The Marie Curie Science Research Center

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Summary of Papers

Treatment of Rheumatoid Arthritis

Background: Methotrexate (MTX), sulfonamides, hydroxychloroquine, and leflunomide have consistently resulted in remission with relatively mild to moderate adverse effects in patients with rheumatoid arthritis (RA). Modern medications outperform traditional treatments in that they target the pathological processes that underlie the development of RA.

Methods: Following PRISMA guidelines, the authors accomplished a systematic review of the clinical efficacy of RA drugs, including the biologics such as Tumor Necrosis Factor-alpha inhibitors (TNF-α i) like Etanercept, Infliximab, Golimumab, and Adalimumab, kinase inhibitors (JAK inhibitors including Baricitinib and Tofacitanib), SyK inhibitors like Fos-tamatinib, MAPK inhibitors such as Talmapimod, T-cell inhibitors (Abatacept), IL6 blockers (Tocilizumab), and B cells depleters (Rituximab). These drugs have been found to increase remission rates when combined with MTX. A bioinformatics-based network was designed applying STRING-MODEL and the DrugBank database for the aforementioned drugs and MTX and, finally, employed for this systematic review.

Results: Current research demonstrates that non-TNF-α inhibitor biologicals are particularly helpful in treating patients who did not respond well to conventional medications and TNF-α inhibitors. Despite being effective, these innovative drugs have a higher chance of producing hazardous side effects. The in silico investigations suggested an uncovered molecular interaction in combining MTX with other biological drugs. The STRING-MODEL showed that DHFR, TYMS, and ATIC, as the receptors of MTX, interact with each other but are not connected to the major interacted receptors.

Conclusions: New game-changing drugs including Mavrilimumab, Iguratimod, Upadacitinib, Fenebrutinib, and nanoparticles may be crucial in controlling symptoms in poorly managed RA patients. Emerging therapeutic targets like Toll-like 4 receptors, NLRP3 inflammasome complexes, and mesenchymal stem cells can further transform RA therapy.

Keywords: DMARDS; Inflammatory arthritis; JAK inhibitors; Rheumatoid arthritis; TLR4 receptor inhibition; new targeted therapy.

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Publication's Summary

Potential use of the cholesterol transfer inhibitor U18666A

Cholesterol plays critical functions in arranging the biophysical attributes of proteins and lipids in the plasma membrane. For various viruses, an association with cholesterol for virus entrance and/or morphogenesis has been demonstrated. Therefore, the lipid metabolic pathways and the combination of membranes could be targeted to selectively suppress the virus replication steps as a basis for antiviral treatment. U18666A is a cationic amphiphilic drug (CAD) that affects intracellular transport and cholesterol production. A robust tool for investigating lysosomal cholesterol transfer and Ebola virus infection is an androstenolone derived termed U18666A that suppresses three enzymes in the cholesterol biosynthesis mechanism. In addition, U18666A inhibited low-density lipoprotein (LDL)-induced downregulation of LDL receptor and triggered lysosomal aggregation of cholesterol. According to reports, U18666A inhibits the reproduction of baculoviruses, filoviruses, hepatitis, coronaviruses, pseudorabies, HIV, influenza, and flaviviruses, as well as chikungunya and flaviviruses. U18666A-treated viral infections may act as a novel in vitro model system to elucidate the cholesterol mechanism of several viral infections. In this article, we discuss the mechanism and function of U18666A as a potent tool for studying cholesterol mechanisms in various viral infections.

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Is Minimally Invasive Spinal Surgery (MISS) Superior to Endo

Abstract

Background: Minimally invasive spinal surgery (MISS) and endoscopic spine surgery (ESS) are both well-established surgical techniques for lumbar spinal stenosis; however, there is limited literature comparing the efficacy of the two techniques with respect to radiological decompression data.

Methods: In this review, PubMed, Google Scholar, and Scopus databases were systematically searched from inception until July 2022 for studies that reported the radiological outcomes of endoscopic and minimally invasive approaches for decompressive spinal surgery, namely, the spinal canal area, neural foraminal area, and neural foraminal heights.

Results: Out of the 378 papers initially retrieved using MeSH and keyword search, nine studies reporting preoperative and postoperative spinal areas and foraminal areas and height were finally included in our review. A total of 581 patients: 391 (67.30%) underwent MISS and 190 (32.70%) underwent ESS. The weighted mean difference between the canal diameter in pre-operative and post-operative conditions was 56.64 ± 7.11 mm2 and 79.52 ± 21.31 mm2 in the MISS and ESS groups, respectively. ESS was also associated with higher mean difference in the foraminal area postoperatively (72 ± 1 mm2 vs. 35.81 ± 11.3 mm2 in MISS and ESS groups, respectively) but was comparable to MISS in terms of the foraminal height (0.32 ± 0.037 vs. 0.29 ± 0.03 cm in the MISS and endoscopic groups, respectively).

Conclusions: Compared to MISS, ESS was associated with improved radiological parameters, including spinal canal area and neural foraminal area in the lumbar spinal segments. Both techniques led to the same endpoint of neural decompression when starting with more severe compression. However, the present data does not allow the correlation of the radiographic results with the related clinical outcomes.

