Synthetic Drugs Research Articles

Difficult-to-treat rheumatoid arthritis: what have we learned and what do we still need to learn?

Difficult-to-treat rheumatoid arthritis (D2T RA) is an area of high unmet need. The prevalence reported in the first D2T RA cohort studies ranged from 5.5-27.5%. Key to the definition is a conviction by patient and/or rheumatologist that disease management has become problematic and failure of at least two biological or targeted synthetic disease-modifying antirheumatic drugs. D2T RA is a multifactorial disease state which was reflected in data from D2T RA cohort studies: these pointed towards high prevalence of co-morbidities and/or lower socioeconomic status in D2T RA subgroups, while others had persistent symptoms without these factors being present. A holistic approach is necessary to identify the root problems underlying D2T RA in individual patients. In this review, biological and non-biological drivers that should be considered to be optimized will be discussed in view of what we have learned from patient data emerging from the first D2T RA cohort studies.

Drug utilization and medication adherence for the treatment of psoriatic arthritis: an Italian study.

This study aims to evaluate the persistence, treatment adherence and drug cost associated with biologic and targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in the management of psoriatic arthritis (PsA) in Italy, with a focus on biosimilar drugs. This was a retrospective observational study involving eight hospital pharmacies, between January 2017 and December 2020, on naïve patients with at least one b/tsDMARD dispensation indicated for PsA. Patients were followed up for 12 months and persistence and adherence were evaluated by proportion of days covered (PDC). The originator and biosimilar for adalimumab and etanercept were compared. Furthermore, the real annual cost per patient based on adherence to therapy was calculated. Patients initiating b/tsDMARDs for PsA had a mean persistence of 263 days and 48.6% remained persistent for 1 year. Adherent patients (PDC ≥ 0.8) were 47.6% for the overall population. Similar persistence and adherence were observed between patients treated with the adalimumab originator and its biosimilar, while patients treated with the etanercept originator showed lower persistence and adherence compared to those treated with its biosimilar (mean persistence: 222 vs. 267 days, patient persistent at 1 year: 29.4% vs. 51.5%, mean PDC: 0.53 vs. 0.70, adherent patients: 23.5% vs. 51.5%). The average annual drug cost ranged from €8,724 (etanercept) to €14,783 (ustekinumab), with an annual saving of more than €2,500 by using biosimilars. Poor adherence to medications contributes to suboptimal clinical outcomes. The comparison between biosimilar and originator offers further evidence in support of the biosimilar to optimizing resources in healthcare.

Click Reaction Inspired Enzyme Inhibitors in Diabetes Care: An Update in the Field of Chronic Metabolic Disorder.

Diabetes is a chronic metabolic disorder that impacts all age groups and affects a large population worldwide. Humans receive glucose from almost every food source, and after absorption from the gut, it reaches the liver, which functions as the distribution center for it. The insulin-responsive glucose transporter type 4 (GLUT-4) is a major carrier of glucose to the various cells (majorly expressed in myocytes, adipocytes, and cardiomyocytes) in a well-fed state. In fasting periods, the glucose supply is maintained by glycogenolysis and gluconeogenesis. In diabetes, the distribution of glucose is hampered due to several reasons. Furthermore, to treat this disorder, several drugs have been synthesized, and click chemistry plays an important role. A more recent concept for producing pharmaceuticals with a click chemistry approach makes any reaction more practical and stereospecific, along with a higher yield of products and a smaller number of by-products. This approach comprises a compiled study of the activity of numerous compelling antidiabetic drugs containing 1, 2, 3-triazole derivatives supported by click chemistry. In this review, we discuss the synthetic antidiabetic drugs made via click chemistry and their commendable role in improving diabetes care.

Laser-induced fluorescence spectroscopic investigation of Echium amoenum decoction

