Drug Target InsightsPub Date : 2025-05-09eCollection Date: 2025-01-01DOI: 10.33393/dti.2025.3304
Ankush Kaushik, Jitendra Singh, Zeeshan Fatima, Saif Hameed
{"title":"Establishment and evaluation of a naked-eye diagnostic assay for tuberculosis utilizing reverse isothermal amplification-assisted CRISPR-Cas in resource-limited settings.","authors":"Ankush Kaushik, Jitendra Singh, Zeeshan Fatima, Saif Hameed","doi":"10.33393/dti.2025.3304","DOIUrl":"https://doi.org/10.33393/dti.2025.3304","url":null,"abstract":"<p><strong>Introduction: </strong>The current scenario of tuberculosis (TB) caused by <i>Mycobacterium tuberculosis</i> (MTB) has presented an almost insurmountable challenge to hospitals with high patient numbers. Delayed diagnosis of TB is a major hurdle in preventing the employment of efficient therapeutics, leading to the development of drug resistance. Hence, an easily accessible diagnostic method, particularly for resource for resource-limited settings, is pertinent for the rapid identification of MTB-infected patients. In pursuit of developing such an assay, the present study offers a CLAP-TB (CRISPR-Cas coupled RT-LAMP Amplification Protocol for Tuberculosis) assay, which will allow us to diagnose TB rapidly and visually.</p><p><strong>Methods and results: </strong>Herein, the visual MTB detection consists of a method utilizing 232 different samples (sputum, urine, serum) from 82 patients for reverse transcription loop-mediated isothermal amplification (RT-LAMP). Additionally, the assay also utilizes the integration of a CRISPR-Cas12-based system using different guide RNAs of <i>IS6110</i> and an internal control <i>POP7</i> (human RNase P) genes along with visual detection via lateral flow readout-based dipsticks with the unaided eye (~134 min). Overall, the limit of detection for CLAP-TB assay was up to 1 ag of RNA, while the clinical sensitivity and specificity were 98.27% and 100%, respectively, on the pilot scale.</p><p><strong>Conclusion: </strong>Together, our CLAP-TB assay offers proof of concept for a rapid, sensitive, and specific method with the minimum technical expertise required for TB diagnosis in developing and resource-limited settings.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"19 ","pages":"31-40"},"PeriodicalIF":2.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<i>Withania somnifera</i> root extract (LongeFera<sup>™</sup>) confers beneficial effects on health and lifespan of the model worm <i>Caenorhabditis legans</i>.","authors":"Nidhi Thakkar, Gemini Gajera, Dilip Mehta, Sujit Nair, Vijay Kothari","doi":"10.33393/dti.2025.3368","DOIUrl":"10.33393/dti.2025.3368","url":null,"abstract":"<p><strong>Background: </strong><i>Withania somnifera</i> is among the most widely prescribed medicinal plants in traditional Indian medicine. Hydroalcoholic extract of the roots of this plant was investigated for its effects on the overall health and lifespan of the model worm <i>Caenorhabditis elegans</i>.</p><p><strong>Methods: </strong>The extract's effect on worm lifespan and fertility was observed microscopically. Worm motility was quantified through an automated worm tracker. The metabolic activity of the worms was captured using the Alamar Blue® assay. Differential gene expression in extract-treated worms was revealed through a whole transcriptome approach.</p><p><strong>Results: </strong>Extract-exposed gnotobiotic worms, in the absence of any bacterial food, registered longer lifespan, higher fertility, better motility, and metabolic activity. Whole transcriptome analysis of the extract-treated worms revealed the differential expression of the genes associated with lifespan extension, eggshell assembly and integrity, progeny formation, yolk lipoproteins, collagen synthesis, cuticle molting, etc. This extract seems to exert its beneficial effect on <i>C. elegans</i> partly by triggering the remodeling of the developmentally programmed apical extracellular matrix (aECM). Differential expression of certain important genes (<i>cpg-2</i>, <i>cpg-3, sqt-1, dpy-4, dpy-13,</i> and <i>col</i> <i>-17</i>) was confirmed through PCR assay too. Some of the differently expressed genes (<i>gfat-2, unc-68, dpy-4, dpy</i> <i>-13, col-109, col-169,</i> and <i>rmd-1</i>) in worms experiencing pro-health effect of the extract were found through co-occurrence analysis to have their homologous counterpart in humans.</p><p><strong>Conclusions: </strong>Our results validate the suitability of <i>W. somnifera</i> extract as a nutraceutical for healthy aging.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"19 ","pages":"18-30"},"PeriodicalIF":2.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug Target InsightsPub Date : 2025-03-10eCollection Date: 2025-01-01DOI: 10.33393/dti.2025.3271
