Pub Date : 2025-04-29DOI: 10.1007/s44446-025-00007-5
Yusuf S Althobaiti, Areej H Alshanbari, Doaa S Alshoaibi, Eman Abdulghani Khan, Hanan A Alghamdi, Saud S Aljuaid, Ammar A Alzilifi, Nwaf K Alsulimani, Osama A Alrizqi, Turki Alkhalifa, Ahmad Almalki, Walaa F Alsanie, Ahmed Gaber, Hashem O Alsaab
The primary ingredient in captagon, a medication that is frequently abused in the Middle East, is fenethylline (FEN), which breaks down into theophylline and amphetamines (AMP). Due to the limited supply of genuine Captagon, fake Captagon (CC) has surfaced, comprising a variety of chemicals such as lidocaine, theophylline, AMP, caffeine, and diphenhydramine. This study compares the neurobehavioral consequences of CC with FEN, emphasizing the higher health concerns associated with CC. A total of 36 male Sprague Dawley rats were split up into five groups: CC (50 or 100 mg/kg), FEN (50 or 100 mg/kg), and control. Following therapy, body temperature and locomotor activity were recorded. Using quantitative real-time PCR (qRT-PCR), the expression of the Brain-Derived Neurotrophic Factor (BDNF) gene was examined in prefrontal cortex (PFC) samples. The findings indicated a higher risk of lethal hyperthermia because CC significantly increased body temperature and locomotor activity in comparison to FEN. Furthermore, a significant reduction in BDNF mRNA levels in the PFC following CC exposure raised the possibility of long-term cognitive and neuroplasticity deficits. According to these results, CC poses a significantly bigger risk because of its unexpected composition and more severe neurobehavioral effects, even though FEN is a recognized social menace. The present study underscores the pressing necessity of public health measures to curb the proliferation and misuse of CC. To lessen these new medications' detrimental effects on people and society as a whole, education about their risks and initiatives to stop their usage are crucial.
{"title":"Neurobehavioral and molecular changes in rats exposed to either captagon or counterfeit captagon.","authors":"Yusuf S Althobaiti, Areej H Alshanbari, Doaa S Alshoaibi, Eman Abdulghani Khan, Hanan A Alghamdi, Saud S Aljuaid, Ammar A Alzilifi, Nwaf K Alsulimani, Osama A Alrizqi, Turki Alkhalifa, Ahmad Almalki, Walaa F Alsanie, Ahmed Gaber, Hashem O Alsaab","doi":"10.1007/s44446-025-00007-5","DOIUrl":"10.1007/s44446-025-00007-5","url":null,"abstract":"<p><p>The primary ingredient in captagon, a medication that is frequently abused in the Middle East, is fenethylline (FEN), which breaks down into theophylline and amphetamines (AMP). Due to the limited supply of genuine Captagon, fake Captagon (CC) has surfaced, comprising a variety of chemicals such as lidocaine, theophylline, AMP, caffeine, and diphenhydramine. This study compares the neurobehavioral consequences of CC with FEN, emphasizing the higher health concerns associated with CC. A total of 36 male Sprague Dawley rats were split up into five groups: CC (50 or 100 mg/kg), FEN (50 or 100 mg/kg), and control. Following therapy, body temperature and locomotor activity were recorded. Using quantitative real-time PCR (qRT-PCR), the expression of the Brain-Derived Neurotrophic Factor (BDNF) gene was examined in prefrontal cortex (PFC) samples. The findings indicated a higher risk of lethal hyperthermia because CC significantly increased body temperature and locomotor activity in comparison to FEN. Furthermore, a significant reduction in BDNF mRNA levels in the PFC following CC exposure raised the possibility of long-term cognitive and neuroplasticity deficits. According to these results, CC poses a significantly bigger risk because of its unexpected composition and more severe neurobehavioral effects, even though FEN is a recognized social menace. The present study underscores the pressing necessity of public health measures to curb the proliferation and misuse of CC. To lessen these new medications' detrimental effects on people and society as a whole, education about their risks and initiatives to stop their usage are crucial.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 1-2","pages":"7"},"PeriodicalIF":3.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112406","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}
Pub Date : 2025-04-29DOI: 10.1007/s44446-025-00001-x
Hadeel Almasoud, Fares A Alzahrani, Saud Alarifi, Badr Aldahmash, Bader Almutairi, Abdullah A AlKahtane, Khadijah N Yaseen, Bashayer Aljuhani, Saad Alkahtani
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with limited therapeutic options and poor prognosis for advanced stages. This study investigates the synergistic anticancer effects of Ramucirumab (RAM), a VEGFR-2 inhibitor, and 5-Azacytidine (5-Aza), a hypomethylating agent, on HCC cells, focusing on mechanisms of cytotoxicity, DNA damage, apoptosis, and cell cycle modulation. HuH-7 cells were treated with RAM and 5-Aza, alone and in combination, across varying concentrations. Cell viability was assessed using the Neutral Red Uptake assay, while DNA damage and apoptosis were evaluated through the TUNEL assay and protein array analysis. The expression of cell cycle and inflammatory genes was analyzed using quantitative real-time PCR (qRT-PCR). Result shows combination treatment significantly enhanced cytotoxicity compared to individual dose-dependent therapies. DNA damage was markedly increased in RAM-treated cells, with upregulation of apoptotic proteins CAS3, BID, BAD, p53, and FAS observed. In contrast, apoptotic proteins were markedly decreased in combination-treated cells. Cell cycle arrest was evident through the downregulation of key regulatory genes, including MCM2, MCM3, cyclin B1, and CDK2. Inflammatory cytokines IL-1β and IL-6 were repressed, while COX2 expression was elevated, suggesting oxidative stress as a possible mechanism. In conclusion, the synergistic effects of RAM and 5-Aza in HCC cells are mediated through increased damage to DNA, apoptosis, and arrest of cell cycle, offering potential treatment strategy for advanced HCC. Further experiments conducted in vivo are warranted to validate these findings and optimize treatment regimens.