Herbs containing medicinal ingredients with nutritional value have recently gained attention as an alternative to synthetic drugs. Aside from their pharmaceutical worthiness, a variety of naturally occurring chromophores with specific optical properties have made them valuable sources of natural pigments for many biophotonic applications. Echium Amoenum (EA) is one of the colorful flowers that has been used in traditional medicine for a long time. To our knowledge, although several studies have been carried out on the characterization of EA ingredients and their chemical activities, information on EA fluorescence is still lacking. Here, laser induced fluorescence (LIF) features of the decoction of EA petals were evaluated and found to be highly dependent on the excitation wavelength, EA concentration, and detection geometry. The abundance of pigments, the boundaries of their absorption/emission spectral regions, and the corresponding energy transfer ascertain the contribution of certain chromophores to the cumulative fluorescence activity. Upon deconvolution of the LIF spectra, it was revealed that the different emission bands of rosmarinic acid (corresponding to its dissociated forms) and the luminescent activity of luteolin and β-carotene mainly determine the quantum distribution of the fluorescence of EA. Angular measurement of LIF in a symmetric cylindrical arrangement revealed the presence of the inner filters mainly due to the reabsorption of LIF photons by anthocyanins (flavone, pelargonidin, delphinidin and cyanidin) and carotenoids. We hope that the obtained results will be useful in various fields of photochemistry and biophotonics.

An Assessment of Antidepressant Activity of Etlingera elatior Alone and in Combination with Fluoxetine

Aim: Present study deals to access the antidepressant activity of Etlingera elatior leaves extract in rodent. Background: Etlingera elatior is a species of herbaceous perennial plant in the family Zingiberaceae; native to Indonesia, Thailand, Malaysia and New Guinea. Depression is one of the most common mental disorders affecting humans, pathological basis of which is not fully understood. The current antidepressant drugs have several adverse effects including their effects on cognition. Therefore, natural product are being evaluated for their antidepressant activities. Objective: In this study, Etlingera elatior leaf extracts are being evaluated for antidepressant activity in rodent models. A wide range of synthetic medicines that can be used to treat depression which may exerts various side effects such as dry mouth, gastrointestinal problems, nausea, respiratory problems, cardiac arrhythmias, drowsiness, anxiety etc. Hence, it becomes essential to discover new anti-depressant drug with more potency, efficacy and safety profile than those of marketed synthetic drugs. Methods: Using the forced swimming test, the tail suspension test, mouse 5-HTP-induced head twitches and estimation of brain lipid peroxidation modelsthe antidepressant efficacy of Etlingera elatior ethanolic extract was examined. Imipramine was used as reference standards. result: According to our study, Etlingera elatior significantly (p0.01) reduced immobility in tail suspension, forced swimming, and 5-HTP-induced head twitches in mice with depression that were comparable to imipramine. Results: According to our study, Etlingera elatior significantly (p 0.01) reduced immobility in tail suspension, forced swimming, and 5-HTP-induced head twitches in mice with depression that were comparable to imipramine. Conclusion: Based on the results obtained we can conclude that Etlingera elatior leaves extract possess significant antidepressant activity. The antidepressant effectiveness of Etlingera elatior leaves extract can be confirmed in the future by adding more models, and attempts can also be made to isolate and characterise the phytoconstituents responsible for the pharmacological action.

A smart lab on a wearable microneedle patch with convolutional neural network‐enhanced colorimetry for early warning of syndrome of inappropriate antidiuretic hormone secretion

AbstractFrequent nocturia‐induced nighttime visits aggravate falls in seniors, requiring synthetic antidiuretic drugs that risk the dangerous syndrome of inappropriate antidiuretic hormone secretion (SIADH), thus the detection of sodium ion and uric acid alterations during treatment is obligatory for drug‐safe management. Herein, we design a convolutional neural network (CNN)‐enhanced smart wearable microneedle array‐based colorimetric (WMNC) sensor to independently detect in vivo interstitial fluid (ISF) sodium ions and uric acid alterations. The WMNC sensor is composed of a vacuum tube‐driven microneedle array patch and a built‐in colorimetric sensing paper, enabling an efficient ISF extraction and rapid colorimetric assay. Furthermore, leveraging self‐designed CNNs, the WMNC sensor efficiently eliminates the influence of ambient light on colorimetric outcomes, facilitating a rapid and accurate colorimetric result classification. This study provides an ISF‐based rapid, intuitionistic, user‐friendly, wearable point‐of‐care technique for the elderly suffering from nocturia in monitoring their health status for early warnings of SIADH.

Automated mental health screening in pediatric lupus: associations with disease features and treatment.

