One of the fundamental reactions of the innate immune responses to pathogen infection is the rele... more One of the fundamental reactions of the innate immune responses to pathogen infection is the release of pro-inflammatory cytokines, including IL-1β, processed by the NLRP3 inflammasome. The stimulator of interferon genes (STING) has the essential roles in innate immune response against pathogen infections. Here we reveal a distinct mechanism by which STING regulates the NLRP3 inflammasome activation, IL-1β secretion, and inflammatory responses in human cell lines, mice primary cells, and mice. Interestingly, upon HSV-1 infection and cytosolic DNA stimulation, STING binds to NLRP3 and promotes the inflammasome activation through two approaches. First, STING recruits NLRP3 and facilitates NLRP3 localization in the endoplasmic reticulum, thereby facilitating the inflammasome formation. Second, STING interacts with NLRP3 and attenuates K48-and K63-linked polyubiquitination of NLRP3, thereby promoting the inflammasome activation. Collectively, we demonstrate that the cGAS-STING-NLRP3 signaling is essential for host defense against HSV-1 infection.
SARS-CoV-2, a zoonotic virus, emerged in China causes Coronavirus Disease-2019 (COVID-19). Senior... more SARS-CoV-2, a zoonotic virus, emerged in China causes Coronavirus Disease-2019 (COVID-19). Senior citizens and people with co-infections, genetic diseases, immune-compromised states, and cardiovascular diseases are at higher risk. There is no approved vaccine or drug available to treat COVID-19, although a few antivirals, interferon, and other drugs have reduced viral load in infected patients. However, these drugs have not been significantly effective in European countries. More than 40 different strains of SARS-CoV-2 have been detected in various parts of the world; they might have adapted themselves to the environmental conditions and have become resistant to therapeutic strategies. Many developed and developing countries are facing shortages of surgical masks and other protection tools. So far, the strategies developed by Chinese authorities have efficiently mitigated the SARS-CoV-2 transmission and limited mortality rate to less than 4%, with more than 78,000 people recovered f...
Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a major... more Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a major pathological feature of Coronavirus Disease 2019 (COVID-19) and a crucial determinant in COVID-19 prognosis. Understanding the mechanism underlying the SARS-CoV-2-induced cytokine storm is critical for COVID-19 control. Here, we identify that SARS-CoV-2 ORF3a and host hypoxia-inducible factor-1α (HIF-1α) play key roles in the virus infection and pro-inflammatory responses. RNA sequencing shows that HIF-1α signaling, immune response, and metabolism pathways are dysregulated in COVID-19 patients. Clinical analyses indicate that HIF-1α production, inflammatory responses, and high mortalities occurr in elderly patients. HIF-1α and pro-inflammatory cytokines are elicited in patients and infected cells. Interestingly, SARS-CoV-2 ORF3a induces mitochondrial damage and Mito-ROS production to promote HIF-1α expression, which subsequently facilitates SARS-CoV-2 infection and cytokines production....
SARS-CoV-2, a zoonotic virus, emerged in China causes Coronavirus Disease-2019 (COVID-19). Senior... more SARS-CoV-2, a zoonotic virus, emerged in China causes Coronavirus Disease-2019 (COVID-19). Senior citizens and people with co-infections, genetic diseases, immune-compromised states, and cardiovascular diseases are at higher risk. There is no approved vaccine or drug available to treat COVID-19, although a few antivirals, interferon, and other drugs have reduced viral load in infected patients. However, these drugs have not been significantly effective in European countries. More than 40 different strains of SARS-CoV-2 have been detected in various parts of the world; they might have adapted themselves to the environmental conditions and have become resistant to therapeutic strategies. Many developed and developing countries are facing shortages of surgical masks and other protection tools. So far, the strategies developed by Chinese authorities have efficiently mitigated the SARS-CoV-2 transmission and limited mortality rate to less than 4%, with more than 78,000 people recovered f...
Background: Coronary vascular disease (CVD) is the premier cause of fatality in the world. In Pak... more Background: Coronary vascular disease (CVD) is the premier cause of fatality in the world. In Pakistan, 30 to 40% of all deaths occur due to CVD. The emergency department triage is carried out to prioritize the care of critical patients. Errors during triage may lead to mortality and morbidity of the patient. The current study's objective is to determine the triage process of acute myocardial infarction patients and its associated accuracy and delays during the acute myocardial infarction process of care in the emergency department. Methods: In this descriptive study, data were collected retrospectively from Shifa International Hospital. The consent was taken from participating Registered nurses (RNs) who were involved in the triage process. Nurses with experience of less than 1 year in the emergency department were not part of the study, while only those patients with symptoms indicative of Acute Myocardial Infarction and age of 21 years or older were included in the current st...
Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a major... more Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a major pathological feature of Coronavirus Disease 2019 (COVID-19) and a crucial determinant in COVID-19 prognosis. Understanding the mechanism underlying the SARS-CoV-2-induced cytokine storm is critical for COVID-19 control. Here, we identify that SARS-CoV-2 ORF3a and host hypoxia-inducible factor-1α (HIF-1α) play key roles in the virus infection and pro-inflammatory responses. RNA sequencing shows that HIF-1α signaling, immune response, and metabolism pathways are dysregulated in COVID-19 patients. Clinical analyses indicate that HIF-1α production, inflammatory responses, and high mortalities occurr in elderly patients. HIF-1α and pro-inflammatory cytokines are elicited in patients and infected cells. Interestingly, SARS-CoV-2 ORF3a induces mitochondrial damage and Mito-ROS production to promote HIF-1α expression, which subsequently facilitates SARS-CoV-2 infection and cytokines production....
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Background: Coronary vascular disease (CVD) is the premier cause of fatality in the world. In Pak... more Background: Coronary vascular disease (CVD) is the premier cause of fatality in the world. In Pakistan, 30 to 40% of all deaths occur due to CVD. The emergency department triage is carried out to prioritize the care of critical patients. Errors during triage may lead to mortality and morbidity of the patient. The current study's objective is to determine the triage process of acute myocardial infarction patients and its associated accuracy and delays during the acute myocardial infarction process of care in the emergency department. Methods: In this descriptive study, data were collected retrospectively from Shifa International Hospital. The consent was taken from participating Registered nurses (RNs) who were involved in the triage process. Nurses with experience of less than 1 year in the emergency department were not part of the study, while only those patients with symptoms indicative of Acute Myocardial Infarction and age of 21 years or older were included in the current st...
Frontiers in Bioengineering and Biotechnology, 2021
Bone serves to maintain the shape of the human body due to its hard and solid nature. A loss or w... more Bone serves to maintain the shape of the human body due to its hard and solid nature. A loss or weakening of bone tissues, such as in case of traumatic injury, diseases (e.g., osteosarcoma), or old age, adversely affects the individual’s quality of life. Although bone has the innate ability to remodel and regenerate in case of small damage or a crack, a loss of a large volume of bone in case of a traumatic injury requires the restoration of bone function by adopting different biophysical approaches and chemotherapies as well as a surgical reconstruction. Compared to the biophysical and chemotherapeutic approaches, which may cause complications and bear side effects, the surgical reconstruction involves the implantation of external materials such as ceramics, metals, and different other materials as bone substitutes. Compared to the synthetic substitutes, the use of biomaterials could be an ideal choice for bone regeneration owing to their renewability, non-toxicity, and non-immunoge...
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Zika virus (ZIKV) is a kind of flavivirus emerged in French Polynesia and Brazil, and has led to ... more Zika virus (ZIKV) is a kind of flavivirus emerged in French Polynesia and Brazil, and has led to a worldwide public health concern since 2016. ZIKV infection causes various neurological conditions, which are associated with fetus brain development or peripheral and central nervous systems (PNS/CNS) functional problems. To date, no vaccine or any specific antiviral therapy against ZIKV infection are available. It urgently needs efforts to explore the underlying molecular mechanisms of ZIKV-induced neural pathogenesis. ZIKV favorably infects neural and glial cells specifically astrocytes, consequently dysregulating gene expression and pathways with impairment of process neural cells. In this study, we applied a model for ZIKV replication in mouse primary astrocytes (MPAs) and profiled temporal alterations in the host transcriptomes upon ZIKV infection. Among the RNA-sequencing data of 27,812 genes, we examined 710 genes were significantly differentially expressed by ZIKV, which lead t...
Frontiers in Bioengineering and Biotechnology, 2021
Bone serves to maintain the shape of the human body due to its hard and solid nature. A loss or w... more Bone serves to maintain the shape of the human body due to its hard and solid nature. A loss or weakening of bone tissues, such as in case of traumatic injury, diseases (e.g., osteosarcoma), or old age, adversely affects the individual’s quality of life. Although bone has the innate ability to remodel and regenerate in case of small damage or a crack, a loss of a large volume of bone in case of a traumatic injury requires the restoration of bone function by adopting different biophysical approaches and chemotherapies as well as a surgical reconstruction. Compared to the biophysical and chemotherapeutic approaches, which may cause complications and bear side effects, the surgical reconstruction involves the implantation of external materials such as ceramics, metals, and different other materials as bone substitutes. Compared to the synthetic substitutes, the use of biomaterials could be an ideal choice for bone regeneration owing to their renewability, non-toxicity, and non-immunoge...
