{"title":"The Impact of Pdcd4, a Translation Inhibitor, on Drug Resistance.","authors":"Qing Wang, Hsin-Sheng Yang","doi":"10.3390/ph17101396","DOIUrl":"https://doi.org/10.3390/ph17101396","url":null,"abstract":"<p><p>Programmed cell death 4 (Pdcd4) is a tumor suppressor, which has been demonstrated to efficiently suppress tumorigenesis. Biochemically, Pdcd4 binds with translation initiation factor 4A and represses protein translation. Beyond its role in tumor suppression, growing evidence suggests that Pdcd4 enhances the chemosensitivity of several anticancer drugs. To date, numerous translational targets of Pdcd4 have been identified. These targets govern important signal transduction pathways, and their attenuation may improve chemosensitivity or overcome drug resistance. This review will discuss the signal transduction pathways regulated by Pdcd4 and the potential mechanisms through which Pdcd4 enhances chemosensitivity or counteracts drug resistance.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gamze Camlik, Besa Bilakaya, Esra Küpeli Akkol, Adrian Joshua Velaro, Siddhanshu Wasnik, Adi Muradi Muhar, Ismail Tuncer Degim, Eduardo Sobarzo-Sánchez
{"title":"Oral Active Carbon Quantum Dots for Diabetes.","authors":"Gamze Camlik, Besa Bilakaya, Esra Küpeli Akkol, Adrian Joshua Velaro, Siddhanshu Wasnik, Adi Muradi Muhar, Ismail Tuncer Degim, Eduardo Sobarzo-Sánchez","doi":"10.3390/ph17101395","DOIUrl":"https://doi.org/10.3390/ph17101395","url":null,"abstract":"<p><strong>Background/objectives: </strong>Metformin (Met), an oral drug used to treat type II diabetes, is known to control blood glucose levels. Metformin carbon quantum dots (MetCQDs) were prepared to enhance the bioavailability and effectiveness of metformin. Several studies have shown that carbon quantum dots (CQDs) have attractive properties like small particle size, high penetrability, low cytotoxicity, and ease of synthesis. CQDs are made from a carbon source, namely, citric acid, and a heteroatom, such as nitrogen. The active molecule can be a carbon source or a heteroatom, as reported here.</p><p><strong>Methods: </strong>This study aims to produce MetCQDs from an active molecule. MetCQDs were successfully produced by microwave-based production methods and characterized. The effect of the MetCQDs was tested in Wistar albino rats following a Streptozocin-induced diabetic model.</p><p><strong>Results: </strong>The results show that the products have a particle size of 9.02 ± 0.04 nm, a zeta potential of -10.4 ± 0.214 mV, and a quantum yield of 15.1 ± 0.045%. Stability studies and spectrophotometric analyses were carried out and the effectiveness of MetCQDs evaluated in diabetic rats. The results show a significant reduction in blood sugar levels (34.1-51.1%) compared to the group receiving only metformin (37.1-55.3%) over a period of 30 to 360 min. Histopathological examinations of the liver tissue indicate improvement in the liver health indicators of the group treated with MetCQDs.</p><p><strong>Conclusions: </strong>Based on these results, the products have potential therapeutic advantages in diabetes management through their increased efficacy and may have reduced side effects compared to the control group.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510116/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aniélen D da Silva, Mateus Fracasso, Nathieli B Bottari, Taís V Palma, Ana M Engelmann, Milagros F V Castro, Charles E Assmann, Vitor Mostardeiro, Karine P Reichert, Jelson Nauderer, Marcelo L da Veiga, Maria Izabel U M da Rocha, Luiz Claudio Milleti, Gabriella B das Neves, Samanta Gundel, Aline F Ourique, Silvia G Monteiro, Vera M Morsch, Maria Rosa Chitolina, Aleksandro S Da Silva
