A Case Report on a Syndesmotic Ankle Injury Treated With Arthrex TightRope.

Syndesmotic ankle injuries, often referred to as "high ankle sprains," pose intricate challenges in orthopedic practice, particularly among athletes engaged in high-impact sports. Conventional treatments have encompassed conservative approaches and the use of syndesmotic screws, each beset by inherent limitations. The Arthrex TightRope system has emerged as a pioneering alternative, heralded for its capacity to facilitate physiologic micromotion, eliminate the necessity for hardware removal, and expedite early rehabilitation. This case report delineates the management of a 29-year-old male professional soccer player who suffered a trimalleolar ankle fracture compounded by a severe syndesmotic injury subsequent to a road traffic accident. The patient underwent a comprehensive treatment involving open reduction and internal fixation (ORIF) of all three malleoli, complemented by syndesmotic stabilization employing the Arthrex TightRope system. Post-operative care encompassed a regimen of gradual weight-bearing and methodical rehabilitation. At the one-year follow-up, the patient demonstrated excellent ankle joint function devoid of pain or complications related to hardware, underscoring the efficacy of managing syndesmotic and malleolar fractures successfully. This case underscores the potential advantages of integrating traditional ORIF techniques with contemporary syndesmotic fixation strategies like the TightRope system for complex ankle fractures, advocating for further research to refine their optimal utilization in clinical settings.

Total Knee Arthroplasty With Long-Stem Implant: A Case Report of a Patient With Extreme Varus Deformity.

Constrained implants have become more common in difficult primary total knee arthroplasty (TKA) cases in recent years because they may more effectively and conveniently handle the substantial instability that is evident in osteoarthritis of knees with severe varus deformity. However, the need for a constrained TKA in such conditions is controversial, as constraint implants come with a bargain of stability for longitivity. In this case report, we have successfully shown that even in cases of significant instability and bone loss, intraoperative conversion to a restricted device is rarely necessary. In our case report, a 83-year-old female had complaints of severe pain in bilateral knees, with the right knee more than the left knee, since 12 years with severe varus deformity in the right knee. Physical examination revealed swelling and medial joint line tenderness with restriction of range of motion in bilateral knees. Pre-anesthetic checkup of the patient was done and patient was given clearance for surgery under American Society of Anesthesiologist (ASA)-2, total knee arthroplasty with a long stem was done, extreme varus deformity was corrected, osteophytes removed and tibial bone loss was repaired with bone cement. Post operatively patient showed significant improvement and McMaster University and Western Ontario Osteoarthritis Index (WOMAC) and Knee Society Scores (KSS) for pain, stiffness, and physical function during everyday activities were significantly improved compared to pre-operative assessment.

Bone Morphogenetic Proteins: A Promising Approach for Enhancing Fracture Healing.

Fracture healing is a complex biological process that can be delayed or impaired in certain situations. Bone morphogenetic proteins (BMPs) have emerged as a promising therapeutic strategy to promote bone formation and accelerate fracture healing. This editorial talks about the current understanding of BMPs, their mechanisms of action in fracture healing, and their potential applications in orthopedic trauma management. We also discuss the ongoing challenges and future directions for research on BMPs in fracture healing.

Exploring the globoid cell leukodystrophy protein network and therapeutic interventions.