{"title":"Enhancing hepatocellular carcinoma treatment: synergistic cytotoxicity and mechanistic insights of Ramucirumab and 5-Azacytidine combination therapy.","authors":"Hadeel Almasoud, Fares A Alzahrani, Saud Alarifi, Badr Aldahmash, Bader Almutairi, Abdullah A AlKahtane, Khadijah N Yaseen, Bashayer Aljuhani, Saad Alkahtani","doi":"10.1007/s44446-025-00001-x","DOIUrl":"10.1007/s44446-025-00001-x","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with limited therapeutic options and poor prognosis for advanced stages. This study investigates the synergistic anticancer effects of Ramucirumab (RAM), a VEGFR-2 inhibitor, and 5-Azacytidine (5-Aza), a hypomethylating agent, on HCC cells, focusing on mechanisms of cytotoxicity, DNA damage, apoptosis, and cell cycle modulation. HuH-7 cells were treated with RAM and 5-Aza, alone and in combination, across varying concentrations. Cell viability was assessed using the Neutral Red Uptake assay, while DNA damage and apoptosis were evaluated through the TUNEL assay and protein array analysis. The expression of cell cycle and inflammatory genes was analyzed using quantitative real-time PCR (qRT-PCR). Result shows combination treatment significantly enhanced cytotoxicity compared to individual dose-dependent therapies. DNA damage was markedly increased in RAM-treated cells, with upregulation of apoptotic proteins CAS3, BID, BAD, p53, and FAS observed. In contrast, apoptotic proteins were markedly decreased in combination-treated cells. Cell cycle arrest was evident through the downregulation of key regulatory genes, including MCM2, MCM3, cyclin B1, and CDK2. Inflammatory cytokines IL-1β and IL-6 were repressed, while COX2 expression was elevated, suggesting oxidative stress as a possible mechanism. In conclusion, the synergistic effects of RAM and 5-Aza in HCC cells are mediated through increased damage to DNA, apoptosis, and arrest of cell cycle, offering potential treatment strategy for advanced HCC. Further experiments conducted in vivo are warranted to validate these findings and optimize treatment regimens.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 1-2","pages":"6"},"PeriodicalIF":3.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112353","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}
Emerging research indicates that natural killer (NK) cell-derived exosomes (NK-exo) play a significant role in cancer development. However, their regulatory mechanisms, particularly in pancreatic cancer, remain poorly elucidated. This study employed an in vitro co-culture system and an in vivo subcutaneous tumor model to evaluate the anti-tumor effect of NK-exo on pancreatic cancer. Umbilical cord blood (UCB)-derived NK-exo displayed characteristic exosomal morphology, size, and marker expression and was internalized by PANC- 1 cells. NK-exo significantly and dose-dependently reduce cell proliferation, migration, and invasion (P < 0.01). Further analysis demonstrated that NK-exo induced mitochondrial apoptosis in PANC- 1 cells by altering reactive oxygen species (ROS, P < 0.0001) and mitochondrial membrane potential (MPP) levels (P < 0.0001), effects that were significantly diminished with N-acetylcysteine (NAC) treatment (P < 0.0001). Furthermore, NK-exo treated PANC- 1 cells showed upregulation of the apoptotic markers Caspase3 (P < 0.0001) and Caspase9 (P = 0.0086) and reduced the release of PGC- 1α (P = 0.0064), TFAM (P < 0.0001), and SOD2 (P = 0.0021) as demonstrated by qRT-PCR. Western blot analyses revealed a dose dependent significant elevation of total Caspase3, Caspase9, Bax, and cytochrome c level and depression in the anti-apoptotic Bcl- 2. Animal experiments further confirmed that NK-exo treatment significantly reduced tumor volume and weight and increased Bax protein expression relative to the tumor model group. These findings indicate that NK-exo can enter PANC- 1 cells via endocytosis, induce mitochondrial oxidative damage, and suppress PANC- 1 cell progression, thereby demonstrating a robust anti-pancreatic cancer effect.