Abdur Rauf, Waqas Alam, Momin Khan, Hany W Darwish, Maria Daglia, Ahmed A Elhenawy, Haroon Khan
{"title":"Exploring the in vitro anti-diabetic potential and in silico studies of 2, 3 and 2, 6-dichloroIndolinone.","authors":"Abdur Rauf, Waqas Alam, Momin Khan, Hany W Darwish, Maria Daglia, Ahmed A Elhenawy, Haroon Khan","doi":"10.33393/dti.2025.3271","DOIUrl":"10.33393/dti.2025.3271","url":null,"abstract":"<p><strong>Introduction: </strong>Adequate hyperglycemic control is still a huge challenge with the clinically used therapeutics. New, more effective anti-diabetic agents are on the top list of drug discovery projects.</p><p><strong>Methods: </strong>This article deals with the in vitro anti-diabetic potential of 2, 3 dichloroIndolinone (C1) and 2, 6-dichloroIndolinone (C2) on α-glucosidase and α-amylase followed by in silico analysis.</p><p><strong>Results: </strong>Both compounds, C-1 and C-2, caused significant inhibition of α-glucosidase at various test concentrations with IC<sub>50</sub> of 35.266 μM and 38. 379 μM, respectively. Similarly, compounds C-1 and C-2 elicited significant anti-α-amylase action with IC<sub>50</sub> values of 42.449 μM and 46.708 μM, respectively. The molecular docking investigation regarding the α-glucosidase and α-amylase binding site was implemented to attain better comprehension with respect to the pattern in which binding mechanics occur between the C1 and C2 molecules and the active sites, which illustrated a higher binding efficacy in appraisal with reference inhibitor and acarbose. The interactions between the active compounds C1 and C2 with the active site residues were mainly polar bonds, hydrogen bonding, π-π, and π-H interactions, which contributed to a strong alignment with the enzyme backbone. Similarly, effective binding is frequently indicated by a strong and stable hydrogen-bonding pattern, which is suggested by the minimal fluctuation in MM-PBSA values.</p><p><strong>Conclusion: </strong>In short, this study will contribute to providing these compounds with an improved anti-diabetic profile and decreased toxicity.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"19 ","pages":"11-17"},"PeriodicalIF":2.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug Target InsightsPub Date : 2025-01-13eCollection Date: 2025-01-01DOI: 10.33393/dti.2025.3171
Abhay P Mishra, Masande Yalo, Jennifer Nambooze, Carolina H Pohl, Gabré Kemp, Lekgoana K Setsiba, Motlalepula G Matsabisa
{"title":"Characterization and enhanced antibiofilm activity of <i>Annona muricata</i> extract in combination with fluconazole against <i>Candida albicans</i>.","authors":"Abhay P Mishra, Masande Yalo, Jennifer Nambooze, Carolina H Pohl, Gabré Kemp, Lekgoana K Setsiba, Motlalepula G Matsabisa","doi":"10.33393/dti.2025.3171","DOIUrl":"https://doi.org/10.33393/dti.2025.3171","url":null,"abstract":"<p><strong>Introduction: </strong><i>Candida albicans</i> biofilm formation is a significant contributor to antifungal resistance, necessitating new treatment strategies. <i>Annona muricata</i> Lin., a traditional herbal remedy, has shown promise in combating microbial infections. The purpose of this study was to assess the antibiofilm activity of the methanol extract of <i>A. muricata</i> leaves alone or with the addition of fluconazole against <i>C. albicans</i>.</p><p><strong>Methods: </strong>Phytochemicals from the methanol extract were analyzed by LC-MS, the XTT assay was used for metabolic activity, and morphological characteristics were examined using scanning electron microscopy (SEM). Molecular docking screening of identified compounds in <i>A. muricata</i> methanol leaves extract against a Sap3 receptor (PDB: 2H6T) was also performed.