Potential Side Effects Research Articles

Proteome-wide Mendelian randomization identifies therapeutic targets for ankylosing spondylitis.

Ankylosing Spondylitis (AS) is a chronic inflammatory disorder which can lead to considerable pain and disability. Mendelian randomization (MR) has been extensively applied for repurposing licensed drugs and uncovering new therapeutic targets. Our objective is to pinpoint innovative therapeutic protein targets for AS and assess the potential adverse effects of druggable proteins. We conducted a comprehensive proteome-wide MR study to assess the causal relationships between plasma proteins and the risk of AS. The plasma proteins were sourced from the UK Biobank Pharma Proteomics Project (UKB-PPP) database, encompassing GWAS data for 2,940 plasma proteins. Additionally, GWAS data for AS were extracted from the R9 version of the Finnish database, including 2,860 patients and 270,964 controls. The colocalization analysis was executed to identify shared causal variants between plasma proteins and AS. Finally, we examined the potential adverse effects of druggable proteins for AS therapy by conducting a phenome-wide association study (PheWAS) utilizing the extensive Finnish database in version R9, encompassing 2,272 phenotypes categorized into 46 groups. The findings revealed a positive genetic association between the predicted plasma levels of six proteins and an elevated risk of AS, while two proteins exhibited an inverse association with AS risk (P fdr < 0.05). Among these eight plasma proteins, colocalization analysis identified AIF1, TNF, FKBPL, AGER, ALDH5A1, and ACOT13 as shared variation with AS(PPH3+PPH4>0.8), suggesting that they represent potential direct targets for AS intervention. Further phenotype-wide association studies have shown some potential side effects of these six targets (P fdr < 0.05). Our investigation examined the causal connections between six plasma proteins and AS, providing a comprehensive understanding of potential therapeutic targets.

Exploring the Impact of the Gamified Metaverse on Knowledge Acquisition and Library Anxiety in Academic Libraries

This paper investigates the potential of the Gamified Metaverse as a platform for promoting library services. The study compares the effectiveness of a traditional library program with a Metaverse-based library program in terms of knowledge acquisition and library anxiety. The research also examines students’ perceptions of implementing gamification within the context of the Gamified Metaverse platform. A mixed-methods approach was adopted, including pre- and post-test analysis, statistical analysis, and qualitative data collection. The results indicate that both the traditional and Metaverse-based library programs effectively increased the participants’ knowledge, with no significant difference between the two approaches. However, the Metaverse-based program was found to be less effective in facilitating interaction with librarians and reducing library anxiety. Additionally, students expressed positive perceptions of implementing gamification in the Gamified Metaverse platform, finding it engaging and motivating. These findings contribute to the understanding of the effect of the Metaverse as a tool for promoting library services and enhancing knowledge acquisition. However, it is not as effective in reducing library anxiety, particularly in terms of interaction with librarians and staff. It should be noted that the platform may have limitations such as high costs and potential side effects of virtual reality, making it more suitable as an additional tool for promoting library services, taking into account its feasibility and potential benefits for specific student populations and larger libraries.

Expert dialogue on topical minocycline gel in acne vulgaris: minologue India

Acne vulgaris is a common skin disorder with a global prevalence of about 9.4%. Oral antibacterials are recommended but they are associated with potential systemic side effects. Topical minocycline 4% has been recently approved by the United States Food and Drug Administration (US-FDA) for the management of moderate to severe acne. Although efficacy and safety are established, little is known of its real word usage. To review and appraise existing literature and make recommendations on the real world usage and positioning of topical minocycline 4% in acne management. The minocycline 4% consensus was developed by nine acne experts and was evidence-based on a review of recent topical minocycline 4% literature. A total of 11 questions were discussed regarding different domains like positioning of topical minocycline in acne management as monotherapy and combination therapy, safety and use in special population. Several recommendations were given regarding topical minocycline use like: no monotherapy use; consider use in combination with other anti-acne treatments like isotretinoin, adapalene and benzoyl peroxide; not recommended to be combined with systemic antibiotics; low chances for hyperpigmentation; use of sun protection measures; consider risk benefit ratio in pregnancy; use in lactation not recommended; and can be used only in children &gt;9 years of age. This consensus has discussed and answered many real world usage questions and place in therapy for topical minocycline in acne management and finds it a useful addition to the existing armamentarium.