{"title":"Effects of Free and Nanoencapsulated Benznidazole in Acute <i>Trypanosoma cruzi</i> Infection: Role of Cholinergic Pathway and Redox Status.","authors":"Aniélen D da Silva, Mateus Fracasso, Nathieli B Bottari, Taís V Palma, Ana M Engelmann, Milagros F V Castro, Charles E Assmann, Vitor Mostardeiro, Karine P Reichert, Jelson Nauderer, Marcelo L da Veiga, Maria Izabel U M da Rocha, Luiz Claudio Milleti, Gabriella B das Neves, Samanta Gundel, Aline F Ourique, Silvia G Monteiro, Vera M Morsch, Maria Rosa Chitolina, Aleksandro S Da Silva","doi":"10.3390/ph17101397","DOIUrl":"https://doi.org/10.3390/ph17101397","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The <i>Trypanosoma cruzi</i> infection promotes an intense inflammatory process that affects several tissues. The cholinergic system may exert a regulatory immune response and control the inflammatory process. This study aimed to evaluate the comparative effect of free and nanoencapsulated benznidazole in acute <i>T. cruzi</i> infection to assess hematological, biochemical, and oxidative status triggered by the cholinergic system. <b>Methods</b>: For this, fifty female Swiss mice were distributed in eight groups, i.e., uninfected and infected animals under four treatment protocols: untreated (control-CT); vehicle treatment (Eudragit L 100-EL-100); benznidazole treatment (BNZ); and nanoencapsulated benznidazole treatment (NBNZ). After eight treatment days, the animals were euthanized for sample collection. <b>Results</b>: The peak of parasitemia was at day 7 p.i., and the BNZ and NBNZ controlled and reduced the parasite rate but showed no efficacy in terms of total elimination of parasites analyzed by RT-PCR in both infected groups. The infection promotes significant anemia, leukopenia, and thrombocytopenia, which the BNZ improves. There was an increase in AChE activity during infection, leading to a pro-inflammatory response and an increase in M1 and M2 mACh receptors in the BNZ group, showing that the treatment interacted with the cholinergic pathway. In addition, a pro-oxidative response was characterized in the infection and mainly in the infected BNZ and NBNZ groups. The histopathological analysis showed significative splenomegaly and inflammatory infiltrate in the heart, liver, and spleen. <b>Conclusions</b>: The administration of the BNZ or NBNZ reverses hematological, hepatic, and renal alterations through cholinergic signaling and stimulates a pro-inflammatory response during acute <i>T. cruzi</i> infection.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Protective Capacity of <i>Helichrysum italicum</i> Infusion Against Intestinal Barrier Disruption and Translocation of <i>Salmonella</i> Infantis.","authors":"Katja Kramberger, Katja Bezek Kranjc, Zala Jenko Pražnikar, Darja Barlič-Maganja, Saša Kenig","doi":"10.3390/ph17101398","DOIUrl":"https://doi.org/10.3390/ph17101398","url":null,"abstract":"<p><strong>Background: </strong><i>Helichrysum italicum</i> is a Mediterranean plant with well-known anti-inflammatory activity, but our previous whole transcriptome analysis has found that <i>H. italicum</i> infusion (HII) can also affect cytoskeletal rearrangement and tight junctions. The goal of the present study was to determine if HII improves the intestinal barrier (IB) dysfunction and by what mechanism.</p><p><strong>Methods: </strong>Caco-2 cells on Transwell inserts were used as a model of IB permeability. Heat-killed (HKB) or live <i>Salmonella</i> Infantis bacteria were used to induce IB integrity disruption upon three different testing conditions: pre-, co-, and post-treatment with 0.2 v/v% HII. Transepithelial electrical resistance values were used as an indicator of monolayer integrity before and after all treatments, and RT-PCR was used to assess the expression of tight junction proteins (TJPs) and inflammatory cytokines known to regulate intestinal permeability.</p><p><strong>Results: </strong>We found that all three treatments with HII improved the HKB-induced integrity disruption and decreased the down-regulation of <i>TJP1</i>, <i>OCLN</i>, and <i>CLDN1</i>, with the greatest effect observed in the pre-treated cells. Treatment with HII also decreased the up-regulation of <i>CLDN2</i>, <i>TNF-α</i>, <i>IL-1β</i>, and <i>IL-6</i>. In addition, pre-treatment of Caco-2 cells with HII prevented translocation of <i>S.</i> Infantis but did not prevent adhesion and invasion.</p><p><strong>Conclusion: </strong>This study showed that HII can improve inflammation-disrupted IB function by indirect modulation of mRNA expression of TJPs, especially in a preventive manner.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thalisson A de Souza, Luiz H A Pereira, Alan F Alves, Douglas Dourado, Jociano da S Lins, Marcus T Scotti, Luciana Scotti, Lucas S Abreu, Josean F Tavares, Marcelo S Silva
