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1.
Cureus ; 16(4): e57938, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38738158

RESUMO

This comprehensive review explores the mechanical and anatomical axis approaches in total knee replacement (TKR) surgery, addressing the ongoing debate within the orthopedic community. Emphasizing the significance of TKR in alleviating knee-related disorders, this review underscores the pivotal role of accurate alignment in achieving optimal surgical outcomes. The purpose is to navigate the divide between the well-established mechanical axis approach, focusing on a straight-line alignment, and the anatomical axis approach, aligning with natural knee landmarks. The analysis delves into the advantages, disadvantages, and clinical implications of each approach, offering a nuanced perspective on their efficacy. The conclusion emphasizes a patient-centric approach, recommending the adoption of hybrid strategies and the incorporation of emerging technologies for enhanced precision. The future of TKR aligns with personalized medicine, leveraging advancements in computer-assisted navigation, robotics, and patient-specific implants. Ongoing professional development and interdisciplinary collaboration are crucial for surgeons, and as the field evolves, innovations in artificial intelligence, imaging, and 3D printing are expected to shape the trajectory of TKR alignment approaches.

2.
Cureus ; 16(3): e56052, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38618445

RESUMO

A rare benign bone condition called monostotic fibrous dysplasia (MFD) is characterized by the growth of fibrous tissue in place of a normal bone. It may lead to deformity in the affected bone, pain, and a pathologic fracture due to bone weakness. Hereunder, a case report of MFD in a 17-year-old male adolescent presenting to the hospital with localized bone pain and swelling in his right tibia is presented. After clinical examination and radiographic imaging, a provisional diagnosis of benign osteolytic lesion was considered. A magnetic resonance imaging (MRI) scan of the leg suggested the possibility of fibrous dysplasia or adamantinoma. The patient was managed with an intralesional curettage of the dysplastic bone and packing the cavity with blocks of a synthetic bone. The excised material was sent for histopathology, which established the diagnosis of fibrous dysplasia.

3.
Cureus ; 16(3): e55525, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38576658

RESUMO

Diabetes is a chronic metabolic disorder characterized by elevated levels of glucose in the blood. This causes small nerve polyneuropathy resulting in diabetic foot ulcers. A diabetic foot ulcer is an open sore or wound that develops as a result of chronic diabetes. Indocyanine green angiography (ICGA) near-infrared (NIR) can provide real-time visualization of blood flow within the microvasculature of the underlying organ. Here, we discuss a 63-year-old patient who came with a diabetic foot ulcer over his right great toe. His blood glucose level was 208 mg/dl. He drinks alcohol occasionally and smokes regularly. The tissue perfusion of his right foot was checked using the indocyanine green dye, after which orthopedic surgeons were consulted, and the gangrenous part was amputated.

4.
Plant Physiol Biochem ; 208: 108513, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38513519

RESUMO

Plants evolved several acquired tolerance traits for drought stress adaptation to maintain the cellular homeostasis. Drought stress at the anthesis stage in rice affects productivity due to the inefficiency of protein synthesis machinery. The effect of translational mechanisms on different pathways involved in cellular tolerance plays an important role. We report differential responses of translation-associated mechanisms in rice using polysome bound mRNA sequencing at anthesis stage drought stress in resistant Apo and sensitive IR64 genotypes. Apo maintained higher polysomes with 60 S-to-40 S and polysome-to-monosome ratios which directly correlate with protein levels under stress. IR64 has less protein levels under stress due to defective translation machinery and reduced water potential. Many polysome-bound long non-coding RNAs (lncRNA) were identified in both genotypes under drought, influencing translation. Apo had higher levels of N6-Methyladenosine (m6A) mRNA modifications that contributed for sustained translation. Translation machinery in Apo could maintain higher levels of photosynthetic machinery-associated proteins in drought stress, which maintain gas exchange, photosynthesis and yield under stress. The protein stability and ribosome biogenesis mechanisms favoured improved translation in Apo. The phytohormone signalling and transcriptional responses were severely affected in IR64. Our results demonstrate that, the higher translation ability of Apo favours maintenance of photosynthesis and physiological responses that are required for drought stress adaptation.


