39 results on '"Saadullah Khattak"'
Search Results
2. Exploring the antibacterial and dermatitis-mitigating properties of chicken egg white-synthesized zinc oxide nano whiskers
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Sidikov Akmal Abdikakharovich, Mohd A. Rauf, Saadullah Khattak, Junaid Ali Shah, Lamya Ahmed Al-Keridis, Nawaf Alshammari, Mohd Saeed, and Sadykov Aslan Igorevich
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ZnO-NWs ,antibacterial ,anti-biofilm ,electron microscopy ,E.coli ,S.aureus ,Microbiology ,QR1-502 - Abstract
IntroductionZinc oxide nanoparticles (ZnO-NPs) have garnered considerable interest in biomedical research primarily owing to their prospective therapeutic implications in combatting pathogenic diseases and microbial infections. The primary objective of this study was to examine the biosynthesis of zinc oxide nanowhiskers (ZnO-NWs) using chicken egg white (albumin) as a bio-template. Furthermore, this study aimed to explore the potential biomedical applications of ZnO NWs in the context of infectious diseases.MethodsThe NWs synthesized through biological processes were observed using electron microscopy, which allowed for detailed examination of their characteristics. The results of these investigations indicated that the NWs exhibited a size distribution ranging from approximately 10 to 100 nm. Fourier-transform infrared spectroscopy (FTIR) and scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) mapping analyses successfully corroborated the size, dimensions, and presence of biological constituents during their formation. In this study, XTT assay and confocal imaging were employed to provide evidence of the efficacy of ZnO-NWs in the eradication of bacterial biofilms. The target bacterial strains were Staphylococcus aureus and Escherichia coli. Furthermore, we sought to address pertinent concerns regarding the biocompatibility of the ZnO-NWs. This was achieved through comprehensive evaluation of the absence of cytotoxicity in normal HEK-293T and erythrocytes.ResultsThe findings of this investigation unequivocally confirmed the biocompatibility of the ZnO-NWs. The biosynthesized ZnO-NWs demonstrated a noteworthy capacity to mitigate the dermatitis-induced consequences induced by Staphylococcus aureus in murine models after a therapeutic intervention lasting for one week.DiscussionThis study presents a comprehensive examination of the biosynthesis of zinc oxide nanowhiskers (ZnO-NWs) derived from chicken egg whites. These findings highlight the considerable potential of biosynthesized ZnO-NWs as a viable option for the development of therapeutic agents targeting infectious diseases. The antibacterial efficacy of ZnO-NWs against both susceptible and antibiotic-resistant bacterial strains, as well as their ability to eradicate biofilms, suggests their promising role in combating infectious diseases. Furthermore, the confirmed biocompatibility of ZnO-NWs opens avenues for their safe use in biomedical applications. Overall, this research underscores the therapeutic promise of ZnO-NWs and their potential significance in future biomedical advancements.
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- 2023
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3. The double-edged sword role of hydrogen sulfide in hepatocellular carcinoma
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Huijie Zhao, Yanting Zhang, Xiaodi Fu, Chaoren Chen, Saadullah Khattak, and Honggang Wang
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hydrogen sulfide ,hepatocellular carcinoma ,apoptosis ,cystathione gamma-lyase ,3-mercaptopyruvate sulfurtransferase ,Therapeutics. Pharmacology ,RM1-950 - Abstract
With an increasing worldwide prevalence, hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver in the world. It is also the primary reason for cancer-related death in the world. The pathogenesis of HCC is complex, such as DNA methylation changes, immune regulatory disorders, cell cycle disorders, chromosomal instability, and so on. Although many studies have been conducted on HCC, the molecular mechanisms of HCC are not completely understood. At present, there is no effective treatment for HCC. Hydrogen sulfide (H2S) has long been regarded as a toxic gas with the smell of rotten eggs, but recent studies have shown that it is an important gasotransmitter along with carbon monoxide (CO) and nitric oxide (NO). Increasing evidence indicates that H2S has multiple biological functions, such as anti-inflammation, anti-apoptosis, anti-oxidative stress, and so on. Recently, a lot of evidence has shown that H2S has a “double-edged sword” effect in HCC, but the mechanism is not fully understood. Here, we reviewed the progress on the role and mechanism of H2S in HCC in recent years, hoping to provide a theoretical reference for future related research.
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- 2023
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4. Editorial: Evolution, pathogenesis, host interactions and therapeutic strategies against monkeypox virus
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Mehboob Hoque, Sneha Singh, and Saadullah Khattak
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monkeypox (MPX) ,orthopox virus ,epidemiology ,public health concerns ,diagnosis ,treatment ,Microbiology ,QR1-502 - Published
- 2023
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5. A pH-responsive bi-MIL-88B MOF coated with folic acid-conjugated chitosan as a promising nanocarrier for targeted drug delivery of 5-Fluorouracil
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Muhammad Usman Akbar, Saadullah Khattak, Malik Ihsanullah Khan, Umair Ali Khan Saddozai, Nemat Ali, Abdullah F. AlAsmari, Muhammad Zaheer, and Muhammad Badar
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metal-organic framework ,folic acid -chitosan ,stimuli responsive ,drug delivery ,targeted therapy ,anticancer ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Cancer has remained one of the leading causes of death worldwide, with a lack of effective treatment. The intrinsic shortcomings of conventional therapeutics regarding tumor specificity and non-specific toxicity prompt us to look for alternative therapeutics to mitigate these limitations. In this regard, we developed multifunctional bimetallic (FeCo) bi-MIL-88B-FC MOFs modified with folic acid—conjugated chitosan (FC) as drug delivery systems (DDS) for targeted delivery of 5-Fluorouracil (5-FU). The bi-MIL-88B nanocarriers were characterized through various techniques, including powder X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray, thermogravimetric analysis, and Fourier transform infrared spectroscopy. Interestingly, 5-FU@bi-MIL-88B-FC showed slower release of 5-FU due to a gated effect phenomenon endowed by FC surface coating compared to un-modified 5-FU@bi-MIL-88B. The pH-responsive drug release was observed, with 58% of the loaded 5-FU released in cancer cells mimicking pH (5.2) compared to only 24.9% released under physiological pH (5.4). The in vitro cytotoxicity and cellular internalization experiments revealed the superiority of 5-FU@bi-MIL-88B-FC as a highly potent targeted DDS against folate receptor (FR) positive SW480 cancer cells. Moreover, due to the presence of Fe and Co in the structure, bi-MIL-88B exhibited peroxidase-like activity for chemodynamic therapy. Based on the results, 5-FU@bi-MIL-88B-FC could serve as promising candidate for smart DDS by sustained drug release and selective targeting.