{"title":"Exosomes derived from umbilical cord blood NK cells inhibit the progression of pancreatic cancer by targeting ROS-mediated mitochondrial dysfunction.","authors":"Yanyun Zheng, Xinfeng Zou, Qun Li, Dongjun Jiang, Feng Zhu, Yanqun Wu","doi":"10.1007/s44446-025-00009-3","DOIUrl":"10.1007/s44446-025-00009-3","url":null,"abstract":"<p><p>Emerging research indicates that natural killer (NK) cell-derived exosomes (NK-exo) play a significant role in cancer development. However, their regulatory mechanisms, particularly in pancreatic cancer, remain poorly elucidated. This study employed an in vitro co-culture system and an in vivo subcutaneous tumor model to evaluate the anti-tumor effect of NK-exo on pancreatic cancer. Umbilical cord blood (UCB)-derived NK-exo displayed characteristic exosomal morphology, size, and marker expression and was internalized by PANC- 1 cells. NK-exo significantly and dose-dependently reduce cell proliferation, migration, and invasion (P < 0.01). Further analysis demonstrated that NK-exo induced mitochondrial apoptosis in PANC- 1 cells by altering reactive oxygen species (ROS, P < 0.0001) and mitochondrial membrane potential (MPP) levels (P < 0.0001), effects that were significantly diminished with N-acetylcysteine (NAC) treatment (P < 0.0001). Furthermore, NK-exo treated PANC- 1 cells showed upregulation of the apoptotic markers Caspase3 (P < 0.0001) and Caspase9 (P = 0.0086) and reduced the release of PGC- 1α (P = 0.0064), TFAM (P < 0.0001), and SOD2 (P = 0.0021) as demonstrated by qRT-PCR. Western blot analyses revealed a dose dependent significant elevation of total Caspase3, Caspase9, Bax, and cytochrome c level and depression in the anti-apoptotic Bcl- 2. Animal experiments further confirmed that NK-exo treatment significantly reduced tumor volume and weight and increased Bax protein expression relative to the tumor model group. These findings indicate that NK-exo can enter PANC- 1 cells via endocytosis, induce mitochondrial oxidative damage, and suppress PANC- 1 cell progression, thereby demonstrating a robust anti-pancreatic cancer effect.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 1-2","pages":"8"},"PeriodicalIF":3.0,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112361","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}
Pub Date : 2025-04-24DOI: 10.1007/s44446-025-00014-6
Yousif A Kariri
Prostate cancer (PCa) is one of the most common male cancers and the second leading cause of cancer-related deaths among males worldwide. Efforts to increase men's awareness, understanding of the symptoms and risk factors, and provision of early medical assistance are crucial for the prevention and detection of PCa. This study assessed the level of awareness, knowledge, and screening for PCa among male participants in Najran, Saudi Arabia. A cross-sectional study was conducted with 341 male participants from 19 June 2024 to 25 September 2024. An online questionnaire was used to collect data. Bivariate data were analyzed and associations were considered significant when the p-value was ≤ 0.05. A total of 341 completed survey samples were collected. The mean age of the participants was 42 years (SD ± 8.17). The study found that most participants (70.4%) had adequate knowledge of PCa. However, only 30.5% were aware of the prostate-specific antigen (PSA) test, while a small minority (3.2%) had visited a specialized physician regarding PCa. The findings suggest that about 70% of male participants in Najran, Saudi Arabia, have an adequate level of awareness regarding the risk factors and screening for PCa. Recommendations include organizing more awareness campaigns, sharing information on social media, encouraging men to undergo screening tests, providing health education to primary care physicians and public-based organizations, and conducting further studies with larger numbers of participants to increase PCa awareness in Najran Province, Saudi Arabia.