{"title":"<i>Jatropha</i> Diterpenes: An Updated Review Concerning Their Structural Diversity, Therapeutic Performance, and Future Pharmaceutical Applications.","authors":"Thalisson A de Souza, Luiz H A Pereira, Alan F Alves, Douglas Dourado, Jociano da S Lins, Marcus T Scotti, Luciana Scotti, Lucas S Abreu, Josean F Tavares, Marcelo S Silva","doi":"10.3390/ph17101399","DOIUrl":"https://doi.org/10.3390/ph17101399","url":null,"abstract":"<p><p>The <i>Euphorbiaceae</i> family is a rich source of bioactive terpenoids. Among its genera, <i>Jatropha</i> is a conspicuous producer of diterpenes and includes approximately 175 species, many of which have medicinal uses. To date, 140 diterpenes from <i>Jatropha</i> (JTDs) have been reported. Given their structural diversity and notable biological activities, this work aims to highlight the pharmaceutical potential of JTDs. To achieve this goal, an extensive literature review was conducted, encompassing studies on structural elucidation through NMR and pharmacological assays, both in vitro and in vivo. Based on 132 selected papers, a thorough discussion is presented on the biosynthesis, extraction, isolation, and structural characterization of JTDs, including a compilation of their <sup>13</sup>C NMR chemical shifts. The review also covers their synthetic production and biological effects. Additionally, an in silico analysis predicting the drug-likeness of 141 JTDs was carried out. Notably, the occurrence of macrocyclic diterpenes has doubled in the past decade, and the summary of their NMR data provides a useful resource for future research. Furthermore, 21 distinct pharmacological activities were identified, with potent cytotoxic effects targeting new molecular pathways being particularly significant. Recent advances highlight the contributions of modern approaches in organic synthesis and the pharmacological evaluation of natural products. The drug-likeness analysis identified JTD classes and compounds with favorable physicochemical and ADMET features for pharmaceutical development. In light of these findings, the use of nanotechnology is proposed as a future direction for continued research on JTDs, a fascinating class of natural compounds. This work opens up new avenues for the study of <i>Euphorbiaceae</i> species, particularly the <i>Jatropha</i> genus and its bioactive compounds.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Seung-Chan An, Hak Hoon Jun, Kyeong Mi Kim, Issac Kim, Sujin Choi, Hyunjeong Yeo, Soonchul Lee, Hyun-Ju An
{"title":"Auranofin as a Novel Anticancer Drug for Anaplastic Thyroid Cancer.","authors":"Seung-Chan An, Hak Hoon Jun, Kyeong Mi Kim, Issac Kim, Sujin Choi, Hyunjeong Yeo, Soonchul Lee, Hyun-Ju An","doi":"10.3390/ph17101394","DOIUrl":"https://doi.org/10.3390/ph17101394","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Anaplastic thyroid cancer (ATC) is an aggressive and rare cancer with a poor prognosis, and traditional therapies have limited efficacy. This study investigates drug repositioning, focusing on auranofin, a gold-based drug originally used for rheumatoid arthritis, as a potential treatment for ATC. <b>Methods:</b> Auranofin was identified from an FDA-approved drug library and tested on two thyroid cancer cell lines, 8505C and FRO. Antitumor efficacy was evaluated through gene and protein expression analysis using Western blot, FACS, and mRNA sequencing. In vivo experiments were conducted using subcutaneous injections in nude mice to confirm the anticancer effects of auranofin. <b>Results:</b> Auranofin induced reactive oxygen species (ROS) production and apoptosis, leading to a dose-dependent reduction in cell viability, G1/S phase cell cycle arrest, and altered expression of regulatory proteins. It also inhibited cancer stem cell activity and suppressed epithelial-mesenchymal transition. mRNA sequencing revealed significant changes in the extracellular matrix-receptor interaction pathway, supported by Western blot results. In vivo xenograft models demonstrated strong antitumor activity. <b>Conclusions:</b> Auranofin shows promise as a repurposed therapeutic agent for ATC, effectively inhibiting cell proliferation, reducing metastasis, and promoting apoptosis. These findings suggest that auranofin could play a key role in future ATC treatment strategies.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kimia Hosseini, Andrea Cediel-Ulloa, Mohamed H Al-Sabri, Anna Forsby, Robert Fredriksson
