In recent years, the incidence of cancers, inflammatory diseases, Alzheimer’s disease, glucose metabolism disorder and diabetes has increased alarmingly which demands more research into the discovery of new drug candidates to treat these human diseases. Main phytochemicals from Humulus lupulus L. (hops) have been demonstrated to have positive impacts on human health, and prenylated flavonoids are one of the major groups of bioactive phytochemicals found in this plant. Thus, this review summarizes the role of major prenylated components in hops in human diseases including cancer, inflammation and viral infections. In silico studies of prenylated bioactive compounds against various drug targets such as histone deactylases (HDACs), sirtuins (SIRTs), and acetylcholinesterase (AChE), and the molecular molecular interactions between protein and ligand have also been included. Furthermore, the structure-activity relationships (SAR) studies on these compounds are highlighted. This review concludes that the prenylated phytochemicals from H. lupulus L., including xanthohumol (XN), isoxanthohumol (IXN), 8-prenylnaringenin (8-PN) and 6-prenylnaringenin (6-PN), have promising roles in human health and may contribute to new drug discovery and development.
{"title":"<b>Major Bioactive Prenylated Flavonoids from <i>Humulus lupulus</i> L., Their Applications in Human Diseases and Structure-Activity Relationships (SAR) – A Review</b>","authors":"Ferah Comert Onder, Sevil Kalin, Nebahat Sahin, Gulce Davutlar, Khaled A.N. Abusharkh, Ozlem Maraba, Rabia Selina Hal, Mehmet Ay, Lutfun Nahar, Satyajit D. Sarker","doi":"10.34172/ps.2023.18","DOIUrl":"https://doi.org/10.34172/ps.2023.18","url":null,"abstract":"In recent years, the incidence of cancers, inflammatory diseases, Alzheimer’s disease, glucose metabolism disorder and diabetes has increased alarmingly which demands more research into the discovery of new drug candidates to treat these human diseases. Main phytochemicals from Humulus lupulus L. (hops) have been demonstrated to have positive impacts on human health, and prenylated flavonoids are one of the major groups of bioactive phytochemicals found in this plant. Thus, this review summarizes the role of major prenylated components in hops in human diseases including cancer, inflammation and viral infections. In silico studies of prenylated bioactive compounds against various drug targets such as histone deactylases (HDACs), sirtuins (SIRTs), and acetylcholinesterase (AChE), and the molecular molecular interactions between protein and ligand have also been included. Furthermore, the structure-activity relationships (SAR) studies on these compounds are highlighted. This review concludes that the prenylated phytochemicals from H. lupulus L., including xanthohumol (XN), isoxanthohumol (IXN), 8-prenylnaringenin (8-PN) and 6-prenylnaringenin (6-PN), have promising roles in human health and may contribute to new drug discovery and development.","PeriodicalId":20042,"journal":{"name":"Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135759794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Samar A. Antar, Aymen Halouani, Cherry Gad, Ahmed Ali Al-Karmalawy
Cadmium (Cd) is a toxic heavy metal that is known to accumulate in various organs and tissues in the body, including the testes. Exposure to Cd has been shown to cause significant testicular damage, including impaired spermatogenesis and decreased fertility in both humans and animals. This damage is thought to be due to Cd-induced oxidative stress and inflammation, which can lead to cellular damage and apoptosis. Cd has also been shown to disrupt the blood-testis barrier, leading to increased permeability and an altered testicular microenvironment. In addition, Cd exposure has been linked to changes in hormone levels, including decreased testosterone production and altered gonadotropin secretion. Reactive oxygen species (ROS) and an imbalance in the activity of antioxidant enzymes cause oxidative stress. The nuclear factor kappa-B (NF-κB) signaling system, which controls multiple genes involved in inflammatory responses including tumor necrosis factor (TNF-α), is activated by oxidative stress. These effects can contribute to decreased sperm count, motility, and viability. Efforts to reduce exposure to Cd may help to prevent or mitigate the harmful effects on testicular function. This can be achieved through occupational and environmental regulations, as well as public education and awareness programs. In this review, we highlight many of the principal mechanisms included in testicular damage. These pathways could be considered promising targets for the development of potential therapies for a variety of important human diseases.