In this real-world registry, EVAR was more often offered in cases with suitable anatomy, in parti... more In this real-world registry, EVAR was more often offered in cases with suitable anatomy, in particular with adequate and safe proximal sealing zone. Under these conditions, EVAR can be safely offered to young and low-risk patients, providing excellent early outcomes and low 6-year mortality, aorta-related mortality, and reintervention rates.
Zika virus (ZIKV) is a kind of flavivirus emerged in French Polynesia and Brazil, and has led to ... more Zika virus (ZIKV) is a kind of flavivirus emerged in French Polynesia and Brazil, and has led to a worldwide public health concern since 2016. ZIKV infection causes various neurological conditions, which are associated with fetus brain development or peripheral and central nervous systems (PNS/CNS) functional problems. To date, no vaccine or any specific antiviral therapy against ZIKV infection are available. It urgently needs efforts to explore the underlying molecular mechanisms of ZIKV-induced neural pathogenesis. ZIKV favorably infects neural and glial cells specifically astrocytes, consequently dysregulating gene expression and pathways with impairment of process neural cells. In this study, we applied a model for ZIKV replication in mouse primary astrocytes (MPAs) and profiled temporal alterations in the host transcriptomes upon ZIKV infection. Among the RNA-sequencing data of 27,812 genes, we examined 710 genes were significantly differentially expressed by ZIKV, which lead t...
Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused coronavirus d... more Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused coronavirus disease 2019 (COVID-19) epidemic in China, December 2019. The clinical features and treatment of COVID-19 patients remain largely elusive. However, accurate detection is required for SARS-CoV-2 infection diagnosis. We aimed to evaluate the antibodies-based test and nucleic acid-based test for SARS-CoV-2-infected patients. Methods: We retrospectively studied 133 patients diagnosed with SARS-CoV-2 and admitted to Renmin Hospital of Wuhan University, China, from January 23 to March 1, 2020. Demographic data, clinical records, laboratory tests, and outcomes were collected. Data were accessed by SARS-CoV-2 IgM-IgG antibody test and real-time reverse transcriptase PCR (RT-PCR) detection for SARS-CoV-2 nucleic acid in COVID-19 patients. Results: Of 133 COVID-19 patients, there were 44 moderate cases, 52 severe cases, and 37 critical cases with no differences in gender and age among three subgroups. In RT-PCR detection, the positive rate was 65.9%, 71.2%, and 67.6% in moderate, severe, and critical cases, respectively. Whereas the positive rate of IgM/IgG antibody detection in patients was 79.5%/93.2%, 82.7%/100%, and 73.0%/97.3% in moderate, severe, and critical cases, respectively. Moreover, the IgM and IgG antibodies concentrations were also examined with no differences among three subgroups. Conclusion: The IgM-IgG antibody test exhibited a useful adjunct to RT-PCR detection, and improved the accuracy in COVID-19 diagnosis regardless of the severity of illness, which provides an effective complement to the false-negative results from a nucleic acid test for SARS-CoV-2 infection diagnosis after onsets. recovered during the first 50 days of the outbreak in China [1,2]. As of June 6, 2020, it has been reported 6,663,304 confirmed cases and 392,802 deaths by SARS-CoV-2 infection among over 200 countries and territories [3]. To mitigate the risk of spread it is necessary to investigate and develop effective treatment and diagnostic options. The signs and symptoms of SARS-CoV-2 infection are not specific, most are associated with respiratory complications after onsets such as cough
In this real-world registry, EVAR was more often offered in cases with suitable anatomy, in parti... more In this real-world registry, EVAR was more often offered in cases with suitable anatomy, in particular with adequate and safe proximal sealing zone. Under these conditions, EVAR can be safely offered to young and low-risk patients, providing excellent early outcomes and low 6-year mortality, aorta-related mortality, and reintervention rates.
was deleted from the reference list; its citation at the end of the last sentence of the first pa... more was deleted from the reference list; its citation at the end of the last sentence of the first paragraph of the introduction was deleted, and its citation at the end of the sentence reading "Later, the infectious agent responsible for this atypical pneumonia was confirmed and reported as coronavirus SARS-CoV-2, which caused the first fatality in early January 2020" in the first paragraph of the "Epidemiology and Clinical Features of Human Coronaviruses" section was changed to a citation of reference 37.