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- 2023
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6. Vaccinomics-based next-generation multi-epitope chimeric vaccine models prediction against Leishmania tropica - a hierarchical subtractive proteomics and immunoinformatics approach
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Sara Aiman, Abbas Ahmad, Azmat Ali Khan, Amer M. Alanazi, Abdus Samad, Syed Luqman Ali, Chunhua Li, Zhiguang Ren, Asifullah Khan, and Saadullah Khattak
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leishmaniasis ,reverse vaccinology ,multi-epitope vaccine design ,immunoinformatics ,tropical diseases ,vaccine design ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Leishmania tropica is a vector-borne parasitic protozoa that is the leading cause of leishmaniasis throughout the global tropics and subtropics. L. tropica is a multidrug-resistant parasite with a diverse set of serological, biochemical, and genomic features. There are currently no particular vaccines available to combat leishmaniasis. The present study prioritized potential vaccine candidate proteins of L. tropica using subtractive proteomics and vaccinomics approaches. These vaccine candidate proteins were downstream analyzed to predict B- and T-cell epitopes based on high antigenicity, non-allergenic, and non-toxic characteristics. The top-ranked overlapping MHC-I, MHC-II, and linear B-cell epitopes were prioritized for model vaccine designing. The lead epitopes were linked together by suitable linker sequences to design multi-epitope constructs. Immunogenic adjuvant sequences were incorporated at the N-terminus of the model vaccine constructs to enhance their immunological potential. Among different combinations of constructs, four vaccine designs were selected based on their physicochemical and immunological features. The tertiary structure models of the designed vaccine constructs were predicted and verified. The molecular docking and molecular dynamic (MD) simulation analyses indicated that the vaccine design V1 demonstrated robust and stable molecular interactions with toll-like receptor 4 (TLR4). The top-ranked vaccine construct model-IV demonstrated significant expressive capability in the E. coli expression system during in-silico restriction cloning analysis. The results of the present study are intriguing; nevertheless, experimental bioassays are required to validate the efficacy of the predicted model chimeric vaccine.
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- 2023
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7. Nanotechnology prospects in brain therapeutics concerning gene-targeting and nose-to-brain administration
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Dong-Dong Wu, Yasmine Ahmed Salah, Ebenezeri Erasto Ngowi, Yan-Xia Zhang, Saadullah Khattak, Nazeer Hussain Khan, Yan Wang, Tao Li, Zi-Hua Guo, Yan-Mei Wang, and Xin-Ying Ji
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Pharmacology ,Genetics ,Science - Abstract
Summary: Neurological diseases are one of the most pressing issues in modern times worldwide. It thus possesses explicit attention from researchers and medical health providers to guard public health against such an expanding threat. Various treatment modalities have been developed in a remarkably short time but, unfortunately, have yet to lead to the wished-for efficacy or the sought-after clinical improvement. The main hurdle in delivering therapeutics to the brain has always been the blood-brain barrier which still represents an elusive area with lots of mysteries yet to be solved. Meanwhile, nanotechnology has emerged as an optimistic platform that is potentially holding the answer to many of our questions on how to deliver drugs and treat CNS disorders using novel technologies rather than the unsatisfying conventional old methods. Nanocarriers can be engineered in a way that is capable of delivering a certain therapeutic cargo to a specific target tissue. Adding to this mind-blowing nanotechnology, the revolutionizing gene-altering biologics can have the best of both worlds, and pave the way for the long-awaited cure to many diseases, among those diseases thus far are Alzheimer’s disease (AD), brain tumors (glioma and glioblastoma), Down syndrome, stroke, and even cases with HIV. The review herein collects the studies that tested the mixture of both sciences, nanotechnology, and epigenetics, in the context of brain therapeutics using three main categories of gene-altering molecules (siRNA, miRNA, and CRISPR) with a special focus on the advancements regarding the new favorite, intranasal route of administration.
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- 2023
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8. Drugs being tested against covid-19 to slow down its spread and find effective treatment: A systematic review.
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Arsalan Rasheed, Μalaika Νοοr, Τahir Usman, Rizwana Bilqees, Muhammad Afnan, Saira Gul, Naimat Ullah Khan, Saadullah Khattak, Irfan Khattak, and Assar Ali Shah
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systematic review ,coronavirus ,sars-cov-2 ,covid-19 ,drugs ,treatment ,clinical science ,Medicine - Abstract
Background: The SARS-COV-2's spread from continent to the continent has resulted in an increased number of mutations in the viral gene encoding proteins. As a result, mutations in target proteins provide a significant challenge in creating antiviral drugs and vaccines. The present review discussed the COVID-19 epidemiology and the effects of drugs being tested against COVID-19/SARS-COV-2. Dosage of these drugs along with associated challenges was also discussed. Methodology: Systematic review was conducted after a thorough search in the "PubMed, NIH, Elsevier, Scopus, Web of Science, Science Direct, and Google Scholar database. 45 studies on drugs associated with COVID-19 fulfilled the inclusion criteria and were selected for this review. Results: The FDA only accepted the Remdesivir drug against SARS-COV-2, as the hospitalized patients recovered very quickly by taking it. Antiviral EIDD-2801 has been found to make the SARS-COV-2 unable to infect cells by causing genetic modifications in the virus RNA. Similarly, Nitazoxanide appeared beneficial against SARS-COV-2 in a primary intervention and severe conditions (including pregnancy) without undesirable effects on the newborns. Children with mild cases can be handled solely by proper caring. Conclusion: Although Remdesivir and Dexamethasone are recommended in severe cases, clinical trials are ongoing to investigate other possible therapies like MAb and Convalescent Plasma antibodies for COVID-19. Older drugs (usually used to treat other conditions) are also under-tested by researchers to see if they are effective for COVID-19. Further tests are essential to validate whether any of the mentioned above possible therapies would be helpful for COVID-19 treatment.
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- 2022
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9. Monkeypox Entry and Emergence Preparation in Pakistan
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Saadullah Khattak, Yasir Ali, Zhiguang Ren, and Xin-Ying Ji
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n/a ,Science - Abstract
Monkeypox (Mpox) is a virus that first emerged in Africa in 1970 [...]