镉(Cd)是一种有毒的重金属，已知会积聚在身体的各个器官和组织中，包括睾丸。暴露于Cd已被证明会对人类和动物的睾丸造成严重损害，包括精子发生受损和生育能力下降。这种损伤被认为是由于cd诱导的氧化应激和炎症，这可能导致细胞损伤和凋亡。Cd也被证明会破坏血睾丸屏障，导致渗透性增加和睾丸微环境改变。此外，接触Cd还与激素水平的变化有关，包括睾酮分泌减少和促性腺激素分泌改变。活性氧(ROS)和抗氧化酶活性失衡导致氧化应激。核因子κ b (NF-κB)信号系统控制包括肿瘤坏死因子(TNF-α)在内的多个参与炎症反应的基因，可被氧化应激激活。这些影响会导致精子数量、活力和生存能力下降。努力减少接触镉可能有助于预防或减轻对睾丸功能的有害影响。这可以通过职业和环境法规，以及公众教育和意识项目来实现。在这篇综述中，我们强调了睾丸损伤的许多主要机制。这些途径可以被认为是开发各种重要人类疾病的潜在疗法的有希望的靶点。
{"title":"<b>An Overview of the Mechanisms of Cadmium-induced Toxicity in the Male Reproductive System</b>","authors":"Samar A. Antar, Aymen Halouani, Cherry Gad, Ahmed Ali Al-Karmalawy","doi":"10.34172/ps.2023.10","DOIUrl":"https://doi.org/10.34172/ps.2023.10","url":null,"abstract":"Cadmium (Cd) is a toxic heavy metal that is known to accumulate in various organs and tissues in the body, including the testes. Exposure to Cd has been shown to cause significant testicular damage, including impaired spermatogenesis and decreased fertility in both humans and animals. This damage is thought to be due to Cd-induced oxidative stress and inflammation, which can lead to cellular damage and apoptosis. Cd has also been shown to disrupt the blood-testis barrier, leading to increased permeability and an altered testicular microenvironment. In addition, Cd exposure has been linked to changes in hormone levels, including decreased testosterone production and altered gonadotropin secretion. Reactive oxygen species (ROS) and an imbalance in the activity of antioxidant enzymes cause oxidative stress. The nuclear factor kappa-B (NF-κB) signaling system, which controls multiple genes involved in inflammatory responses including tumor necrosis factor (TNF-α), is activated by oxidative stress. These effects can contribute to decreased sperm count, motility, and viability. Efforts to reduce exposure to Cd may help to prevent or mitigate the harmful effects on testicular function. This can be achieved through occupational and environmental regulations, as well as public education and awareness programs. In this review, we highlight many of the principal mechanisms included in testicular damage. These pathways could be considered promising targets for the development of potential therapies for a variety of important human diseases.","PeriodicalId":20042,"journal":{"name":"Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135252469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: This research intended to discover the significance of miR-138 (microRNA 138) on the expression profile, proliferation, and the associated regulatory mechanisms in prostate cancer (PCa). Methods: Thirty-five specimens of prostate were studied to evaluate the expression level of miR138 by RT-qPCR (Quantitative reverse transcription polymerase chain reaction). Bioinformatics analysis was performed to search for the target genes of miR-138; and ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase), CCND1 (cyclin D1), CCND3 (cyclin D3), VIM (vimentin), TWIST1 (twist family bHLH transcription factor 1), HIF1A (hypoxia-inducible factor 1 subunit alpha), and TERT (telomerase reverse transcriptase) genes were selected. Then, the biological role of miR-138 and CCND1 in the progression of PCa was investigated using RT-qPCR and luciferase reporter gene assay. Finally, overexpression of miR-138 on the proliferation in PCa cell lines was analyzed using the MTT (3-(4, 5-dimethylthiazol-2-Yl)-2, 5-diphenyltetrazolium bromide, Sigma, Germany) assay. Results: RT-qPCR