Assuntos
Resistência à Seca , Oryza , Oryza/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fotossíntese , Secas , Polirribossomos/metabolismo , Estresse Fisiológico/genética
5.
Int Orthop ; 48(5): 1303-1311, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38499714

RESUMO

PURPOSE: AI has shown promise in automating and improving various tasks, including medical image analysis. Distal humerus fractures are a critical clinical concern that requires early diagnosis and treatment to avoid complications. The standard diagnostic method involves X-ray imaging, but subtle fractures can be missed, leading to delayed or incorrect diagnoses. Deep learning, a subset of artificial intelligence, has demonstrated the ability to automate medical image analysis tasks, potentially improving fracture identification accuracy and reducing the need for additional and cost-intensive imaging modalities (Schwarz et al. 2023). This study aims to develop a deep learning-based diagnostic support system for distal humerus fractures using conventional X-ray images. The primary objective of this study is to determine whether deep learning can provide reliable image-based fracture detection recommendations for distal humerus fractures. METHODS: Between March 2017 and March 2022, our tertiary hospital's PACS data were evaluated for conventional radiography images of the anteroposterior (AP) and lateral elbow for suspected traumatic distal humerus fractures. The data set consisted of 4931 images of patients seven years and older, after excluding paediatric images below seven years due to the absence of ossification centres. Two senior orthopaedic surgeons with 12 + years of experience reviewed and labelled the images as fractured or normal. The data set was split into training sets (79.88%) and validation tests (20.1%). Image pre-processing was performed by cropping the images to 224 × 224 pixels around the capitellum, and the deep learning algorithm architecture used was ResNet18. RESULTS: The deep learning model demonstrated an accuracy of 69.14% in the validation test set, with a specificity of 95.89% and a positive predictive value (PPV) of 99.47%. However, the sensitivity was 61.49%, indicating that the model had a relatively high false negative rate. ROC analysis showed an AUC of 0.787 when deep learning AI was the reference and an AUC of 0.580 when the most senior orthopaedic surgeon was the reference. The performance of the model was compared with that of other orthopaedic surgeons of varying experience levels, showing varying levels of diagnostic precision. CONCLUSION: The developed deep learning-based diagnostic support system shows potential for accurately diagnosing distal humerus fractures using AP and lateral elbow radiographs. The model's specificity and PPV indicate its ability to mark out occult lesions and has a high false positive rate. Further research and validation are necessary to improve the sensitivity and diagnostic accuracy of the model for practical clinical implementation.


Assuntos
Fraturas Ósseas , Fraturas Distais do Úmero , Humanos , Criança , Inteligência Artificial , Fraturas Ósseas/diagnóstico por imagem , Radiografia , Algoritmos , Estudos Retrospectivos
6.
Cureus ; 16(2): e53895, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38465082

RESUMO

Periprosthetic fractures (PPF) of the femur in connection with total hip arthroplasty are becoming common and also frequently challenging to repair. Such patients typically are frail, elderly, and have osteoporosis. Owing to a scarcity of research there are no clear strategies for its effective management. However, the Vancouver classification may help in facilitating treatment decisions. For fractures around a loose femoral prosthesis (types B2 and B3), revision using a modular uncemented long stem, with or without additional fracture fixation, has been known to provide a reliable outcome. It is prudent to treat osteoporosis for fracture healing and to prevent further fractures. In this case report, we share our experience with the use of an uncemented modular long femoral stem prosthesis with a cerclage wiring technique for the management of Vancouver type B3 PPF of the left femur in a 63-year-old male patient. Revision arthroplasty using a long stem prosthesis with a cerclage wiring technique can provide better fixation, stability, and functional outcomes for the patient.

7.
Cureus ; 16(1): e52708, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38384607

RESUMO

This comprehensive review examines the intricate relationship between genetic variations in collagen-encoding genes and their implications in intervertebral disc degeneration (IVDD). Intervertebral disc degeneration is a prevalent spinal condition characterized by structural and functional changes in intervertebral discs (IVDs), and understanding its genetic underpinnings is crucial for advancing diagnostic and therapeutic strategies. The review begins by exploring the background and importance of collagen in IVDs, emphasizing its role in providing structural integrity. It then delves into the significance of genetic variations within collagen-encoding genes, categorizing and discussing their potential impact on disc health. The methods employed in studying these variations, such as genome-wide association studies (GWASs) and next-generation sequencing (NGS), are also reviewed. The subsequent sections analyze existing literature to establish associations between genetic variations and IVDD, unraveling molecular mechanisms linking genetic factors to disc degeneration. The review concludes with a summary of key findings, implications for future research and clinical practice, and a reflection on the importance of understanding genetic variations in collagen-encoding genes to diagnose and treat IVDD. The insights gleaned from this review contribute to our understanding of IVDD and hold promise for the development of personalized interventions based on individual genetic profiles.