</p><p><strong>Results: </strong>The LC-MS analysis detected 17 possible phytochemicals. The methanol extract showed a dose-dependent inhibition of biofilm formation, with maximum inhibition of ~60% observed at 240 μg/ml, and inhibition by fluconazole increased from 32% to 76% as the concentration increased from 15 to 240 μg/ml. The combination of <i>A. muricata</i> and fluconazole increased the inhibition significantly, from 74% to 78% at 15 μg/ml to 240 μg/mL, respectively. SEM of control and treated <i>C. albicans</i> biofilms showed an altered morphology and loss of cell integrity by the combination, corroborating the findings. Plant phytochemicals also possess high binding affinity (-9.7 to 8.0 kcal/mol, respectively) for the Sap3 enzyme and may therefore have therapeutic potential against <i>C. albicans</i>.</p><p><strong>Conclusion: </strong>Consequently, the findings indicate that compounds in the <i>A. muricata</i> methanol extract may function in concert with fluconazole at sub-inhibitory concentrations to suppress <i>C. albicans</i> biofilm formation. This finding paves the way for the formulation and development of antifungal treatment regimens that may limit the development of fluconazole resistance employing this plant part.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"19 ","pages":"1-10"},"PeriodicalIF":2.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729473/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug Target InsightsPub Date : 2024-12-12eCollection Date: 2024-01-01DOI: 10.33393/dti.2024.3213
Carlotta Galeone, Federica Turati, Massimo Nicolò, Mariacristina Parravano, Stela Vujosevic, Laura Bianchino, Emilia Sicari, Paolo Lanzetta
{"title":"Faricimab versus the standard of care for neovascular age-related macular degeneration in Italy: an indirect treatment comparison.","authors":"Carlotta Galeone, Federica Turati, Massimo Nicolò, Mariacristina Parravano, Stela Vujosevic, Laura Bianchino, Emilia Sicari, Paolo Lanzetta","doi":"10.33393/dti.2024.3213","DOIUrl":"10.33393/dti.2024.3213","url":null,"abstract":"<p><strong>Objectives: </strong>To assess through an indirect treatment comparison (ITC) the potential benefit of faricimab over the anti-vascular endothelial growth factor (VEGF) real-life scenario, hereby defined standard of care (SoC), in Italy, that is, aflibercept, bevacizumab, and ranibizumab, in patients with neovascular age-related macular degeneration (nAMD) naïve to any anti-VEGF treatment.</p><p><strong>Methods: </strong>Individual patient-level data from the phase III clinical trials TENAYA and LUCERNE (faricimab cohort) and the real-world study RADIANCE (RADIANCE cohort) were used. Efficacy was evaluated with changes in best corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to 1 year (week 52 in the RADIANCE and week 48 in the faricimab cohorts, respectively). Propensity score-based inverse probability of treatment weighting was utilized to balance cohorts and mitigate bias due to potential confounding. Sensitivity analyses were performed to evaluate treatment differences adjusted for the number of injections.</p><p><strong>Results: </strong>The ITC included 513 patients treated with faricimab and 263 patients treated with SoC. At 1 year, faricimab showed a greater mean BCVA gain (treatment difference +5.4 letters, p<0.001) and CST reduction (treatment difference -71.8 μm, p<0.001) compared to SoC. Sensitivity analyses confirmed the robustness of results, showing a BCVA improvement of +4.0 letters and a CST reduction of -71.5 μm in favor of faricimab.</p><p><strong>Conclusions: </strong>Despite the limitations due to the use of ITC and the comparison between clinical trials and real-world cohorts, the present analysis suggests potential benefits in terms of vision gain and CST reduction in naïve nAMD patients treated with faricimab compared with SoC in a real-world setting.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"18 ","pages":"105-111"},"PeriodicalIF":2.0,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug Target InsightsPub Date : 2024-12-11eCollection Date: 2024-01-01DOI: 10.33393/dti.2024.3219
