed for many autoimmune diseases and chronic inflammatory skin diseases such as hidradenitis suppurative, psoriasis, etc. We report a case of lichenoid drug eruption secondary to adalimumab, a rare side effect, in a 62-year-old female with ulcerative colitis. The skin eruption appeared two weeks after initiating adalimumab. A skin biopsy was taken, and the histopathological findings correlated with a lichenoid drug eruption. Although rare, drug-induced lichen planus has been associated with adalimumab. Early recognition and a high index of suspicion are key in the prompt management of these cases. The discontinuation of adalimumab must be carefully weighed against its therapeutic benefits, as the discontinuation might trigger a severe form of inflammation in the primary autoimmune disease being treated. Extreme caution, early intervention, and a multidisciplinary approach are best for the overall well-being and optimal care of the individual.

Diethylenetriaminepentaacetic Acid-based Conducting Solid Polymer Electrolytes Impede Lithium Dendrites and Impart Antioxidant Capacity in Lithium-Ion Batteries.

In the development of lithium-ion batteries (LIBs), cheaper and safer solid polymer electrolytes are expected to replace combustible organic liquid electrolytes to meet the larger market demand. However, low ionic conductivity and inadequate cycling stability impede their commercial viability. Herein, a novel flexible conducting solid polymer electrolytes (CSPEs) based on polyvinyl alcohol (PVA) and ion-polarized diethylenetriaminepentaacetic acid (P-DETP) is developed for the first time and applied in LIBs. PVA and P-DETP form a compact polymer network through hydrogen bonding, enhancing the thermomechanical stability of CSPE while restricting the migration of larger anions. Furthermore, density functional theory calculations confirm that P-DETP can facilitate the dissociation of Li+-TFSI- via electrostatic attraction, resulting in increased mobility of lithium ions. Additionally, P-DETP contributes to the formation of a stable electrode-electrolyte interface layer, effectively suppressing the growth of lithium dendrites and improving antioxidant capacity. These synergistic effects enable CSPE to exhibit remarkable properties including high ionic conductivity (2.8 × 10-4 S cm-1), elevated electrochemical potential (5.1 V), and excellent lithium transference number (0.869). Notably, the P-DETP/LiTFSI CSPE demonstrates stable performance not only in LiFePO4 batteries but also adapts to high-nickel ternary LiNi0.88Co0.06Mn0.06O2 cathode, highlighting its immense potential for application in high energy density LIBs.

Comparative mitochondrial genomics analysis of selected species of Schizothoracinae sub family to explore the differences at mitochondrial DNA level.

A comprehensive analysis of the whole mitochondrial genomes of the Schizothoracinae subfamily of the family Cyprinidae has been revealed for the first time. The species analyzed include Schizothorax niger, Schizothorax esocinus, Schizothorax labiatus and Schizothorax plagoistomus. The total mitochondrial DNA (mtDNA) length was determined to be 16585 bp, 16583 bp, 16582 bp and 16576 bp, respectively with 13 protein-coding genes, 2 rRNA genes, 22 tRNA genes and 2 non-coding area genes. The combined mean base compositions of the four species were as follows: A: 29.91 % T: 25.47 % G: 17.65 % C 27.01 %. The range of the GC content is 45-44 %, respectively. All protein coding genes (PCGs) commenced with the typical ATG codon, except for the cytochrome c oxidase subunit 1 (COX1) gene with GTG. The analysis of vital amino acid biosynthesis genes (COX1, ATPase 6, ATPase 8) in four different species revealed no significant differences. All 13 PCGs had Ka/Ks ratios that were all lesser than one, demonstrating purifying selection on those molecules. These tRNA genes were predicted to fold into the typical cloverleaf secondary structures with normal base pairing and ranged in size from 66 to 75 nucleotides. Additionally, the phylogenetic tree analysis revealed that S. esocinus species that was most alike to S. labiatus. This study provides critical data for phylogenetic analysis of the Schizothoracinae subfamily, which will help to resolve taxonomic difficulties and identify evolutionary links. Detailed mtDNA data are an invaluable resource for studying genetic diversity, population structure, and gene flow. Understanding genetic makeup can help inform conservation plans, identify unique populations, and track genetic variation to ensure effective preservation.