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- 2023
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10. The monkeypox diagnosis, treatments and prevention: A review
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Saadullah Khattak, Mohd Ahmar Rauf, Yasir Ali, Muhammad Tufail Yousaf, Zhihui Liu, Dong-Dong Wu, and Xin-Ying Ji
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monkeypox (MPX) ,epidemiology ,diagnosis ,treatment ,public health concerns ,Microbiology ,QR1-502 - Abstract
The world is currently dealing with a second viral outbreak, monkeypox, which has the potential to become an epidemic after the COVID-19 pandemic. People who reside in or close to forest might be exposed indirectly or at a low level, resulting in subclinical disease. However, the disease has lately emerged in shipped African wild mice in the United States. Smallpox can cause similar signs and symptoms to monkeypox, such as malaise, fever, flu-like signs, headache, distinctive rash, and back pain. Because Smallpox has been eliminated, similar symptoms in a monkeypox endemic zone should be treated cautiously. Monkeypox is transmitted to humans primarily via interaction with diseased animals. Infection through inoculation via interaction with skin or scratches and mucosal lesions on the animals is conceivable significantly once the skin barrier is disrupted by scratches, bites, or other disturbances or trauma. Even though it is clinically unclear from other pox-like infections, laboratory diagnosis is essential. There is no approved treatment for human monkeypox virus infection, however, smallpox vaccination can defend counter to the disease. Human sensitivity to monkeypox virus infection has grown after mass vaccination was discontinued in the 1980s. Infection may be prevented by reducing interaction with sick patients or animals and reducing respiratory exposure among people who are infected.
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- 2023
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11. Comparative efficacy of amphotericin B-loaded chitosan nanoparticles and free amphotericin B drug against Leishmania tropica
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Aamir Sohail, Rahat Ullah Khan, Momin Khan, Mehvish Khokhar, Safat Ullah, Arshad Ali, Hazrat Bilal, Saadullah Khattak, Mirwaise Khan, and Baseer Ahmad
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Amphotericin B ,Antileishmanial activity ,Cutaneous leishmaniasis ,Chitosan nanoparticles ,Drug delivery ,MTT assay ,Science - Abstract
Abstract Background The preparation of an effective drug delivery formulation is an urgent need to treat cutaneous leishmaniasis (CL). Pentavalent antimonials and Amphotericin B (AmB) are considered to treat leishmaniasis; however, their clinical usage is hampered by poor solubility, high cost, toxicity, and the emergence of drug-resistant Leishmania spp. The drug delivery systems (DDS) could be used as an alternative treatment option for the treatment of CL to circumvent these problems. We tested the antileishmanial efficacies of free AmB and amphotericin B-loaded chitosan nanoparticles (AmB-CNPs) under in vitro conditions. Results Chitosan nanoparticles (CNPs) were synthesized using the ionic gelation method with negatively charged tripolyphosphate (TPP). During the synthesis of CNPs, AmB was incorporated into the nanoparticles (NPs). The NPs were characterized for their size, surface morphology, encapsulation efficacy (EE), drug loading content (DLC), and surface charge using different techniques. Their efficacy was evaluated against promastigotes and axenic amastigotes forms of Leishmania tropica using MTT assay. The synthesized AmB-CNPs displayed a spherical shape with a mean particle size of 118 nm, a positive zeta potential of (+ 6.21 ± 2.02 mV), and an encapsulation efficacy of 88%. Dynamic light scattering technique (DLS) shows that the average size of prepared AmB-CNPs was 95.5 nm. Free AmB presented very low efficacy (only 65% and 67% inhibition of the promastigotes and axenic amastigotes parasite load), whereas AmB-CNPs exhibited 90% and 84% parasite inhibition after 72 h incubation. The AmB-CNPs exhibited significantly higher efficacy than free AmB in terms of reduction in parasite viability. Half-maximal inhibitory concentration (IC50) measured values of the AmB-CNPs were significant lowers than free AmB. Conclusions The present data indicated that AmB-CNPs exhibited vigorous anti-leishmanial activity than free AmB by dose and time-dependent manner. This formulation can be used for local therapy of CL after in vivo efficacy conformational studies.
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- 2021
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12. Clinical Manifestation, Transmission, Pathogenesis, and Diagnosis of Monkeypox Virus: A Comprehensive Review
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Faheem Anwar, Fatima Haider, Sarmir Khan, Ibrar Ahmad, Naveed Ahmed, Muhammad Imran, Summya Rashid, Zhi-Guang Ren, Saadullah Khattak, and Xin-Ying Ji
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monkeypox virus ,emerging viruses ,vaccination ,pathogenicity ,outbreak ,Science - Abstract
Monkeypox virus is a double-stranded DNA virus species that causes disease in humans and mammals. It is a zoonotic virus belongs the genus Orthopoxviral, the family of Poxviridae, associated with the smallpox virus in many aspects. The first human case of monkeypox was reported throughout the Democratic Republic of Congo in 1970. In April 2022, several cases were recorded in widespread regions of Africa, the Northern and western hemispheres. The current review spotlights taxonomic classification, clinical presentations during infection, and the pathogenicity of the monkeypox virus in humans. Furthermore, the current review also highlights different diagnostics used for virus detection.
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- 2023
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13. Fragment-Based Approaches Identified Tecovirimat-Competitive Novel Drug Candidate for Targeting the F13 Protein of the Monkeypox Virus
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Yasir Ali, Hina Imtiaz, Muhammad Mutaal Tahir, Fouzia Gul, Umair Ali Khan Saddozai, Ashfaq ur Rehman, Zhi-Guang Ren, Saadullah Khattak, and Xin-Ying Ji
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monkeypox virus ,fragment-based drug design ,tecovirimat ,F13 protein ,molecular dynamics simulation ,Microbiology ,QR1-502 - Abstract
Monkeypox is a serious public health issue in tropical and subtropical areas. Antivirals that target monkeypox proteins might lead to more effective and efficient therapy. The F13 protein is essential for the growth and maturation of the monkeypox virus. F13 inhibition might be a viable therapeutic target for monkeypox. The in silico fragment-based drug discovery method for developing antivirals may provide novel therapeutic options. In this study, we generated 800 compounds based on tecovirimat, an FDA-approved drug that is efficacious at nanomolar quantities against monkeypox. These compounds were evaluated to identify the most promising fragments based on binding affinity and pharmacological characteristics. The top hits from the chemical screening were docked into the active site of the F13 protein. Molecular dynamics simulations were performed on the top two probable new candidates from molecular docking. The ligand–enzyme interaction analysis revealed that the C2 ligand had lower binding free energy than the standard ligand tecovirimat. Water bridges, among other interactions, were shown to stabilize the C2 molecule. Conformational transitions and secondary structure changes in F13 protein upon C2 binding show more native three-dimensional folding of the protein. Prediction of pharmacological properties revealed that compound C2 may be promising as a drug candidate for monkeypox fever. However, additional in vitro and in vivo testing is required for validation.