Thembelihle H Nxasana, Innocensia M Mangoato, Patriciah M Masiu, Abhay P Mishra, Motlalepula G Matsabisa
{"title":"Investigating the combinatory effect of <i>Sclerocarya birrea</i> with doxorubicin against selected colorectal cancer cell lines.","authors":"Thembelihle H Nxasana, Innocensia M Mangoato, Patriciah M Masiu, Abhay P Mishra, Motlalepula G Matsabisa","doi":"10.33393/dti.2024.3219","DOIUrl":"10.33393/dti.2024.3219","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer incidences continue to increase annually, worldwide. Herbal plants with antiproliferative properties received research interest as agents that can be adjuvant therapies with chemotherapy drugs to enhance their efficacy and reverse drug resistance.</p><p><strong>Methods: </strong><i>Sclerocarya birrea</i> ethanolic (SBE) and aqueous (SBW) extracts combined with doxorubicin (DOX) against drug-sensitive and drug-resistant colorectal cancer cells were investigated for their potential adjuvant and drug resistance reversal. The extracts were assessed for their potential anticancer activities on HCT15 and HT29 cell lines as well as their doxorubicin potentiating and drug resistance reversal effects respectively. The extracts were assessed for their cytotoxicity on normal 3T3-L1 fibroblast cells.</p><p><strong>Results: </strong>Both SBE and SBW extracts exhibited no toxicity against normal 3T3 cells and showed low activity on the HT29 cell line. Contrarily, resistant HCT15 cells showed moderate to low activity with significantly higher inhibitory concentration (IC)<sub>50</sub> values. The combination of SBE with DOX and SBW with DOX resulted in antagonistic interactions, causing an increase in IC<sub>50</sub> values for HT29 and HCT15 cells. In contrast, the combination of DOX and verapamil (VER) produced an additive effect, with no change in their IC<sub>50</sub> values.</p><p><strong>Conclusion: </strong>Based on the findings from the combination treatment, the SBE and SBW extracts demonstrated higher efficacy and synergistic effects combined with DOX at IC<sub>75</sub> compared to the combination of DOX and VER, suggesting their potential as anticancer agents. However, further research on both the SBE and SBW extracts' mechanisms of action and in vivo effects is warranted.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"18 ","pages":"94-104"},"PeriodicalIF":2.0,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11638844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug Target InsightsPub Date : 2024-10-22eCollection Date: 2024-01-01DOI: 10.33393/dti.2024.3169
Ali Hendi Alghamdi, Aimun A E Ahmed, Mahadi Bashir, Haidar Abdalgadir, Asaad Khalid, Mohamed E Abdallah, Riyad Almaimani, Bassem Refaat, Ashraf N Abdalla
{"title":"Cytotoxic activity, selectivity, and clonogenicity of fruits and resins of Saudi medicinal plants against human liver adenocarcinoma.","authors":"Ali Hendi Alghamdi, Aimun A E Ahmed, Mahadi Bashir, Haidar Abdalgadir, Asaad Khalid, Mohamed E Abdallah, Riyad Almaimani, Bassem Refaat, Ashraf N Abdalla","doi":"10.33393/dti.2024.3169","DOIUrl":"https://doi.org/10.33393/dti.2024.3169","url":null,"abstract":"<p><strong>Background: </strong>Edible fruits and resins provide various benefits to mankind including potential medicinal applications. This study aimed to determine the cytotoxicity, selectivity, and clonogenicity of fruits and exudates of certain Saudi medicinal plants (<i>Anethum graveolens</i> (BEP-09), <i>Opuntia ficus-indica</i> (L.) Miller (BEP-10), <i>Boswellia serrata</i> Roxb. ex Colebr. (BEP-11), and <i>Commiphora myrrha</i> (BEP-12)) against human liver adenocarcinoma (HepG2).</p><p><strong>Methods: </strong>Initial cytotoxicity and cell line selectivity against different cell lines were screened using MTT assay. The most promising extract was subjected to gas chromatography-mass spectrometry (GC-MS) analysis to determine the main phytoconstituents. Clonogenicity was checked for the most active extract.