showed that the expression of miR-138 downregulated in PCa tissues and cell lines. Bioinformatics analysis and RT-qPCR assay demonstrated that CCND1 expression level was negatively correlated with miR-138 in PCa tissues and the PC3 cell line. Moreover, CCND1 was predicted to be the target gene of miR138 in the PC3 cell line based on the results of luciferase reporter gene assay. Substantially, over-expression of miR138-5p mimic could inhibit the expression level of CCND1 gene in PC3 cell lines. Lastly, over-expression of miR-138 inhibited the proliferative capacities in PC3 and DU-145 cells. Conclusion: Our research introduces miR-138 as a negative regulator of CCND1 in the progression of PCa with an inhibitory impact on the proliferation rate of PCa cell lines. This regulatory mechanism could be utilized for the design and target selection of remedial miRNA-based approaches.
{"title":"<b>Microrna 138 Upregulation is Associated with Decreasing Levels of <i>CCND1</i> Gene Expression and Promoting Cell Death in Human Prostate Cancer Cell Lines</b>","authors":"Nasrin Haghighi-Najafabadi, Shima Fayaz, Mahboubeh Berizi, Ghazal Haddad, Pezhman Fard-Esfahani","doi":"10.34172/ps.2023.17","DOIUrl":"https://doi.org/10.34172/ps.2023.17","url":null,"abstract":"Background: This research intended to discover the significance of miR-138 (microRNA 138) on the expression profile, proliferation, and the associated regulatory mechanisms in prostate cancer (PCa). Methods: Thirty-five specimens of prostate were studied to evaluate the expression level of miR138 by RT-qPCR (Quantitative reverse transcription polymerase chain reaction). Bioinformatics analysis was performed to search for the target genes of miR-138; and ABL1 (ABL proto-oncogene 1, non-receptor tyrosine kinase), CCND1 (cyclin D1), CCND3 (cyclin D3), VIM (vimentin), TWIST1 (twist family bHLH transcription factor 1), HIF1A (hypoxia-inducible factor 1 subunit alpha), and TERT (telomerase reverse transcriptase) genes were selected. Then, the biological role of miR-138 and CCND1 in the progression of PCa was investigated using RT-qPCR and luciferase reporter gene assay. Finally, overexpression of miR-138 on the proliferation in PCa cell lines was analyzed using the MTT (3-(4, 5-dimethylthiazol-2-Yl)-2, 5-diphenyltetrazolium bromide, Sigma, Germany) assay. Results: RT-qPCR showed that the expression of miR-138 downregulated in PCa tissues and cell lines. Bioinformatics analysis and RT-qPCR assay demonstrated that CCND1 expression level was negatively correlated with miR-138 in PCa tissues and the PC3 cell line. Moreover, CCND1 was predicted to be the target gene of miR138 in the PC3 cell line based on the results of luciferase reporter gene assay. Substantially, over-expression of miR138-5p mimic could inhibit the expression level of CCND1 gene in PC3 cell lines. Lastly, over-expression of miR-138 inhibited the proliferative capacities in PC3 and DU-145 cells. Conclusion: Our research introduces miR-138 as a negative regulator of CCND1 in the progression of PCa with an inhibitory impact on the proliferation rate of PCa cell lines. This regulatory mechanism could be utilized for the design and target selection of remedial miRNA-based approaches.","PeriodicalId":20042,"journal":{"name":"Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135876545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Complex interplays happen in absorption and function of iron, zinc and