1.Hypoxic Stress Induces Complement-Mediated Lysis of Mesenchymal Stem Cells by Downregulating Factor H and CD59
Ramada R. KHASWANEH ; Ejlal ABU-EL-RUB ; Ayman ALZU’BI ; Fatimah A. ALMAHASNEH ; Rawan. A. ALMAZARI ; Heba F. AI-JARIRI ; Raed M. AL-ZOUBI
Tissue Engineering and Regenerative Medicine 2025;22(1):105-112
BACKGROUND:
Factor H and membrane inhibitor of reactive lysis (CD59) are key regulators of complement activation.Mesenchymal stem cells (MSCs) secrete Factor H and express CD59 to protect themselves from complement-mediated damage. Severe hypoxia found to decrease the survival chances of MSCs after transplantation; however, little is known about the impact of severe hypoxia on modulating the complement system activity and its effect on MSCs survival. Our study seeks to explore the effect of severe hypoxia on modulating the complement cascade in MSCs.
METHODS:
Human adipose tissue-derived MSCs (hAD-MSCs) were cultured under severe hypoxia using 400 lM Cobalt Chloride (CoCl2) for 48 h. The protein expressions of survival marker; Phosphoinositide 3-kinases (PI3K), and proapoptotic marker; Caspase-3 were assessed using western blotting. The level of complement system related factors; Factor H, CD59, C3b, iC3b, C5b, C9, and the complement membrane attack complex (MAC) were analyzed using Elisa assays, western blotting, and immunocytochemistry.
RESULTS:
Our results showed for the first time that severe hypoxia can significantly impair Factor H secretion and CD59 expression in MSCs. This has been associated with upregulation of MAC complex and increased level of cell lysis and apoptosis marked by downregulation of PI3K and upregulation of Annexin v and Caspase-3.
CONCLUSION
The loss of Factor H and CD59 in hypoxic MSCs can initiate their lysis and apoptosis mediated by activating MAC complex. Preserving the level of Factor H and CD59 in MSCs has significant clinical implication to increase their retention rate in hypoxic conditions and prolong their survival.
2.Hypoxic Stress Induces Complement-Mediated Lysis of Mesenchymal Stem Cells by Downregulating Factor H and CD59
Ramada R. KHASWANEH ; Ejlal ABU-EL-RUB ; Ayman ALZU’BI ; Fatimah A. ALMAHASNEH ; Rawan. A. ALMAZARI ; Heba F. AI-JARIRI ; Raed M. AL-ZOUBI
Tissue Engineering and Regenerative Medicine 2025;22(1):105-112
BACKGROUND:
Factor H and membrane inhibitor of reactive lysis (CD59) are key regulators of complement activation.Mesenchymal stem cells (MSCs) secrete Factor H and express CD59 to protect themselves from complement-mediated damage. Severe hypoxia found to decrease the survival chances of MSCs after transplantation; however, little is known about the impact of severe hypoxia on modulating the complement system activity and its effect on MSCs survival. Our study seeks to explore the effect of severe hypoxia on modulating the complement cascade in MSCs.
METHODS:
Human adipose tissue-derived MSCs (hAD-MSCs) were cultured under severe hypoxia using 400 lM Cobalt Chloride (CoCl2) for 48 h. The protein expressions of survival marker; Phosphoinositide 3-kinases (PI3K), and proapoptotic marker; Caspase-3 were assessed using western blotting. The level of complement system related factors; Factor H, CD59, C3b, iC3b, C5b, C9, and the complement membrane attack complex (MAC) were analyzed using Elisa assays, western blotting, and immunocytochemistry.
RESULTS:
Our results showed for the first time that severe hypoxia can significantly impair Factor H secretion and CD59 expression in MSCs. This has been associated with upregulation of MAC complex and increased level of cell lysis and apoptosis marked by downregulation of PI3K and upregulation of Annexin v and Caspase-3.
CONCLUSION
The loss of Factor H and CD59 in hypoxic MSCs can initiate their lysis and apoptosis mediated by activating MAC complex. Preserving the level of Factor H and CD59 in MSCs has significant clinical implication to increase their retention rate in hypoxic conditions and prolong their survival.
