Microplastic's Contamination in the Hemolymph and Organs (Gills and Hepatopancreas) of Perna viridis.

The issue of microplastics (MPs) has emerged as a significant concern globally, with discussions surrounding the potential environmental impact of these tiny plastic particles becoming increasingly prevalent. This study aimed to identify the concentration and characteristics of MPs in hemolymph and organs (gills and hepatopancreas) of green mussels (Perna viridis) that are frequently consumed by people in Pangkajene Kepulauan, South Sulawesi Province, Indonesia. Green mussels were collected from two different sampling sites for comparison. Screening was carried out on dispensed hemolymph and dissected organs to identify the characteristics of MPs. Surface seawater sampling was added as information on MP's characteristics from the mussel habitat. Visual observation of MP's characteristics using a stereomicroscope in laminar flow is to prevent contamination. The identification of MP's polymer type is using FTIR-ATR. The results showed that hemolymph, hepatopancreas, gills, and surface water were concentrated with MPs. Small (2-3.9 cm) green mussels accumulated more MPs than medium (4-5.9 cm) and large (> 6 cm). MPs characteristics of fiber shape, transparent color, and size 0.1-0.5 mm were dominant in all samples. A total of seven polymers of MPs were identified with polyethylene and polystyrene types most frequently found from all samples. Based on this study, green mussels are good for biomonitoring of MPs.

Vonoprazan vs. Proton Pump Inhibitors for Treatment and Prevention of Gastric and/or Duodenal Ulcers: A Systematic Review with Meta-Analysis.

INTRODUCTION: Although Vonoprazan, a potassium-competitive acid blocker, is superior to proton pump inhibitors (PPIs) in treating Helicobacter pylori and erosive esophagitis, its efficacy for treating gastric and/or duodenal ulcers remains controversial. This meta-analysis summarizes the efficacy and safety of Vonoprazan vs. PPI for treating and preventing gastric and/or duodenal ulcers. METHODS: Only randomized controlled trials randomizing gastric and/or duodenal ulcer patients, regardless of etiology, into Vonoprazan or any PPI and indexed in Embase, Medline, and CENTRAL until March 2, 2024 were searched. Primary outcomes were ulcer healing rates at Weeks 2, 4, 6, and 8 and recurrence rates at Week 24. Other outcomes included shrinkage rates, any adverse events (AEs), serious AEs (SAEs), and risks of delayed bleeding and perforation. The overall risk ratio (RR) and mean difference were pooled using the random-effects model. The risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) Tool. RESULTS: Fifteen studies comprising 43 reports were included in the analysis. Healing rates of gastric and/or duodenal ulcers were similar in both Vonoprazan and PPI groups at all weeks (Week 2 RR 1.02 [95% CI 0.89-1.16]; Week 4 0.99 [95% CI 0.95-1.04]; Week 6 1.00 [95% CI 0.96-1.03]; Week 8 0.99 [95% CI 0.95-1.03]). The recurrence prevention of peptic ulcers was not different in Vonoprazan 10 mg (RR 0.48; 95% CI 0.18-1.27) or 20 mg (0.60; 95% CI 0.28-1.30) to PPI. Shrinkage rates, any AEs, SAEs, and risks of delayed bleeding and perforation were similar in both groups. CONCLUSION: Vonoprazan is not significantly better than PPI in treating and preventing gastric and/or duodenal ulcers.

Charting New Territories in Obesity Management- Traditional Techniques to Tirzepatide.