copper. Both zinc deficiency and excess may lead to anemia. In Iran, commonly available supplements for chronic kidney disease (CKD) patients contain 25 mg-zinc (Zn). This study compared 25 mg versus 7.5 mg dose of zinc in anemia of CKD patients, the latter dose approximates to recommended dietary intake (RDI) of zinc. Methods: In this double-blinded clinical trial, 51 non-dialysis CKD patients were randomized to continue previous formulation (25 mg-Zn group) or change to a new preparation (7.5 mg-Zn group) for three months. Blood counts and serum iron, zinc and copper status were compared between and within the groups. Results: At the end of the study, serum copper and ceruloplasmin concentrations were significantly higher in 7.5 mg-Zn group compared with those in 25 mg-Zn arm (115.04± 23.05 vs. 102.48±14.98 µg/dL; P= 0.02 and 29.97±7.94 vs. 25.42±4.23 mg/dL; P= 0.01, respectively). Serum zinc levels did not differ between two groups (76.73±15.35 vs. 77.68±18.07 µg/dL for 7.5 mg-Zn and 25 mg-Zn groups, respectively; P= 0.84). After three months, patients in 7.5 mg-Zn group experienced increase in their Hb (11.11±1.17 vs. 10.72±1.03 g/dL; P= 0.04), HCT (35.28± 4.01 vs. 33.96± 3.74%; P= 0.03), MCV (86.30 (81.40-90.82) vs. 86.00 (80.35-88.77) ¦L; P= 0.01) and ferritin (202.60 (79.29-298.97) vs. 129.07 (42.25-225.87) ng/mL; P<0.001) compared to their baseline values. Conclusion: Reducing zinc content to its RDI value in supplement for CKD patients led to increased serum copper and ceruloplasmin concentrations. Moreover, patients who switched to RDI zinc-containing formula experienced a significant rise in blood hemoglobin. hematocrit, mean corpuscular volume (MCV), and ferritin concentration.
{"title":"<b>Effect of Recommended Dietary Intake versus Higher Doses of Supplemental Zinc on Iron and Copper Deficiency Anemia Among Patients with Chronic Kidney Diseases, A Double-Blinded, Randomized Clinical Trial</b>","authors":"Zahra Nazari-Taloki, Ebrahim Salehifar, Atieh Makhlough, Simin Dashti-Khavidaki","doi":"10.34172/ps.2023.14","DOIUrl":"https://doi.org/10.34172/ps.2023.14","url":null,"abstract":"Background: Complex interplays happen in absorption and function of iron, zinc and copper. Both zinc deficiency and excess may lead to anemia. In Iran, commonly available supplements for chronic kidney disease (CKD) patients contain 25 mg-zinc (Zn). This study compared 25 mg versus 7.5 mg dose of zinc in anemia of CKD patients, the latter dose approximates to recommended dietary intake (RDI) of zinc. Methods: In this double-blinded clinical trial, 51 non-dialysis CKD patients were randomized to continue previous formulation (25 mg-Zn group) or change to a new preparation (7.5 mg-Zn group) for three months. Blood counts and serum iron, zinc and copper status were compared between and within the groups. Results: At the end of the study, serum copper and ceruloplasmin concentrations were significantly higher in 7.5 mg-Zn group compared with those in 25 mg-Zn arm (115.04± 23.05 vs. 102.48±14.98 µg/dL; P= 0.02 and 29.97±7.94 vs. 25.42±4.23 mg/dL; P= 0.01, respectively). Serum zinc levels did not differ between two groups (76.73±15.35 vs. 77.68±18.07 µg/dL for 7.5 mg-Zn and 25 mg-Zn groups, respectively; P= 0.84). After three months, patients in 7.5 mg-Zn group experienced increase in their Hb (11.11±1.17 vs. 10.72±1.03 g/dL; P= 0.04), HCT (35.28± 4.01 vs. 33.96± 3.74%; P= 0.03), MCV (86.30 (81.40-90.82) vs. 86.00 (80.35-88.77) ¦L; P= 