Cancer Prevention and Treatment Based on Lifestyles.

Cancer morbidity and mortality incidence are rapidly increasing over the period of time. Cancer prevention, alongside innovative therapies and earlier detection, is considered a key strategy for reducing the overall cancer burden. Substantial evidence indicates a clear correlation between lifestyle factors and changes in nutrient metabolism. Approximately 5-10% of all cancer cases are attributed to genetic factors, whereas 90-95% are due to environmental and lifestyle factors, suggesting that lifestyle interventions have significant prospects for preventing various cancers. Healthy lifestyle changes, in particular healthy diets, physical activity, staying at a healthy weight, reduction or elimination of tobacco/alcohol consumption, and avoiding exposure to radiation and other carcinogens, are significant factors to be considered to tackle the challenges associated with cancer in modern society. This chapter aims to provide lifestyle intervention strategies to improve cancer prevention and risk reduction while promoting the health of cancer patients. The therapeutic role of some dietary regimens and supplements, as well as complementary and alternative health approaches, in cancer treatment is also discussed.

Leveraging chorionic villus biopsies for the derivation of patient-specific trophoblast stem cells.

Human trophoblast stem (TS) cells are an informative in vitro model for the generation and testing of biologically meaningful hypotheses. The goal of this project was to derive patient-specific TS cell lines from clinically available chorionic villus sampling biopsies. Cell outgrowths were captured from human chorionic villus tissue specimens cultured in modified human TS cell medium. Cell colonies emerged early during the culture and cell lines were established and passaged for several generations. Karyotypes of the newly established chorionic villus-derived trophoblast stem (TS CV ) cell lines were determined and compared to initial genetic diagnoses from freshly isolated chorionic villi. Phenotypes of TSCV cells in the stem state and following differentiation were compared to cytotrophoblast-derived TS (TS CT ) cells. TSCV and TSCT cells uniformly exhibited similarities in the stem state and following differentiation into syncytiotrophoblast and extravillous trophoblast cells. Chorionic villus tissue specimens provide a valuable source for TS cell derivation. They expand the genetic diversity of available TS cells and are associated with defined clinical outcomes. TSCV cell lines provide a new set of experimental tools for investigating trophoblast cell lineage development.

Evaluation of Demographic and Clinical Characteristics of Turkish Patients With Primary Cutaneous Melanoma: A 5-Year Experience of a Tertiary Referral Center.

INTRODUCTION: Data about the demographic and clinical characteristics of melanoma patients in Turkey is limited. OBJECTIVES: Data about the demographic and clinical characteristics of melanoma patients in Turkey is limited. We aimed to review the features of patients with primary cutaneous melanoma (PCM) diagnosed and treated in a tertiary referral center. METHODS: The medical records of melanoma patients followed up by the Departments of Dermatology and Medical Oncology were retrospectively reviewed. RESULTS: Within a 5-year period, 180 patients had been diagnosed with melanoma. Of all, 158 (87.8%) had PCM, 9 (5%) had mucosal melanoma, 9 (5%) had unknown primary melanoma, and 4 (2.2%) had ocular melanoma. Of 146 patients with PCM, 32.9% had stage I, 28.8% had stage II, 17.8% had stage III, and 20.5% had stage IV disease. The most common subtype was superficial spreading melanoma (38.8%). A statistically significant correlation was found between the patients Breslow thickness and lymph node involvement, histopathological subtype, and tumor ulceration (P < 0.001). Among all PCM patients, those in stage IV had the lowest 5-year survival rate when compared to the other disease stages (P < 0.001). CONCLUSIONS: Relatively younger age at melanoma diagnosis, frequent presence of thick (> 4 mm) tumor, and frequent acral lentiginous subtype are the most remarkable features that suggest the low awareness and knowledge of melanoma in our population.

A Classification for Gastric Outlet Obstruction in Childhood: Extending Beyond Infantile Hypertrophic Pyloric Stenosis.