{"title":"Assessment of prostate cancer awareness and screening knowledge among men in Najran, Saudi Arabia: a cross-sectional study.","authors":"Yousif A Kariri","doi":"10.1007/s44446-025-00014-6","DOIUrl":"10.1007/s44446-025-00014-6","url":null,"abstract":"<p><p>Prostate cancer (PCa) is one of the most common male cancers and the second leading cause of cancer-related deaths among males worldwide. Efforts to increase men's awareness, understanding of the symptoms and risk factors, and provision of early medical assistance are crucial for the prevention and detection of PCa. This study assessed the level of awareness, knowledge, and screening for PCa among male participants in Najran, Saudi Arabia. A cross-sectional study was conducted with 341 male participants from 19 June 2024 to 25 September 2024. An online questionnaire was used to collect data. Bivariate data were analyzed and associations were considered significant when the p-value was ≤ 0.05. A total of 341 completed survey samples were collected. The mean age of the participants was 42 years (SD ± 8.17). The study found that most participants (70.4%) had adequate knowledge of PCa. However, only 30.5% were aware of the prostate-specific antigen (PSA) test, while a small minority (3.2%) had visited a specialized physician regarding PCa. The findings suggest that about 70% of male participants in Najran, Saudi Arabia, have an adequate level of awareness regarding the risk factors and screening for PCa. Recommendations include organizing more awareness campaigns, sharing information on social media, encouraging men to undergo screening tests, providing health education to primary care physicians and public-based organizations, and conducting further studies with larger numbers of participants to increase PCa awareness in Najran Province, Saudi Arabia.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 1-2","pages":"5"},"PeriodicalIF":3.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112341","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}
Pub Date : 2025-04-24DOI: 10.1007/s44446-025-00011-9
Mahdi H Alsugoor
Despite the serious side effects associated with anabolic-androgenic steroids (AAS) being well-documented, their widespread misuse for bodybuilding and endurance enhancement continues to be a concern worldwide. A substantial number of studies have been conducted, both internationally and in Saudi Arabia, to investigate knowledge, attitudes, and practices with respect to AAS use among gym users. These studies have been conducted in various cities throughout Saudi Arabia and have focused primarily on male gym users; however, no local studies have been conducted in Al-Qassim province. Therefore, this study aimed to investigate the knowledge, attitudes, and practices around AAS use of both male and female gym users in Al-Qassim Province. This community-based, cross-sectional, questionnaire-based study was conducted from January 2022 to March 2022 and recruited 415 gym users from 24 gyms in Al-Qassim. In the results, 62.9% of the participants were men, and 37.1% were women. The participants demonstrated diverse levels of knowledge about AAS: 74% had heard about AAS, and 72.8% and 71.6% were aware of AAS's effects on muscle and body weight, respectively. However, only 13.3% knew that AAS could cause breast enlargement. Regarding participants' attitudes towards AAS, the majority of the participants (83.6%) believed that using AAS harms health, and 52% and 52.8% of participants believed that there should be punishments for people who use or sell AAS, respectively, while 62.4% of participants felt sorry for AAS users. Our findings on participants' practices showed that 37.3% of participants knew someone who uses AAS, and most importantly, that 19.5% of the gym users (19.2% and 20.1% of male and female users, respectively) admitted that they have used AAS. 51.1% of the participants believed that these AAS are easy to obtain. The study also found a significant relationship between AAS use and sociodemographic variables, including marital status (p = 0.031), time spent in the gym (p = 0.016), chronic diseases (p = 0.028), and smoking (p = 0.031). In conclusion, despite the participants' relatively good knowledge, attitudes, and practices concerning AAS use, they lack knowledge on certain side effects. This could direct policymakers in managing and acting to increase awareness for bodybuilders and the public. In addition, the high prevalence of AAS users could alert the ministries of health and other related ministries to the need for strict rules, especially those stopping or at least minimising accessibility to these substances.
{"title":"Knowledge, attitude and practice towards anabolic-androgenic steroids utilisation among gymnasium attendees in Al-Qassim Province, Saudi Arabia.","authors":"Mahdi H Alsugoor","doi":"10.1007/s44446-025-00011-9","DOIUrl":"10.1007/s44446-025-00011-9","url":null,"abstract":"<p><p>Despite the serious side effects associated with anabolic-androgenic steroids (AAS) being well-documented, their widespread misuse for bodybuilding and endurance enhancement continues to be a concern worldwide. A substantial number of studies have been conducted, both internationally and in Saudi Arabia, to investigate knowledge, attitudes, and practices with respect to AAS use among gym users. These studies have been conducted in various cities throughout Saudi Arabia and have focused primarily on male gym users; however, no local studies have been conducted in Al-Qassim province. Therefore, this study aimed to investigate the knowledge, attitudes, and practices around AAS use of both male and female gym users in Al-Qassim Province. This community-based, cross-sectional, questionnaire-based study was conducted from January 2022 to March 2022 and recruited 415 gym users from 24 gyms in Al-Qassim. In the results, 62.9% of the participants were men, and 37.1% were women. The participants demonstrated diverse levels of knowledge about AAS: 74% had heard about AAS, and 72.8% and 71.6% were aware of AAS's effects on muscle and body weight, respectively. However, only 13.3% knew that AAS could cause breast enlargement. Regarding participants' attitudes towards AAS, the majority of the participants (83.6%) believed that using AAS harms health, and 52% and 52.8% of participants believed that there should be punishments for people who use or sell AAS, respectively, while 62.4% of participants felt sorry for AAS users. Our findings on participants' practices showed that 37.3% of participants knew someone who uses AAS, and most importantly, that 19.5% of the gym users (19.2% and 20.1% of male and female users, respectively) admitted that they have used AAS. 51.1% of the participants believed that these AAS are easy to obtain. The study also found a significant relationship between AAS use and sociodemographic variables, including marital status (p = 0.031), time spent in the gym (p = 0.016), chronic diseases (p = 0.028), and smoking (p = 0.031). In conclusion, despite the participants' relatively good knowledge, attitudes, and practices concerning AAS use, they lack knowledge on certain side effects. This could direct policymakers in managing and acting to increase awareness for bodybuilders and the public. In addition, the high prevalence of AAS users could alert the ministries of health and other related ministries to the need for strict rules, especially those stopping or at least minimising accessibility to these substances.