Periplcymarin targets glycolysis and mitochondrial oxidative phosphorylation of esophageal squamous cell carcinoma: Implication in anti-cancer therapy

BackgroundEsophageal squamous cell carcinoma (ESCC) is the predominant histological subtype of esophageal cancer (EC) in China, and demonstrates varying levels of resistance to multiple chemotherapeutic agents. Our previous studies have proved that periplocin (CPP), derived from the extract of cortex periplocae, exhibiting the capacity to hinder proliferation and induce apoptosis in ESCC cells. Several studies have identified additional anti-cancer constituents in the extract of cortex periplocae, named periplcymarin (PPM), sharing similar compound structure with CPP. Nevertheless, the inhibitory effects of PPM on ESCC and their underlying mechanisms remain to be further elucidated. PurposeThe aim of this study was to investigate function of PPM inhibiting the growth of ESCC in vivo and in vitro and to explore its underlying mechanism, providing the potential anti-tumor drug for ESCC. MethodsInitially, a comparative analysis was conducted on the inhibitory activity of three naturally compounds obtained from the extract of cortex periplocae on ESCC cells. Among these compounds, PPM was chosen for subsequent investigation owing to its comparatively structure and anti-tumor activity simultaneously. Subsequently, a series of biological functional experiments were carried out to assess the impact of PPM on the proliferation, apoptosis and cell cycle arrest of ESCC cells in vitro. In order to elucidate the molecular mechanism of PPM, various methodologies were employed, including bioinformatics analyses and mechanistic experiments such as high-performance liquid chromatography combined with mass spectrometry (HPLC-MS), cell glycolysis pressure and mitochondrial pressure test. Additionally, the anti-tumor effects of PPM on ESCC cells and potential toxic side effects were evaluated in vivo using the nude mice xenograft assay. ResultsOur study revealed that PPM possesses the ability to impede the proliferation of ESCC cells, induce apoptosis, and arrest the cell cycle of ESCC cells in the G2/M phase in vitro. Mechanistically, PPM exerted its effects by modulating glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), as confirmed by glycolysis pressure and mitochondrial pressure tests. Moreover, rescue assays demonstrated that PPM inhibits glycolysis and OXPHOS in ESCC cells through the PI3K/AKT and MAPK/ERK signaling pathways. Additionally, we substantiated that PPM effectively suppresses the growth of ESCC cells in vivo, with only modest potential toxic side effects. ConclusionOur study provides novel evidence that PPM has the potential to simultaneously target glycolysis and mitochondrial OXPHOS in ESCC cells. This finding highlights the need for further investigation into PPM as a promising therapeutic agent that targets the tumor glucose metabolism pathway in ESCC.

Proteome-Wide Mendelian Randomization and Colocalization Analysis Identify Therapeutic Targets for Knee and Hip Osteoarthritis.

Osteoarthritis (OA) is a common degenerative disease. Although some biomarkers and drug targets of OA have been discovered and employed, limitations and challenges still exist in the targeted therapy of OA. Mendelian randomization (MR) analysis has been regarded as a reliable analytic method to identify effective therapeutic targets. Thus, we aimed to identify novel therapeutic targets for OA and investigate their potential side effects based on MR analysis. In this study, two-sample MR, colocalization analysis, summary-data-based Mendelian randomization (SMR) and Mendelian randomization phenome-wide association study (MR-PheWAS) were conducted. We firstly analyzed data from 4907 plasma proteins to identify potential therapeutic targets associated with OA. In addition, blood expression quantitative trait loci (eQTLs) data sources were used to perform additional validation. A protein-protein interaction (PPI) network was also constructed to delve into the interactions among identified proteins. Then, MR-PheWASs were utilized to assess the potential side effects of core therapeutic targets. After MR analysis and FDR correction, we identified twelve proteins as potential therapeutic targets for knee OA or hip OA. Colocalization analysis and additional validation supported our findings, and PPI networks revealed the interactions among identified proteins. Finally, we identified MAPK3 (OR = 0.855, 95% CI: 0.791-0.923, p = 6.88 × 10-5) and GZMK (OR = 1.278, 95% CI: 1.131-1.444, p = 8.58 × 10-5) as the core therapeutic targets for knee OA, and ITIH1 (OR = 0.847, 95% CI: 0.784-0.915, p = 2.44 × 10-5) for hip OA. A further MR phenome-wide association study revealed the potential side effects of treatments targeting MAPK3, GZMK, and ITIH1. This comprehensive study indicates twelve plasma proteins with potential roles in knee and hip OA as therapeutic targets. This advancement holds promise for the progression of OA drug development, and paves the way for more efficacious treatments of OA.