Patients with childhood-onset systemic lupus erythematosus (c-SLE) have higher rates of depression than their peers, which has been associated with worse medical outcomes. Therefore, it is imperative that their mental health be addressed. We utilized quality improvement (QI) methodology to automate mental health screening for patients with lupus within a pediatric rheumatology clinic. The retrospective cohort study aims to evaluate the association between mental health screening outcomes and demographics, medications, and disease activity measures in patients with childhood lupus. The mental health QI team at a quaternary pediatric rheumatology center implemented an automated process for mental health screening in patients with c-SLE. Patients seen between 2017 and June 2023 with a diagnosis of c-SLE were identified using International Classification of Disease -Clinical Modification (ICD-CM) codes. Disease activity was assessed with the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2K). Medications were identified on outpatient and inpatient orders for conventional synthetic and biologic disease-modifying anti-rheumatic drugs, hydroxychloroquine, corticosteroids, and aspirin. Mental health screening was accomplished with the Patient Health Questionnaire (PHQ). Descriptive statistics, univariate and multivariate linear regression were used. Between January 2017 and June 2023, 117 patients with c-SLE (41% with lupus nephritis) completed 534 total screenings. Each patient completed PHQ screenings, a median of 5 [interquartile range 2, 6] times. Screening increased when the screening process was automated. Those who were Black, female, or prescribed leflunomide, mycophenolate, and corticosteroids had higher PHQ scores. Mental health support is essential for patients with chronic rheumatologic diseases such as SLE. Sustainable processes for quickly identifying depression are needed for optimal care of patients with SLE. Our process of automated, streamlined mental health screening successfully increased the screening of patients with SLE at every visit and led to timely interventions for positive PHQ scores. Higher PHQ scores were correlated with patients on leflunomide, mycophenolate, and corticosteroids. Future research should identify modifiable risk factors for high PHQ scores that the medical team can target.

Peripheral blood immunophenotypic diversity in patients with rheumatoid arthritis and its impact on therapeutic responsiveness

ObjectiveConsidering the diverse aetiologies and immunodysregulatory statuses observed in each patient with rheumatoid arthritis (RA), stratification based on peripheral blood immunophenotyping holds the potential to enhance therapeutic responses to molecular...

Biologic and targeted synthetic disease-modifying anti-rheumatic drugs improve body composition in rheumatoid arthritis patients more than conventional synthetic disease-modifying anti-rheumatic drugs: Results from the PRESENT study.

The effects of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) and conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) on body composition and muscle function in rheumatoid arthritis (RA) patients requiring treatment enhancement were compared. This multicenter, prospective, observational study (PRESENT Study) divided RA patients non-randomly into a csDMARD group (n = 100) and a b/tsDMARD group (n = 100). Changes in body composition and muscle function were examined in 80 patients in each group followed for 52 weeks. The percentages of new-onset and improved sarcopenia over 1 year were investigated. Patients in the b/tsDMARD group were divided into three groups by drug type: TNF inhibitors (n = 30), non-TNF inhibitors (n = 23), and JAK inhibitors (n = 27). Baseline median age and disease duration were 70.0 and 4.0 years, respectively. Changes in weight (24 and 52 weeks) and muscle mass (52 weeks) were significantly higher in the b/tsDMARD group (p = .035, p < .001, and p = .002, respectively). On multivariate logistic regression analysis, b/tsDMARD treatment (OR 3.21, p = .002), DAS28-ESR (OR 0.65 p = .011), and muscle mass (OR 0.90, p = .023) were independently associated with increased muscle mass at 52 weeks. The percentages of new-onset and improved sarcopenia were almost equal. There were no significant differences in the time-dependent changes (52 weeks) of clinical status, body composition, muscle function, and status of sarcopenia among TNF inhibitors, non-TNF inhibitors, and JAK inhibitors. Weight and muscle mass increased significantly more with b/tsDMARD than with csDMARD treatment. There were no differences in body composition changes by mode of action with b/tsDMARDs.

Evaluating the Antibacterial and Anti‐Biofilm Properties of Chitosan Nanoemulsion Containing Euphorbia hebecarpa Plant Extract Against Escherichia coli and Staphylococcus aureus