BACKGROUND: Obesity, a pervasive global health challenge affecting more than 2 billion people, requires comprehensive interventions. Traditional approaches, including lifestyle modification, and diverse drugs targeting a gastrointestinal hormone, including glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (Liraglutide, Semaglutide, Exenatide, Albiglutide, Dulaglutide, Lixisenatide, Orlistat, Phentermine/Topiramate, Lorcaserin, Sibutramine, and Rimonabant) offer tailored strategies; yet their effectiveness is limited and some drugs were taken off the market. Moreover, various surgical modalities, such as Roux-en-Y Bypass surgery, sleeve gastrectomy, intragastric balloons, biliopancreatic diversion with duodenal switch, laparoscopic adjustable gastric band, and vagal nerve blockade can be considered but are associated with numerous side effects and require careful monitoring. Consequently, there is a pressing need for novel anti-obesity treatments. METHODS: This comprehensive review was based on the available data to discuss the traditional pharmaceutical and surgical therapeutical strategies for obesity, going further to discuss tirzepatide's mode of action, its outcomes for obesity, and the associated side effects. RESULTS: In this landscape, tirzepatide, initially designed for type 2 diabetes management, emerges as a potential game-changer. Functioning as a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, it not only addresses control but also introduces a fresh perspective on weight reduction. This review intricately explores tirzepatide's mechanism, dissecting insights from clinical studies and positioning it as a major force in obesity treatment. CONCLUSIONS: In the middle of significant shifts in obesity management, tirzepatide presents itself as a promising and cost-effective intervention. Its Food and Drug Administration approval marks a milestone in the realm of obesity therapeutics. Going beyond a recapitulation of findings, the conclusion emphasizes the imperative for ongoing exploration and vigilant safety monitoring in tirzepatide's application.

Fine-tuning plant valuable secondary metabolite biosynthesis via small RNA manipulation: strategies and potential.

Plants produce secondary metabolites that serve various functions, including defense against biotic and abiotic stimuli. Many of these secondary metabolites possess valuable applications in diverse fields, including medicine, cosmetic, agriculture, and food and beverage industries, exhibiting their importance in both plant biology and various human needs. Small RNAs (sRNA), such as microRNA (miRNA) and small interfering RNA (siRNA), have been shown to play significant roles in regulating the metabolic pathways post-transcriptionally by targeting specific key genes and transcription factors, thus offering a promising tool for enhancing plant secondary metabolite biosynthesis. In this review, we summarize current approaches for manipulating sRNAs to regulate secondary metabolite biosynthesis in plants. We provide an overview of the latest research strategies for sRNA manipulation across diverse plant species, including the identification of potential sRNAs involved in secondary metabolite biosynthesis in non-model plants. We also highlight the potential future research directions, focusing on the manipulation of sRNAs to produce high-value compounds with applications in pharmaceuticals, nutraceuticals, agriculture, cosmetics, and other industries. By exploring these advanced techniques, we aim to unlock new potentials for biotechnological applications, contributing to the production of high-value plant-derived products.

Deferasirox nanosuspension loaded dissolving microneedles for ocular drug delivery.

Deferasirox (DFS) is an oral iron chelator that is employed in retinal ailments as a neuroprotectant against retinal injury and thus has utility in treating disorders such as excitoneurotoxicity and age-related macular degeneration (AMD). However, the conventional oral route of administration can present several disadvantages, e.g., the need for more frequent dosing and the first-pass effect. Microneedles (MNs) are minimally invasive systems that can be employed for intrascleral drug delivery without pain and can advantageously replace intravitreal injections therapy (IVT) as well as conventional oral routes of delivery for DFS. In this study, DFS was formulated into a nanosuspension (NS) through wet media milling employing PVA as a stabilizer, which was successfully loaded into polymeric dissolving MNs. DFS exhibited a 4-fold increase in solubility in DFS-NS compared to that of pure DFS. Moreover, the DFS-NSs exhibited excellent short-term stability and enhanced thermal stability, as confirmed through thermogravimetric analysis (TGA) studies. The mechanical characterization of the DFS-NS loaded ocular microneedles (DFS-NS-OcMNs), revealed that the system was sufficiently strong for effective scleral penetration. Optical coherence tomography (OCT) images confirmed the insertion of 81.23 ± 7.35 % of the total height of the MN arrays into full-thickness porcine sclera. Scleral deposition studies revealed 64 % drug deposition after just 5 min of insertion from DFS-NS-loaded ocular microneedles (OcMNs), which was almost 5 times greater than the deposition from pure DFS-OcMNs. Furthermore, both DFS and DFS-NS-OcMN exhibited remarkable cell viability when evaluated on human retinal pigment (ARPE) cells, suggesting their safety and appropriateness for use in the human eye. Therefore, loading DFS-NS into novel MN devices is a promising technique for effectively delivering DFS to the posterior segment of the eye in a minimally invasive manner.