Globoid cell leukodystrophy is a severe rare disorder characterized by white matter degradation, resulting in a progressive loss of physical and mental abilities and has extremely limited therapeutic interventions. Therefore, this study aimed to delve into the Globoid cell leukodystrophy associated intricate network of differentially expressed genes (p < 0.05, |Fc|> 1) to identify potential druggable targets and possible therapeutic interventions using small molecules. The disease-associated neuronal protein circuit was constructed and analyzed, identifying 53 nodes (minimum edge cutoff 1), among which five (FOS, FOSB, GDNF, GFRA1, and JUN) were discerned as potential core protein nodes. Although our research enumerates the potential small molecules to target various protein nodes in the proposed disease network, we particularly underscore T-5224 to inhibit c-Jun activity as JUN was identified as one of the pivotal elements within the disease-associated neuronal protein circuit. The evaluation of T-5224 binding energy (- 11.0 kcal/mol) from docking study revealed that the compound to exhibit a notable affinity towards Jun/CRE complex. Moreover, the structural integrity of complex was affirmed through comprehensive molecular dynamics simulations, indicating a stable hydrophilic interaction between T-5224 and the Jun/CRE complex, thereby enhancing protein compactness and reducing solvent accessibility. This binding energy was further substantiated by free binding analysis, revealing a substantial thermodynamics complex state (- 448.00 ± 41.73 kJ/mol). Given that this investigation is confined to a computational framework, we additionally propose a hypothetical framework to ascertain the feasibility of inhibiting the Jun/CRE complex with T-5224 against Globoid cell leukodystrophy, employing a combination of in vitro and in vivo methodologies as a prospective avenue of this study.

Multifaceted targets of cannabidiol in epilepsy: Modulating glutamate signaling and beyond.

Cannabidiol has been reported to interact with broad-spectrum biological targets with pleiotropic pharmacology including epilepsy although a cohesive mechanism is yet to be determined. Even though some studies propose that cannabidiol may manipulate glutamatergic signals, there is insufficient evidence to support cannabidiol direct effect on glutamate signaling, which is important in intervening epilepsy. Therefore, the present study aimed to analyze the epilepsy-related targets for cannabidiol, assess the differentially expressed genes with its treatment, and identify the possible glutamatergic signaling target. In this study, the epileptic protein targets of cannabidiol were identified using the Tanimoto coefficient and similarity index-based targets fishing which were later overlapped with the altered expression, epileptic biomarkers, and genetically altered proteins in epilepsy. The common proteins were then screened for possible glutamatergic signaling targets with differentially expressed genes. Later, molecular docking and simulation were performed using AutoDock Vina and GROMACS to evaluate binding affinity, ligand-protein stability, hydrophilic interaction, protein compactness, etc. Cannabidiol identified 30 different epilepsy-related targets of multiple protein classes including G-protein coupled receptors, enzymes, ion channels, etc. Glutamate receptor 2 was identified to be genetically varied in epilepsy which was targeted by cannabidiol and its expression was increased with its treatment. More importantly, cannabidiol showed a direct binding affinity with Glutamate receptor 2 forming a stable hydrophilic interaction and comparatively lower root mean squared deviation and residual fluctuations, increasing protein compactness with broad conformational changes. Based on the cheminformatic target fishing, evaluation of differentially expressed genes, molecular docking, and simulations, it can be hypothesized that cannabidiol may possess glutamate receptor 2-mediated anti-epileptic activities.

A Neglected Fracture of Acetabulum Treated With Total Hip Replacement.

Total hip replacement (THR) for osteoarthritis or inflammatory arthritis yields better outcomes than THR for patients with neglected acetabular fractures. The inferior clinical results mostly arise from an unforeseen bone deficit, making the treatment more time-consuming and complex for instances requiring acetabular restoration and bone grafting. There is a lack of research on the clinical results of THR in cases where acetabular fractures have been overlooked. A 55-year-old male patient presented with a malunited anterior column of the acetabulum, non-union of the posterior column with protrusion, and a significant impaction fracture in the femoral head. He was then treated with open reduction and internal fixation (ORIF) of acetabular columns, along with the use of a reconstruction cage and bone grafting. At the five-year follow-up, the patient had a good outcome. The keys to success include meticulous preoperative planning using radiography and computed tomography (CT) scans, sufficient exposure to define the fracture pattern, and the availability of a full range of devices and backup implants. If there are any prior implants, they should only be removed if they are infected or in the way of cup implantation. However, if there is a significant amount of bone loss, complex fractures may require extensive repair using revision total hip arthroplasty (THA) implants.