Polymer based nanoparticles for drug delivery is an alternative approach to overcome drug resista... more Polymer based nanoparticles for drug delivery is an alternative approach to overcome drug resistance and drug toxicity especially for cutaneous leishmaniasis treatment. The present study shows synthesis and characterization of Miltefosine loaded chitosan nanoparticles (MFS-CNPs). The synthesized MFS-CNPs were experimented to evaluate the in vitro cytotoxicity and efficacy of the synthesized drug loaded nanoparticles by hemolysis assay and 3-(4, 5- dimethylthiazol-2-yl)-2,5-diphenyletetrazolium bromide (MTT) assay. MFS-CNPs were synthesized by ionic gelation method with sodium tripolyphosphate. The characterization of synthesized NPs was performed to observe the surface morphology, encapsulation efficacy, drug loading content, average size, and zeta potential. In vitro MTT assay was performed to calculate half maximal inhibitory concentration value of synthesized nanoparticles against promastigotes and axenic amastigotes of L. tropica. By using Scanning electron microscope, MFS-CNPs displayed spherical shape having a mean size of 70 nm along with high EE (97%), DLC (91%) and negative surface charge (− 28.0 mV). Dynamic light scattering shows the average size of NPs was 91.4 nm. Moreover, less than 5% hemolytic activity was observed in MFS-CNPs as compared to free MFS in different concentrations (100 μg/ml, 125 μg/ml, 150 μg/ml).It was observed that the effect of MFS-CNPs and free MFS on both forms of the parasite was dose and time dependent. However, the cytotoxic effects of MFS-CNPs were more salient than free MFS on both forms of L. tropica. Using MTT assay, free MFS presented low efficacy at higher concentrations (30 µg/ml) with 21.4 ± 1.3 and 20.5 ± 1.4 mean viability rate of the promastigotes and axenic amastigotes, respectively after 72 h incubation. While MFS-CNPs showed strong antileishmanial effects on both forms of L. tropica (11 ± 0.3 and 14 ± 0.8) mean viability rate after 72 h incubation at (30 µg/ml). When analyzed statistically by the software, Graph Pad Prism version 5, the IC50 value of MFS-CNPs (0.0218 ± 0.01 µg/ml) against promastigotes was effective than free MFS (0.3548 ± 0.17 µg/ml). Similarly, MFS-CNPs activity against axenic amastigotes (0.1008 ± 0.02 µg/ml) was potent than free MFS (0.5320 ± 0.21 µg/ml). Hence, MFS-CNPs exhibited significant antileishmanial activity in vitro. In conclusion, MFS-CNPs manifested enhanced in vitro Leishmanicidal and less hemolytic activity; however more studies are needed to support its efficacy in both animal and human cutaneous leishmaniasis.
Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused coronavirus d... more Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused coronavirus disease 2019 (COVID-19) epidemic in China, December 2019. The clinical features and treatment of COVID-19 patients remain largely elusive. However, accurate detection is required for SARS-CoV-2 infection diagnosis. We aimed to evaluate the antibodies-based test and nucleic acid-based test for SARS-CoV-2-infected patients. Methods: We retrospectively studied 133 patients diagnosed with SARS-CoV-2 and admitted to Renmin Hospital of Wuhan University, China, from January 23 to March 1, 2020. Demographic data, clinical records, laboratory tests, and outcomes were collected. Data were accessed by SARS-CoV-2 IgM-IgG antibody test and real-time reverse transcriptase PCR (RT-PCR) detection for SARS-CoV-2 nucleic acid in COVID-19 patients. Results: Of 133 COVID-19 patients, there were 44 moderate cases, 52 severe cases, and 37 critical cases with no differences in gender and age among three subgroups. In RT-PCR detection, the positive rate was 65.9%, 71.2%, and 67.6% in moderate, severe, and critical cases, respectively. Whereas the positive rate of IgM/IgG antibody detection in patients was 79.5%/93.2%, 82.7%/100%, and 73.0%/97.3% in moderate, severe, and critical cases, respectively. Moreover, the IgM and IgG antibodies concentrations were also examined with no differences among three subgroups. Conclusion: The IgM-IgG antibody test exhibited a useful adjunct to RT-PCR detection, and improved the accuracy in COVID-19 diagnosis regardless of the severity of illness, which provides an effective complement to the false-negative results from a nucleic acid test for SARS-CoV-2 infection diagnosis after onsets. recovered during the first 50 days of the outbreak in China [1,2]. As of June 6, 2020, it has been reported 6,663,304 confirmed cases and 392,802 deaths by SARS-CoV-2 infection among over 200 countries and territories [3]. To mitigate the risk of spread it is necessary to investigate and develop effective treatment and diagnostic options. The signs and symptoms of SARS-CoV-2 infection are not specific, most are associated with respiratory complications after onsets such as cough
One of the fundamental reactions of the innate immune responses to pathogen infection is the rele... more One of the fundamental reactions of the innate immune responses to pathogen infection is the release of pro-inflammatory cytokines, including IL-1β, processed by the NLRP3 inflammasome. The stimulator of interferon genes (STING) has the essential roles in innate immune response against pathogen infections. Here we reveal a distinct mechanism by which STING regulates the NLRP3 inflammasome activation, IL-1β secretion, and inflammatory responses in human cell lines, mice primary cells, and mice. Interestingly, upon HSV-1 infection and cytosolic DNA stimulation, STING binds to NLRP3 and promotes the inflammasome activation through two approaches. First, STING recruits NLRP3 and facilitates NLRP3 localization in the endoplasmic reticulum, thereby facilitating the inflammasome formation. Second, STING interacts with NLRP3 and attenuates K48-and K63-linked polyubiquitination of NLRP3, thereby promoting the inflammasome activation. Collectively, we demonstrate that the cGAS-STING-NLRP3 signaling is essential for host defense against HSV-1 infection.