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 1-2","pages":"4"},"PeriodicalIF":3.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112403","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}
Breast cancer remains one of the most challenging and widespread cancers among women globally that warrants further investigations for novel agents to minimize side effects and disease recurrence. In this study, a soil bacterium was isolated and 16S rRNA nucleotide sequence homology and resultant phylogenetic tree analysis confirmed Bacillus subtills (CP020102.1). The crude extract of bacterial strain showed cytotoxicity (cell viability 63.1%) against human breast cancer cell line MCF-7 through MTT assay followed by further analysis through preparative HPLC showing 29 active fractions. Among all fractions, fraction 16 demonstrated cytotoxic potential as low as 54.03%. The spectral data of LC-MS, NMR and FTIR identified the bioactive compound as isatin based bacterial metabolite (Z)-N'-(1-hexyl-2-oxoindolin-3-ylidene)-4-methylbenzenesulfonohydrazide. This bioactive compound upon in silico docking analysis with HER2 showed a binding energy of -8.8 kcal/mol. ADMET calculations determined the pharmacokinetic behavior of the compound revealing acceptable distribution and absorption profiles. The drug-likeness of the compound was confirmed based on the Lipinski rule with zero violations. Molecular dynamic simulation (MDS) was also performed for 100 ns and a stable RMSF plot was observed. The results strongly propose that the identified compound has immense potential to be considered a drug candidate to develop further against human breast cancer.
{"title":"Characterization of soil-derived Bacillus subtilis metabolites against breast cancer: In vitro and in silico studies.","authors":"Ayesha Irfan Hashmi, Mehwish Iqtedar, Hamid Saeed, Nadeem Ahmed, Roheena Abdullah, Afshan Kaleem, Muhammad Athar Abbasi","doi":"10.1007/s44446-025-00006-6","DOIUrl":"10.1007/s44446-025-00006-6","url":null,"abstract":"<p><p>Breast cancer remains one of the most challenging and widespread cancers among women globally that warrants further investigations for novel agents to minimize side effects and disease recurrence. In this study, a soil bacterium was isolated and 16S rRNA nucleotide sequence homology and resultant phylogenetic tree analysis confirmed Bacillus subtills (CP020102.1). The crude extract of bacterial strain showed cytotoxicity (cell viability 63.1%) against human breast cancer cell line MCF-7 through MTT assay followed by further analysis through preparative HPLC showing 29 active fractions. Among all fractions, fraction 16 demonstrated cytotoxic potential as low as 54.03%. The spectral data of LC-MS, NMR and FTIR identified the bioactive compound as isatin based bacterial metabolite (Z)-N'-(1-hexyl-2-oxoindolin-3-ylidene)-4-methylbenzenesulfonohydrazide. This bioactive compound upon in silico docking analysis with HER2 showed a binding energy of -8.8 kcal/mol. ADMET calculations determined the pharmacokinetic behavior of the compound revealing acceptable distribution and absorption profiles. The drug-likeness of the compound was confirmed based on the Lipinski rule with zero violations. Molecular dynamic simulation (MDS) was also performed for 100 ns and a stable RMSF plot was observed. The results strongly propose that the identified compound has immense potential to be considered a drug candidate to develop further against human breast cancer.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 1-2","pages":"3"},"PeriodicalIF":3.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112347","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}
Pub Date : 2025-04-16DOI: 10.1007/s44446-025-00008-4
Widad M Al-Bishri, Rasha M A Mousa, Hanaa A S Alghamdi
One of the most common chronic conditions of peptic ulcer is gastric ulcer (GU), which is recognized as a high-risk illness in the present-day lifestyle. Originating from Asia and Europe, Beetroot (Beta vulgaris L.) is packed with high amounts of bioactive compounds like betanin and phenolics. These contribute to its nutritional value and overall health benefits. In this work, varying concentrations (0.5% to 7% w/v) of beta-cyclodextrin (β-CD) and hydroxypropyl-beta-cyclodextrin (HP-β-CD) were used to improve the efficiency of extracting beetroot components with water, using both stirring and ultrasound techniques. The presence of 5% (w/v) HP-β-CD during extraction appeared the maximum values of total phenolic compounds and betanin (3.1 mcg/mL and 3.01 mg/mL, respectively). The extraction recoveries of betanin at 5% (w/v) HP-β-CD emerging with magnetic stirring were 73%, 36% and 50% against water, ethanol and β-CD, respectively. The reproducibility of extraction procedure was found to be 0.86% relative standard deviation (RSD) indicating the highest precision of the beetroot modified HP-β-CD extraction procedure. Then, rats that had been treated with either HP-β-CD-modified aqueous extract of beetroot, omeprazole (20 mg/kg, orally administered) or both were studied to assess whether they helped reduce ethanol-induced GU. The combined treatment of HP-β-CD modified beetroot extract with omeprazole brought a significant decrease in the increased levels of serum oxidative stress malonaldehyde and nitric oxide, inflammatory markers myeloperoxidase, interleukin-10, interleukin-6 and tumor necrosis factor-α. It also restored the decreased levels of antioxidant glutathione and cyclo-protective prostaglandin E2 in comparison to the positive control. Furthermore, the proposed combination of beetroot-modified aqueous extract and omeprazole exhibited less severe histopathological damage in comparison to the positive control. Therefore, a novel synergistic pharmaceutical treatment using HP-β-CD modified aqueous extract of beetroot and omeprazole was presented to enhance GU healing.