8.
Cureus ; 16(1): e53033, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38410349

RESUMO

Soft tissue angiofibroma is a pathology consisting of a benign fibrous vascularized tumor that mimics low-grade sarcoma. Such tumors frequently arise in the extremities, more commonly in the lower extremities, presenting as a slow-growing, painless swelling. Females are more commonly affected than males. We present the case of a 42-year-old male with a slow-growing, painless mass on the extensor aspect of his left foot. Differential diagnoses considered were soft tissue fibrosarcoma, liposarcoma, and sebaceous cysts. Surgical excision of the tumor was done, and upon histopathology, there were multiple lobules with well-circumscribed, alternating areas of collagenous and myxoid tissues. There was a prominent small vascular network with uniformly arranged spindle cells consisting of pale eosinophil-rich cytoplasm and small ovoid nuclei, fine chromatin, and an indistinct nucleolus. There are not many reported cases of this clinical entity, and every new case reported brings light to the pathology and progression of this tumor. Understanding this pathology is necessary since it mimics many other skin and soft tissue tumors.

9.
Cureus ; 16(1): e53173, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38420086

RESUMO

Synovial chondromatosis is a rare and benign disorder that involves the synovial lining of joints, synovial sheaths and bursae. The synovial layer of the joint is affected by a metaplastic process which in turn converts it into cartilagenous tissue. Eventually, it gets dislodged and transformed into a loose body in the large joints. We report the case of a 24-year-old young athlete who presented with complaints of painful movements and restriction of joint movements associated with a growing deformity in the right knee joint. This case report aims to describe a rare synovial pathology that necessitated arthroscopic synovectomy and diagnostic arthroscopy to treat, particularly in younger individuals. The atypical feature, in this case, was metaplastic development from the peripheral joint capsule attached to the surrounding cartilage, which, to the extent that the authors are aware, has only been documented in one instance in the record. Magnetic resonance imaging (MRI) was performed which demonstrated evidence of the joint effusion, synovial hypertrophy and a loose calcific body just anterior of the distal femoral condyle causing pressure over the patellar tendon anteriorly as well as a hyper-dense cyst in the popliteal region. Treatment often requires partial or complete synovectomy with either an arthroscopic or open approach.

10.
Oxf Open Immunol ; 4(1): iqad008, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38089636

RESUMO

Malaria and tuberculosis remain highly prevalent infectious diseases and continue to cause significant burden worldwide. Endemic regions largely overlap, and co-infections are expected to occur frequently. Surprisingly, malaria-tuberculosis co-infection is relatively understudied. Malaria has long been known to have immunomodulatory effects, for example resulting in reduced vaccination responses against some pathogens, and it is conceivable that this also plays a role if co-infection occurs. Data from animal studies indeed suggest clinically important effects of malaria-tuberculosis co-infection on the immune responses with potential consequences for the pathophysiology and clinical course of both infections. Specifically, rodent studies consistently show reduced control of mycobacteria during malaria infection. Although the underlying immunological mechanisms largely remain unclear, an altered balance between pro- and anti-inflammatory responses may play a role. Some observations in humans also support the hypothesis that malaria infection skews the immune responses against tuberculosis, but data are limited. Further research is needed to unravel the underlying immunological mechanisms and delineate possible implications of malaria-tuberculosis co-infection for clinical practice.

11.
Cureus ; 15(11): e48750, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38094554

RESUMO

Orthopedic surgeries, ranging from joint replacements to fracture fixations, are integral procedures that enhance the quality of life for countless individuals. Effective postoperative pain management is crucial in ensuring optimal patient recovery and satisfaction. This comprehensive review analyzes the diverse array of analgesic modalities employed in orthopedic practice for postoperative pain relief. The review systematically explores the pharmacological landscape of analgesics commonly used in orthopedic settings, including opioids, non-steroidal anti-inflammatory drugs, acetaminophen, and adjuvant medications. Emphasis is placed on their mechanisms of action, efficacy profiles, and potential adverse effects. Special attention is given to the evolving role of multimodal analgesia, which combines various agents to achieve synergistic pain control while minimizing individual drug-related complications. Furthermore, the review addresses the emerging trends and advancements in postoperative analgesia within orthopedics, such as integrating regional anesthesia techniques, peripheral nerve blocks, and novel pharmacological agents. A critical evaluation of evidence-based practices and recent clinical trials is incorporated to guide practitioners in making informed decisions regarding postoperative pain management. Consideration is also given to the individualized nature of pain experiences and the importance of patient-centric approaches. The review underscores the significance of tailoring analgesic regimens based on patient characteristics, surgical procedures, and potential complications, fostering a personalized and effective pain management strategy. In conclusion, this comprehensive review is valuable for orthopedic practitioners, anesthetists, and healthcare professionals involved in postoperative care. By synthesizing current knowledge and highlighting evolving trends, the review contributes to the ongoing dialogue on optimizing pain management strategies in orthopedic practice, ultimately improving patient outcomes and satisfaction.