3.Hypoxic Stress Induces Complement-Mediated Lysis of Mesenchymal Stem Cells by Downregulating Factor H and CD59
Ramada R. KHASWANEH ; Ejlal ABU-EL-RUB ; Ayman ALZU’BI ; Fatimah A. ALMAHASNEH ; Rawan. A. ALMAZARI ; Heba F. AI-JARIRI ; Raed M. AL-ZOUBI
Tissue Engineering and Regenerative Medicine 2025;22(1):105-112
BACKGROUND:
Factor H and membrane inhibitor of reactive lysis (CD59) are key regulators of complement activation.Mesenchymal stem cells (MSCs) secrete Factor H and express CD59 to protect themselves from complement-mediated damage. Severe hypoxia found to decrease the survival chances of MSCs after transplantation; however, little is known about the impact of severe hypoxia on modulating the complement system activity and its effect on MSCs survival. Our study seeks to explore the effect of severe hypoxia on modulating the complement cascade in MSCs.
METHODS:
Human adipose tissue-derived MSCs (hAD-MSCs) were cultured under severe hypoxia using 400 lM Cobalt Chloride (CoCl2) for 48 h. The protein expressions of survival marker; Phosphoinositide 3-kinases (PI3K), and proapoptotic marker; Caspase-3 were assessed using western blotting. The level of complement system related factors; Factor H, CD59, C3b, iC3b, C5b, C9, and the complement membrane attack complex (MAC) were analyzed using Elisa assays, western blotting, and immunocytochemistry.
RESULTS:
Our results showed for the first time that severe hypoxia can significantly impair Factor H secretion and CD59 expression in MSCs. This has been associated with upregulation of MAC complex and increased level of cell lysis and apoptosis marked by downregulation of PI3K and upregulation of Annexin v and Caspase-3.
CONCLUSION
The loss of Factor H and CD59 in hypoxic MSCs can initiate their lysis and apoptosis mediated by activating MAC complex. Preserving the level of Factor H and CD59 in MSCs has significant clinical implication to increase their retention rate in hypoxic conditions and prolong their survival.
4.Hypoxic Stress Induces Complement-Mediated Lysis of Mesenchymal Stem Cells by Downregulating Factor H and CD59
Ramada R. KHASWANEH ; Ejlal ABU-EL-RUB ; Ayman ALZU’BI ; Fatimah A. ALMAHASNEH ; Rawan. A. ALMAZARI ; Heba F. AI-JARIRI ; Raed M. AL-ZOUBI
Tissue Engineering and Regenerative Medicine 2025;22(1):105-112
BACKGROUND:
Factor H and membrane inhibitor of reactive lysis (CD59) are key regulators of complement activation.Mesenchymal stem cells (MSCs) secrete Factor H and express CD59 to protect themselves from complement-mediated damage. Severe hypoxia found to decrease the survival chances of MSCs after transplantation; however, little is known about the impact of severe hypoxia on modulating the complement system activity and its effect on MSCs survival. Our study seeks to explore the effect of severe hypoxia on modulating the complement cascade in MSCs.
METHODS:
Human adipose tissue-derived MSCs (hAD-MSCs) were cultured under severe hypoxia using 400 lM Cobalt Chloride (CoCl2) for 48 h. The protein expressions of survival marker; Phosphoinositide 3-kinases (PI3K), and proapoptotic marker; Caspase-3 were assessed using western blotting. The level of complement system related factors; Factor H, CD59, C3b, iC3b, C5b, C9, and the complement membrane attack complex (MAC) were analyzed using Elisa assays, western blotting, and immunocytochemistry.
RESULTS:
Our results showed for the first time that severe hypoxia can significantly impair Factor H secretion and CD59 expression in MSCs. This has been associated with upregulation of MAC complex and increased level of cell lysis and apoptosis marked by downregulation of PI3K and upregulation of Annexin v and Caspase-3.