{"title":"Innovative approaches for beetroot (Beta Vulgaris L.) aqueous extraction by cyclodextrins and its use to alleviate ethanol induced gastric ulcer in rats.","authors":"Widad M Al-Bishri, Rasha M A Mousa, Hanaa A S Alghamdi","doi":"10.1007/s44446-025-00008-4","DOIUrl":"10.1007/s44446-025-00008-4","url":null,"abstract":"<p><p>One of the most common chronic conditions of peptic ulcer is gastric ulcer (GU), which is recognized as a high-risk illness in the present-day lifestyle. Originating from Asia and Europe, Beetroot (Beta vulgaris L.) is packed with high amounts of bioactive compounds like betanin and phenolics. These contribute to its nutritional value and overall health benefits. In this work, varying concentrations (0.5% to 7% w/v) of beta-cyclodextrin (β-CD) and hydroxypropyl-beta-cyclodextrin (HP-β-CD) were used to improve the efficiency of extracting beetroot components with water, using both stirring and ultrasound techniques. The presence of 5% (w/v) HP-β-CD during extraction appeared the maximum values of total phenolic compounds and betanin (3.1 mcg/mL and 3.01 mg/mL, respectively). The extraction recoveries of betanin at 5% (w/v) HP-β-CD emerging with magnetic stirring were 73%, 36% and 50% against water, ethanol and β-CD, respectively. The reproducibility of extraction procedure was found to be 0.86% relative standard deviation (RSD) indicating the highest precision of the beetroot modified HP-β-CD extraction procedure. Then, rats that had been treated with either HP-β-CD-modified aqueous extract of beetroot, omeprazole (20 mg/kg, orally administered) or both were studied to assess whether they helped reduce ethanol-induced GU. The combined treatment of HP-β-CD modified beetroot extract with omeprazole brought a significant decrease in the increased levels of serum oxidative stress malonaldehyde and nitric oxide, inflammatory markers myeloperoxidase, interleukin-10, interleukin-6 and tumor necrosis factor-α. It also restored the decreased levels of antioxidant glutathione and cyclo-protective prostaglandin E2 in comparison to the positive control. Furthermore, the proposed combination of beetroot-modified aqueous extract and omeprazole exhibited less severe histopathological damage in comparison to the positive control. Therefore, a novel synergistic pharmaceutical treatment using HP-β-CD modified aqueous extract of beetroot and omeprazole was presented to enhance GU healing.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 1-2","pages":"2"},"PeriodicalIF":3.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112399","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}
Ovarian cancer (OC) is the fourth leading cancer form in Jazan, Saudi Arabia. However, limited awareness and delayed healthcare-seeking behaviors might negatively impact screening uptake and early diagnosis. This study aimed to assess awareness and knowledge of OC, and related risk factors among the female population of Jazan region, Saudi Arabia. A cross-sectional web-based survey was conducted asking questions about the general awareness, knowledge, and awareness of risk factors associated with OC using a self-administered questionnaire. Descriptive statistics, chi-square tests, and Pearson's correlation analysis were used to analyze the data and a p ≤ 0.05 was considered statistically significant. Of the 465 participants, 433 completed the questionnaire (response rate = 93%). Internal reliability of questionnaire sections was found acceptable (Cronbach's alpha = 0.794, 0.738, and 0.816). Alarmingly, a significant majority of respondents exhibited poor general awareness (85%), poor knowledge (89.1%), and poor awareness of risk factors (86.1%). Only a small tested population showed good to moderate awareness (14.9%), knowledge (10.9%), and awareness of risk factors (13.8%). Significant positive correlations were observed between OC awareness and knowledge (r = 0.60, p < 0.01), OC awareness and risk factor awareness (r = 0.515, p < 0.01), as well as between knowledge and risk factor awareness (r = 0.634, p < 0.01). Limited awareness of OC and its risk factors were noted in the women population of Jazan region which highlights the importance and critical need for targeted educational initiatives aimed to improve the general public understanding and to promote preventive and screening measures.