</p><p><strong>Results: </strong>The selected plants' fruits and resins possess a significant cytotoxic activity estimated as IC<sub>50</sub>. The fruit of BEP-10 was found to be the most active extract against liver cancer cells (IC<sub>50</sub> = 2.82) comparable to both doxorubicin (IC<sub>50</sub> = 1.40) and camptothecin (IC<sub>50</sub> = 1.11). It showed a selectivity index of 4.47 compared to the normal human foetal lung fibroblast (MRC5) cells. BEP-10 showed a dose-dependent clonogenic effect against HepG2 cells comparable to the effect of doxorubicin. The GC-MS chromatogram of BEP-10 extract revealed the presence of eight small polar molecules, representing 73% of the total identified compounds and the rest three molecules (27%) were non-polar constituents. The furan derivatives represent the chief components in BEP-10 (16.3%), while the aldehyde 5-(hydroxymethyl)-2-furancarboxaldehyde was found to be the main molecule (13.2%).</p><p><strong>Conclusion: </strong>The fruits of BEP-10 have a potential cytotoxic effect particularly against HepG2. The identified phytoconstituents in the tested plant extract might contribute to the investigated cytotoxic activity.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"18 ","pages":"84-93"},"PeriodicalIF":2.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11500103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Drug Target InsightsPub Date : 2024-10-07eCollection Date: 2024-01-01DOI: 10.33393/dti.2024.3060
Hafiz Muhammad Aslam, Azka Sohail, Ammara Shahid, Maham Abdul Bari Khan, Muhammad Umar Sharif, Razia Kausar, Samia Nawab, Waqas Farooq, Kashif Jilani, Majeeda Rasheed
{"title":"Levofloxacin induces erythrocyte contraction leading to red cell death.","authors":"Hafiz Muhammad Aslam, Azka Sohail, Ammara Shahid, Maham Abdul Bari Khan, Muhammad Umar Sharif, Razia Kausar, Samia Nawab, Waqas Farooq, Kashif Jilani, Majeeda Rasheed","doi":"10.33393/dti.2024.3060","DOIUrl":"10.33393/dti.2024.3060","url":null,"abstract":"<p><strong>Background: </strong>Levofloxacin, a fluoroquinolone, is an extensively used antibiotic effective against both positively and negatively staining bacteria. It works by inhibiting bacterial topoisomerase type II and topoisomerase type IV, resulting in impaired DNA synthesis and bacterial cell death. Eryptosis is another term for apoptotic cell death of erythrocyte marked by cell shrinkage, phosphatidylserine (PS) flipping, and membrane blebbing.</p><p><strong>Methods: </strong>The intent of the present research was to look at the eryptotic effect of levofloxacin by exposing erythrocytes to therapeutical doses (7, 14 µM) of levofloxacin for 48 hours. Cell size evaluation, PS subjection to outside, and calcium channel inhibition were carried out to investigate eryptosis. Oxidative stress generated by levofloxacin was measured as a putative mechanism of eryptosis using glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase activities. Similarly, hemolysis measurements demonstrated levofloxacin's cytotoxic effect.</p><p><strong>Results: </strong>Our findings showed that therapeutic doses of levofloxacin can cause a considerable decline in antioxidant enzymes activities, as well as induce cell shrinkage, PS externalization, and hemolysis in erythrocytes. The role of calcium in triggering erythrocyte shrinkage was also confirmed.</p><p><strong>Conclusion: </strong>In conclusion, our findings showed that the indicated levofloxacin doses caused oxidative stress, which leads to erythrocyte death via eryptosis and hemolysis. These findings emphasize the importance of using levofloxacin with caution and the need for additional research to mitigate these side effects.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"18 ","pages":"78-83"},"PeriodicalIF":2.0,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11462248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Enhancement of apoptosis in Caco-2, Hep-G2, and HT29 cancer cell lines following exposure to <i>Toxoplasma gondii</i> peptides.","authors":"Firooz Shahrivar, Javid Sadraei, Majid Pirestani, Ehsan Ahmadpour","doi":"10.33393/dti.2024.3177","DOIUrl":"10.33393/dti.2024.3177","url":null,"abstract":"<p><strong>Objective: </strong>Cancer or neoplasm is a cosmopolitan catastrophe that results in more than 20 million new cases and 10 million deaths every year. Some factors lead to carcinogenesis like infectious diseases. Parasites like <i>Toxoplasma gondii</i>, by its components, could modulate the cancer system by inducing apoptosis. The objective of this investigation is to assess the potential of peptides derived from <i>T. gondii</i> in combating cancer by examining their effects on Caco-2, Hep-G2, and HT29 cell lines.