SARS-CoV-2, a zoonotic virus, emerged in China causes Coronavirus Disease-2019 (COVID-19). Senior... more SARS-CoV-2, a zoonotic virus, emerged in China causes Coronavirus Disease-2019 (COVID-19). Senior citizens and people with co-infections, genetic diseases, immune-compromised states, and cardiovascular diseases are at higher risk. There is no approved vaccine or drug available to treat COVID-19, although a few antivirals, interferon, and other drugs have reduced viral load in infected patients. However, these drugs have not been significantly effective in European countries. More than 40 different strains of SARS-CoV-2 have been detected in various parts of the world; they might have adapted themselves to the environmental conditions and have become resistant to therapeutic strategies. Many developed and developing countries are facing shortages of surgical masks and other protection tools. So far, the strategies developed by Chinese authorities have efficiently mitigated the SARS-CoV-2 transmission and limited mortality rate to less than 4%, with more than 78,000 people recovered f...
Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a major... more Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a major pathological feature of Coronavirus Disease 2019 (COVID-19) and a crucial determinant in COVID-19 prognosis. Understanding the mechanism underlying the SARS-CoV-2-induced cytokine storm is critical for COVID-19 control. Here, we identify that SARS-CoV-2 ORF3a and host hypoxia-inducible factor-1α (HIF-1α) play key roles in the virus infection and pro-inflammatory responses. RNA sequencing shows that HIF-1α signaling, immune response, and metabolism pathways are dysregulated in COVID-19 patients. Clinical analyses indicate that HIF-1α production, inflammatory responses, and high mortalities occurr in elderly patients. HIF-1α and pro-inflammatory cytokines are elicited in patients and infected cells. Interestingly, SARS-CoV-2 ORF3a induces mitochondrial damage and Mito-ROS production to promote HIF-1α expression, which subsequently facilitates SARS-CoV-2 infection and cytokines production....
SARS-CoV-2, a zoonotic virus, emerged in China causes Coronavirus Disease-2019 (COVID-19). Senior... more SARS-CoV-2, a zoonotic virus, emerged in China causes Coronavirus Disease-2019 (COVID-19). Senior citizens and people with co-infections, genetic diseases, immune-compromised states, and cardiovascular diseases are at higher risk. There is no approved vaccine or drug available to treat COVID-19, although a few antivirals, interferon, and other drugs have reduced viral load in infected patients. However, these drugs have not been significantly effective in European countries. More than 40 different strains of SARS-CoV-2 have been detected in various parts of the world; they might have adapted themselves to the environmental conditions and have become resistant to therapeutic strategies. Many developed and developing countries are facing shortages of surgical masks and other protection tools. So far, the strategies developed by Chinese authorities have efficiently mitigated the SARS-CoV-2 transmission and limited mortality rate to less than 4%, with more than 78,000 people recovered f...
Background: Coronary vascular disease (CVD) is the premier cause of fatality in the world. In Pak... more Background: Coronary vascular disease (CVD) is the premier cause of fatality in the world. In Pakistan, 30 to 40% of all deaths occur due to CVD. The emergency department triage is carried out to prioritize the care of critical patients. Errors during triage may lead to mortality and morbidity of the patient. The current study's objective is to determine the triage process of acute myocardial infarction patients and its associated accuracy and delays during the acute myocardial infarction process of care in the emergency department. Methods: In this descriptive study, data were collected retrospectively from Shifa International Hospital. The consent was taken from participating Registered nurses (RNs) who were involved in the triage process. Nurses with experience of less than 1 year in the emergency department were not part of the study, while only those patients with symptoms indicative of Acute Myocardial Infarction and age of 21 years or older were included in the current st...
Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a major... more Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a major pathological feature of Coronavirus Disease 2019 (COVID-19) and a crucial determinant in COVID-19 prognosis. Understanding the mechanism underlying the SARS-CoV-2-induced cytokine storm is critical for COVID-19 control. Here, we identify that SARS-CoV-2 ORF3a and host hypoxia-inducible factor-1α (HIF-1α) play key roles in the virus infection and pro-inflammatory responses. RNA sequencing shows that HIF-1α signaling, immune response, and metabolism pathways are dysregulated in COVID-19 patients. Clinical analyses indicate that HIF-1α production, inflammatory responses, and high mortalities occurr in elderly patients. HIF-1α and pro-inflammatory cytokines are elicited in patients and infected cells. Interestingly, SARS-CoV-2 ORF3a induces mitochondrial damage and Mito-ROS production to promote HIF-1α expression, which subsequently facilitates SARS-CoV-2 infection and cytokines production....
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Background: Coronary vascular disease (CVD) is the premier cause of fatality in the world. In Pak... more Background: Coronary vascular disease (CVD) is the premier cause of fatality in the world. In Pakistan, 30 to 40% of all deaths occur due to CVD. The emergency department triage is carried out to prioritize the care of critical patients. Errors during triage may lead to mortality and morbidity of the patient. The current study's objective is to determine the triage process of acute myocardial infarction patients and its associated accuracy and delays during the acute myocardial infarction process of care in the emergency department. Methods: In this descriptive study, data were collected retrospectively from Shifa International Hospital. The consent was taken from participating Registered nurses (RNs) who were involved in the triage process. Nurses with experience of less than 1 year in the emergency department were not part of the study, while only those patients with symptoms indicative of Acute Myocardial Infarction and age of 21 years or older were included in the current st...
Frontiers in Bioengineering and Biotechnology, 2021
Bone serves to maintain the shape of the human body due to its hard and solid nature. A loss or w... more Bone serves to maintain the shape of the human body due to its hard and solid nature. A loss or weakening of bone tissues, such as in case of traumatic injury, diseases (e.g., osteosarcoma), or old age, adversely affects the individual’s quality of life. Although bone has the innate ability to remodel and regenerate in case of small damage or a crack, a loss of a large volume of bone in case of a traumatic injury requires the restoration of bone function by adopting different biophysical approaches and chemotherapies as well as a surgical reconstruction. Compared to the biophysical and chemotherapeutic approaches, which may cause complications and bear side effects, the surgical reconstruction involves the implantation of external materials such as ceramics, metals, and different other materials as bone substitutes. Compared to the synthetic substitutes, the use of biomaterials could be an ideal choice for bone regeneration owing to their renewability, non-toxicity, and non-immunoge...
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Zika virus (ZIKV) is a kind of flavivirus emerged in French Polynesia and Brazil, and has led to ... more Zika virus (ZIKV) is a kind of flavivirus emerged in French Polynesia and Brazil, and has led to a worldwide public health concern since 2016. ZIKV infection causes various neurological conditions, which are associated with fetus brain development or peripheral and central nervous systems (PNS/CNS) functional problems. To date, no vaccine or any specific antiviral therapy against ZIKV infection are available. It urgently needs efforts to explore the underlying molecular mechanisms of ZIKV-induced neural pathogenesis. ZIKV favorably infects neural and glial cells specifically astrocytes, consequently dysregulating gene expression and pathways with impairment of process neural cells. In this study, we applied a model for ZIKV replication in mouse primary astrocytes (MPAs) and profiled temporal alterations in the host transcriptomes upon ZIKV infection. Among the RNA-sequencing data of 27,812 genes, we examined 710 genes were significantly differentially expressed by ZIKV, which lead t...
Frontiers in Bioengineering and Biotechnology, 2021
Bone serves to maintain the shape of the human body due to its hard and solid nature. A loss or w... more Bone serves to maintain the shape of the human body due to its hard and solid nature. A loss or weakening of bone tissues, such as in case of traumatic injury, diseases (e.g., osteosarcoma), or old age, adversely affects the individual’s quality of life. Although bone has the innate ability to remodel and regenerate in case of small damage or a crack, a loss of a large volume of bone in case of a traumatic injury requires the restoration of bone function by adopting different biophysical approaches and chemotherapies as well as a surgical reconstruction. Compared to the biophysical and chemotherapeutic approaches, which may cause complications and bear side effects, the surgical reconstruction involves the implantation of external materials such as ceramics, metals, and different other materials as bone substitutes. Compared to the synthetic substitutes, the use of biomaterials could be an ideal choice for bone regeneration owing to their renewability, non-toxicity, and non-immunoge...