ABSTRACTThe use of nanoparticles as drug‐carrying systems in medicine has received much attention, and on the other hand, the use of plants with medicinal properties has advantages over synthetic drugs. This study aims to improve the antibacterial and anti‐biofilm properties of Euphorbia hebecarpa plant extract using chitosan nanoparticles. Extraction were performed using the modified maceration and methanol solvent. The agar disc diffusion method was carried out to investigate the antimicrobial effects and MIC at an optical density (OD) of 630 nm. The anti‐biofilm agent's influence was measured at OD 570 nm, and the metabolic activity of bacteria in the damaged biofilm was determined using triphenyl tetrazolium chloride (TTC) staining. The nanoparticles were obtained by following the ionic gelation method and its characteristics were evaluated. Chitosan nanoparticles loaded with plant extract were found to be spherical shape with hydrodynamic diameter of 142 nm, a polydispersity index (PDI) of 0.184, a zeta potential of +28.6 mV. It was determined that the loading capacity (% LC) and encapsulation efficiency (% EE) percentages were 33% and 40%, respectively. The diameter of the inhibition zone in the agar disc diffusion test for both bacteria using nanoparticles loaded with the extract increased compared with control groups. Also, at a concentration of 4 mg/mL of loaded nanoparticles, 49.33% of Escherichia coli biofilm and 62.7% of Staphylococcus aureus biofilm were destroyed. The data obtained from the tests performed in this study show that the use of Euphorbia plant extract in the form of chitosan nanoparticles can have more antimicrobial and anti‐biofilm effects.

Multicenter observational study on the efficacy of selective Janus Kinase-1 inhibitor upatacitinib in rheumatoid arthritis.

Upadacitinib (UPA) is a selective, reversible Janus kinase inhibitor (JAKi) approved for the treatment of RA. However, there is still no solid evidence on the long-term efficacy of UPA in treated patients. The purpose of this study was to determine the efficacy of UPA to obtain remission or low disease activity (LDA) in a series of UPA patients in patients with RA after 6 and 12 months of treatment in a real-world setting. A series of 111 consecutive patients treated with UPA in 23 rheumatology centers were enrolled. Personal history, treatment history and disease activity at baseline, after 6 and 12 months were recorded. Intention-to-treat (ITT) and per-protocol (PP) analyses assessed achievement of remission or LDA or defined as DAS28 <2.6 and ≤3.2, respectively. Logistic regression analysis examined the role of several independent factors on the reduction of disease activity after 6 months of treatment. Of the initial group of 111 subjects at baseline, 86 and 29 participants completed clinical assessments at 6 and 12 months. According to ITT analysis, the rates of remission and LDA were 18% and 18% at 6 months and 31.5% and 12.5% at 12 months, respectively. PP analysis showed higher rates of remission and LDA at 6 (23.3% and 19.8%) and 12 months (55.2% and 20.7%). Results of multivariate logistic regression analysis indicated that a low DAS28 score (P=0.045) was the only predictor of achieving remission at 6 months. None of the baseline factors predicted remission/LDA at 6 months. RA patients treated with UPA achieved a significant rate of disease remission or LDA in a real-world setting. The 6-month response was found to depend only on the baseline value of DAS28, while it was not influenced by other factors such as disease duration, line of treatment or concomitant therapy with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or corticosteroids.

Targeting Cervical Cancer Stem Cells by Phytochemicals.

Cervical cancer (CaCx) poses a significant global health challenge, ranking as the fourth most common cancer among women worldwide. Despite the emergence of advanced treatment strategies, recurrence remains a bottleneck in favorable treatment outcomes and contributes to poor prognosis. The chemo- or radio-therapy resistance coupled with frequent relapse of more aggressive tumors are some key components that contribute to CaCx-related mortality. The onset of therapy resistance and relapse are attributed to a small subset of, slow-proliferating Cancer Stem Cells (CSC). These CSCs possess the properties of tumorigenesis, self-renewal, and multi-lineage differentiation potential. Because of slow cycling, these cells maintain themselves in a semi-quiescent stage and protect themselves from different anti-proliferative anti-cancer drugs. Keeping in view recent advances in their phenotypic and functional characterization, the feasibility of targeting CSC and associated stem cell signaling bears a strong translational value. The presence of CSC has been reported in CaCx (CCSC) which remains a forefront area of research. However, we have yet to identify clinically useful leads that can target CCSC. There is compelling evidence that phytochemicals, because of their advantages over synthetic anticancer drugs, could emerge as potential therapeutic leads to target these CCSCs. The present article examined the potential of phytochemicals with reported anti-CSC properties and evaluated their future in preclinical and clinical applications against CaCx.

Efficacy and safety of filgotinib in patients with rheumatoid arthritis: week 156 interim results from a long-term extension study

BackgroundJanus kinase inhibitors are an effective option for achieving sustained remission or low disease activity in patients with rheumatoid arthritis (RA) following inadequate response to conventional synthetic disease-modifying anti-rheumatic drugs....

Effect of apremilast on hand and whole-body MRI assessments of inflammation in patients with psoriatic arthritis (MOSAIC): a phase 4, multicentre, single-arm, open-label study.