CONCLUSION
The loss of Factor H and CD59 in hypoxic MSCs can initiate their lysis and apoptosis mediated by activating MAC complex. Preserving the level of Factor H and CD59 in MSCs has significant clinical implication to increase their retention rate in hypoxic conditions and prolong their survival.
5.Hypoxic Stress Induces Complement-Mediated Lysis of Mesenchymal Stem Cells by Downregulating Factor H and CD59
Ramada R. KHASWANEH ; Ejlal ABU-EL-RUB ; Ayman ALZU’BI ; Fatimah A. ALMAHASNEH ; Rawan. A. ALMAZARI ; Heba F. AI-JARIRI ; Raed M. AL-ZOUBI
Tissue Engineering and Regenerative Medicine 2025;22(1):105-112
BACKGROUND:
Factor H and membrane inhibitor of reactive lysis (CD59) are key regulators of complement activation.Mesenchymal stem cells (MSCs) secrete Factor H and express CD59 to protect themselves from complement-mediated damage. Severe hypoxia found to decrease the survival chances of MSCs after transplantation; however, little is known about the impact of severe hypoxia on modulating the complement system activity and its effect on MSCs survival. Our study seeks to explore the effect of severe hypoxia on modulating the complement cascade in MSCs.
METHODS:
Human adipose tissue-derived MSCs (hAD-MSCs) were cultured under severe hypoxia using 400 lM Cobalt Chloride (CoCl2) for 48 h. The protein expressions of survival marker; Phosphoinositide 3-kinases (PI3K), and proapoptotic marker; Caspase-3 were assessed using western blotting. The level of complement system related factors; Factor H, CD59, C3b, iC3b, C5b, C9, and the complement membrane attack complex (MAC) were analyzed using Elisa assays, western blotting, and immunocytochemistry.
RESULTS:
Our results showed for the first time that severe hypoxia can significantly impair Factor H secretion and CD59 expression in MSCs. This has been associated with upregulation of MAC complex and increased level of cell lysis and apoptosis marked by downregulation of PI3K and upregulation of Annexin v and Caspase-3.
CONCLUSION
The loss of Factor H and CD59 in hypoxic MSCs can initiate their lysis and apoptosis mediated by activating MAC complex. Preserving the level of Factor H and CD59 in MSCs has significant clinical implication to increase their retention rate in hypoxic conditions and prolong their survival.
6.The Effectiveness of the Long-Lasting Insecticidal Nets in Controlling Malaria Vector: A Meta-Analysis of Experimental Hut Studies
Muhammad Faiz Mohd Ishak ; Mohd Shahrol Abd Wahil ; Haniff Mohd Nawi ; Azmawati Mohammed Nawi ; Norfazilah Ahmad ; Fatimah Ahmedy ; Mohammad Saffree Jeffree ; Syed Sharizman Syed Abdul Rahim ; Mohd Rohaizat Hassan
International Journal of Public Health Research 2025;15(1):2215-2229
Malaria is a life-threatening, preventable, and curable vector borne disease caused by parasites that are transmitted to people through the bites of infected female Anopheles. The WHO Global Report 2010-2016 reported insecticide resistance in malaria. The main objective of this study is to determine the effectiveness of new generation Long-Lasting Insecticidal Nets (LLIN) compared to standard LLIN and untreated nets in terms of the mortality rate of adult female Anopheles gambiae. A comprehensive review of the literature was published in three databases (PubMed, Ovid, EBSCO Host) since 2010. Publications were searched with keywords including malaria, long-lasting treated bed net, long lasting insecticide-treated bed net, LLIN, and experimental hut. The search has identified 60 articles. Based on the PRISMA flowchart, 10 articles are qualified for data collection and analysis. The gathered data was analysed using Review Manager. Following meta-analysis between subgroups, a risk difference of 0.31 between standard LLINs versus untreated net (p<0.001, I²=100% 95% CI:0.01,0.60). A comparison of upgraded LLINs with the untreated net has shown a significant difference with a pooled risk difference of 0.54 favours upgraded LLINs (p<0.001, I²=100% 95% CI: 0.54,0.84). Comparison between upgraded LLINs versus standard gave an overall risk difference of 0.24 (p < 0.001, I² = 100%, 95% CI: 0.10–0.39). Upgraded LLINs significantly increase Anophelesmortality compared to standard LLINs and untreated nets, suggesting their potential for improved malaria control. Thus, using upgraded nets in the field and translating them into malaria preventive programs would help achieve the target and improve healthoutcomes for those living in endemic areas.