0.01) and ferritin (202.60 (79.29-298.97) vs. 129.07 (42.25-225.87) ng/mL; P<0.001) compared to their baseline values. Conclusion: Reducing zinc content to its RDI value in supplement for CKD patients led to increased serum copper and ceruloplasmin concentrations. Moreover, patients who switched to RDI zinc-containing formula experienced a significant rise in blood hemoglobin. hematocrit, mean corpuscular volume (MCV), and ferritin concentration.","PeriodicalId":20042,"journal":{"name":"Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136381824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: The exploration of bryophytes biodiversity in Indonesia due to its abundance and the bioactivity of its phytochemical content, such as alkaloids and polyphenols, has received increased interest. Despite some species proven to possess pharmacological properties, the antiproliferative study of Indonesian native moss, such as the Pogonatum genus, is limited. Hence, this study aims to evaluate the anticancer effects of Pogonatum neesii Dozy antiproliferative activity on colon and cervical cancer through in silico and in vitro methods. Methods: Molecular docking analysis using Autodock VINA in PyRx softwre was conducted between natural compounds found on P. neesii and several target proteins, DNA (cytosine-5)- methyltransferase 1 (DMT-1) (Protein Data Bank (PDB) id: 4WXX) in colon cancer and B-cell lymphoma 2 (Bcl-2) (PDB id: 4LXD) in cervical cancer. Afterwards, total phenolic and alkaloid contents were measured. Subsequently, P. neesii was tested on HaCaT (keratinocytes), HEK293 (human embryonic kidney), HT-29 (colorectal cancer models) and HeLa (cervical cancer model) to observe its cytotoxicity. Results: Out of eight compounds, chlorogenate was found to exert the best binding energy with target proteins, although it had lower binding affinity than the protein’s natural ligand. However, the biological, drug-likeness, and toxicity analysis suggested the drug potency of the compound, thus we did the in vitro analysis. P. neesii showed significant cytotoxic effects on HT-29 and HeLa cells, while it did not exert any cytotoxic effects on HaCaT and HEK-293 cells, at the same concentrations. Conclusion: P. neesii has been shown to have the potential as an anticancer agent through in silico and in vitro analysis, where the extract showed selective cytotoxicity towards cancer cell lines and cytocompatibility towards normal cell lines. Chlorogenate was pinpointed as the compound with the most activity and interaction with the target proteins in both cancers.
{"title":"<b>Cytotoxic Activity of Indonesian <i>Pogonatum neesii</i> Dozy from Cibodas Botanical Garden: <i>In Silico</i> Molecular Docking and <i>In Vitro</i> Evaluation</b>","authors":"Rizky Nurdiansyah, Agus Budiawan Naro Putra, Ainun Nadhifah, Erika Chriscensia, Ulung Khoe Gondo Kusumo, Stephanie Angela Yosiano, Anastasia Beatrix Musung, Sintikhe A Wenas, Steve Makalew, Patricia Lovina, Intani Quarta Lailaty, Fransisca Aurelia Rahmad, Fandi Sutanto, Pietradewi Hartrianti","doi":"10.34172/ps.2023.11","DOIUrl":"https://doi.org/10.34172/ps.2023.11","url":null,"abstract":"Background: The exploration of bryophytes biodiversity in Indonesia due to its abundance and the bioactivity of its phytochemical content, such as alkaloids and polyphenols, has received increased interest. Despite some species proven to possess pharmacological properties, the antiproliferative