The Psoriatic Arthritis Magnetic Resonance Imaging Scoring System (PsAMRIS) and MRI Whole-Body Scoring System for Inflammation in Peripheral Joints and Entheses in Inflammatory Arthritis (MRI-WIPE) have not been used together to assess treatment of psoriatic arthritis in a clinical trial. We aimed to assess the effect of apremilast treatment on inflammation, with outcomes measured by PsAMRIS and MRI-WIPE. MOSAIC was a phase 4, multicentre, single-arm, open-label study conducted at 29 sites across ten countries (Belgium, Canada, Denmark, Germany, Italy, Russia, Spain, Switzerland, the UK, and the USA). Adults aged 18 years or older with a documented diagnosis of psoriatic arthritis for a duration of 3 months to 5 years self-enrolled and were included if they met the classification criteria for active psoriatic arthritis at screening. Patients were required to have at least three swollen and three tender joints with hand involvement and at least one active enthesitis site according to the Spondyloarthritis Research Consortium of Canada enthesitis index or the Leeds enthesitis index. Patients were excluded if they had previous treatment with a biological disease-modifying antirheumatic drug or previous treatment with more than two conventional synthetic disease-modifying antirheumatic drugs. After a 5-day titration period, patients received apremilast 30 mg orally twice per day. Concomitant stable methotrexate up to 25 mg per week was permitted. The primary endpoint was change from baseline to week 24 in a composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis in the hand as assessed by PsAMRIS. The full analysis set and safety population included all enrolled patients who received at least one dose of apremilast. This completed study is registered with ClinicalTrials.gov (NCT03783026). Between Feb 6, 2019, and May 11, 2022, 123 patients were enrolled in the MOSAIC study. Of these 123 patients, 122 (99%) were treated with apremilast and included in the full analysis set and safety population. 67 (55%) of 122 patients were female, 55 (45%) were male, and 116 (95%) were White. 80 (66%) of 122 patients completed 48 weeks of treatment. The least squares mean change from baseline to week 24 in the composite inflammation score of bone marrow oedema, synovitis, and tenosynovitis as assessed by PsAMRIS was -2·32 (95% CI -4·73 to 0·09). 95 (78%) of 122 patients had at least one treatment-emergent adverse event. Six (5%) patients had a severe treatment-emergent adverse event and six (5%) patients had a serious treatment-emergent adverse event. No serious treatment-emergent adverse events were considered to be related to apremilast. Apremilast improved inflammation in joints and entheses on assessment of MRI measures in the hand and the whole body. Our findings encourage the use of MRI, including whole-body MRI, as an objective outcome measure in trials in patients with psoriatic arthritis. Amgen.

Natural Polyphenol-Rich Inhibitors of Pancreatic Lipase for Obesity Management – A Systematic Review

Background: Obesity, a critical public health challenge, is associated with an increased risk of chronic diseases such as cardiovascular disease, diabetes, and cancer. Body mass index (BMI) categorizes obesity levels, with trends indicating a growing prevalence worldwide. Dietary choices and sedentary lifestyles contribute significantly to this condition, yet treatments remain limited by side effects. Pancreatic lipase, the primary enzyme in dietary fat digestion, presents a promising target for obesity management. Inhibitors of pancreatic lipase reduce fat absorption, lowering caloric intake and aiding in weight management. Synthetic inhibitors like orlistat are effective but lead to adverse gastrointestinal and systemic effects, creating a demand for safer alternatives. Methods: A thorough literature review was conducted using PubMed, Elsevier, ScienceDirect, and Google Scholar databases, employing search terms such as "herbal drugs," "polyphenols," "pancreatic lipase inhibitors," "antilipase," "natural products," and "antiobesity herbal drugs." Discussion and Conclusion: Polyphenol-rich plants such as Camellia sinensis (tea), Coffea (coffee), Punica granatum (pomegranate), Vitis vinifera (grape), and Curcuma longa (turmeric) exhibit natural pancreatic lipase inhibitory properties, offering therapeutic potential for obesity management. This review explores the bioactive compounds in these plants, emphasizing their efficacy and minimal side effects compared to synthetic drugs, and underscores the importance of further research in developing natural, polyphenol-based treatments for obesity.

Systematic Review on Herbal Preparations for Controlling Visceral Hypersensitivity in Functional Gastrointestinal Disorders.