卵巢癌(OC)是沙特阿拉伯吉赞的第四大癌症形式。然而,有限的认识和延迟就医行为可能会对筛查和早期诊断产生负面影响。本研究旨在评估沙特阿拉伯吉赞地区女性人群对卵巢癌的认知及相关危险因素。一项基于网络的横断面调查采用自我管理的问卷,询问与OC相关的风险因素的一般意识、知识和意识。采用描述性统计、卡方检验和Pearson相关分析对数据进行分析,p≤0.05为差异有统计学意义。在465名参与者中,433人完成了问卷调查(回复率为93%)。问卷各部分的内部信度可接受(Cronbach’s alpha = 0.794、0.738和0.816)。令人震惊的是,绝大多数受访者表现出较差的一般意识(85%)、较差的知识(89.1%)和较差的风险因素意识(86.1%)。只有一小部分受测人群对危险因素表现出良好到中度的意识(14.9%)、知识(10.9%)和意识(13.8%)。认知与认知之间存在显著正相关(r = 0.60, p
{"title":"Assessment of knowledge and awareness about ovarian cancer and its risk factors among women in Jazan, Saudi Arabia: a cross-sectional study.","authors":"Gulrana Khuwaja, Mohd Shahnawaz Ansari, Shamama Javed, Waquar Ahsan, Hafiz Makeen, Khalid Zoghebi, Asim Najmi, Amani Khardali, Abdulrahman N Qramish, Khalid Aidarous Ageeli","doi":"10.1007/s44446-025-00002-w","DOIUrl":"10.1007/s44446-025-00002-w","url":null,"abstract":"<p><p>Ovarian cancer (OC) is the fourth leading cancer form in Jazan, Saudi Arabia. However, limited awareness and delayed healthcare-seeking behaviors might negatively impact screening uptake and early diagnosis. This study aimed to assess awareness and knowledge of OC, and related risk factors among the female population of Jazan region, Saudi Arabia. A cross-sectional web-based survey was conducted asking questions about the general awareness, knowledge, and awareness of risk factors associated with OC using a self-administered questionnaire. Descriptive statistics, chi-square tests, and Pearson's correlation analysis were used to analyze the data and a p ≤ 0.05 was considered statistically significant. Of the 465 participants, 433 completed the questionnaire (response rate = 93%). Internal reliability of questionnaire sections was found acceptable (Cronbach's alpha = 0.794, 0.738, and 0.816). Alarmingly, a significant majority of respondents exhibited poor general awareness (85%), poor knowledge (89.1%), and poor awareness of risk factors (86.1%). Only a small tested population showed good to moderate awareness (14.9%), knowledge (10.9%), and awareness of risk factors (13.8%). Significant positive correlations were observed between OC awareness and knowledge (r = 0.60, p < 0.01), OC awareness and risk factor awareness (r = 0.515, p < 0.01), as well as between knowledge and risk factor awareness (r = 0.634, p < 0.01). Limited awareness of OC and its risk factors were noted in the women population of Jazan region which highlights the importance and critical need for targeted educational initiatives aimed to improve the general public understanding and to promote preventive and screening measures.</p>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"33 1-2","pages":"1"},"PeriodicalIF":3.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12102031/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112336","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}
Pub Date : 2024-12-01DOI: 10.1016/j.jsps.2024.102210
Wenjie Hu , Xueyan Kuang , Yao Zhang , Yimin Luo , Litao Zhang
Phenylacetylglycine (PAGly) is a small molecule derived from phenylalanine in the gut via glycine degradation and conjugation. It has been associated with both the progression of atherosclerosis and protective effects on the myocardium. This study evaluated the function and the underlying mechanisms of PAGly in a rat cerebral ischemia/reperfusion (I/R) injury model. The results indicated that PAGly markedly alleviated cerebral infarct volume (P = 0.0024) and improved the neurobehavioral outcomes (P = 0.0149) after I/R injury. PAGly is structurally analogous to catecholamines and binds to β2-adrenergic receptors (β2AR) on microglia without altering the expression of these receptors (P = 0.9137), but instead inhibiting their activity. It was also observed that when β2AR was engaged in microglia, PAGly suppressed the release of TNF-α (P = 0.0018), IL-1β (P = 0.0310), and IL-6 (P = 0.0017), thereby reducing neuronal apoptosis (P = 0.000003). Furthermore, the protective effect of PAGly diminished after the administration of β2AR-specific agonist fenoterol (P = 0.0055). These data indicate that PAGly mitigates cerebral I/R injury by inhibiting microglial inflammation via β2AR, highlighting its potential as a therapeutic agent. These findings position PAGly as a promising candidate for therapeutic intervention in cerebrovascular injuries, warranting further exploration in clinical settings.