{"title":"Assessing the Neurodevelopmental Impact of Fluoxetine, Citalopram, and Paroxetine on Neural Stem Cell-Derived Neurons.","authors":"Kimia Hosseini, Andrea Cediel-Ulloa, Mohamed H Al-Sabri, Anna Forsby, Robert Fredriksson","doi":"10.3390/ph17101392","DOIUrl":"https://doi.org/10.3390/ph17101392","url":null,"abstract":"<p><strong>Background/objectives: </strong>Many pregnant women globally suffer from depression and are routinely prescribed selective serotonin reuptake inhibitors (SSRIs). These drugs function by blocking the re-uptake of serotonin by the serotonin transporter (SERT) into neurons, resulting in its accumulation in the presynaptic cleft. Despite a large amount of research suggesting a potential link to neurodevelopmental disorders in children whose mothers took these drugs during pregnancy, their possible adverse effects are still debated, and results are contradictory. On the other hand, there is an immediate need for improved cell-based models for developmental neurotoxicity studies (DNT) to minimize the use of animals in research.</p><p><strong>Methods: </strong>In this study, we aimed to assess the effects of clinically relevant concentrations of paroxetine (PAR), fluoxetine (FLX), and citalopram (CIT)-on maturing neurons derived from human neural stem cells using multiple endpoints.</p><p><strong>Results: </strong>Although none of the tested concentrations of FLX, CIT, or PAR significantly affected cell viability, FLX (10 µM) exhibited the highest reduction in viability compared to the other drugs. Regarding neurite outgrowth, CIT did not have a significant effect. However, FLX (10 µM) significantly reduced both mean neurite outgrowth and mean processes, PAR significantly reduced mean processes, and showed a trend of dysregulation of multiple genes associated with neuronal development at therapeutic-relevant serum concentrations.</p><p><strong>Conclusions: </strong>Transcriptomic data and uptake experiments found no SERT activity in the system, suggesting that the adverse effects of FLX and PAR are independent of SERT.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142516579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alexandre Coelho Serquiz, Joana de Angelis da Costa Barros Gomes, Naisandra Bezerra da Silva Farias, Denise Mafra, Pietra Maria Pereira de Lima, Daniella de Oliveira Coutinho, Fernanda Priscila Barbosa Ribeiro, Hugo Alexandre de Oliveira Rocha, José Luiz de Brito Alves
{"title":"Protective Effects of Annona Atemoya Extracts on Inflammation, Oxidative Stress, and Renal Function in Cadmium-Induced Nephrotoxicity in Wistar Rats.","authors":"Alexandre Coelho Serquiz, Joana de Angelis da Costa Barros Gomes, Naisandra Bezerra da Silva Farias, Denise Mafra, Pietra Maria Pereira de Lima, Daniella de Oliveira Coutinho, Fernanda Priscila Barbosa Ribeiro, Hugo Alexandre de Oliveira Rocha, José Luiz de Brito Alves","doi":"10.3390/ph17101393","DOIUrl":"https://doi.org/10.3390/ph17101393","url":null,"abstract":"<p><strong>Background: </strong>Cadmium (Cd), a highly toxic heavy metal from agricultural activities, and its exposure can lead to impaired renal function by increasing reactive oxygen species. The atemoya fruit is known for its high phenolic and antioxidant compounds. This study aimed to evaluate the effects of atemoya extracts on renal function, oxidative stress parameters, and inflammatory biomarkers in a cadmium-induced nephrotoxicity model.</p><p><strong>Methods: </strong>Three aqueous extracts were prepared from different parts of the atemoya fruit: seeds, peel, and pulp. Twenty-five male <i>Wistar</i> rats were allocated into four groups: control, seed, peel, and pulp extracts at 2 g/kg for 25 days. All treatment groups administered intraperitoneal injections of cadmium chloride (CdCl<sub>2</sub>) (2 mg/kg) to induce renal damage.