Investigation of cathinone analogs targeting human dopamine transporter using molecular modeling.

In a step towards understanding the structure-property relationship among Synthetic Cathinones (SCs), a combined methodology based on Density Functional Theory (DFT), Administration, Distribution, Metabolism, Excretion, and Toxicity (ADMET) predictions, docking and molecular dynamics simulations have been applied to correlate physicochemical descriptors of various SCs to their biological activity. The results from DFT and molecular docking studies correlate well with each other explaining the biological activity trends of the studied SCs. Quantum mechanical descriptors viz. polarizability, electron affinity, ionization potential, chemical hardness, electronegativity, molecular electrostatic potential, and ion interaction studies unravel the distinguishingly reactive nature of Group D (pyrrolidine substituted) and Group E (methylenedioxy and pyrrolidine substituted) compounds. According to ADMET analysis, Group D and Group E molecules have a higher probability of permeating through the blood-brain barrier. Molecular docking results indicate that Phe76, Ala77, Asp79, Val152, Tyr156, Phe320, and Phe326 constitute the binding pocket residues of hDAT in which the most active ligands MDPV, MDPBP, and MDPPP are bound. Finally, to validate the derived quantum chemical descriptors and docking results, Molecular Dynamics (MD) simulations are performed with homology-modelled hDAT (human dopamine transporter). The MD simulation results revealed that the majority of SCs remain stable within the hDAT protein's active sites via non-bonded interactions after 100 ns long simulations. The findings from DFT, ADMET analysis, molecular docking, and molecular dynamics simulation studies complement each other suggesting that pyrrolidine-substituted SCs (Group D and E), specifically, MPBP and PVN are proven potent SCs along with MDPV, validating various experimental observations.Communicated by Ramaswamy H. Sarma.

Effect of benthic and planktonic diatoms on the growth and biochemical composition of the commercial macroalga Pyropia haitanensis.

This study delves into how two ecotypes of diatom affect the Pyropia haitanensis, a valuable and commercial red macroalga. We co-cultivated P. haitanensis with a planktonic diatom Skeletonema costatum and benthic diatom Navicula climacospheniae. The results showed that benthic diatom significantly hindered P. haitanensis growth, while planktonic ones had no major impact. The macroalga restrained planktonic diatom growth but did not affect benthic diatom. Photosynthetic pigments of macroalga, except chlorophyll, were higher, indicating stress when exposed to diatoms. Microscopic images revealed dense benthic diatom attachment, potentially stressing thalli due to limited light and EPS secretion. Total carbohydrate slightly decreased in both diatom treatments, while total protein significantly decreased with increasing benthic diatom densities. In summary, benthic diatom notably influenced P. haitanensis growth, pigments, and total protein levels. This study sheds light on the interaction between microalgal ecotypes and commercial macroalga P. haitanensis, which is crucial for its economic significance.

Synergistic effects of Momordica charantia, Nigella sativa, and Anethum graveolens on metabolic syndrome targets: In vitro enzyme inhibition and in silico analyses.