Current trends in Nigella sativa L. (Black seed) from traditional to modern medicine with advances in extraction, formulation, quality control, regulatory status, and pharmacology

For the first time ever, this novel review enters the enigmatic world of the L. (black seed), known for centuries as a potent source of healing including their relevance to the food and pharmaceutical industries. Written at professional and reference level, it is directed at normal readers with more professional scientists in pharmacy and food science affiliations to serve as a rich source of data on black seed. We embark on an exploration that encompasses the background, significance, and objectives guiding our exploration. Detailed botanical and chemical profiles unravel the mysteries of the black seed, providing insight into its taxonomy, morphology, and chemical composition. Traditional uses, extraction methods, and formulation approaches paint a comprehensive picture of the versatile ways in which the black seed has been employed throughout history. Quality control and standardization practices ensure the integrity of black seed-derived products, while a global regulatory overview brings into focus the challenges and triumphs of incorporating this botanical powerhouse into mainstream pharmacopeias. As we delve into the pharmacological activities, clinical studies, and efficacy of the black seed, we confront safety considerations and potential side effects. The exploration extends into the future, addressing the challenges in commercialization, identifying research gaps, and concluding with the implications of our findings for both healthcare and industry. It should therefore be of special value to researchers affiliated with food science and technology, pharmacy, and pharmaceutical producers requiring up-to-date information on their raw materials, which will probably already have been processed, at least in part.

HYDROXYAPATITE NANOPARTICLES: A REVIEW OF THEIR EMERGING ROLE IN DRUG DELIVERY APPLICATIONS

This literature review assesses existing research on hydroxyapatite-based drug delivery systems, with a focus on evaluating their effectiveness. Researchers are actively exploring strategies to enhance drug loading capacity, involving surface modifications of nanoparticles and the innovation of novel drug encapsulation techniques. Elevating drug loading has the potential to clearly increase the therapeutic efficacy of these systems. Stability issues also present a challenge in the clinical translation of nanoparticle-based drug delivery systems. Furthermore, scientists are underway to minimize potential side effects by judiciously selecting biocompatible materials for nanoparticle synthesis and conducting comprehensive toxicity studies before advancing to clinical trials.

Where does the EU-path on new genomic techniques lead us?

Recently, the European Commission (EC) published a regulatory proposal on plants generated with new genomic techniques (NGTs) (5 July 2023). According to this proposal, NGT plant applications are categorized into category 1 NGT (NGT1) and category 2 NGT (NGT2) based on their molecular characteristics, which diverges from the current legislation centered around Directive 2001/18/EC. To demonstrate where the path of the proposal leads to in practice, we applied the proposed criteria for categorization to a list of NGT plant applications currently in the commercialization pipeline. Combining literature research and a descriptive statistical approach, we can show that 94% of the plant applications affected by the EC proposal, would be classified as NGT1 and thus would receive market approval without risk assessment, monitoring, and sufficient labeling provisions. The remaining 6% of applications would be classified as NGT2 plants, for which, in deviation from the current regulation, an adapted risk assessment is proposed. Screening of the intended traits in the pipeline highlights that certain NGT1 plants can pose similar environmental risks (e.g., invasiveness) to other genetically modified organisms (GMOs), as defined in Directive 2001/18/EC. For example, NGT1 applications based on RNA interference technology can exhibit insecticidal effects with potential side effects on non-target organisms (i.e., other insects). Our quantitative and case-specific elaboration of how the current EC regulatory proposal would affect the environment, health, and consumer protection will be informative for decision-makers and politicians.

Attitudes on participation in clinical drug trials: A nationally representative survey of older adults with multimorbidity.