Visceral hypersensitivity (VH) is an overreaction of the gastrointestinal (GI) tract to various stimuli and is characterized by hyperalgesia and/or allodynia. VH contributes to the etiology of many GI dysfunctions, particularly irritable bowel syndrome (IBS). Although the exact mechanisms underlying VH are yet to be found, inflammation and oxidative stress, psychosocial factors, and sensorimotor alterations may play significant roles in it. In this review, we provide an overview of VH and its pathophysiological function in GI disorders. Adverse effects of synthetic drugs may make herbal agents a good candidate for pain management. Therefore, in this review, we will discuss the efficacy of herbal agents in the management of VH with a focus on their anti-inflammatory and antioxidant potentials. Data were extracted from clinical and animal studies published in English between 2004 and June, 2020, which were collected from PubMed, Google Scholar, Scopus, and Cochrane Library. Overall, Radix, Melissia, Glycyrrhizae, Mentha, and Liquorice were the most efficient herbals for VH management in IBS and dyspepsia, predominantly through modulation of the mRNA expression of transient receptor potential vanilloid type-1 (TRPV1) and suppression of 5- hydroxytryptamine 3 (5-HT3) or the serotonin receptors. Considering the positive effects of herbal formulations in VH management, further research on novel herbal and/or herbal/chemical preparations is warranted.

Abutilon indicum-mediated green synthesis of NiO and ZnO nanoparticles: Spectral profiling and anticancer potential against human cervical cancer for public health progression

BackgroundIntegrating nanomedicines for targeted cancer treatment and pursuing medicinally valuable components from nature are crucial for sustainable, potent alternatives to synthetic drugs in combating fatal diseases like cancer. Hence, a green synthesis of nickel oxide (NiO NPs) and zinc oxide nanoparticles (ZnO NPs) has been carried out by using the leaf extract of medicinally important plant Abutilonindicum. This sustainable approach to medical developments not only reduces the environmental effect of standard synthesis methods and offers new options for novel cancer therapeutics, but it also advances public health by using natural resources in a sustainable manner. MethodsThe synthesized nanoparticles were characterized by employing spectro-analytical techniques like UV–vis, FT-IR, SEM and powder XRD. Synthesized nanparticles were evaluated in the human cervical cancer cells (HeLa). ResultsNi-O stretching vibrations were observed at 402 cm−1, whereas that of Zn-O stretching was observed at 409 cm−1in the FT-IR spectrum, confirming the formation of nanoparticles. The XRD pattern revealed the crystallite size range of 1.35–2.84 nm for NiO NPs and 7.71–56.80 nm for ZnO NPs. The morphology of the nanoparticles, as indicated by the SEM images, was rod-like for NiO NPs and rock-shaped for ZnO NPs. Further, the cancer cell growth inhibition activity of the nanoparticles was examined by MTT assay against human cervical cancer cells (HeLa) proliferation and compared with cisplatin. MTT assay elucidated the significant anticancer efficacy of the synthesized nanoparticles, showcasing low IC50 values of 29±0.5 µg/ml for NiO NPs and 32±0.7 µg/ml for ZnO NPs. Furthermore, the anticancer activity of the NiO NPs was investigated using the Trypan blue dye exclusion technique, emphasizing the pronounced cytotoxic impact of NiO NPs on cancer cell viability. The outcomes underscore the notable anticancer properties of plant extract mediated metal nanoparticles as promising contenders for advancing cancer treatment modalities.

Exploring the inhibitory potential of hormone replacement therapy drugs on glutathione transferase P1-1