In this real-world registry, EVAR was more often offered in cases with suitable anatomy, in parti... more In this real-world registry, EVAR was more often offered in cases with suitable anatomy, in particular with adequate and safe proximal sealing zone. Under these conditions, EVAR can be safely offered to young and low-risk patients, providing excellent early outcomes and low 6-year mortality, aorta-related mortality, and reintervention rates.
Zika virus (ZIKV) is a kind of flavivirus emerged in French Polynesia and Brazil, and has led to ... more Zika virus (ZIKV) is a kind of flavivirus emerged in French Polynesia and Brazil, and has led to a worldwide public health concern since 2016. ZIKV infection causes various neurological conditions, which are associated with fetus brain development or peripheral and central nervous systems (PNS/CNS) functional problems. To date, no vaccine or any specific antiviral therapy against ZIKV infection are available. It urgently needs efforts to explore the underlying molecular mechanisms of ZIKV-induced neural pathogenesis. ZIKV favorably infects neural and glial cells specifically astrocytes, consequently dysregulating gene expression and pathways with impairment of process neural cells. In this study, we applied a model for ZIKV replication in mouse primary astrocytes (MPAs) and profiled temporal alterations in the host transcriptomes upon ZIKV infection. Among the RNA-sequencing data of 27,812 genes, we examined 710 genes were significantly differentially expressed by ZIKV, which lead t...
Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused coronavirus d... more Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused coronavirus disease 2019 (COVID-19) epidemic in China, December 2019. The clinical features and treatment of COVID-19 patients remain largely elusive. However, accurate detection is required for SARS-CoV-2 infection diagnosis. We aimed to evaluate the antibodies-based test and nucleic acid-based test for SARS-CoV-2-infected patients. Methods: We retrospectively studied 133 patients diagnosed with SARS-CoV-2 and admitted to Renmin Hospital of Wuhan University, China, from January 23 to March 1, 2020. Demographic data, clinical records, laboratory tests, and outcomes were collected. Data were accessed by SARS-CoV-2 IgM-IgG antibody test and real-time reverse transcriptase PCR (RT-PCR) detection for SARS-CoV-2 nucleic acid in COVID-19 patients. Results: Of 133 COVID-19 patients, there were 44 moderate cases, 52 severe cases, and 37 critical cases with no differences in gender and age among three subgroups. In RT-PCR detection, the positive rate was 65.9%, 71.2%, and 67.6% in moderate, severe, and critical cases, respectively. Whereas the positive rate of IgM/IgG antibody detection in patients was 79.5%/93.2%, 82.7%/100%, and 73.0%/97.3% in moderate, severe, and critical cases, respectively. Moreover, the IgM and IgG antibodies concentrations were also examined with no differences among three subgroups. Conclusion: The IgM-IgG antibody test exhibited a useful adjunct to RT-PCR detection, and improved the accuracy in COVID-19 diagnosis regardless of the severity of illness, which provides an effective complement to the false-negative results from a nucleic acid test for SARS-CoV-2 infection diagnosis after onsets. recovered during the first 50 days of the outbreak in China [1,2]. As of June 6, 2020, it has been reported 6,663,304 confirmed cases and 392,802 deaths by SARS-CoV-2 infection among over 200 countries and territories [3]. To mitigate the risk of spread it is necessary to investigate and develop effective treatment and diagnostic options. The signs and symptoms of SARS-CoV-2 infection are not specific, most are associated with respiratory complications after onsets such as cough
In this real-world registry, EVAR was more often offered in cases with suitable anatomy, in parti... more In this real-world registry, EVAR was more often offered in cases with suitable anatomy, in particular with adequate and safe proximal sealing zone. Under these conditions, EVAR can be safely offered to young and low-risk patients, providing excellent early outcomes and low 6-year mortality, aorta-related mortality, and reintervention rates.
was deleted from the reference list; its citation at the end of the last sentence of the first pa... more was deleted from the reference list; its citation at the end of the last sentence of the first paragraph of the introduction was deleted, and its citation at the end of the sentence reading "Later, the infectious agent responsible for this atypical pneumonia was confirmed and reported as coronavirus SARS-CoV-2, which caused the first fatality in early January 2020" in the first paragraph of the "Epidemiology and Clinical Features of Human Coronaviruses" section was changed to a citation of reference 37.