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- 2023
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14. Assessment of General Populations Knowledge, Attitude, and Perceptions Toward the Coronavirus Disease (COVID-19): A Cross-Sectional Study From Pakistan
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Saadullah Khattak, Maqbool Khan, Tahir Usman, Johar Ali, Dong-Xing Wu, Muhammad Jahangir, Kashif Haleem, Pir Muhammad, Mohd Ahmar Rauf, Kamran Saddique, Nazeer Hussain Khan, Tao Li, Dong-Dong Wu, and Xin-Ying Ji
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knowledge ,attitude ,perceptions ,coronavirus disease 2019 ,Pakistan ,Medicine (General) ,R5-920 - Abstract
Background: Coronavirus disease 2019 (COVID-19) is a global health threat and caused a universal psychosocial impact on the general population. Therefore, the knowledge, attitude, and perceptions (KAPs) of the general population are critical for the development and effective implementation of standard operating procedures (SOP) to contain the contagion and minimize the losses. Therefore, the current study was conducted to understand and evaluate the KAPs of Pakistani populations toward the COVID-19.Methods: An online cross-sectional study was carried out among participants from 1 May to 30 July 2020 in different areas of Pakistan. The respondents of the study were the general population with age ≥ 18 years. The poll URL was posted on several channels after a call for participation. Other social media platforms such as WeChat, WhatsApp, Facebook, Twitter, Instagram, Messenger, and LinkedIn were engaged to maximize general population engagement. The questionnaire included details about sociodemographic, knowledge about COVID-19, perceptions toward universal safety precautions of COVID-19, and beliefs attitude toward the COVID-19. The obtained data were exported into a Microsoft Excel spreadsheet and SPSS software version 21 for windows. The descriptive statistics values were presented in frequencies and percentages. Binary logistic regression, Chi-square test, and one-way ANOVA were applied to analyze the participants' socio-demographic characteristics and variables related to KAPs. P-value < 0.05 was recorded as significant.Results: A total of 1,000 participants were invited of which 734 participated in this study. The response rate was 73.4% (734/1,000). The gender, marital status, education, and residence showed a significant association with the knowledge score. The majority of the study participants were thinking that COVID-19 may be more dangerous in elderly individuals 94.5% (n = 700), and individuals with chronic diseases or severe complications 96.7% (n = 710) (p = 0.00). More than half of the participants 52.5% (n = 385) showed their concern that either they or their family members might get the infection. More than 98% (n = 703), (P-value = 0.00) of the participants held that COVID-19 would be successfully controlled in Pakistan by following the standard SOPs and government guidelines.Conclusion: This study showed that the general population of Pakistan has good awareness and reasonable attitudes and perceptions toward the full features of the COVID-19. The current study suggests that mass-level effective health education programs are necessary for developing countries to improve and limit the gap between KAP toward COVID-19.
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- 2021
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15. Role of Nanomedicine-Based Therapeutics in the Treatment of CNS Disorders
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Zi-Hua Guo, Saadullah Khattak, Mohd Ahmar Rauf, Mohammad Azam Ansari, Mohammad N. Alomary, Sufyan Razak, Chang-Yong Yang, Dong-Dong Wu, and Xin-Ying Ji
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central nervous system disorders ,blood–brain barrier ,nanomedicine ,immunotherapy ,nanotechnology ,Organic chemistry ,QD241-441 - Abstract
Central nervous system disorders, especially neurodegenerative diseases, are a public health priority and demand a strong scientific response. Various therapy procedures have been used in the past, but their therapeutic value has been insufficient. The blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier is two of the barriers that protect the central nervous system (CNS), but are the main barriers to medicine delivery into the CNS for treating CNS disorders, such as brain tumors, Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease. Nanotechnology-based medicinal approaches deliver valuable cargos targeting molecular and cellular processes with greater safety, efficacy, and specificity than traditional approaches. CNS diseases include a wide range of brain ailments connected to short- and long-term disability. They affect millions of people worldwide and are anticipated to become more common in the coming years. Nanotechnology-based brain therapy could solve the BBB problem. This review analyzes nanomedicine’s role in medication delivery; immunotherapy, chemotherapy, and gene therapy are combined with nanomedicines to treat CNS disorders. We also evaluated nanotechnology-based approaches for CNS disease amelioration, with the intention of stimulating the immune system by delivering medications across the BBB.
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- 2023
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16. Define the Two Molecular Subtypes of Epithelioid Malignant Pleural Mesothelioma
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Umair Ali Khan Saddozai, Fengling Wang, Saadullah Khattak, Muhammad Usman Akbar, Muhammad Badar, Nazeer Hussain Khan, Lu Zhang, Wan Zhu, Longxiang Xie, Yongqiang Li, Xinying Ji, and Xiangqian Guo
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mesothelioma ,gene expression ,molecular subtype ,subtype-specific treatment ,Cytology ,QH573-671 - Abstract
Malignant pleural mesothelioma (MPM) is a fatal disease of respiratory system. Despite the availability of invasive biomarkers with promising results, there are still significant diagnostic and therapeutic challenges in the treatment of MPM. One of three main mesothelioma cell types, epithelioid mesothelioma makes up approximately 70% of all mesothelioma cases. Different observational findings are under process, but the molecular heterogeneity and pathogenesis of epithelioid malignant pleural mesothelioma (eMPM) are still not well understood. Through molecular analysis, expression profiling data were used to determine the possibility and optimal number of eMPM molecular subtypes. Next, clinicopathological characteristics and different molecular pathways of each subtype were analyzed to prospect the clinical applications and advanced mechanisms of eMPM. In this study, we identified two distinct epithelioid malignant pleural mesothelioma subtypes with distinct gene expression patterns. Subtype I eMPMs were involved in steroid hormone biosynthesis, porphyrin and chlorophyll metabolism, and drug metabolism, while subtype II eMPMs were involved in rational metabolism, tyrosine metabolism, and chemical carcinogenesis pathways. Additionally, we identified potential subtype-specific therapeutic targets, including CCNE1, EPHA3, RNF43, ROS1, and RSPO2 for subtype I and CDKN2A and RET for subtype II. Considering the need for potent diagnostic and therapeutic biomarkers for eMPM, we are anticipating that our findings will help both in exploring underlying mechanisms in the development of eMPM and in designing targeted therapy for eMPM.