Potential anti-HIV and antitrypanosomal components revealed in Sorindeia nitidula via LC-ESI-QTOF-MS/MS.

Sorindeia nitidula (Anacardiaceae) is used by traditional practitioners to treat influenza illnesses with cephalgia and febrile aches. However, the potential active ingredients for its remarkable antioxidant, anti-HIV and antitrypanosomal activities remain unexplored. The present study aims to evaluate the antioxidant, anti-HIV and antitrypanosomal activities of the ethyl acetate extract of S. nitidula (SN) in order to screen out the bioactive compounds and to analyze their possible mechanisms of action. Overall, 21 phenolic compounds were annotated, by using the MS and MS/MS information provided by the QTOF-MS. In vitro assays on the extract revealed potent antioxidant (IC50 = 0.0129 ± 0.0001 mg/mL), anti-HIV (IC50 = 1.736 ± 0.036 µM), antitrypanosomal (IC50 = 1.040 ± 0.010 µM) activities. Furthermore, SN did not present cytotoxic effect on HeLa cancer cell lines. The integrated strategy based on LC-ESI-QTOF-MS/MS provided a powerful tool and a multidimensional perspective for further exploration of active ingredients in S. nitidula responsible for the antioxidant, anti-HIV and antitrypanosomal activities.

Thiourea-functionalized aminoglutethimide derivatives as anti-leishmanial agents.

Aim: We aim to develop new anti-leishmanial agents against Leishmania major and Leishmania tropica.Materials & methods: A total of 23 thiourea derivatives of (±)-aminoglutethimide were synthesized and evaluated for in vitro activity against promastigotes of L. major and L. tropica.Results & conclusion: The N-benzoyl analogue 7p was found potent (IC50 = 12.7 µM) against L. major and non toxic to normal cells. The docking studies, indicates that these inhibitors may target folate and glycolytic pathways of the parasite. The N-hexyl compound 7v was found strongly active against both species, and lacked cytotoxicity against normal cells, whereas compound 7r, with a 3,5-bis-(tri-fluoro-methyl)phenyl unit, was active against Leishmania, but was cytotoxic in nature. Compound 7v was thus identified as a hit for further studies.

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A prospective, observational, multicentre study to evaluate the efficacy of brivaracetam as adjuvant therapy for epilepsy: The Bravo study.

Background: Epilepsy is a persistent tendency to experience epileptic seizures and can lead to various neurobiological disorders, with an elevated risk of premature mortality. This study evaluates the efficacy of brivaracetam adjuvant therapy in patients with epilepsy. Methods: A prospective observational multicentre study that was conducted in Pakistan from March to September 2022, by using a non-probability convenience sampling technique. The population consisted of 543 individuals with a diagnosis of epilepsy for whom adjunctive brivaracetam (Brivera; manufactured by Helix Pharma Pvt Ltd., Sindh, Pakistan) was recommended by the treating physician. The research sample was drawn from various private neurology clinics of Karachi, Lahore, Rawalpindi, Islamabad and Peshawar. Data originating from routine patient visits, and assessments at three study time points, were recorded in the study case report form. Results: Across 18 clinical sites, 543 individuals participated, with a mean age of 32.9 years. The most prescribed dosages were 50 mg BD, followed by 100 mg BD. Notably, brivaracetam combined with divalproex sodium was the most prevalent treatment, followed by brivaracetam with levetiracetam. At both the 14th and 90th day assessments, a significant reduction in seizure frequency was observed, with 63.1% of individuals showing a favourable response by day 90. Treatment-naive individuals exhibited higher rates of seizure freedom and response compared with treatment-resistant individuals. Conclusions: The study demonstrates the effectiveness of brivaracetam combination therapy in epilepsy management, with notable reductions in seizure frequency and favourable clinical responses observed, particularly in treatment-naive individuals.