Older adults with multimorbidity are under-represented in clinical drug trials. Their inclusion will not increase unless they are willing and able to participate. Data on motivators and barriers to participation in trials of new medications of older adults with multimorbidity are needed. Cross-sectional internet and telephone survey of a nationally representative sample of adults ≥65 years with ≥3 chronic conditions (NORC University of Chicago Amerispeak Panel) conducted from March-April, 2023 to determine motivators and barriers to drug trial participation, described graphically and using statistics. Surveyed 1318 (1142 Internet, 176 phone) with mean age 72.3 ± 6.3 (SD), 52% women; race: 83% White, 10% Black or African American, 5% Hispanic or Latino, 1.1% Asian; 4.4 ± 1.9 chronic conditions (of 16 queried), taking 7.5 ± 3.3 medications. Barriers included fear of side effects (48%), taking too many medications (44%), placebo (44%), mobility (33%), bathroom needs (25%), hearing (19%), eyesight (15%), video visits (33%; higher in women, Black or African-American respondents, and those ≥80 years). Sixty-five percent would join all in-person trials, 49% would join all-video trials. Travel >1 h was difficult for 66%, most difficult for women. Trust was a concern in 25% of Black respondents. Caregiving responsibilities or lack of time were not obstacles. Participants were most likely to consider a drug trial for a problem they have (63%) versus prevention (44%) and if invited by a physician (80%) or University healthcare system (58%). Getting better care was ranked very important (79%) followed by helping others (57%). Major concerns of older patients with multimorbidity about participation in drug trials are potential side effects, taking too many medicines, and video visits. Physicians have the greatest influence on decisions and in-person visits are preferred. Proposed changes in trial design to increase enrollment of under-represented older adults may not align with patient-reported preferences.

Integrated Electrochemical Aptasensor Array toward Monitoring Anticancer Drugs in Sweat.

In the realm of clinical practice, the concurrent utilization of anticancer medications can enhance their overall therapeutic efficacy. However, it is crucial to acknowledge that the interactions among these anticancer drugs can potentially yield detrimental consequences on their intended outcomes. Consequently, the assessment of both anticancer potency and potential toxic side effects is greatly refined when multiple anticancer drugs are simultaneously detected and evaluated. Here, we designed a wearable electrochemical aptasensor array for monitoring multiple anticancer drugs in sweat. The integrated sensor array consists of three working electrodes modified with three different aptamers (Apt1, Apt2, and Apt3), a Au counter electrode, and a Ag/AgCl reference electrode. Molecular docking simulations were performed to show the binding affinities between three anticancer drugs and their corresponding aptamers. Various eigenvalues were derived from the square-wave voltammetry electrochemical signals, and these data sets were subjected to rigorous analysis through multivariate data analysis techniques. This analytical approach demonstrated exceptional performance by achieving flawless 100% accuracy in the precise identification of nine anticancer drugs consistently at uniform concentrations. Furthermore, the integrated wearable sensor array exhibited impressive capabilities, correctly recognizing all nine anticancer drugs with 100% accuracy and successfully distinguishing between these drugs in artificial sweat samples. The proposed sensor array presents good stability for 15 days. Flexibility tests showed stable device performance after 500 twisting cycles. This innovative wearable sensing array represents a novel approach for achieving real-time monitoring and precise adjustment of drug dosages. It offers invaluable insights for tailoring the treatment of anticancer drugs to individual patients, predicting both drug efficacy and potential adverse reactions within the field of clinical medicine.

Prediction and detection of side effects severity following COVID-19 and influenza vaccinations: utilizing smartwatches and smartphones

Vaccines stand out as one of the most effective tools in our arsenal for reducing morbidity and mortality. Nonetheless, public hesitancy towards vaccination often stems from concerns about potential side effects, which can vary from person to person. As of now, there are no automated systems available to proactively warn against potential side effects or gauge their severity following vaccination. We have developed machine learning (ML) models designed to predict and detect the severity of post-vaccination side effects. Our study involved 2111 participants who had received at least one dose of either a COVID-19 or influenza vaccine. Each participant was equipped with a Garmin Vivosmart 4 smartwatch and was required to complete a daily self-reported questionnaire regarding local and systemic reactions through a dedicated mobile application. Our XGBoost models yielded an area under the receiver operating characteristic curve (AUROC) of 0.69 and 0.74 in predicting and detecting moderate to severe side effects, respectively. These predictions were primarily based on variables such as vaccine type (influenza vs. COVID-19), the individual's history of side effects from previous vaccines, and specific data collected from the smartwatches prior to vaccine administration, including resting heart rate, heart rate, and heart rate variability. In conclusion, our findings suggest that wearable devices can provide an objective and continuous method for predicting and monitoring moderate to severe vaccine side effects. This technology has the potential to improve clinical trials by automating the classification of vaccine severity.