</p><p><strong>Materials and methods: </strong>Candidate peptide by its similarity to anticancer compounds was predicted through the computer-based analysis/platform. The impact of the peptide on cell viability, cell proliferation, and gene expression was evaluated through the utilization of MTT assay, flow cytometry, and real-time polymerase chain reaction (PCR) methodologies.</p><p><strong>Results: </strong>The cell viability rate exhibited a significant decrease (p < 0.001) across all cell lines when exposed to a concentration of ≤160 μg. Within the 48-hour timeframe, the half maximal inhibitory concentration (IC<sub>50</sub>) for HT29 and Hep-G2 cell lines was determined to be 107.2 and 140.6 μg/mL, respectively. Notably, a marked decrease in the expression levels of <i>Bcl2</i> and <i>APAF1</i> genes was observed in both the Hep-G2 and HT29 cell lines.</p><p><strong>Conclusion: </strong>These findings indicate that the <i>T. gondii</i> peptide affected cancer cell mortality and led to changes in the expression of genes associated with apoptosis.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"18 ","pages":"70-77"},"PeriodicalIF":2.0,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142361314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Deciphering the molecular mechanisms underlying anti-pathogenic potential of a polyherbal formulation Enteropan® against multidrug-resistant <i>Pseudomonas aeruginosa</i>.","authors":"Sweety Parmar, Gemini Gajera, Nidhi Thakkar, Hanmanthrao S Palep, Vijay Kothari","doi":"10.33393/dti.2024.3082","DOIUrl":"10.33393/dti.2024.3082","url":null,"abstract":"<p><strong>Objective: </strong>Anti-pathogenic potential of a polyherbal formulation Enteropan® was investigated against a multidrug-resistant strain of the bacterium <i>Pseudomonas aeruginosa</i>.</p><p><strong>Methods: </strong>Growth, pigment production, antibiotic susceptibility, etc., were assessed through appropriate <i>in vitro</i> assays. Virulence of the test pathogen was assessed employing the nematode worm <i>Caenorhabditis elegans</i> as a model host. Molecular mechanisms underlining the anti-pathogenic activity of the test formulation were elucidated through whole transcriptome analysis of the extract-exposed bacterial culture.</p><p><strong>Results: </strong>Enteropan-pre-exposed <i>P. aeruginosa</i> displayed reduced (~70%↓) virulence towards the model host <i>C. elegans</i>. Enteropan affected various traits like biofilm formation, protein synthesis and secretion, quorum-modulated pigment production, antibiotic susceptibility, nitrogen metabolism, etc., in this pathogen. <i>P. aeruginosa</i> could not develop complete resistance to the virulence-attenuating activity of Enteropan even after repeated exposure to this polyherbal formulation. Whole transcriptome analysis showed 17% of <i>P. aeruginosa</i> genome to get differentially expressed under influence of Enteropan. Major mechanisms through which Enteropan exerted its anti-virulence activity were found to be generation of nitrosative stress, oxidative stress, envelop stress, quorum modulation, disturbance of protein homeostasis and metal homeostasis. Network analysis of the differently expressed genes resulted in identification of 10 proteins with high network centrality as potential targets from among the downregulated genes. Differential expression of genes coding for five (<i>rpoA</i>, <i>tig</i>, <i>rpsB</i>, <i>rpsL</i>, and <i>rpsJ</i>) of these targets was validated through real-time polymerase chain reaction too, and they can further be pursued as potential targets by various drug discovery programmes.</p>","PeriodicalId":11326,"journal":{"name":"Drug Target Insights","volume":"18 ","pages":"54-69"},"PeriodicalIF":2.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}