study of Indonesian native moss, such as the Pogonatum genus, is limited. Hence, this study aims to evaluate the anticancer effects of Pogonatum neesii Dozy antiproliferative activity on colon and cervical cancer through in silico and in vitro methods. Methods: Molecular docking analysis using Autodock VINA in PyRx softwre was conducted between natural compounds found on P. neesii and several target proteins, DNA (cytosine-5)- methyltransferase 1 (DMT-1) (Protein Data Bank (PDB) id: 4WXX) in colon cancer and B-cell lymphoma 2 (Bcl-2) (PDB id: 4LXD) in cervical cancer. Afterwards, total phenolic and alkaloid contents were measured. Subsequently, P. neesii was tested on HaCaT (keratinocytes), HEK293 (human embryonic kidney), HT-29 (colorectal cancer models) and HeLa (cervical cancer model) to observe its cytotoxicity. Results: Out of eight compounds, chlorogenate was found to exert the best binding energy with target proteins, although it had lower binding affinity than the protein’s natural ligand. However, the biological, drug-likeness, and toxicity analysis suggested the drug potency of the compound, thus we did the in vitro analysis. P. neesii showed significant cytotoxic effects on HT-29 and HeLa cells, while it did not exert any cytotoxic effects on HaCaT and HEK-293 cells, at the same concentrations. Conclusion: P. neesii has been shown to have the potential as an anticancer agent through in silico and in vitro analysis, where the extract showed selective cytotoxicity towards cancer cell lines and cytocompatibility towards normal cell lines. Chlorogenate was pinpointed as the compound with the most activity and interaction with the target proteins in both cancers.","PeriodicalId":20042,"journal":{"name":"Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136381823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Group B Streptococcus (GBS) is a bacterium commonly isolated from the vagina. Silver nanoparticles (SNPs) are potential antibacterial agents, and studies have shown their toxic effects. Vitamin C (VC) is an essential vitamin with a protective role against toxicological conditions. We aimed to the evaluation therapeutic effects of the co-administration of SNPs and VC on vaginal infection caused by GBS in mice models. Methods: Vaginitis model was established by intravaginal inoculation of GBS. The Co-administration of SNPs and VC was used to treat the infections. The antibacterial activity of SNPs was determined by the minimum inhibitory concentration. The toxicity of nanoparticles was measured by MTT assay. The microbial load and estrous cycle of mice during treatment were evaluated. Finally, blood samples and vaginal tissue sections were isolated and analyzed. Results: The results showed that SNPs have excellent effects on GBS, and the MIC was 512 ppm. Cell viability after exposure at 512 ppm of SNPs was 32.11% but after treatment with VC increased viability at 512 ppm of nanoparticles to 65.32%. In mice that received SNPs and VC at the same time, the bacteria were completely removed from the vagina, and estrus cycle returned to normal cycle. Analysis of the prepared blood samples and microscopic examination of the vaginal sections confirmed the results. Conclusion: SNPs have a potential antibacterial effect on GBS. But nanoparticles have toxic effects on mammalian cells. The simultaneous use of VC, as a powerful antioxidant, can completely eliminate this toxic effect of nanoparticles.