Aim: Glutathione transferase P1-1 (GST P1-1) plays a crucial role in the human phase II detoxication system and is implicated in drug resistance in certain cancer cells. Analogs of drugs used in Hormone Replacement Therapy (HRT) have been reported to exhibit inhibition of various GSTs. This study aims to investigate the inhibitory potential of several HRT drugs on GST P1-1 for the possible use of counteracting drug resistance and for other therapeutic purposes. Materials and Methods: GST P1-1 was expressed and then purified in a single step using Nickel Sepharose affinity chromatography. Synthetic drugs that are used in HRT were screened for inhibition of GST P1-1 using 1-chloro-2,4-dinitrobenzene as the substrate. The IC50 value of the most potent compound was calculated and binding location and formation of bonds to GST P1-1 were identified through docking analysis. Results: Screening the inhibitory effect of eight synthetic estrogenic drugs reveals that estradiol valerate is the most potent inhibitor, showing 72 ± 4% inhibition of GST P1-1. This effect is followed by estradiol cypionate 53 ± 5%, mestranol 39 ± 4%, and estradiol propionate 35 ± 2%. The most potent compound estradiol valerate has an IC50 value of 30 ± 2 μM. According to docking analysis, it binds to the H-site of the enzyme where the residues Phe9, Arg14, Val36, Trp39, Ile105, Tyr109, Pro203, Asn207, and Gln210 were within 5 Å proximity of the ligand. Estradiol valerate forms Pi-alkyl interactions with Phe9 and Val36, as well as an alkyl interaction with Ile104. Conclusion: Estradiol valerate is a modest inhibitor for hGST P1-1, however it fits in the area of H-site of the enzyme and forms bonds with critical key residues. Understanding its binding site on the enzyme is critical for designing other inhibitors targeting GSTs or possibility for the potential use as a substrate with other GSTs.

Colchicine, serotobenine, and kinobeon A: novel therapeutic compounds in Carthamus tinctorius L. for the management of diabetes

Diabetes, a global health concern, poses increasing mortality risks. The pathogenesis of diabetes involves multiple mechanisms, with oxidative stress being one of the key contributors. As synthetic drugs have various side effects, which can be minimized by using herbal plants. This study focuses on the In vitro antioxidant potential, α-amylase inhibition potential, identification of bioactive compounds, and hub genes in diabetes treatment mechanism by using C. tinctorius Extraction of C. tinctorious lead and flower was performed using different solvents (Distilled water, methanol, chloroform, and Dimethyl ether). After extraction different concentrations range from 25–200 mg/mL) was made and checked against activities. The antioxidant potential was assessed using 2, 2-diphenyl-1-picrylhydrazyl (DPPH), total phenolic contents (TPC), and total antioxidant capacity (TAC) assays, while antidiabetic activity was evaluated through α-amylase inhibition assay. Phytochemicals was identified by GC–MS analysis, followed by ADMET screening and network pharmacology analysis using Swiss Target Prediction, Gene Card, DesGeNet, DAVID, STRING, Cytoscape, and drug revitalization databases. Results revealed positive correlations with DPPH, TAC, and TPC. Methanol extract exhibited the highest inhibitory concentration. Screening of 46 compounds was performed by studying their pharmacokinetic properties which revealed 9 compounds effective against 204 diabetes targets. Moreover, their network analysis identified four hub genes, including AKT1, JUN, EGFR, and MMP9. These genes found highly associated with drugs like Colchicine and Serotobenine. Revitalization analysis also highlighted four genes (EGFR, PTGS2, AKT1, and MMP9) strongly correlated with FDA-approved drugs. The study suggests C. tinctorius methanol extract is a potential source for novel drugs.Graphical

Update of the Consensus Statement of the Spanish Society of Rheumatology on the use of biological and synthetic targeted therapies in rheumatoid arthritis

ObjectiveTo update the consensus document of the Spanish Society of Rheumatology (SER) regarding the use of targeted biological and synthetic therapies in rheumatoid arthritis (RA) with the aim of assisting clinicians in their therapeutic decisions. MethodsA panel of 13 experts was assembled through an open call by SER. We employed a mixed adaptation-elaboration-update methodology starting from the 2015 Consensus Document of the Spanish Society of Rheumatology on the use of biological therapies in RA. Starting with systematic reviews (SR) of recommendations from EULAR 2019, American College of Rheumatology 2021, and GUIPCAR 2017, we updated the search strategies for the PICO questions of GUIPCAR. An additional SR was conducted on demyelinating disease in relation to targeted biological and synthetic therapies. Following the analysis of evidence by different panelists, consensus on the wording and level of agreement for each recommendation was reached in a face-to-face meeting. ResultsThe panel established 5 general principles and 15 recommendations on the management of RA. These encompassed crucial aspects such as the importance of early treatment, therapeutic goals in RA, monitoring frequency, the use of glucocorticoids, the application of conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), biological DMARDs (bDMARDs), and targeted synthetic DMARDs. Additionally, recommendations on dose reduction of these drugs in stable patients were included. This update also features recommendations on the use of bDMARDs and Janus Kinase inhibitors in some specific clinical situations, such as patients with lung disease, a history of cancer, heart failure, or demyelinating disease. ConclusionsThis update provides recommendations on key aspects in the management of RA using targeted biological and synthetic therapies.