Neuro-regeneration or Repair: Cell Therapy of Neurological Disorders as A Way Forward.

The human central nervous system (CNS) has a limited capacity for regeneration and repair, as many other organs do. Partly as a result, neurological diseases are the leading cause of medical burden globally. Most neurological disorders cannot be cured, and primary treatments focus on managing their symptoms and slowing down their progression. Cell therapy for neurological disorders offers several therapeutic potentials and provides hope for many patients. Here we provide a general overview of cell therapy in neurological disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Wilson's disease (WD), stroke and traumatic brain injury (TBI), involving many forms of stem cells, including embryonic stem cells and induced pluripotent stem cells. We also address the current concerns and perspectives for the future. Most studies for cell therapy in neurological diseases are in the pre-clinical stage, and there is still a great need for further research to translate neural replacement and regenerative therapies into clinical settings.

Effects of Lactococcus lactis on colorectal cancer in various terms: a narrative review.

Introduction: Colorectal cancer is one of the most common cancers with an increasing number of cases. Various studies have found an association between the gut microbiota balance and colorectal cancer incidence. Lactococcus lactis is a probiotic bacterium found in fermented foods, particularly yogurt and cheese. This probiotic has been shown to reduce various anti-inflammatory and pro-inflammatory agents that trigger cancer, such as interleukin (IL)-6, IL-18, tumour necrosis factor-alpha (TNF-α), and natural killer (NK) cells. Methods: Full-text articles and original research published in the last ten years were used as references, and "Lactococcus and colorectal cancer" as keywords. The reference search is on several databases, such as PubMed, ScienceDirect, ProQuest, and Nature. Searching results obtained eleven articles. Discussion: Lactococcus lactis does have a perfect role in suppressing cancer cells. Lactococcus lactis has anti-proliferative effects associated with decreased cyclin D1 expression in SW480 cell lines, decreased NK cells, reduced cancer cell viability, decreased IL-8 levels, and decreased IL-6. Conclusion: Lactococcus lactis contains nisin, which can suppress various gene, protein, and cytokine expressions that play a role in cancer cell growth. Probiotics can inhibit colorectal cancer without significant side effects.

Participants' Experiences and Satisfaction With Sun Protection Factor (SPF) 100 Sunscreen in Actual Use Conditions.

Background and objective Exposure to sunlight's ultraviolet (UV) radiation poses various health risks, including sunburn, skin damage, and heightened skin cancer risk. Sunblock usage has surged due to widespread advertising campaigns. Individuals spending time outdoors should employ protective measures like wearing hats, applying sunblock with a high sun protection factor (SPF), covering exposed skin, and seeking shade to mitigate UV exposure's harmful effects. This study's objective is to assess participants' experiences and satisfaction with SPF 100 sunscreen in actual use conditions. Methodology This study employed a prospective, single-center design involving 100 participants aged 18 to 70 years. Eligible individuals had Fitzpatrick skin types I-III and were engaged in outdoor activities, excluding those with certain medical conditions or medication use. Each participant received sunscreen tubes (Solero SPF 100, Helix Pharma Pvt. Ltd., Karachi, Pakistan), and clinical evaluations were conducted on the day before and after and day 22 visits, with sunblock application and UV-induced erythema assessments performed. Results Our study enrolled participants with a mean age of 25.6 ± 7.1 years, ranging from 15 to 55 years, with females comprising 84% (84) of the sample. Results revealed widespread satisfaction and acceptance of SPF 100 sunscreen, without any reported adverse reactions. A significant majority expressed their willingness to purchase and recommend the sunscreen to others. Furthermore, the majority of healthcare providers expressed satisfaction with prescribing this sunscreen.  Conclusions In conclusion, SPF 100 sunscreen demonstrated excellent tolerability and acceptability among participants, suggesting its potential utility in both personal sun protection routines and clinical settings.