{"title":"<b>Therapeutic Effects of Co-administration of Silver Nanoparticles and Vitamin C on Vaginal Infection Caused by Group B <i>Streptococcus</i></b>","authors":"Zhale Mansoori, Khosrow Chehri, Ahmad Gharzi","doi":"10.34172/ps.2023.13","DOIUrl":"https://doi.org/10.34172/ps.2023.13","url":null,"abstract":"Background: Group B Streptococcus (GBS) is a bacterium commonly isolated from the vagina. Silver nanoparticles (SNPs) are potential antibacterial agents, and studies have shown their toxic effects. Vitamin C (VC) is an essential vitamin with a protective role against toxicological conditions. We aimed to the evaluation therapeutic effects of the co-administration of SNPs and VC on vaginal infection caused by GBS in mice models. Methods: Vaginitis model was established by intravaginal inoculation of GBS. The Co-administration of SNPs and VC was used to treat the infections. The antibacterial activity of SNPs was determined by the minimum inhibitory concentration. The toxicity of nanoparticles was measured by MTT assay. The microbial load and estrous cycle of mice during treatment were evaluated. Finally, blood samples and vaginal tissue sections were isolated and analyzed. Results: The results showed that SNPs have excellent effects on GBS, and the MIC was 512 ppm. Cell viability after exposure at 512 ppm of SNPs was 32.11% but after treatment with VC increased viability at 512 ppm of nanoparticles to 65.32%. In mice that received SNPs and VC at the same time, the bacteria were completely removed from the vagina, and estrus cycle returned to normal cycle. Analysis of the prepared blood samples and microscopic examination of the vaginal sections confirmed the results. Conclusion: SNPs have a potential antibacterial effect on GBS. But nanoparticles have toxic effects on mammalian cells. The simultaneous use of VC, as a powerful antioxidant, can completely eliminate this toxic effect of nanoparticles.","PeriodicalId":20042,"journal":{"name":"Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135314432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abdollah Arjmand, Elaheh Azizi Javan, J. Shahraki, Rozhin Shaboustani, Enayatollah Seydi, J. Pourahmad
Background: Clozapine (CLZ) and risperidone (RIS) are drugs that have the ability to disrupt mitochondrial function. Also, these drugs increase the level of free radicals. Mitochondrial dysfunction plays a role in the etiology of various diseases. Replacement and treatment of defective mitochondria with healthy mitochondria have been considered. Mitochondrial therapy (mitotherapy) or exogenous mitochondria transplantation is a method that can be used to replace dysfunctional mitochondria with healthy mitochondria. This method can help in the treatment of diseases related to mitochondria. Methods: In this study, we investigated the transplantation effect of isolated lymphocyte mitochondria on the toxicity induced by CLZ and RIS on human blood lymphocytes. Lymphocytes were isolated using the Ficoll standard method. Mitochondria of human lymphocytes were used for mitotherapy. This study was conducted in 6 groups. After treatment, the level of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), reduced glutathione (GSH) content, oxidized glutathione (GSSG) content, and adenosine triphosphate (ATP) content were evaluated. Results: Our data showed that CLZ (70 µm) and RIS (24 nM) caused cytotoxicity on human blood lymphocytes which are associated with ROS generation, collapse in MMP, decrease in GSH content, increase in GSSG content and change in ATP content. Mitochondria transplantation results showed that adding mitochondria of lymphocytes could protect the lymphocytes against the toxicity effects caused by CLZ and RIS. Furthermore, the results showed that pre-incubation with cytochalasin D considerably reserved the protective effects of mitotherapy in the human lymphocytes. Conclusion: We proposed that mitochondria transplantation or mitotherapy-affected blood lymphocytes with exogenous mitochondria could be used to treat CLZ and RIS-induced toxicity.
{"title":"Mitochondrial Transplantation Attenuates Toxicity in Human Lymphocytes Caused by Clozapine and Risperidone","authors":"Abdollah Arjmand, Elaheh Azizi Javan, J. Shahraki, Rozhin Shaboustani, Enayatollah Seydi, J. Pourahmad","doi":"10.34172/ps.2023.12","DOIUrl":"https://doi.org/10.34172/ps.2023.12","url":null,"abstract":"Background: Clozapine (CLZ) and risperidone (RIS) are drugs that have the ability to disrupt mitochondrial function. Also, these drugs increase the level of free radicals. Mitochondrial dysfunction plays a role in the etiology of various diseases. Replacement and treatment of defective mitochondria with healthy mitochondria have been considered. Mitochondrial therapy (mitotherapy) or exogenous mitochondria transplantation is a method that can be used to replace dysfunctional mitochondria