{"title":"Neuroprotective effects of phenylacetylglycine via β2AR on cerebral ischemia/reperfusion injury in rats","authors":"Wenjie Hu , Xueyan Kuang , Yao Zhang , Yimin Luo , Litao Zhang","doi":"10.1016/j.jsps.2024.102210","DOIUrl":"10.1016/j.jsps.2024.102210","url":null,"abstract":"<div><div>Phenylacetylglycine (PAGly) is a small molecule derived from phenylalanine in the gut <em>via</em> glycine degradation and conjugation. It has been associated with both the progression of atherosclerosis and protective effects on the myocardium. This study evaluated the function and the underlying mechanisms of PAGly in a rat cerebral ischemia/reperfusion (I/R) injury model. The results indicated that PAGly markedly alleviated cerebral infarct volume (<em>P</em> = 0.0024) and improved the neurobehavioral outcomes (<em>P</em> = 0.0149) after I/R injury. PAGly is structurally analogous to catecholamines and binds to β2-adrenergic receptors (β2AR) on microglia without altering the expression of these receptors (<em>P</em> = 0.9137), but instead inhibiting their activity. It was also observed that when β2AR was engaged in microglia, PAGly suppressed the release of TNF-α (<em>P</em> = 0.0018), IL-1β (<em>P</em> = 0.0310), and IL-6 (<em>P</em> = 0.0017), thereby reducing neuronal apoptosis (<em>P</em> = 0.000003). Furthermore, the protective effect of PAGly diminished after the administration of β2AR-specific agonist fenoterol (<em>P</em> = 0.0055). These data indicate that PAGly mitigates cerebral I/R injury by inhibiting microglial inflammation <em>via</em> β2AR, highlighting its potential as a therapeutic agent. These findings position PAGly as a promising candidate for therapeutic intervention in cerebrovascular injuries, warranting further exploration in clinical settings.</div></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 12","pages":"Article 102210"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142748188","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}
Pub Date : 2024-12-01DOI: 10.1016/j.jsps.2024.102212
Mohammed M. Almutairi , Abdulrahman Althekair , Fahad Almutairi , Mohammed Alatabani , Abdulaziz Alsaikhan
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by persistent, age-inappropriate levels of inattention and/or hyperactive-impulsive behaviors. Previous investigations reveal that disrupted mitochondrial physiological homeostasis may contribute to ADHD. Several factors, including environmental factors, metabolic dysregulation, oxidative stress, neuroinflammation, and genetic abnormalities, can lead to mitochondrial dysfunction and impaired mitophagic pathways. Several investigations have been established a connection between mitochondrial dysfunction in ADHD and variations in monoaminergic genes, including dopamine receptors, dopamine transporters, norepinephrine transporters, serotonin transporters, and synaptic genes. The interplay between mitochondrial homeostasis and mitophagy in ADHD provides a promising research area and understating this interaction may help in the investigation of pathophysiological mechanisms and the innovation of novel therapeutic approaches to ADHD. Accordingly, this review explores previous studies that have investigated the mitochondrial abnormalities and dysfunctions in mitophagy at the cellular and molecular level in the development of ADHD.
{"title":"Mitochondrial dysfunction and mitophagy in ADHD: Cellular and molecular mechanisms","authors":"Mohammed M. Almutairi , Abdulrahman Althekair , Fahad Almutairi , Mohammed Alatabani , Abdulaziz Alsaikhan","doi":"10.1016/j.jsps.2024.102212","DOIUrl":"10.1016/j.jsps.2024.102212","url":null,"abstract":"<div><div>Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by persistent, age-inappropriate levels of inattention and/or hyperactive-impulsive behaviors. Previous investigations reveal that disrupted mitochondrial physiological homeostasis may contribute to ADHD. Several factors, including environmental factors, metabolic dysregulation, oxidative stress, neuroinflammation, and genetic abnormalities, can lead to mitochondrial dysfunction and impaired mitophagic pathways. Several investigations have been established a connection between mitochondrial dysfunction in ADHD and variations in monoaminergic genes, including dopamine receptors, dopamine transporters, norepinephrine transporters, serotonin transporters, and synaptic genes. The interplay between mitochondrial homeostasis and mitophagy in ADHD provides a promising research area and understating this interaction may help in the investigation of pathophysiological mechanisms and the innovation of novel therapeutic approaches to ADHD. Accordingly, this review explores previous studies that have investigated the mitochondrial abnormalities and dysfunctions in mitophagy at the cellular and molecular level in the development of ADHD.</div></div>","PeriodicalId":49257,"journal":{"name":"Saudi Pharmaceutical Journal","volume":"32 12","pages":"Article 102212"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143164407","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}