Rebamipide Prevents the Hemoglobin Drop Related to Mucosal-Damaging Agents at a Level Comparable to Proton Pump Inhibitors.

: The effect of proton pump inhibitors (PPIs) on the lower gastrointestinal (GI) tract is uncertain, with potential to worsen damage. This study aimed to find the best method for protecting the entire GI tract from mucosal damage. : A retrospective cohort study at Samsung Medical Center (2002-2019) included 195,817 patients prescribed GI mucosa-damaging agents. The primary goal was to assess the effectiveness of GI protective agents in preventing significant hemoglobin drops (>2 g/dL), indicating overall GI mucosal damage. Self-controlled case series and landmark analysis were used to address biases in real-world data. : The incidence rate ratios for rebamipide, PPI, and histamine-2 receptor antagonist (H2RA) were 0.34, 0.33, and 0.52, respectively. Rebamipide showed a significantly lower incidence rate than H2RA and was comparable to PPIs. Landmark analysis revealed significant reductions in hemoglobin drop risk with rebamipide and H2RA, but not with PPI. : Rebamipide, like PPIs, was highly effective in preventing blood hemoglobin level decreases, as shown in real-world data. Rebamipide could be a comprehensive strategy for protecting the entire GI tract, especially when considering PPIs' potential side effects on the lower GI tract.

A Review of High-Intensity Focused Ultrasound

For 80 years, high-intensity focused ultrasound (HIFU) has been the subject of interest in medical research. It is a non-invasive procedure that causes the death of cells in a very select area through one of two mechanisms, either heat or cavitation. While diagnostic ultrasound is well known in the medical profession and ultrasound is also used in physiotherapy, high-intensity focused ultrasound is less known but is becoming increasingly important as a non-invasive tool that can be used in many ways, including in the treatment of several cancers as well as benign uterine fibroids. Other interesting developments are underway, including its use in the treatment through an intact skull of essential tremors and the tremor associated with Parkinson’s disease, and in a modified form, it is used to target drug delivery to the brain due to its potential opening of the blood–brain barrier. The depth of penetration of HIFU is variable depending on the type of transducer used and the distance from it. Clinical trials of abdominal malignancies and benign uterine fibroids are reviewed in this article along with potential side effects of the procedure. Over the past two decades, the technology has improved considerably, and the clinical indications have broadened. The current limitations of the technology are also discussed, along with the potential advances in the field that may be made over the next decade.

HER2-Positive Early Breast Cancer: Time for Ultimate De-Escalation?

De-escalation is currently taking place in both the surgical and systemic treatment of breast cancer. The introduction of trastuzumab, the first monoclonal antibody against the HER2 receptor, over 20 years ago was a milestone in the treatment of HER2-positive breast cancer and marked the beginning of a new era in targeted tumor therapy. In the sense of de-escalation, omitting non-targeted cytotoxic chemotherapy altogether is often hailed as the ultimate goal of oncological research. Especially in cases of small, node-negative, HER2-positive early breast cancer, it remains a challenge for clinicians to establish the safest and most efficient treatment plan while considering the significant potential for toxic side effects associated with chemotherapy and HER2-targeted therapy, and the generally excellent prognosis. In this context, several ongoing studies are currently assessing chemotherapy-free regimens as part of strategies aimed at de-escalating therapy in the field of HER2-positive early breast cancer. Despite the promising early results of these studies, the combination of anti-HER2 treatment with a chemotherapy backbone remains the standard of care.