with healthy mitochondria. This method can help in the treatment of diseases related to mitochondria. Methods: In this study, we investigated the transplantation effect of isolated lymphocyte mitochondria on the toxicity induced by CLZ and RIS on human blood lymphocytes. Lymphocytes were isolated using the Ficoll standard method. Mitochondria of human lymphocytes were used for mitotherapy. This study was conducted in 6 groups. After treatment, the level of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), reduced glutathione (GSH) content, oxidized glutathione (GSSG) content, and adenosine triphosphate (ATP) content were evaluated. Results: Our data showed that CLZ (70 µm) and RIS (24 nM) caused cytotoxicity on human blood lymphocytes which are associated with ROS generation, collapse in MMP, decrease in GSH content, increase in GSSG content and change in ATP content. Mitochondria transplantation results showed that adding mitochondria of lymphocytes could protect the lymphocytes against the toxicity effects caused by CLZ and RIS. Furthermore, the results showed that pre-incubation with cytochalasin D considerably reserved the protective effects of mitotherapy in the human lymphocytes. Conclusion: We proposed that mitochondria transplantation or mitotherapy-affected blood lymphocytes with exogenous mitochondria could be used to treat CLZ and RIS-induced toxicity.","PeriodicalId":20042,"journal":{"name":"Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139356450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Antar, Ayman M. Mahmoud, W. Abdo, Cherry Gad, A. Al-karmalawy
An immune system response known as inflammation can be carried on by a variety of things, such as infections, damaged cells, and noxious substances. These factors may cause acute or chronic inflammatory responses in the heart, pancreas, liver, kidney, lungs, brain, colon, and reproductive system, which may cause disease or tissue damage. Inflammatory cells and signaling pathways are activated by both pathogenic and non-pathogenic agents, cell injury, and infectious agents. The most ubiquitous types of these include tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), High mobility group box 1 protein (HMGB1), mitogen-activated protein kinase (MAPK), monocyte chemoattractant protein (MCP1), interleukin 1 beta (IL1β), and Janus kinase-signal transducer and activator of transcription (JAK-STAT). Severe inflammation has the potential to cause systemic inflammatory response syndrome. The most severe forms of this condition are characterized by hyperinflammation and can cause organ damage, shock, and even death. We concentrate on the origin of inflammation, all conceivable inflammatory mechanisms, and organ-specific inflammatory responses in this study on inflammatory reactions inside organs.
{"title":"A Comprehensive Overview of Organ Inflammatory Responses: Genesis, Possible Mechanisms, and Mediators of Inflammation","authors":"S. Antar, Ayman M. Mahmoud, W. Abdo, Cherry Gad, A. Al-karmalawy","doi":"10.34172/ps.2023.9","DOIUrl":"https://doi.org/10.34172/ps.2023.9","url":null,"abstract":"An immune system response known as inflammation can be carried on by a variety of things, such as infections, damaged cells, and noxious substances. These factors may cause acute or chronic inflammatory responses in the heart, pancreas, liver, kidney, lungs, brain, colon, and reproductive system, which may cause disease or tissue damage. Inflammatory cells and signaling pathways are activated by both pathogenic and non-pathogenic agents, cell injury, and infectious agents. The most ubiquitous types of these include tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), High mobility group box 1 protein (HMGB1), mitogen-activated protein kinase (MAPK), monocyte chemoattractant protein (MCP1), interleukin 1 beta (IL1β), and Janus kinase-signal transducer and activator of transcription (JAK-STAT). Severe inflammation has the potential to cause systemic inflammatory response syndrome. The most severe forms of this condition are characterized by hyperinflammation and can cause organ damage, shock, and even death. We concentrate on the origin of inflammation, all conceivable inflammatory mechanisms, and organ-specific inflammatory responses in this study on inflammatory reactions inside organs.","PeriodicalId":20042,"journal":{"name":"Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139359126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"<b>Exploiting Advances in Automation and Artificial Intelligence to Find Drugs for Neglected Tropical Diseases</b>","authors":"David Alan Winkler","doi":"10.34172/ps.2023.15","DOIUrl":"https://doi.org/10.34172/ps.2023.15","url":null,"abstract":"","PeriodicalId":20042,"journal":{"name":"Pharmaceutical Sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135155542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：