BACKGROUND/AIMS:  Gastric outlet obstruction (GOO) is a rare condition in childhood, with the exception of infantile hypertrophic pyloric stenosis (IHPS). However, no classification exists from a pediatric gastroenterologist's perspective. MATERIALS AND METHODS:  The patients with a diagnosis of GOO between 2009 and 2020 were reviewed retrospectively. We classified the patients according to GOO: presence of clinical findings accompanied by radiological and/or endoscopic findings; clinical status: intractable nonbilious postprandial vomiting alone or with abdominal pain, early satiety, weight loss, postprandial abdominal distension, and malnutrition; radiology: delayed gastric emptying and dilated stomach; endoscopy: nonbilious gastric contents after 6-8 hours of emptying and/or failed pyloric intubation; physical examination: visible gastric peristalsis. RESULTS:  A total of 30 GOO patients (15 patients with IHPS, 1 patient with annular pancreas, 4 patients with gastric volvulus, 2 patients with duodenal atresia, 2 patients with antral web, 1 patient with late-onset hypertrophic pyloric stenosis (LHPS) had surgical treatment, and remaining 5 patients had medical treatment) were enrolled to the study. The median age was 8 months (range: 3 months-16 years), and 14 patients were female. Mitochondrial disorders, LHPS, metabolic disorders, and eosinophilic gastrointestinal system diseases were added to Sharma's GOO classification, and the classification has been expanded. CONCLUSION:  This is the first and largest study of GOO in children. From the perspective of pediatric gastroenterology, new diseases will be addressed, and definitions will be highlighted with our classification for GOO in childhood.

Monoterpenoid synergy: a new frontier in biological applications.

Monoterpenoids, compounds found in various organisms, have diverse applications in various industries. Their effectiveness is influenced by the oil's chemical composition, which in turn is influenced by plant genotype, environmental conditions, cultivation practices, and plant development stage. They are used in various industries due to their distinctive odor and taste, serving as ingredients, additives, insecticides, and repellents. These compounds have synergistic properties, resulting in superior combined effects over discrete ones, potentially beneficial for various health purposes. Many experimental studies have investigated their interactions with other ingredients and their antibacterial, insecticidal, antifungal, anticancer, anti-inflammatory, and antioxidant properties. This review discusses potential synergistic interactions between monoterpenoids and other compounds, their sources, and biological functions. It also emphasizes the urgent need for more research on their bioavailability and toxicity, underlining the importance and relevance of this comprehensive study in the current scientific landscape.

Genome wide identification of phenylalanine ammonia-lyase (PAL) gene family in Cucumis sativus (cucumber) against abiotic stress.

Phenylalanine ammonia lyase (PAL) is a widely studied enzyme in plant biology due to its role in connecting primary metabolism to secondary phenylpropanoid metabolism, significantly influencing plant growth, development, and stress response. Although PAL genes have been extensively studied in various plant species but their exploration in cucumber has been limited. This study successfully identified 11 CsPAL genes in Cucumis sativus (cucumber). These CsPAL genes were categorized based on their conserved sequences revealing patterns through MEME analysis and multiple sequence alignment. Interestingly, cis-elements related to stress were found in the promoter regions of CsPAL genes, indicating their involvement in responding to abiotic stress. Furthermore, these gene's promoters contained components associated with light, development and hormone responsiveness. This suggests that they may have roles in hormone developmental processes. MicroRNAs were identified as a key regulators for the CsPAL genes, playing a crucial role in modulating their expression. This discovery underscores the complex regulatory network involved in the plant's response to various stress conditions. The influence of these microRNAs further highlights the complicated mechanisms that plants use to manage stress. Gene expression patterns were analyzed using RNA-seq data. The significant upregulation of CsPAL9 during HT3h (heat stress for 3 h) and the heightened upregulation of both CsPAL9 and CsPAL7 under HT6h (heat stress for 6 h) in the transcriptome study suggest a potential role for these genes in cucumber's tolerance to heat stress. This comprehensive investigation aims to enhance our understanding of the PAL gene family's versatility, offering valuable insights for advancements in cucumber genetics.