RUQYAH: LISTENING TO QURANIC VERSES, A DISEASE TREATMENT STRATEGY

The global Muslim population has surpassed two million, and Islamic principles emphasize accepting teachings from the Holy Quran and Sunnah for theoretical and practical guidance. Among these teachings is the recommendation to seek healing through reciting the Quran, known as 'Ruqyah Shar'iyya.' Despite its significance, medical professionals in Muslim-majority countries often need more awareness of Ruqyah, leading to an overreliance on pharmacological treatments with potential side effects. This study aims to increase awareness among healthcare providers about authentic and updated knowledge regarding Islamic teachings related to disease treatment through listening to the Quran and supplications. Through a descriptive literature review, the research explores critical terms such as Ruqyah, shifa (healing), treatment by Quran, spiritual treatment, Islamic treatment, and supplication in various sources, including the Quran, Hadith books, Google Scholar, and PubMed. While pharmacological treatments remain the primary approach for many diseases, this study suggests that non-pharmacological strategies, such as Quran recitation (Ruqyah) and specific supplications, align with the recommendations of Prophet Mohammad (ﷺ). Training doctors, nurses, and healthcare providers in the Muslim community to incorporate Ruqyah into their practice or involving Ruqyah professionals for Muslim patients can offer additional treatment options. This approach promotes healing without side effects and enhances patients' patience, satisfaction, and overall well-being. Such practices improve quality of life and foster trust in the doctor-patient relationship.

Haemoglobin Bart's Hydrops Fetalis: Charting the Past and Envisioning the Future.

Haemoglobin Bart's hydrops fetalis syndrome (BHFS) represents the most severe form of α-thalassaemia, arising from deletion of the duplicated α-globin genes from both alleles. The absence of α-globin leads to the formation of non-functional haemoglobin Bart's (γ4) or haemoglobin H (HbH: β4) resulting in severe anaemia, tissue hypoxia, and, in some cases, variable congenital or neurocognitive abnormalities. BHFS is the most common cause of hydrops fetalis in Southeast Asia; however, owing to global migration, the burden of this condition is increasing worldwide. With the availability of intensive perinatal care and intrauterine transfusions, an increasing number of patients survive with this condition. The current approach to long-term management of survivors involves regular blood transfusions and iron chelation, a task made challenging by the need for intensified transfusions to suppress the production of non-functional HbH-containing erythrocytes. While our knowledge of outcomes of this condition is evolving, it seems, in comparison to individuals with transfusion-dependent β-thalassaemia, those with BHFS may face an elevated risk of complications arising from chronic anaemia and hypoxia, ongoing haemolysis, iron overload, and from their respective treatments. Although stem cell transplantation remains a viable option for a select few, it is not without potential side effects. Looking ahead, potential advancements in the form of genetic engineering and innovative therapeutic approaches, such as the reactivation of embryonic α-like globin gene expression, hold promise for furthering the treatment of this condition. Prevention remains a crucial aspect of care, particularly in areas with high prevalence or limited resources.

Sarcoid-like reaction and hypothyroidism induced by PD-1 inhibitor treatment in metastatic renal cell carcinoma: a case report and literature review

BackgroundPembrolizumab is among the approved treatments for a variety of cancer types, including clear cell renal cell carcinoma (ccRCC). It has contributed to enhancing the prognosis of renal cell carcinoma. However, it is essential to be aware of the numerous potential immune-related side effects associated with its use.Case presentationA 69-year-old patient with a history of metastatic renal cell carcinoma has been undergoing treatment with Pembrolizumab, an immune checkpoint inhibitor. The medication has led to the development of a sarcoid-like reaction, initially misinterpreted as cancer recurrence and progression. Additionally, the patient has experienced new-onset hypothyroidism, which has been attributed to the immunotherapy.ConclusionClinicians, including oncologists, endocrinologists, and radiologists, should maintain a high level of suspicions and awareness regarding the potential adverse events associated with newly introduced immunotherapies like pembrolizumab. This knowledge is crucial for the accurate diagnosis and appropriate management of patients receiving these treatments.