Momordica charantia, Nigella sativa, and Anethum graveolens are established medicinal plants possessing noted anti-diabetic and anti-obesity properties. However, the molecular mechanisms underscoring their inhibitory effects on pancreatic lipase, α-glucosidase, and HMG-CoA reductase remain unexplored. This study aimed to elucidate the efficacy of various NS, MC, and AG blends in modulating the enzymatic activity of pancreatic lipase, HMG-CoA reductase, and a-glucosidase, utilizing an integrative approach combining in vitro assessments and molecular modeling techniques. A factorial design matrix generated eight distinct concentration combinations of NS, MC, and AG, subsequently subjected to in vitro enzyme inhibition assays. Molecular docking analyses using AutoDock Vina, molecular dynamics simulations, MMPBSA calculations, and principal component analysis, were executed with Gromacs to discern the interaction dynamics between the compounds and target enzymes. A formulation comprising NS:MC:AG at a 215:50:35 µg/mL ratio yielded significant inhibition of pancreatic lipase (IC50: 74.26 ± 4.27 µg/mL). Moreover, a concentration combination of 215:80:35 µg/mL effectively inhibited both α-glucosidase (IC50: 66.09 ± 3.98 µg/mL) and HMGCR (IC50: 129.03 µg/mL). Notably, MC-derived compounds exhibited superior binding affinity towards all three enzymes, compared to their reference molecules, with diosgenin, Momordicoside I, and diosgenin displaying binding affinities of -11.0, -8.8, and -7.9 kcal/mol with active site residues of pancreatic lipase, α-glucosidase, and HMGCR, respectively. Further, 100 ns molecular dynamics simulations revealed the formation and stabilization of non-bonded interactions between the compounds and the enzymes' active site residues. Through a synergistic application of in vitro and molecular modeling methodologies, this study substantiated the potent inhibitory activity of the NS:MC:AG blend (at a ratio of 215:80:35 µg/mL) and specific MC compounds against pancreatic lipase, α-glucosidase, and HMGCR. These findings provide invaluable insights into the molecular underpinnings of these medicinal plants' anti-diabetic and anti-obesity effects and may guide future therapeutic development.

The allelopathic potential of red macroalga Pyropia haitanensis solvent extracts on controlling bloom-forming microalgae: Insights into the inhibitory compounds.

Various strategies have been explored to mitigate the impact of harmful algal blooms (HABs). While chemical and physical methods have traditionally been employed to regulate microalgal growth, their prolonged adverse effects on the ecosystem are a cause for concern. Recognizing the integral role of macroalgae within the ecosystem, this study reveals the anti-algal properties of solvent-based extracts derived from the red macroalga Pyropia haitanensis as a means of preventing microalgal blooms. In our investigation, we initially assessed the growth-inhibitory effects of methanol and acetone extracts from P. haitanensis on five microalgae known to contribute to bloom-formation. Significantly reduced growth was observed in all microalgal species when inoculated with both methanol and acetone extracts. Further analysis revealed the effectiveness of the methanol extract (ME), and further fractionation with petroleum ether (PE), ethyl acetate (EA), and n-butanol (NB) for testing against Skeletonema costatum and Pseudo-nitzschia pungens. The methanol fractions exhibited strong inhibition, resulting in the complete elimination of both microalgae after 96 hours of exposure to PE, EA, and NB extracts. Gas Chromatography-Mass Spectroscopy (GC-MS) analysis of the ME and its solvent fractions identified 49 confirmed compounds. These compounds are likely potential contributors to the observed inhibition of microalgal growth. In conclusion, our findings suggest that solvent extracts from P. haitanensis possess substantial potential for the control of HABs, offering a promising avenue for further research and application in ecosystem management.

Investigation of alpha amylase inhibitors from Bidens pilosa L. by in silico and in vitro studies.