12.
Cureus ; 15(10): e47410, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38022148

RESUMO

The primary posterior stabilizer of the knee is the posterior cruciate ligament (PCL), the largest intra-articular ligament in the human knee. One of the four primary ligaments of the knee joint, the PCL, serves to support the tibia on the femur. An extreme force applied anteriorly to the proximal tibia of the flexed knee results in trauma to the PCL. Dashboard injuries, which occur when the knee is driven into the dashboard after a collision with a motor vehicle, are frequent causes. Grade 1 and 2 acute injuries are often addressed conservatively due to the PCL's natural capacity for mending. If a grade 3 injury occurs, a cautious trial can be conducted on elderly or low-demand patients. When standard treatment for isolated grade 3 injuries has failed, surgery is advised. Single-bundle or double-bundle techniques using either transtibial tunnel or tibial inlay techniques are among the reconstruction approaches. Restoring the natural kinematics of the knee and forestalling persistent posterior and mixed rotatory knee laxity are the ultimate goals of treating PCL injuries through a personalized strategy. These injuries may become more common in the future as more people participate in sports. As a result of ongoing instability, discomfort, diminished function, and the emergence of inflammatory and degenerative disorders of joints, PCL rips are becoming more well-acknowledged as a cause of morbidity and decreased function.

13.
Cureus ; 15(10): e47984, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38034236

RESUMO

The outbreak of COVID-19 was seen first in Wuhan, China, on December 31, 2019. Following this, the virus has emerged, mutated, and spread to all parts of the world, taking many lives. Scientists and healthcare workers all over the world have been involved in developing vaccines and drugs to prevent the deadly virus from spreading. In this review article, we focus on how the human body responds to immune responses by producing antibodies against our immune system and serum levels in different age groups. Few studies are being considered, which include data collected from adults in the UK community, health workers from Oxfordshire, studies from the UK, healthcare workers at a university healthcare center in Turkey, and lastly, non-seropositive and seronegative healthcare workers in the USA children's hospital, respectively, and their responses to the goal. In addition to focusing on this study and its results, we also discuss the role of different vaccines and their development and antibody responses in the body due to natural and post-vaccine infections that include both doses in humans. We focus mainly on immunoglobulin M (IgM) and immunoglobulin G (IgG) levels in the serum produced by plasma cells, as they are involved in the first line of defense against the disease. With the development of effective vaccines and their production, trial, and market distribution to needy people, there are certain prospects for slowing down the progression of the virus, reducing mortality, and preventing re-infection in humans. However impactful and beneficial these vaccines have proven, they also carry a certain amount of danger to the people taking them. We also discuss in this article certain infrequent hematological and cardiovascular complications of the vaccine and their effect on the population.

14.
J Biomol Struct Dyn ; : 1-19, 2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37811543

RESUMO

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.

15.
Cureus ; 15(9): e44929, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37818500

RESUMO

Kohler's disease is characterized by osteochondritis of the navicular bone due to various factors like the lack of blood supply and late ossification of the bone. In particular, it is a disease of the pediatric age group, which has male preponderance. It may present with bony pain unilaterally or, at times, be asymptomatic and diagnosed accidentally. Clinical presentation and radiological investigations are the mainstay of diagnosis. This self-limiting condition requires only symptomatic conservative management. A surgical approach is not yet indicated. One such case of bilateral Kohler's disease is presented in this report. Here, we discuss the disease's presentation, examination, treatment, and prognosis.