7.Autophagic cell death induction in a clinical isolate of Acanthamoeba sp. treated with methanolic extracts of Pereskia bleo Kuh
Razifah Mohd Razali ; Fatin Amira Abdullah ; Nur Nabilah Mohd Basri ; Syed Ahmad Tajudin Tuan Johari ; Thivyan Manisekaran ; Fatimah Hashim
Malaysian Journal of Microbiology 2024;20(no.2):224-236
Aims:
This study was aimed to investigate the effects of methanol extracts from various parts of the Pereskia bleo Kuhn plant on Acanthamoeba sp. The antioxidant levels of each extract from different plant parts were measured after the extraction process. These extracts were then exposed to Acanthamoeba sp. to assess dose-response, IC50 values, changes in cell morphology, internal cell activity and apoptosis based on alterations in phospholipids.
Methodology and results:
The total phenolic content, carotenoid estimation and antioxidant activity of the leaves, flowers and fruits of P. bleo were measured based on 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH) assay. Its anti-amoebic properties were tested using 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay for the IC50 determination. The morphological and biochemical changes in the Acanthamoeba sp. were observed under light and fluorescence microscopy using the acridine orange and propidium iodide double staining (AO/PI). The IC50 values of P. bleo leaves, flowers and fruits methanolic extracts were 5.884%, 0.1646% and 20.69%, respectively. Morphological observation displayed shortened acanthapodia with darkened cytoplasms. AO/PI-stained Acanthamoeba sp. cells appear with orange-fluorescent organelles in their green cytoplasm, indicating autophagic cell deaths. Apoptotic and necrotic Acanthamoeba sp. cells were absent based on Annexin V labelling.
Conclusion, significance and impact of study:
This study confirmed that the methanolic crude extracts of P. bleo exhibit high cytotoxic potential towards Acanthamoeba sp. trophozoites by inducing an autophagic mode of cell death.
8.Bicycle-related traumatic injuries:a retrospective study during COVID-19 pandemic
Jie Er Janice Soo ; Zhang Helen YUAN ; Lim Hsiang GEK ; Lateef FATIMAH
World Journal of Emergency Medicine 2024;15(4):256-262
BACKGROUND:This study aimed to review bicycle-related injuries during the COVID-19 pandemic to assist with reinforcement or implementation of new policies for injury prevention. METHODS:This is a retrospective descriptive analysis of injuries sustained during cycling for patients 18 years old and above who presented to Singapore General Hospital from January to June 2021.Medical records were reviewed and consolidated.Descriptive analyses were used to summarize patient characteristics,and differences in characteristics subgrouped by triage acuity and discharge status were analyzed. RESULTS:The study included 272 patients with a mean age of 43 years and a male predominance(71.7%).Most presented without referrals(88.2%)and were not conveyed by ambulances(70.6%).Based on acuity category,there were 24(8.8%)Priority 1(P1)patients with 7 trauma activations,174(64.0%)and 74(27.2%)P2 and P3 patients respectively.The most common injuries were fractures(34.2%),followed by superficial abrasion/contusion(29.4%)and laceration/wound(19.1%).Thirteen(4.8%)patients experienced head injury and 85 patients(31.3%)were documented to be wearing a helmet.The majority occurred on the roads as traffic accidents(32.7%).Forty-two patients(15.4%)were admitted with a mean length of stay of 4.1 d and 17(6.3%)undergone surgical procedures.Out of 214(78.7%)discharged patients,no re-attendances or mortality were observed.In the subgroup analysis,higher acuity patients were generally older,with higher proportions of head injuries leading to admission. CONCLUSION:Our study highlights significant morbidities in bicycle-related injuries.There is also a high proportion of fractures in the young healthy male population.Injury prevention is paramount and we propose emphasizing helmet use and road user safety.