Polymer based nanoparticles for drug delivery is an alternative approach to overcome drug resista... more Polymer based nanoparticles for drug delivery is an alternative approach to overcome drug resistance and drug toxicity especially for cutaneous leishmaniasis treatment. The present study shows synthesis and characterization of Miltefosine loaded chitosan nanoparticles (MFS-CNPs). The synthesized MFS-CNPs were experimented to evaluate the in vitro cytotoxicity and efficacy of the synthesized drug loaded nanoparticles by hemolysis assay and 3-(4, 5- dimethylthiazol-2-yl)-2,5-diphenyletetrazolium bromide (MTT) assay. MFS-CNPs were synthesized by ionic gelation method with sodium tripolyphosphate. The characterization of synthesized NPs was performed to observe the surface morphology, encapsulation efficacy, drug loading content, average size, and zeta potential. In vitro MTT assay was performed to calculate half maximal inhibitory concentration value of synthesized nanoparticles against promastigotes and axenic amastigotes of L. tropica. By using Scanning electron microscope, MFS-CNPs displayed spherical shape having a mean size of 70 nm along with high EE (97%), DLC (91%) and negative surface charge (− 28.0 mV). Dynamic light scattering shows the average size of NPs was 91.4 nm. Moreover, less than 5% hemolytic activity was observed in MFS-CNPs as compared to free MFS in different concentrations (100 μg/ml, 125 μg/ml, 150 μg/ml).It was observed that the effect of MFS-CNPs and free MFS on both forms of the parasite was dose and time dependent. However, the cytotoxic effects of MFS-CNPs were more salient than free MFS on both forms of L. tropica. Using MTT assay, free MFS presented low efficacy at higher concentrations (30 µg/ml) with 21.4 ± 1.3 and 20.5 ± 1.4 mean viability rate of the promastigotes and axenic amastigotes, respectively after 72 h incubation. While MFS-CNPs showed strong antileishmanial effects on both forms of L. tropica (11 ± 0.3 and 14 ± 0.8) mean viability rate after 72 h incubation at (30 µg/ml). When analyzed statistically by the software, Graph Pad Prism version 5, the IC50 value of MFS-CNPs (0.0218 ± 0.01 µg/ml) against promastigotes was effective than free MFS (0.3548 ± 0.17 µg/ml). Similarly, MFS-CNPs activity against axenic amastigotes (0.1008 ± 0.02 µg/ml) was potent than free MFS (0.5320 ± 0.21 µg/ml). Hence, MFS-CNPs exhibited significant antileishmanial activity in vitro. In conclusion, MFS-CNPs manifested enhanced in vitro Leishmanicidal and less hemolytic activity; however more studies are needed to support its efficacy in both animal and human cutaneous leishmaniasis.
Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused coronavirus d... more Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused coronavirus disease 2019 (COVID-19) epidemic in China, December 2019. The clinical features and treatment of COVID-19 patients remain largely elusive. However, accurate detection is required for SARS-CoV-2 infection diagnosis. We aimed to evaluate the antibodies-based test and nucleic acid-based test for SARS-CoV-2-infected patients. Methods: We retrospectively studied 133 patients diagnosed with SARS-CoV-2 and admitted to Renmin Hospital of Wuhan University, China, from January 23 to March 1, 2020. Demographic data, clinical records, laboratory tests, and outcomes were collected. Data were accessed by SARS-CoV-2 IgM-IgG antibody test and real-time reverse transcriptase PCR (RT-PCR) detection for SARS-CoV-2 nucleic acid in COVID-19 patients. Results: Of 133 COVID-19 patients, there were 44 moderate cases, 52 severe cases, and 37 critical cases with no differences in gender and age among three subgroups. In RT-PCR detection, the positive rate was 65.9%, 71.2%, and 67.6% in moderate, severe, and critical cases, respectively. Whereas the positive rate of IgM/IgG antibody detection in patients was 79.5%/93.2%, 82.7%/100%, and 73.0%/97.3% in moderate, severe, and critical cases, respectively. Moreover, the IgM and IgG antibodies concentrations were also examined with no differences among three subgroups. Conclusion: The IgM-IgG antibody test exhibited a useful adjunct to RT-PCR detection, and improved the accuracy in COVID-19 diagnosis regardless of the severity of illness, which provides an effective complement to the false-negative results from a nucleic acid test for SARS-CoV-2 infection diagnosis after onsets. recovered during the first 50 days of the outbreak in China [1,2]. As of June 6, 2020, it has been reported 6,663,304 confirmed cases and 392,802 deaths by SARS-CoV-2 infection among over 200 countries and territories [3]. To mitigate the risk of spread it is necessary to investigate and develop effective treatment and diagnostic options. The signs and symptoms of SARS-CoV-2 infection are not specific, most are associated with respiratory complications after onsets such as cough
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