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- 2022
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17. Assessment of Attitudes and Intentions towards COVID-19 Vaccines and Associated Factors among General Populations of Pakistan: A Cross-Sectional Study
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Saadullah Khattak, Muhammad Idrees, Hafiza Iqra Iqbal, Maqbool Khan, Nasir Assad, Muhammad Naeem Khan, Muhammad Tufail Yousaf, Muhammad Farooq, Chang-Yong Yang, Dong-Dong Wu, and Xin-Ying Ji
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COVID-19 ,vaccines ,attitudes ,intentions ,Pakistan ,Medicine - Abstract
Objective: The goal of public health in combatting COVID-19 is to increase herd immunity. However, vaccine reluctance makes attaining herd immunity a worldwide challenge. This investigation aimed to identify negative and positive attitudes and intentions about COVID-19 vaccinations. Methods: A cross-sectional online survey was conducted once free COVID-19 vaccines became available in Pakistan in 2021. 4392 Pakistanis aged 18 and older were surveyed from seven administrative units between 1 July and 30 August 2021. Online structured questionnaires were utilized to collect data using a simple sampling procedure. The questionnaires were divided into three major sections: sociodemographic, health factors, and attitudes toward COVID-19. Results: The survey link was shared with approximately 4500 participants. 97.6%(4392) completed the survey once begun. Frequency, percentage and Chi-square tests were used to analyze statistical data. Most of the participants in the research were men (2703 (61.54%)), 3277 (74.61%) were aged 18–29 years, and 1824 (41.53%) were residents of the Khyber Pakhtunkhwa province. (18.69%) Respondents expressed COVID-19 vaccine hesitancy, whereas 36.66% of participants liked getting the Sinopharm and Sinovac vaccines and (35.84%) of participants preferred the Pfizer vaccine. A significant number of participants (38.05%) were concerned about the vaccine’s unexpected side effects Thus, it is essential to realize that many participants were concerned about the vaccine’s unexpected side effects. Conclusions: The overall high level of concern about the unforeseen side effects of COVID-19 vaccines, as well as widespread vaccine hesitancy among Pakistani populations and its predictors, should be taken into account if public health intervention campaigns in Pakistan are changing negative attitudes and improving compliance with regard to COVID-19 vaccines.
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- 2022
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18. Nanomedicine: A Promising Way to Manage Alzheimer’s Disease
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Nazeer Hussain Khan, Maria Mir, Ebenezeri Erasto Ngowi, Ujala Zafar, Muhammad Mahtab Aslam Khan Khakwani, Saadullah Khattak, Yuan-Kun Zhai, En-She Jiang, Meng Zheng, Shao-Feng Duan, Jian-She Wei, Dong-Dong Wu, and Xin-Ying Ji
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Alzheheimer’s disease ,pathogenesis ,blood brain barrier ,nanomedicines ,cellular transport ,nanoparticles ,Biotechnology ,TP248.13-248.65 - Abstract
Alzheimer’s disease (AD) is a devastating disease of the aging population characterized by the progressive and slow brain decay due to the formation of extracellular plaques in the hippocampus. AD cells encompass tangles of twisted strands of aggregated microtubule binding proteins surrounded by plaques. Delivering corresponding drugs in the brain to deal with these clinical pathologies, we face a naturally built strong, protective barrier between circulating blood and brain cells called the blood–brain barrier (BBB). Nanomedicines provide state-of-the-art alternative approaches to overcome the challenges in drug transport across the BBB. The current review presents the advances in the roles of nanomedicines in both the diagnosis and treatment of AD. We intend to provide an overview of how nanotechnology has revolutionized the approaches used to manage AD and highlight the current key bottlenecks and future perspective in this field. Furthermore, the emerging nanomedicines for managing brain diseases like AD could promote the booming growth of research and their clinical availability.
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- 2021
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19. Pharmacological Inhibition of Endogenous Hydrogen Sulfide Attenuates Breast Cancer Progression
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Nazeer Hussain Khan, Di Wang, Wenkang Wang, Muhammad Shahid, Saadullah Khattak, Ebenezeri Erasto Ngowi, Muhammad Sarfraz, Xin-Ying Ji, Chun-Yang Zhang, and Dong-Dong Wu
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endogenous hydrogen sulfide ,breast cancer ,apoptosis ,signaling pathway ,tumor growth ,Organic chemistry ,QD241-441 - Abstract
Hydrogen sulfide (H2S), a gaseous signaling molecule, is associated with the development of various malignancies via modulating various cellular signaling cascades. Published research has established the fact that inhibition of endogenous H2S production or exposure of H2S donors is an effective approach against cancer progression. However, the effect of pharmacological inhibition of endogenous H2S-producing enzymes (cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MPST)) on the growth of breast cancer (BC) remains unknown. In the present study, DL-propargylglycine (PAG, inhibitor of CSE), aminooxyacetic acid (AOAA, inhibitor of CBS), and L-aspartic acid (L-Asp, inhibitor of 3-MPST) were used to determine the role of endogenous H2S in the growth of BC by in vitro and in vivo experiments. An in silico study was also performed to confirm the results. Corresponding to each enzyme in separate groups, we treated BC cells (MCF-7 and MDA-MB-231) with 10 mM of PAG, AOAA, and L-Asp for 24 h. Findings reveal that the combined dose (PAG + AOAA + L-Asp) group showed exclusive inhibitory effects on BC cells’ viability, proliferation, migration, and invasion compared to the control group. Further, treated cells exhibited increased apoptosis and a reduced level of phospho (p)-extracellular signal-regulated protein kinases such as p-AKT, p-PI3K, and p-mTOR. Moreover, the combined group exhibited potent inhibitory effects on the growth of BC xenograft tumors in nude mice, without obvious toxicity. The molecular docking results were consistent with the wet lab experiments and enhanced the reliability of the drugs. In conclusion, our results demonstrate that the inhibition of endogenous H2S production can significantly inhibit the growth of human breast cancer cells via the AKT/PI3K/mTOR pathway and suggest that endogenous H2S may act as a promising therapeutic target in human BC cells. Our study also empowers the rationale to design novel H2S-based anti-tumor drugs to cure BC.
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- 2022
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20. Hydrogen Sulfide Biology and Its Role in Cancer
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Saadullah Khattak, Mohd Ahmar Rauf, Nazeer Hussain Khan, Qian-Qian Zhang, Hao-Jie Chen, Pir Muhammad, Mohammad Azam Ansari, Mohammad N. Alomary, Muhammad Jahangir, Chun-Yang Zhang, Xin-Ying Ji, and Dong-Dong Wu
- Subjects
endogenous gases ,hydrogen sulfide ,signaling pathways ,cancer ,translational medicine ,Organic chemistry ,QD241-441 - Abstract
Hydrogen sulfide (H2S) is an endogenous biologically active gas produced in mammalian tissues. It plays a very critical role in many pathophysiological processes in the body. It can be endogenously produced through many enzymes analogous to the cysteine family, while the exogenous source may involve inorganic sulfide salts. H2S has recently been well investigated with regard to the onset of various carcinogenic diseases such as lung, breast, ovaries, colon cancer, and neurodegenerative disorders. H2S is considered an oncogenic gas, and a potential therapeutic target for treating and diagnosing cancers, due to its role in mediating the development of tumorigenesis. Here in this review, an in-detail up-to-date explanation of the potential role of H2S in different malignancies has been reported. The study summarizes the synthesis of H2S, its roles, signaling routes, expressions, and H2S release in various malignancies. Considering the critical importance of this active biological molecule, we believe this review in this esteemed journal will highlight the oncogenic role of H2S in the scientific community.