16.
Saudi J Biol Sci ; 30(9): 103766, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37588570

RESUMO

The present research was framed to determine the key compounds present in the plant Ocimum gratissimum L. targeting protein molecules of Diabetes Mellitus (DM) by employing In-silico approaches. Phytochemicals previously reported to be present in this herb were collated through literature survey and public phytochemical databases, and their probable targets were anticipated using BindingDB (p ≥ 0.7). STRING and KEGG pathway databases were employed for pathway enrichment analysis. Homology modelling was executed to elucidate the structures of therapeutic targets. Further, Phytocompounds from O. gratissimum were subjected for docking with four therapeutic targets of DM by using AutoDock vina through POAP pipeline implementation. 30 compounds were predicted to target 136 protein molecules including aldose reductase, DPP4, alpha-amylase, and alpha-glucosidase. Neuroactive ligand-receptor interaction, MAPK, PI3K-Akt, starch and insulin resistance were predicted to have potentially modulation by phytocompounds. Based on the phytocompound's binding score with the four targets of DM, Rutin scored the lowest binding energy (-11 kcal/mol) with Aldose reductase by forming 17 intermolecular interactions. In conclusion, based on the network and binding score, phytocompounds from O. gratissimum have a synergistic and considerable effect in the management of DM via multi-compound, multi-target, and multi-pathway mechanisms.

17.
J Orthop Case Rep ; 13(7): 121-125, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37521390

RESUMO

Introduction: Multiligament knee injuries (MLKIs) are difficult to manage occurrence and are usually associated with poor functional outcomes. Knee dislocations involving both cruciate ligaments are relatively rare compared to other multifilament injuries involving one cruciate ligament and a collateral ligament. Multiple studies have reported the Tegnor score after surgery as 3 or 4. In 44% of cases with posterolateral corner (PLC) injury and biceps femoris tendon rupture or avulsion of the fibular head, a palsy of the common peroneal nerve (CPN) occurs. About half of these cases do not exhibit functional recovery. Case Report: A 20 years old long jump national athlete sustained varus and hyperextension injury leading to a multiligament knee injury (anterior cruciate ligament, posterior cruciate ligament, PLC, and medial collateral ligament) and CPN palsy. After a staged surgical procedure and structured rehabilitation protocol, the athlete was able to return to preinjury level in 18 months. At present, 4 years postoperatively, the patient can walk full weight-bearing with no instability. On the latest follow-up, the Lachman's test is negative, posterior drawer test negative, varus, and valgus stress test negative. Knee ranges of motion 0 to 140 degrees. The patient reported that Tegnor Score was 8. Conclusion: Surgical management of MKLI with CPN palsy can give reasonable functional outcome.

18.
Molecules ; 28(6)2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36985402

RESUMO

Finding structurally similar compounds in compound databases is highly efficient and is widely used in present-day drug discovery methodology. The most-trusted and -followed similarity indexing method is Tanimoto similarity indexing. Epigenetic proteins like histone deacetylases (HDACs) inhibitors are traditionally used to target cancer, but have only been investigated very recently for their possible effectiveness against rheumatoid arthritis (RA). The synthetic drugs that have been identified and used for the inhibition of HDACs include SAHA, which is being used to inhibit the activity of HDACs of different classes. SAHA was chosen as a compound of high importance as it is reported to inhibit the activity of many HDAC types. Similarity searching using the UNPD database as a reference identified aglaithioduline from the Aglaia leptantha compound as having a ~70% similarity of molecular fingerprints with SAHA, based on the Tanimoto indexing method using ChemmineR. Aglaithioduline is abundantly present in the shell and fruits of A. leptantha. In silico studies with aglaithioduline were carried out against the HDAC8 protein target and showed a binding affinity of -8.5 kcal mol. The complex was further subjected to molecular dynamics simulation using Gromacs. The RMSD, RMSF, compactness and SASA plots of the target with aglaithioduline, in comparison with the co-crystallized ligand (SAHA) system, showed a very stable configuration. The results of the study are supportive of the usage of A. leptantha and A. edulis in Indian traditional medicine for the treatment of pain-related ailments similar to RA. Our study therefore calls for further investigation of A. leptantha and A. edulis for their potential use against RA by targeting epigenetic changes, using in vivo and in vitro studies.