</p><p><strong>Results: </strong>The cadmium-treated groups showed decreased creatinine clearance, SOD, CAT, and GPx activities (<i>p</i> < 0.05) and increased serum levels of TNF-α and IL-6 compared to the control group (<i>p</i> < 0.05). The treatment with seed, peel, and pulp extracts increased creatinine clearance (<i>p</i> < 0.05), increased SOD, CAT, and GPx activities (<i>p</i> < 0.05), and reduced serum levels of TNF-α and IL-6 compared to the Cd group (<i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>This study supports the use of atemoya as a promising candidate for mitigating nephrotoxicity and highlights the importance of its antioxidant and anti-inflammatory properties in renal health.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Amyotrophic Lateral Sclerosis: Insights and New Prospects in Disease Pathophysiology, Biomarkers and Therapies.","authors":"Jameel M Al-Khayri, Mamtha Ravindran, Akshatha Banadka, Chendanda Devaiah Vandana, Kushalva Priya, Praveen Nagella, Kowshik Kukkemane","doi":"10.3390/ph17101391","DOIUrl":"https://doi.org/10.3390/ph17101391","url":null,"abstract":"<p><p>Amyotrophic Lateral Sclerosis (ALS) is a severe neurodegenerative disorder marked by the gradual loss of motor neurons, leading to significant disability and eventual death. Despite ongoing research, there are still limited treatment options, underscoring the need for a deeper understanding of the disease's complex mechanisms and the identification of new therapeutic targets. This review provides a thorough examination of ALS, covering its epidemiology, pathology, and clinical features. It investigates the key molecular mechanisms, such as protein aggregation, neuroinflammation, oxidative stress, and excitotoxicity that contribute to motor neuron degeneration. The role of biomarkers is highlighted for their importance in early diagnosis and disease monitoring. Additionally, the review explores emerging therapeutic approaches, including inhibitors of protein aggregation, neuroinflammation modulators, antioxidant therapies, gene therapy, and stem cell-based treatments. The advantages and challenges of these strategies are discussed, with an emphasis on the potential for precision medicine to tailor treatments to individual patient needs. Overall, this review aims to provide a comprehensive overview of the current state of ALS research and suggest future directions for developing effective therapies.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142516578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting Tumor Hypoxia with Nanoparticle-Based Therapies: Challenges, Opportunities, and Clinical Implications.","authors":"Sujit Kumar Debnath, Monalisha Debnath, Arnab Ghosh, Rohit Srivastava, Abdelwahab Omri","doi":"10.3390/ph17101389","DOIUrl":"https://doi.org/10.3390/ph17101389","url":null,"abstract":"<p><p>Hypoxia is a crucial factor in tumor biology, affecting various solid tumors to different extents. Its influence spans both early and advanced stages of cancer, altering cellular functions and promoting resistance to therapy. Hypoxia reduces the effectiveness of radiotherapy, chemotherapy, and immunotherapy, making it a target for improving therapeutic outcomes. Despite extensive research, gaps persist, necessitating the exploration of new chemical and pharmacological interventions to modulate hypoxia-related pathways. This review discusses the complex pathways involved in hypoxia and the associated pharmacotherapies, highlighting the limitations of current treatments. It emphasizes the potential of nanoparticle-based platforms for delivering anti-hypoxic agents, particularly oxygen (O<sub>2</sub>), to the tumor microenvironment. Combining anti-hypoxic drugs with conventional cancer therapies shows promise in enhancing remission rates. The intricate relationship between hypoxia and tumor progression necessitates novel therapeutic strategies. Nanoparticle-based delivery systems can significantly improve cancer treatment efficacy by targeting hypoxia-associated pathways. The synergistic effects of combined therapies underscore the importance of multimodal approaches in overcoming hypoxia-mediated resistance. Continued research and innovation in this area hold great potential for advancing cancer therapy and improving patient outcomes.</p>","PeriodicalId":20198,"journal":{"name":"Pharmaceuticals","volume":"17 10","pages":""},"PeriodicalIF":4.3,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11510357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142506412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}