Performance of Oriented Strand Board Made of Heat-Treated Bamboo (Dendrocalamus asper (Schult.) Backer) Strands.

This study aimed to analyze the effect of pre-heat treatment on bamboo strand properties and its impact on the properties of the resulting bamboo-oriented strand board (BOSB). Giant bamboo (Dendrocalamus asper (Schult.) Backer) with a density of 0.53 g cm-3 was converted into bamboo strands. These strands were pre-heat-treated at 140 and 160 °C for a duration of 1, 2, and 3 h. Changes in the chemical composition of the strand due to subsequent treatment were assessed. Fourier-transform infrared spectroscopy (FTIR) and X-Ray diffraction analysis (XRD) were used to determine the changes in the chemical composition of bamboo strands. The BOSB panels were produced with a target density of 0.7 g cm-3. The manufacturing of the BOSB was conducted in three layers with a ratio of 25:50:25, bonded with phenol-formaldehyde resin. The physical and mechanical properties of the laboratory-fabricated BOSB were tested in compliance with the criteria given in JIS A 5908 standards. Comparisons were made against OSB CSA 0437.0 Grade O-1 commercial standard. The pre-heat treatment led to chemical alterations within the material when set at 140 and 160 °C for 1 to 3 hours (h). FTIR spectral analysis demonstrated that longer exposure and higher temperatures resulted in fewer functional groups within the bamboo strands. The increased temperature and duration of pre-heat treatment enhanced the crystallinity index (CI). The dimensional stability and mechanical properties of the composites were improved significantly as hemicellulose and extractive content were reduced. This study demonstrated that the pre-heat treatment of bamboo strands at a temperature of 160 °C for a duration of 1 h was an adequate approach for heat modification and fabrication of BOSB panels with acceptable properties according to OSB CSA 0437.0 Grade O-1 commercial standard.

Analysis of molecular subtypes and antibiotic resistance in Treponema pallidum isolates from blood donors in Khyber Pakhtunkhwa, Pakistan.

Syphilis, caused by Treponema pallidum, is resurging globally. Molecular typing allows for the investigation of its epidemiology. In Pakistan and other nations, T. pallidum subsp. pallidum has developed widespread macrolide resistance in the past decade. A study at the Peshawar Regional Blood Centre from June 2020-June 2021 analyzed serum samples from 32,812 blood donors in Khyber Pakhtunkhwa, Pakistan, to assess circulating T. pallidum strains and antibiotic resistance. Blood samples were initially screened for T. pallidum antibodies using a chemiluminescent microparticle immunoassay (CMIA). CMIA-reactive samples underwent polymerase chain reaction (PCR) targeted the polA, tpp47, bmp, and tp0319 genes. PCR-positive samples were further analyzed for molecular subtyping using a CDC-developed procedure and tp0548 gene examination. All PCR-positive samples were analyzed for the presence of point mutations A2058G and A2059G in 23S rRNA, as well as the G1058C mutation in 16S rRNA. These mutations are known to impart antimicrobial resistance to macrolides and doxycycline, respectively. Out of 32,812 serum samples, 272 (0.83%) were CMIA-reactive, with 46 being PCR-positive. Nine T. pallidum subtypes were identified, predominantly 14d/f. The A2058G mutation in 23S rRNA was found in 78% of cases, while G1058C in 16S rRNA and A2059G in 23S rRNA were absent. The research found donor blood useful for assessing T. pallidum molecular subtypes and antibiotic resistance, especially when chancres are not present. The prevalent subtype was 14d/f (51.85%), and the high macrolide resistance of 36 (78%) indicates caution in using macrolides for syphilis treatment in Khyber Pakhtunkhwa, Pakistan.

The nematode effector Mj-NEROSs interacts with Rieske's iron-sulfur protein influencing plastid ROS production to suppress plant immunity.