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- 2022
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21. Roles of Hydrogen Sulfide Donors in Common Kidney Diseases
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Ebenezeri Erasto Ngowi, Muhammad Sarfraz, Attia Afzal, Nazeer Hussain Khan, Saadullah Khattak, Xin Zhang, Tao Li, Shao-Feng Duan, Xin-Ying Ji, and Dong-Dong Wu
- Subjects
H2S donors ,physiological process ,renal dysfunction ,signaling pathways ,common renal diseases ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Hydrogen sulfide (H2S) plays a key role in the regulation of physiological processes in mammals. The decline in H2S level has been reported in numerous renal disorders. In animal models of renal disorders, treatment with H2S donors could restore H2S levels and improve renal functions. H2S donors suppress renal dysfunction by regulating autophagy, apoptosis, oxidative stress, and inflammation through multiple signaling pathways, such as TRL4/NLRP3, AMP-activated protein kinase/mammalian target of rapamycin, transforming growth factor-β1/Smad3, extracellular signal-regulated protein kinases 1/2, mitogen-activated protein kinase, and nuclear factor kappa B. In this review, we summarize recent developments in the effects of H2S donors on the treatment of common renal diseases, including acute/chronic kidney disease, renal fibrosis, unilateral ureteral obstruction, glomerulosclerosis, diabetic nephropathy, hyperhomocysteinemia, drug-induced nephrotoxicity, metal-induced nephrotoxicity, and urolithiasis. Novel H2S donors can be designed and applied in the treatment of common renal diseases.
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- 2020
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22. Potential Biomarkers of miR-371–373 Gene Cluster in Tumorigenesis
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Junaid Ali Shah, Saadullah Khattak, Mohd Ahmar Rauf, Yong Cai, and Jingji Jin
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microRNA ,miR-371–373 gene cluster ,oncogene ,tumor suppressor ,Science - Abstract
microRNAs (miRNAs) are small non-coding RNA transcripts (20–24 nucleotides) that bind to their complementary sequences in the 3′-untranslated regions (3′-UTR) of targeted genes to negatively or positively regulate their expression. miRNAs affect the expression of genes in cells, thereby contributing to several important biological processes, including tumorigenesis. Identifying the miRNA cluster as a human embryonic stem cell (hESC)-specific miRNAs initially led to the identification of miR-371, miR-372, miR-373, and miR-373*, which can ultimately be translated into mature miRNAs. Recent evidence suggests that miR-371–373 genes are abnormally expressed in various cancers and act either as oncogenes or tumor suppressors, indicating they may be suitable as molecular biomarkers for cancer diagnosis and prevention. In this article, we summarize recent studies linking miR-371–373 functions to tumorigenesis and speculate on the potential applications of miR-371–373 as biomarkers for cancer diagnosis and treatment.
- Published
- 2021
- Full Text
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23. Genome-Wide Analysis of Codon Usage Patterns of SARS-CoV-2 Virus Reveals Global Heterogeneity of COVID-19
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Saadullah Khattak, Mohd Ahmar Rauf, Qamar Zaman, Yasir Ali, Shabeen Fatima, Pir Muhammad, Tao Li, Hamza Ali Khan, Azhar Abbas Khan, Ebenezeri Erasto Ngowi, Dong-Dong Wu, and Xin-Ying Ji
- Subjects
Coronavirus ,SARS-CoV-2 ,Codon usage bias ,COVID-19 ,heterogeneity of COVID-19 ,mutational bias ,Microbiology ,QR1-502 - Abstract
The ongoing outbreak of coronavirus disease COVID-19 is significantly implicated by global heterogeneity in the genome organization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The causative agents of global heterogeneity in the whole genome of SARS-CoV-2 are not well characterized due to the lack of comparative study of a large enough sample size from around the globe to reduce the standard deviation to the acceptable margin of error. To better understand the SARS-CoV-2 genome architecture, we have performed a comprehensive analysis of codon usage bias of sixty (60) strains to get a snapshot of its global heterogeneity. Our study shows a relatively low codon usage bias in the SARS-CoV-2 viral genome globally, with nearly all the over-preferred codons’ A.U. ended. We concluded that the SARS-CoV-2 genome is primarily shaped by mutation pressure; however, marginal selection pressure cannot be overlooked. Within the A/U rich virus genomes of SARS-CoV-2, the standard deviation in G.C. (42.91% ± 5.84%) and the GC3 value (30.14% ± 6.93%) points towards global heterogeneity of the virus. Several SARS-CoV-2 viral strains were originated from different viral lineages at the exact geographic location also supports this fact. Taking all together, these findings suggest that the general root ancestry of the global genomes are different with different genome’s level adaptation to host. This research may provide new insights into the codon patterns, host adaptation, and global heterogeneity of SARS-CoV-2.
- Published
- 2021
- Full Text
- View/download PDF
24. The Role of Hydrogen Sulfide in Respiratory Diseases
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Saadullah Khattak, Qian-Qian Zhang, Muhammad Sarfraz, Pir Muhammad, Ebenezeri Erasto Ngowi, Nazeer Hussain Khan, Saqib Rauf, Yi-Zhen Wang, Hui-Wen Qi, Di Wang, Attia Afzal, Xin-Ying Ji, and Dong-Dong Wu
- Subjects
hydrogen sulfide ,respiratory diseases ,metabolism processes ,signaling pathways ,Microbiology ,QR1-502 - Abstract
Respiratory diseases are leading causes of death and disability around the globe, with a diverse range of health problems. Treatment of respiratory diseases and infections has been verified to be thought-provoking because of the increasing incidence and mortality rate. Hydrogen sulfide (H2S) is one of the recognized gaseous transmitters involved in an extensive range of cellular functions, and physiological and pathological processes in a variety of diseases, including respiratory diseases. Recently, the therapeutic potential of H2S for respiratory diseases has been widely investigated. H2S plays a vital therapeutic role in obstructive respiratory disease, pulmonary fibrosis, emphysema, pancreatic inflammatory/respiratory lung injury, pulmonary inflammation, bronchial asthma and bronchiectasis. Although the therapeutic role of H2S has been extensively studied in various respiratory diseases, a concrete literature review will have an extraordinary impact on future therapeutics. This review provides a comprehensive overview of the effective role of H2S in respiratory diseases. Besides, we also summarized H2S production in the lung and its metabolism processes in respiratory diseases.