9.Bicycle-related traumatic injuries:a retrospective study during COVID-19 pandemic
Jie Er Janice Soo ; Zhang Helen YUAN ; Lim Hsiang GEK ; Lateef FATIMAH
World Journal of Emergency Medicine 2024;15(4):256-262
BACKGROUND:This study aimed to review bicycle-related injuries during the COVID-19 pandemic to assist with reinforcement or implementation of new policies for injury prevention. METHODS:This is a retrospective descriptive analysis of injuries sustained during cycling for patients 18 years old and above who presented to Singapore General Hospital from January to June 2021.Medical records were reviewed and consolidated.Descriptive analyses were used to summarize patient characteristics,and differences in characteristics subgrouped by triage acuity and discharge status were analyzed. RESULTS:The study included 272 patients with a mean age of 43 years and a male predominance(71.7%).Most presented without referrals(88.2%)and were not conveyed by ambulances(70.6%).Based on acuity category,there were 24(8.8%)Priority 1(P1)patients with 7 trauma activations,174(64.0%)and 74(27.2%)P2 and P3 patients respectively.The most common injuries were fractures(34.2%),followed by superficial abrasion/contusion(29.4%)and laceration/wound(19.1%).Thirteen(4.8%)patients experienced head injury and 85 patients(31.3%)were documented to be wearing a helmet.The majority occurred on the roads as traffic accidents(32.7%).Forty-two patients(15.4%)were admitted with a mean length of stay of 4.1 d and 17(6.3%)undergone surgical procedures.Out of 214(78.7%)discharged patients,no re-attendances or mortality were observed.In the subgroup analysis,higher acuity patients were generally older,with higher proportions of head injuries leading to admission. CONCLUSION:Our study highlights significant morbidities in bicycle-related injuries.There is also a high proportion of fractures in the young healthy male population.Injury prevention is paramount and we propose emphasizing helmet use and road user safety.
10.Bicycle-related traumatic injuries:a retrospective study during COVID-19 pandemic
Jie Er Janice Soo ; Zhang Helen YUAN ; Lim Hsiang GEK ; Lateef FATIMAH
World Journal of Emergency Medicine 2024;15(4):256-262
BACKGROUND:This study aimed to review bicycle-related injuries during the COVID-19 pandemic to assist with reinforcement or implementation of new policies for injury prevention. METHODS:This is a retrospective descriptive analysis of injuries sustained during cycling for patients 18 years old and above who presented to Singapore General Hospital from January to June 2021.Medical records were reviewed and consolidated.Descriptive analyses were used to summarize patient characteristics,and differences in characteristics subgrouped by triage acuity and discharge status were analyzed. RESULTS:The study included 272 patients with a mean age of 43 years and a male predominance(71.7%).Most presented without referrals(88.2%)and were not conveyed by ambulances(70.6%).Based on acuity category,there were 24(8.8%)Priority 1(P1)patients with 7 trauma activations,174(64.0%)and 74(27.2%)P2 and P3 patients respectively.The most common injuries were fractures(34.2%),followed by superficial abrasion/contusion(29.4%)and laceration/wound(19.1%).Thirteen(4.8%)patients experienced head injury and 85 patients(31.3%)were documented to be wearing a helmet.The majority occurred on the roads as traffic accidents(32.7%).Forty-two patients(15.4%)were admitted with a mean length of stay of 4.1 d and 17(6.3%)undergone surgical procedures.Out of 214(78.7%)discharged patients,no re-attendances or mortality were observed.In the subgroup analysis,higher acuity patients were generally older,with higher proportions of head injuries leading to admission. CONCLUSION:Our study highlights significant morbidities in bicycle-related injuries.There is also a high proportion of fractures in the young healthy male population.Injury prevention is paramount and we propose emphasizing helmet use and road user safety.


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