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The Changing Environment in Postgraduate Education in Orthop

Personalized care models are dominating modern medicine. These models are rooted in teaching future physicians the skill set to keep up with innovation. In orthopedic surgery and neuro-surgery, education is increasingly influenced by augmented reality, simulation, navigation, robotics,and in some cases, artificial intelligence. The postpandemic learning environment has also changed,emphasizing online learning and skill- and competency-based teaching models incorporating clinicaland bench-top research. Attempts to improve work–life balance and minimize physician burnouthave led to work-hour restrictions in postgraduate training programs. These restrictions have made itparticularly challenging for orthopedic and neurosurgery residents to acquire the knowledge and skill set to meet the requirements for certification. The fast-paced flow of information and the rapid imple-mentation of innovation require higher efficiencies in the modern postgraduate training environment.

However, what is taught typically lags several years behind. Examples include minimally invasive tissue-sparing techniques through tubular small-bladed retractor systems, robotic and navigation,endoscopic, patient-specific implants made possible by advances in imaging technology and 3Dprinting, and regenerative strategies. Currently, the traditional roles of mentee and mentor are beingredefined. The future orthopedic surgeons and neurosurgeons involved in personalized surgical pain management will need to be versed in several disciplines ranging from bioengineering, basic research, computer, social and health sciences, clinical study, trial design, public health policy development,

and economic accountability. Solutions to the fast-paced innovation cycle in orthopedic surgery and neurosurgery include adaptive learning skills to seize opportunities for innovation with execution and implementation by facilitating translational research and clinical program development acrosstraditional boundaries between clinical and nonclinical specialties. Preparing the future generationof surgeons to have the aptitude to keep up with the rapid technological advances is challenging for postgraduate residency programs and accreditation agencies. However, implementing clinical protocol change when the entrepreneur–investigator surgeon substantiates it with high-grade clinical evidence is at the heart of personalized surgical pain management.

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Recent Improvements in Therapeutic Treatments of Breast Canc

Breast cancer develops when cells in the breast tissue begin to grow in an uncontrolled manner. These cells usually form a tumor that can often be seen in an x-ray or felt as a lump. The tumor is malignant if the cells invade the surrounding tissues or metastasize to distant organs of the body. In the last ten years, various new drugs have been introduced in the international markets to treat breast cancer. These drugs are administered either orally or via an injection. In this review, an insight is provided into the different signal transduction pathways that are being targeted for the purpose of adjuvant breast cancer treatment by the use of hormone-blocking agents, chemotherapy and monoclonal antibodies.

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Drugs that Target Cellular Signaling Pathways for Breast Ca

The identification of genetic mutations and the exploration of several cellular signaling pathways has led to the development of a number of molecular targeting agents, which can be targeted in several ailments for therapeutic basis. Recently, many drugs have been introduced to treat breast cancer. These drugs are administered either orally or via an injection. These drug delivery systems minimize toxicity and improve efficiency. These new drugs and delivery mechanisms have replaced the older cumbersome strategies and have helped the patients in several ways. They offer greater benefits to patients and have reduced side effects. Keywords: Cellular signaling; breast cancer treatment; genetic mutations.

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Antioxidants Sources

Natural antioxidants are abundant in food and medicinal plants. These natural antioxidants, particularly polyphenols and carotenoids, have numerous biological effects, including anti-inflammatory, anti-aging, anti-atherosclerosis, and anticancer properties. To examine potential cancer prevention agent sources and advance their utilization in useful food varieties, drugs, and food added substances, it is fundamental for separate cell reinforcements from food and restorative plants really and assess them suitably. This paper goes into great detail about the green extraction methods of natural antioxidants, the evaluation of antioxidant activity at the chemical and cellular levels, and their primary sources, which are food and medicinal plants. Keywords: medicinal plants, cellular, prevention, antioxidants, natural, biological effects, anti cancer

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Personalized Medicine in Cancer Pain Management

Background: Previous studies have documented pain as an important concern for quality of life (QoL) and one of the most challenging manifestations for cancer patients. Thus, cancer pain management (CPM) plays a key role in treating pain related to cancer. The aim of this systematic review was to investigate CPM, with an emphasis on personalized medicine, and introduce new pharmacogenomics-based procedures for detecting and treating cancer pain patients. Methods: This study systematically reviewed PubMed from 1990 to 2023 using keywords such as cancer, pain, and personalized medicine. A total of 597 publications were found, and after multiple filtering processes, 75 papers were included. In silico analyses were performed using the GeneCards, STRING-MODEL, miRTargetLink2, and PharmGKB databases. Results: The results reveal that recent reports have mainly focused on personalized medicine strategies for CPM, and pharmacogenomics-based data are rapidly being introduced. The literature review of the 75 highly relevant publications, combined with the bioinformatics results, identified a list of 57 evidence-based genes as the primary gene list for further personalized medicine approaches. The most frequently mentioned genes were CYP2D6, COMT, and OPRM1. Moreover, among the 127 variants identified through both the literature review and data mining in the PharmGKB database, 21 variants remain as potential candidates for whole-exome sequencing (WES) analysis. Interestingly, hsa-miR-34a-5p and hsa-miR-146a-5p were suggested as putative circulating biomarkers for cancer pain prognosis and diagnosis. Conclusions: In conclusion, this study highlights personalized medicine as the most promising strategy in CPM, utilizing pharmacogenomics-based approaches to alleviate cancer pain.

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