- Published
- 2021
- Full Text
- View/download PDF
25. Role of Oxidative Stress in Retinal Disease and the Early Intervention Strategies: A Review
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Jun Wang, Mengling Li, Ziyue Geng, Saadullah Khattak, Xinying Ji, Dongdong Wu, and Yalong Dang
- Subjects
Oxidative Stress ,Aging ,Retinal Diseases ,Infant, Newborn ,Quality of Life ,Humans ,Cell Biology ,General Medicine ,Reactive Oxygen Species ,Biochemistry ,Antioxidants - Abstract
The retina, owing to its cellular anatomy and physical location, is susceptible to generating reactive oxygen species (ROS), which are associated with several major retinal diseases. When ROS exceeds the body’s natural antioxidants, the retina is in a state of oxidative stress, which is recognized as the pathogenesis of retinal diseases. The early stage of the pathogenic process is an adaptive change in which oxidative stress and endogenous defense mechanisms occur. If no treatment is applied, the retinal diseases will progress to the pathological stage with neuronal and vascular dysfunction or damage and even blindness. This review summarizes the role of oxidative stress in several common retinal diseases, including retinitis pigmentosa, age-related macular degeneration, diabetic retinopathy, glaucoma, and retinopathy of prematurity. In addition, we discuss the early intervention strategies for these diseases. An outline is provided to identify potential intervention targets for further research. Early intervention for retinal diseases is necessary and urgent and may offer hope to improve patients’ quality of life through functional vision.
- Published
- 2022
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26. Feedback Modulation between Human INO80 Chromatin Remodeling Complex and miR-372 in HCT116 Cells
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Jin, Junaid Ali Shah, Yujuan Miao, Jinmeng Chu, Wenqi Chen, Qingzhi Zhao, Chengyu Cai, Saadullah Khattak, Fei Wang, and Jingji
- Subjects
cancer ,microRNA ,miR-372-3p ,INO80 chromatin remodeling complex ,transcriptional regulation - Abstract
Human INO80 chromatin remodeling complex (INO80 complex) as a transcription cofactor is widely involved in gene transcription regulation and is frequently highly expressed in tumor cells. However, few reports exist on the mutual regulatory mechanism between INO80 complex and non-coding microRNAs. Herein, we showed evidence that the INO80 complex transcriptionally controls microRNA-372 (miR-372) expression through RNA-Seq analysis and a series of biological experiments. Knocking down multiple subunits in the INO80 complex, including the INO80 catalytic subunit, YY1, Ies2, and Arp8, can significantly increase the expression level of miR-372. Interestingly, mimicking miR-372 expression in HCT116 cells, in turn, post-transcriptionally suppressed INO80 and Arp8 expression at both mRNA and protein levels, indicating the existence of a mutual regulatory mechanism between the INO80 complex and miR-372. The target relationship between miR-372 and INO80 complex was verified using luciferase assays in HCT116 colon cancer cells. As expected, miR-372 mimics significantly suppressed the luciferase activity of pMIR-luc/INO80 and pMIR-luc/Arp8 3′-UTR in cells. In contrast, the miR-372 target sites in the 3′-UTRs linked to the luciferase reporter were mutagenized, and both mutant sites lost their response to miR-372. Furthermore, the mutual modulation between the INO80 complex and miR-372 was involved in cell proliferation and the p53/p21 signaling pathway, suggesting the synergistic anti-tumor role of the INO80 complex and miR372. Our results will provide a solid theoretical basis for exploring miR-372 as a biological marker of tumorigenesis.
- Published
- 2023
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- View/download PDF
27. Comparative efficacy of amphotericin B-loaded chitosan nanoparticles and free amphotericin B drug against Leishmania tropica
- Author
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Hazrat Bilal, Rahat Ullah Khan, Aamir Sohail, Momin Khan, Mehvish Khokhar, Baseer Ahmad, Saadullah Khattak, Arshad Ali, M. M. Khan, and Safat Ullah
- Subjects
Leishmania tropica ,Science ,Pharmacology ,Cutaneous leishmaniasis ,In vivo ,Amphotericin B ,parasitic diseases ,Zeta potential ,medicine ,MTT assay ,IC50 ,General Environmental Science ,biology ,Chemistry ,technology, industry, and agriculture ,Antileishmanial activity ,biology.organism_classification ,medicine.disease ,bacterial infections and mycoses ,Chitosan nanoparticles ,Drug delivery ,General Earth and Planetary Sciences ,medicine.drug - Abstract
Background The preparation of an effective drug delivery formulation is an urgent need to treat cutaneous leishmaniasis (CL). Pentavalent antimonials and Amphotericin B (AmB) are considered to treat leishmaniasis; however, their clinical usage is hampered by poor solubility, high cost, toxicity, and the emergence of drug-resistant Leishmania spp. The drug delivery systems (DDS) could be used as an alternative treatment option for the treatment of CL to circumvent these problems. We tested the antileishmanial efficacies of free AmB and amphotericin B-loaded chitosan nanoparticles (AmB-CNPs) under in vitro conditions. Results Chitosan nanoparticles (CNPs) were synthesized using the ionic gelation method with negatively charged tripolyphosphate (TPP). During the synthesis of CNPs, AmB was incorporated into the nanoparticles (NPs). The NPs were characterized for their size, surface morphology, encapsulation efficacy (EE), drug loading content (DLC), and surface charge using different techniques. Their efficacy was evaluated against promastigotes and axenic amastigotes forms of Leishmania tropica using MTT assay. The synthesized AmB-CNPs displayed a spherical shape with a mean particle size of 118 nm, a positive zeta potential of (+ 6.21 ± 2.02 mV), and an encapsulation efficacy of 88%. Dynamic light scattering technique (DLS) shows that the average size of prepared AmB-CNPs was 95.5 nm. Free AmB presented very low efficacy (only 65% and 67% inhibition of the promastigotes and axenic amastigotes parasite load), whereas AmB-CNPs exhibited 90% and 84% parasite inhibition after 72 h incubation. The AmB-CNPs exhibited significantly higher efficacy than free AmB in terms of reduction in parasite viability. Half-maximal inhibitory concentration (IC50) measured values of the AmB-CNPs were significant lowers than free AmB. Conclusions The present data indicated that AmB-CNPs exhibited vigorous anti-leishmanial activity than free AmB by dose and time-dependent manner. This formulation can be used for local therapy of CL after in vivo efficacy conformational studies.