Assuntos
Artrite Reumatoide , Inibidores de Histona Desacetilases , Humanos , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/química , Amidas , Simulação de Dinâmica Molecular , Epigênese Genética , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Simulação de Acoplamento Molecular , Histona Desacetilases/genética , Proteínas Repressoras
19.
Molecules ; 28(3)2023 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-36770785

RESUMO

Cancer is characterized by the abnormal development of cells that divide in an uncontrolled manner and further take over the body and destroy the normal cells of the body. Although several therapies are practiced, the demand and need for new therapeutic agents are ever-increasing because of issues with the safety, efficacy and efficiency of old drugs. Several plant-based therapeutics are being used for treatment, either as conjugates with existing drugs or as standalone formulations. Withania somnifera (L.) Dunal is a highly studied medicinal plant which is known to possess immunomodulatory activity as well as anticancer properties. The pivotal role of KAT6A in major cellular pathways and its oncogenic nature make it an important target in cancer treatment. Based on the literature and curated datasets, twenty-six compounds from the root of W. somnifera and a standard inhibitor were docked with the target KAT6A using Autodock vina. The compounds and the inhibitor complexes were subjected to molecular dynamics simulation (50 ns) using Desmond to understand the stability and interactions. The top compounds (based on the docking score of less than -8.5 kcal/mol) were evaluated in comparison to the inhibitor. Based on interactions at ARG655, LEU686, GLN760, ARG660, LEU689 and LYS763 amino acids with the inhibitor WM-8014, the compounds from W. somnifera were evaluated. Withanolide D, Withasomniferol C, Withanolide E, 27-Hydroxywithanone, Withanolide G, Withasomniferol B and Sitoindoside IX showed high stability with the residues of interest. The cell viability of human breast cancer MCF-7 cells was evaluated by treating them with W. Somnifera root extract using an MTT assay, which showed inhibitory activity with an IC50 value of 45 µg/mL. The data from the study support the traditional practice of W. somnifera as an anticancer herb.


Assuntos
Neoplasias , Plantas Medicinais , Withania , Vitanolídeos , Humanos , Vitanolídeos/farmacologia , Vitanolídeos/metabolismo , Simulação de Acoplamento Molecular , Withania/química , Plantas Medicinais/metabolismo , Extratos Vegetais/química , Simulação de Dinâmica Molecular , Raízes de Plantas/química , Histona Acetiltransferases
20.
J Biomol Struct Dyn ; 41(22): 12610-12619, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36651083

RESUMO

Pseudomonas aeruginosa is one of the leading opportunistic pathogens that causes nosocomial pneumonia and mostly in people with cystic fibrosis. In the present study, an in-silicoapproach was adopted to identify the novel drug target against Pseudomonas aeruginosa by employing subtractive genomics and molecular docking studies. Each step in the subtractive genomics scrutinized the bacterial proteome and determined a potential drug target against Pseudomonas aeruginosa. 71 essential proteins were obtained from the subcellular localization method that resides in the extracellular region. Metabolic pathways were studied to elucidate the unique pathways where the involvement of proteins present in the pathogen was predicted and a total of 6 unique pathways were determined. By, Genome mining of the source organism Paenibacillusehimensis, 9 ligands were obtained. The molecular docking analysis between the binding site of target protein NDK and ligands was carried out by employing the AutoDock Vina tool. Based on the highest binding affinity, Paenibactin, AnabaenopeptinNZ857 and Nostamide A complex with NDK protein with a lower binding energy of -7.5 kcal/mol, -7.4and -7.2 kcal/molrespectively were considered for the simulation studies. Molecular dynamics simulation studies showed the ligand in complex with protein was highly stable and rigid for a duration of 150 ns. For Paenibactin, AnabaenopeptinNZ857 and Nostamide Acomplex with protein, RMSD plot showed a deviation of ∼0.2-0.3 nm till ∼30ns/50 ns-110ns and further stabilized. The radius of the gyration plot clearly showed that the values stayed at ∼1.45 nm- 1.55 nm showing compactness and stability. The SASA stayed at the range ∼80nm2 and at least one total number of hydrogen bonds was shown throughout the 150 ns simulation for all three possible ligand-protein complexes. In the RMSF plot, the maximum fluctuation was ranged from ∼0.4-0.42 nm at the range between ∼57ns-60ns.The Paenibactin, AnabaenopeptinNZ857 and Nostamide A complex with NDK protein showed a stable, rigid and compact interaction throughout the simulation of duration 150 ns.Communicated by Ramaswamy H. Sarma.


Assuntos
Núcleosídeo-Difosfato Quinase , Pseudomonas aeruginosa , Humanos , Simulação de Acoplamento Molecular , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Núcleosídeo-Difosfato Quinase/genética , Ligantes , Sítios de Ligação , Simulação de Dinâmica Molecular
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