Root-knot nematodes (RKN; Meloidogyne species) are plant pathogens that introduce several effectors in their hosts to facilitate infection. The actual targets and functioning mechanism of these effectors largely remain unexplored. This study illuminates the role and interplay of the Meloidogyne javanica nematode effector ROS suppressor (Mj-NEROSs) within the host plant environment. Mj-NEROSs suppresses INF1-induced cell death as well as flg22-induced callose deposition and reactive oxygen species (ROS) production. A transcriptome analysis highlighted the downregulation of ROS-related genes upon Mj-NEROSs expression. NEROSs interacts with the plant Rieske's iron-sulfur protein (ISP) as shown by yeast-two-hybrid and bimolecular fluorescence complementation. Secreted from the subventral pharyngeal glands into giant cells, Mj-NEROSs localizes in the plastids where it interacts with ISP, subsequently altering electron transport rates and ROS production. Moreover, our results demonstrate that isp Arabidopsis thaliana mutants exhibit increased susceptibility to M. javanica, indicating ISP importance for plant immunity. The interaction of a nematode effector with a plastid protein highlights the possible role of root plastids in plant defense, prompting many questions on the details of this process.

Tracing the contribution and fate of synthetic nitrogen fertilizer in young apple orchard agrosystems.

Excessive synthetic nitrogen (N) inputs in intensive orchard agrosystems of developing countries are a growing concern regarding their adverse impacts on fruit production and the environment. Quantifying the distribution and contribution of fertilizer N is essential for increasing N use efficiency and minimizing N loss in orchards. A 15N tracer experiment was performed in a young dwarf apple orchard over two growing seasons to determine the fertilizer N transformation and fate. Fertilizer N primarily contributed to 25 % to 75 % of soil nitrate in the top 60 cm, but the contribution to soil microbial biomass N and fixed ammonium was <8 %, with the contribution to plant N ranging from 9 % to 19 %. In most growth periods, soil nitrate and fixed ammonium contents derived from native soil with N fertilization were higher than those not receiving N fertilizer. The N use efficiency of plants was only 2.6 % and 4.9 % in the first and second seasons, respectively, in contrast to 56.6 % and 54.0 % of N recovered in soil. Meanwhile, N assimilated into microbial biomass accounted for 0.8 %, and the proportion fixed by clay minerals was 3.5 %-5.2 %. One season after N fertilization, the nitrate below the 1 m soil layers accounted for 4.6 % of the applied N fertilizer, and the proportion increased to 22.5 % after two seasons. The N loss rate via N2O emission was 0.4 % over two years. The application of N fertilizer facilitated indigenous soil N mineralization, and abiotic ammonium fixation more efficiently retained synthetic N than microbial immobilization. These findings provide new insight into orchard N cycling, and attention should be given to the improvement of soil N retention and turnover capacity regulated by soil microbial and abiotic processes, as well as the potential environmental impacts of additional soil N mineralization resulting from prolonged chemical N fertilization.

Synthesis of dimeric 1,2-benzothiazine 1,1-dioxide scaffolds: molecular structures, Hirshfeld surface analysis, DFT and enzyme inhibition studies.

1,2-Benzothiazines are bioactive compounds with diverse pharmacological properties. We report here the synthesis of a series of dimers containing 1,2-benzothiazine scaffolds as potential pharmacophores. The characterization of compounds was done using analytical techniques such as FT-IR, 1H NMR, and elemental analyses. The molecular structures of the compounds (5-8) were confirmed by X-ray crystallography. The molecular interactions in compounds (5-8) were determined by Hirshfeld Surface Analysis (HSA). Density functional theory (DFT) investigations were carried out to calculate vibrational properties, NMR behaviour, dipole moments, molecular electrostatic potential (MEP), frontier molecular orbital (FMO), natural bonding orbital (NBO) analysis and global reactivity descriptors. The global reactivity descriptors indicated the charge transfer reactions and stabilized as follows: 8 > 7 > 6 > 5. In FMO analysis a substantial HOMO-LUMO gap, ranging from 4.43 to 5.12 eV, with high LUMO values was observed for all compounds, while the highest value for linear polarizability was found in compound 8. The in vitro and in silico studies confirm that compound 8 is more active toward AChE and BChE enzymes.