Bidens pilosa L. has been traditionally used as an anti-diabetic herbal medicine; however, its mechanism of action remains elusive. In this study, the potential role of B. pilosa compounds on alpha-amylase inhibition and regulation of multiple pathways was investigated via computational and experimental studies. The phytocompounds were retrieved from plant databases and published literature. The druggability profile of these compounds was predicted using MolSoft. The probable targets of these phytocompounds were predicted using BindingDB (similarity index ≥ 0.7). Further, compound-gene set-pathway and functional enrichment analysis were performed using STRING and KEGG pathway databases. The network between compound-protein-pathway was constructed using Cytoscape. Molecular docking was performed using AutoDock Vina, executed through the POAP pipeline. The stability of the best docked complex was subjected to all-atom molecular dynamics (MD) simulation for 100 ns to investigate their structural stabilities and intermolecular interactions using GROMACS software. Finally, B. pilosa hydroalcoholic extract was subjected to LC-MS and tested for dose- and time-dependent alpha-amylase inhibitory activity. Out of 31 bioactive compounds, 13 were predicted to modulate the human pancreatic alpha-amylase (AMY2A) and 12 pathways associated with diabetes mellitus. PI3K-Akt signaling pathway (hsa04151) scored the lowest false discovery rate by triggering 15 genes. Further intermolecular interaction analysis of the docked complex revealed that Brassidin had the highest active site interaction and lowest binding energy compared to standard acarbose, and MD reveals the formation of a stable complex throughout 100 ns production run. LC-MS analysis revealed the presence of 13 compounds (targeting AMY2A) in B. pilosa hydroalcoholic extract, which showed potent AMY2A inhibition by in vitro studies that corroborate in silico findings for its anti-diabetic activity. Based on these findings, enriched fractions/pure compounds inhibitory activity that can be performed in future for drug discovery. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-023-00187-9.

Computational pharmacology profiling of borapetoside C against melanoma.

Melanoma,also known as a 'black tumor', begins in the melanocytes when cells (that produce pigment) grows out of control. Immunological dysregulation, which raises the risk for multiple illnesses, including melanoma, may be influenced by stress tiggered through viral infection, long term effects of ultraviolet radiation, environmental pollutants etc. Borapetoside C is one of the phytoconstituents from Tinospora crispa, and its biological source has been reported for its antistress property. Network pharmacology and KEGG pathway analysis of borapetoside C-regulated proteins were conducted to identify the hub genes involved in melanoma development. Further, a molecular docking was performed between borapetoside C and targets involved in melanoma. Further, the top 3 complexes were selected based on the binding energy to conduct molecular dynamics simulations to evaluate the stability of ligand-protein complex followed by principal component analysis and dynamic cross-correlation matrix. In addition, borapetoside C was also screened for its pharmacokinetics and toxicity profile. Network Pharmacology studies and KEGG pathway analysis revealed 8 targets involved in melanoma. Molecular docking between borapetoside C and targets involved in melanoma identified 3 complexes with minimum binding i.e. borapetoside C- MAP2K1, MMP9, and EGFR. Further, molecular dynamics simulations showed a stable complex of borapetoside C with MMP9 and EGFR. The present study suggested that borapetoside C may target MMP9 and EGFR to possess an anti-melanoma property. This finding can be useful in developing a novel therapeutic agent against melanoma from a natural source.Communicated by Ramaswamy H. Sarma.

Unraveling snake venom phospholipase A2: an overview of its structure, pharmacology, and inhibitors.

Snake bite is a neglected disease that affects millions of people worldwide. WHO reported approximately 5 million people are bitten by various species of snakes each year, resulting in nearly 1 million deaths and an additional three times cases of permanent disability. Snakes utilize the venom mainly for immobilization and digestion of their prey. Snake venom is a composition of proteins and enzymes which is responsible for its diverse pharmacological action. Snake venom phospholipase A2 (SvPLA2) is an enzyme that is present in every snake species in different quantities and is known to produce remarkable functional diversity and pharmacological action like inflammation, necrosis, myonecrosis, hemorrhage, etc. Arachidonic acid, a precursor to eicosanoids, such as prostaglandins and leukotrienes, is released when SvPLA2 catalyzes the hydrolysis of the sn-2 positions of membrane glycerophospholipids, which is responsible for its actions. Polyvalent antivenom produced from horses or lambs is the standard treatment for snake envenomation, although it has many drawbacks. Traditional medical practitioners treat snake bites using plants and other remedies as a sustainable alternative. More than 500 plant species from more than 100 families reported having venom-neutralizing abilities. Plant-derived secondary metabolites have the ability to reduce the venom's adverse consequences. Numerous studies have documented the ability of plant chemicals to inhibit the enzymes found in snake venom. Research in recent years has shown that various small molecules, such as varespladib and methyl varespladib, effectively inhibit the PLA2 toxin. In the present article, we have overviewed the knowledge of snake venom phospholipase A2, its classification, and the mechanism involved in the pathophysiology of cytotoxicity, myonecrosis, anticoagulation, and inflammation clinical application and inhibitors of SvPLA2, along with the list of studies carried out to evaluate the potency of small molecules like varespladib and secondary metabolites from the traditional medicine for their anti-PLA2 effect.