GBA-related diseases and the application in Tourette syndrome treatment

This paper discusses the gut-brain axis (GBA) and how it takes part in various neurological diseases, including Alzheimers disease (AD), Attention-deficit hyperactivity disorder (ADHD), and Tourette syndrome. The gut microbiota, inducing vital communications with the brain through the GBA, is not to be neglected in maintaining physiological balance, with the potential to become a source of new therapeutic opportunities for treating these diseases. Current studies show that methods such as personalized diets, oral bacteriotherapy, and multi-strain probiotics like SLAB51 and DEX have promising results in treating AD and ADHD through manipulation of the biotas. Based on the analysis of previous research, this paper finds how changes in gut microbiota amount in feces between healthy and TS mice, in particular the decrease in Firmicutes and Actinobacteria, and the increase in Bacteroidetes and Proteobacteria. However, future studies and experiments are required to evaluate potential side effects of microbiome alterations in humans, and potential treatments for Tourettes syndrome based on gut microbiota analysis. The GBA is a promising area for developing new therapeutic approaches for neurological diseases, and future research in this field holds great potential for advancements in the treatment of these disorders currently with no verified cures.

IN SILICO EXPLORATION OF BERBERINE AS A POTENTIAL WOUND HEALING AGENT VIA NETWORK PHARMACOLOGY, MOLECULAR DOCKING, AND MOLECULAR DYNAMICS SIMULATION

Objective: Wound healing remains a complex biological process crucial for tissue repair and homeostasis. Our goal in this paper is to focus on the application of advanced computational techniques to explore the potential of naturally occurring compound berberine in addressing molecular targets related to wound healing. Methods: Network pharmacology, molecular docking analysis, in silico ADMET prediction, and extensive 100 ns molecular dynamics simulations was performed to gain a holistic understanding of the therapeutic potential of berberine against molecular targets involved in wound healing. This study predicted drug-likeness scores, potential side effects, ADMET profiles, carcinogenicity, MolLogP, molecular volume analysis, and molecular polar surface area for berberine. Results: Findings of the study revealed that berberine displayed a remarkable binding affinity for the epidermal growth factor receptor (EGFR), with a binding energy of-8.14 kcal/mol, surpassing the crystal ligand's binding energy of-7.15 kcal/mol. This indicates a strong potential for berberine in modulating EGFR-related pathways critical for wound healing. The culmination of the investigation was a 100 ns molecular dynamics simulation, which demonstrated consistent binding and stability over time, reinforcing the potential of berberine as a wound healing agent. Conclusion: The integration of gene expression analysis, enrichment studies, network analysis, molecular docking, and molecular dynamics simulations unveiled crucial mechanisms underlying efficacy of berberine as a potent wound-healing agent.

Echinatin mitigates sevoflurane-induced neurotoxicity through regulation of ferroptosis and iron homeostasis.

Surgery and anesthesia are vital medical interventions, but concerns over their potential cognitive side effects, particularly with the use of inhalational anesthetics like sevoflurane, have surfaced. This study delves into the neuroprotective potential of Echinatin against sevoflurane-induced neurotoxicity and the underlying mechanisms. Echinatin, a natural compound, has exhibited anti-inflammatory, antioxidant, and anticancer properties. Sevoflurane, while a popular anesthetic, is associated with perioperative neurocognitive disorders (PND) and neurotoxicity. Our investigation began with cellular models, where Echinatin demonstrated a significant reduction in sevoflurane-induced apoptosis. Mechanistically, we identified ferroptosis, a novel form of programmed cell death characterized by iron accumulation and lipid peroxidation, as a key player in sevoflurane-induced neuronal injury. Echinatin notably suppressed ferroptosis in sevoflurane-exposed cells, suggesting a pivotal role in neuroprotection. Expanding our research to a murine model, we observed perturbations in iron homeostasis, inflammatory cytokines, and antioxidants due to sevoflurane exposure. Echinatin treatment effectively restored iron balance, mitigated inflammation, and preserved antioxidant levels in vivo. Behavioral assessments using the Morris water maze further confirmed Echinatin's neuroprotective potential, as it ameliorated sevoflurane-induced spatial learning and memory impairments. In conclusion, our study unveils Echinatin as a promising candidate for mitigating sevoflurane-induced neurotoxicity. Through the regulation of ferroptosis, iron homeostasis, and inflammation, Echinatin demonstrates significant neuroprotection both in vitro and in vivo. These findings illuminate the potential for Echinatin to enhance the safety of surgical procedures involving sevoflurane anesthesia, minimizing the risk of cognitive deficits and neurotoxicity.