Social construction of kentongan for disaster risk reduction in highland java and its potential for educational tool.

Kentongan (bamboo instruments), a traditional Javanese communication tool, continues to exist to this day, and its existence is based on its function, especially in the Java mountains. Therefore, this study aimed to analyze and uncover local wisdom behind the social construction of the Kentongan, exploring the practical and symbolic meanings and the societal and cultural implications. It also explored the community's local knowledge regarding the mitigation of disasters (disaster risk reduction), as well as its cultural heritage within the community's social fabric. To unravel knowledge held by the local community, a qualitative method using a phenomenological approach was adopted, complemented by a thorough review of relevant literature. Furthermore, the snowball approach was employed to select informants, focusing on identifying key individuals who were cross-verified through member checks. The village head and the elders were identified as the key informants, and the data collected were analyzed using an interactive model. The results showed that Kentongan served as a telecommunication tool to signal disasters, alert individuals of dangerous situations, and indicate the presence of fire. Additionally, it served as a means to assemble people or initiate prayers, and the conveyed messages could be inferred through the number of beats and the sounds produced. Empathy and social solidarity emerged as the underlying social values embedded within Kentongan. The associated significance and symbolism were actively practiced and passed down through generations within the community. As a form of indigenous knowledge, Kentongan held great relevance in the lives of the local population, thereby presenting the potential to be integrated into educational contexts as a valuable source of learning.

Label free quantitative proteomic profiling of serum samples of intellectually disabled young patients revealed dysregulation of complement coagulation and cholesterol cascade systems.

Intellectual disability is a heterogeneous disorder, diagnosed using intelligence quotient (IQ) score criteria. Currently, no specific clinical test is available to diagnose the disease and its subgroups due to inadequate understanding of the pathophysiology. Therefore, current study was designed to explore the molecular mechanisms involved in disease perturbation, and to identify potential biomarkers for disease diagnosis and prognosis. A total of 250 participants were enrolled in this study, including 200 intellectually disabled (ID) subjects from the subgroups (mild, moderate, and severe) with age and gender matched healthy controls (n = 50). Initially, IQ testing score and biochemical profile of each subject was generated, followed by label-free quantitative proteomics of subgroups of IQ and healthy control group through nano-LC/MS- mass spectrometry. A total of 310 proteins were identified, among them198 proteins were common among all groups. Statistical analysis (ANOVA) of the subgroups of ID showed 142 differentially expressed proteins, in comparison to healthy control group. From these, 120 proteins were found to be common among all subgroups. The remaining 22 proteins were categorized as exclusive proteins found only in disease subgroups. Furthermore, the hierarchical cluster analysis (HCL) of common significant proteins was also performed, followed by PANTHER protein classification and GO functional enrichment analysis. Results provides that the datasets of differentially expressed proteins, belong to the categories of immune / defense proteins, transfer carrier proteins, apolipoproteins, complement proteins, protease inhibitors, hemoglobin proteins etc., they are known to involvein immune system, and complement and coagulation pathway cascade and cholesterol metabolism pathway. Exclusively expressed 22 proteins were found to be disease stage specific and strong PPI network specifically those that have significant role in platelets activation and degranulation, such as Filamin A (FLNA). Furthermore, to validate the mass spectrometric findings, four highly significant proteins (APOA4, SAP, FLNA, and SERPING) were quantified by ELISA in all the study subjects. AUROC analysis showed a significant association of APOA4 (0.830), FLNA (0.958), SAP (0.754) and SERPING (0.600) with the disease. Apolipoprotein A4 (APOA4) has a significant role in cholesterol transport, and in modulation of glucose and lipid metabolism in the CNS. Similarly, FLNA has a crucial role in the nervous system, especially in the functioning of synaptic network. Therefore, both APOA4, and FLNA proteins represent good potential for candidate biomarkers for the diagnosis and prognosis of the intellectual disability. Overall, serum proteome of ID patients provides valuable information of proteins/pathways that are altered during ID progression.