Intraoperative Identification and Mosaicplasty in a Case of Femur Subchondral Osteoid Osteoma.

Osteoid osteomas (OOs) are non-malignant primary bone abnormalities marked by a central nidus surrounded by reactive sclerosis. They typically manifest as aggravated nocturnal pain that responds to non-steroidal anti-inflammatory drugs (NSAIDs). These growths are most frequently found within the intracortical bone and the diaphysis of elongated bones. Within the realm of uncommon conditions, intra-articular OOs (IAOOs) exhibit distinctive presentations, often leading to postponed or inaccurate diagnoses. We present a patient with OO at the distal femur, accessible through the knee joint, which was intraoperatively identified and localized using a needle pricking technique and treated by arthrotomy and mosaicplasty.

Congenital Pseudoarthrosis of Tibia With Anterolateral Bowing Treated With Ilizarov Ring Fixator: A Case Report.

Congenital pseudarthrosis of the tibia (CPT) is a rare, dysplastic condition that is characterized by a "false joint" in the tibia, leading to potential disability. We present a rare case report of a 12-year-old male from India with a history of neurofibromatosis type 1 (NF1) and anterolateral bowing of the tibia since birth. He sustained a tibial fracture during play. X-ray evaluation confirmed the fracture, and a clinical diagnosis of CPT was established. The treatment involved corticotomy for deformity correction and stabilization using Ilizarov's ring fixation. The procedure was successful, with post-operative radiological evaluations showing significant improvement in the center of rotation of angulation (CORA) from 60° pre-operatively to 25° post-operatively. The patient was discharged with an external fixator and after seven months, transitioned to full weight-bearing ambulation with a specialized brace. The Ilizarov procedure proved to be a safe and effective treatment for CPT, offering benefits such as limb lengthening and ankle stabilization.

Structural insights into modeling of hepatitis B virus reverse transcriptase and identification of its inhibitors from potential medicinal plants of Western Ghats: an in silico and in vitro study.

The present study was proposed to model full-length HBV-RT and investigate the intermolecular interactions of known inhibitor and libraries of phytocompounds to probe the potential natural leads by in silico and in vitro studies. Homology modeling of RT was performed by Phyre2 and Modeller and virtual screening of ligands implemented through POAP pipeline. Molecular dynamics (MD) simulation (100 ns) and MM-GBSA calculations were performed using Schrodinger Desmond and Prime, respectively. Phytocompounds probable host protein targets gene set pathway enrichment and network analysis were executed by KEGG database and Cytoscape software. Prioritized plant extracts/enriched fraction LC-MS analysis was performed and along with pure compound, RT inhibitory activity, time-dependent HBsAg and HBeAg secretion, and intracellular HBV DNA, and pgRNA by qRT-PCR was performed in HepG2.2.15 cell line. Among the screened chemical library of 268 phytocompounds from 18 medicinal plants, 15 molecules from Terminalia chebula (6), Bidens pilosa (5), and Centella asiatica (4)) were identified as potential inhibitors of YMDD and RT1 motif of HBV-RT. MD simulation demonstrated stable interactions of 15 phytocompounds with HBV-RT, of which 1,2,3,4,6-Pentagalloyl Glucose (PGG) was identified as lead molecule. Out of 15 compounds, 11 were predicted to modulate 39 proteins and 15 molecular pathways associated with HBV infection. TCN and TCW (500 µg/mL) showed potent RT inhibition, decreased intracellular HBV DNA, and pgRNA, and time-dependent inhibition of HBsAg and HBeAg levels compared to PGG and Tenofovir Disoproxil Fumarate. We propose that the identified lead molecules from T. chebula as promising and cost-effective moieties for the management of HBV infection.Communicated by Ramaswamy H. Sarma.

Mechanopathology of biofilm-like Mycobacterium tuberculosis cords.

Mycobacterium tuberculosis (Mtb) cultured axenically without detergent forms biofilm-like cords, a clinical identifier of virulence. In lung-on-chip (LoC) and mouse models, cords in alveolar cells contribute to suppression of innate immune signaling via nuclear compression. Thereafter, extracellular cords cause contact-dependent phagocyte death but grow intercellularly between epithelial cells. The absence of these mechanopathological mechanisms explains the greater proportion of alveolar lesions with increased immune infiltration and dissemination defects in cording-deficient Mtb infections. Compression of Mtb lipid monolayers induces a phase transition that enables mechanical energy storage. Agent-based simulations demonstrate that the increased energy storage capacity is sufficient for the formation of cords that maintain structural integrity despite mechanical perturbation. Bacteria in cords remain translationally active despite antibiotic exposure and regrow rapidly upon cessation of treatment. This study provides a conceptual framework for the biophysics and function in tuberculosis infection and therapy of cord architectures independent of mechanisms ascribed to single bacteria.

Unusual Case of Long Head of Biceps Tendon Synovial Chondromatosis.

Introduction: Synovial chondromatosis is a rare benign tumor involving the major joints. This condition results from metaplasia of synovium into chondrocytes leading to formation of multiple loose bodies. Extra articular glenohumeral joint synovial chondromatosis involving long head of biceps is very rare. Case Report: A 38-year-old male presented with history of insidious onset, dull aching pain in right shoulder for 6 months. Clinicoradiological examination revealed calcific mass around the long head of biceps tendon. The calcific mass and loose bodies were removed en bloc. Histopathological examination concurred to be synovial chondromatosis. Conclusion: We hereby report a rare case of long head biceps tendon synovial chondromatosis of shoulder which was successfully treated by combined arthroscopic and open method. The results of surgical excision are excellent.

The marijuana-schizophrenia multifaceted nexus: Connections and conundrums towards neurophysiology.

Delta-9-tetrahydrocannabinol, a component of marijuana, interacts with cannabinoid receptors in brain involved in memory, cognition, and emotional control. However, marijuana use and schizophrenia development is a complicated and contentious topic. As a result, more investigation is needed to understand this relationship. Through the functional enrichment analysis, we report the delta-9-tetrahydrocannabinol to manipulate the homeostatic biological process and molecular function of different macromolecules. Additionally, using molecular docking and subsequent processing for molecular simulations, we assessed the binding ability of delta-9-tetrahydrocannabinol with the estrogen-related protein, dopamine receptor 5, and hyaluronidase. It was found that delta-9-tetrahydrocannabinol may have an impact on the brain's endocannabinoid system and may trigger the schizophrenia progression in vulnerable people. Delta-9-tetrahydrocannabinol may interfere with the biological function of 18 proteins linked to schizophrenia and disrupt the synaptic transmission (dopamine, glutamine, and gamma-aminobutyric acid). It was discovered that it may affect lipid homeostasis, which is closely related to membrane integrity and synaptic plasticity. The negative control of cellular and metabolic processes, fatty acids binding /activity, and the manipulated endocannabinoid system (targeting cannabinoid receptors) were also concerned with delta-9-tetrahydrocannabinol. Hence, this may alter neurotransmitter signaling involved in memory, cognition, and emotional control, showing its direct impact on brain physiological processes. This may be one of the risk factors for schizophrenia development which is also closely tied to some other variables such as frequency, genetic vulnerability, dosage, and individual susceptibility.