- Published
- 2021
28. The deleterious variants of N-acetylgalactosamine-6-sulfatase (GalN6S) enzyme trigger Morquio a syndrome by disrupting protein foldings
- Author
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Jiuyi Li, Waqas Ahmad Khalid, Hina Imtiaz, Lingkun Huang, Yasir Ali, Rimsha Yousaf, Fouzia Gul, Arif Mahmood, Abid Ali Shah, Huiyin Deng, and Saadullah Khattak
- Subjects
Structural Biology ,General Medicine ,Molecular Biology - Abstract
Lysosomal enzymes degrade cellular macromolecules, while their inactivation causes human hereditary metabolic disorders. Mucopolysaccharidosis IVA (MPS IVA; Moquio A syndrome) is one of the lysosomal storage disorders caused by a defective Galactosamine-6-sulfatase (GalN6S) enzyme. In several populations, disease incidence is elevated due to missense mutations brought on by non-synonymous allelic variation in the GalN6S enzyme. Here, we studied the effect of non-synonymous single nucleotide polymorphism (nsSNPs) on the structural dynamics of the GalN6S enzyme and its binding with N-acetylgalactosamine (GalNAc) using all-atom molecular dynamics simulation and an essential dynamics approach. Consequently, in this study, we have identified three functionally disruptive mutations in domain-I and domain-II, that is, S80L, R90W, and S162F, which presumably contribute to post-translational modifications. The study delineated that both domains work cooperatively, and alteration in domain II (S80L, R90W) leads to conformational changes in the catalytic site in domain-I, while mutation S162F mainly provokes higher residual flexibility of domain II. These results show that these mutations impair the hydrophobic core, implying that Morquio A syndrome is caused by misfolding of the GalN6S enzyme. The results also show the instability of the GalN6S-GalNAc complex upon substitution. Overall, the structural dynamics resulting from point mutations give the molecular rationale for Moquio A syndrome and, more importantly, the Mucopolysaccharidoses (MPS) family of diseases, re-establishing MPS IVA as a protein-folding disease. Communicated by Ramaswamy H. Sarma
- Published
- 2023
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29. Impact of the factors shaping gut microbiota on obesity
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Saadullah Khattak, Xin-Ying Ji, Shaofeng Duan, Nazeer Hussain Khan, Yasmeen Ahmed Saleheldin Hassan Helmy, Ebenezeri Erasto Ngowi, Yi-Zhen Wang, Salma Sayed Mohamed Mahmoud, Dongdong Wu, Tao Li, and Qi-Ying Jiang
- Subjects
Dietary Fiber ,Disease ,Overweight ,Gut flora ,Weight Gain ,Bioinformatics ,Applied Microbiology and Biotechnology ,03 medical and health sciences ,Pregnancy ,Weight loss ,Diabetes mellitus ,medicine ,Humans ,Obesity ,Microbiome ,Risk factor ,030304 developmental biology ,0303 health sciences ,Bacteria ,biology ,030306 microbiology ,General Medicine ,medicine.disease ,biology.organism_classification ,Gastrointestinal Microbiome ,Female ,medicine.symptom ,Biotechnology - Abstract
Obesity is considered as a risk factor for chronic health diseases such as heart diseases, cancer, and diabetes 2. Reduced physical activities, lifestyle, poor nutritional diet, and genetics are among the risk factors associated with the development of obesity. In recent years, several studies have explored the link between the gut microbiome and the progression of diseases including obesity, with the shift in microbiome abundance and composition being the main focus. The alteration of gut microbiome composition affects both nutrients metabolism and specific gene expressions thereby disturbing body physiology. Specifically, the abundance of fiber-metabolizing microbes is associated with weight loss and that of protein and fat-metabolizing bacteria with weight gain. Various internal and external factors such as genetics, maternal obesity, mode of delivery, breastfeeding, nutrition, antibiotic use, and the chemical compounds present in the environment are known to interfere with the richness of the gut microbiota (GM), thereby influencing weight gain/loss and ultimately the development of obesity. However, the effectiveness of each factor in potentiating the shift in microbes' abundance to result in significant changes that can lead to obesity is not yet clear. In this review, we will highlight the factors involved in shaping gut microbiota, their influence on obesity and possible interventions. Understanding the influence of these factors on the diversity of the GM and how to improve their effectiveness on disease conditions could be key in the treatment of metabolic diseases.
- Published
- 2021
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30. Role of hydrogen sulfide donors in cancer development and progression
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Qi-Ying Jiang, Saadullah Khattak, Xin-Ying Ji, Dongdong Wu, Shams Uz Zaman, Attia Afzal, Xin Zhang, Ebenezeri Erasto Ngowi, Tao Li, Shaofeng Duan, Muhammad Sarfraz, and Nazeer Hussain Khan
- Subjects
Drug ,Cell type ,Signaling pathways ,media_common.quotation_subject ,Review ,Sulfides ,Applied Microbiology and Biotechnology ,Cellular processes ,03 medical and health sciences ,H2S donors ,Neoplasms ,Animals ,Humans ,Medicine ,Hydrogen Sulfide ,Molecular Targeted Therapy ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,Gasotransmitters ,Cancer ,030304 developmental biology ,media_common ,0303 health sciences ,business.industry ,Autophagy ,Cell Biology ,equipment and supplies ,medicine.disease ,Apoptosis ,Cancer cell ,Disease Progression ,Cancer research ,Signal transduction ,business ,Developmental Biology - Abstract
In recent years, a vast number of potential cancer therapeutic targets have emerged. However, developing efficient and effective drugs for the targets is of major concern. Hydrogen sulfide (H2S), one of the three known gasotransmitters, is involved in the regulation of various cellular activities such as autophagy, apoptosis, migration, and proliferation. Low production of H2S has been identified in numerous cancer types. Treating cancer cells with H2S donors is the common experimental technique used to improve H2S levels; however, the outcome depends on the concentration/dose, time, cell type, and sometimes the drug used. Both natural and synthesized donors are available for this purpose, although their effects vary independently ranging from strong cancer suppressors to promoters. Nonetheless, numerous signaling pathways have been reported to be altered following the treatments with H2S donors which suggest their potential in cancer treatment. This review will analyze the potential of H2S donors in cancer therapy by summarizing key cellular processes and mechanisms involved.
- Published
- 2021
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31. Role of Hydrogen Sulfide in Oral Disease
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Dong-Dong Wu, Ebenezeri Erasto Ngowi, Yuan-Kun Zhai, Yi-Zhen Wang, Nazeer Hussain Khan, Ahmad Fadhil Kombo, Saadullah Khattak, Tao Li, and Xin-Ying Ji
- Subjects
Aging ,Mouth ,Bacteria ,QH573-671 ,Cystathionine gamma-Lyase ,Apoptosis ,Cell Biology ,General Medicine ,Review Article ,Biochemistry ,Oxidative Stress ,Humans ,Mouth Neoplasms ,Hydrogen Sulfide ,Mouth Diseases ,Cytology - Abstract
Oral diseases are among the most common human diseases yet less studied. These diseases affect both the physical, mental, and social health of the patients resulting in poor quality of life. They affect all ages, although severe stages are mostly observed in older individuals. Poor oral hygiene, genetics, and environmental factors contribute enormously to the development and progression of these diseases. Although there are available treatment options for these diseases, the recurrence of the diseases hinders their efficiency. Oral volatile sulfur compounds (VSCs) are highly produced in oral cavity as a result of bacteria activities. Together with bacteria components such as lipopolysaccharides, VSCs participate in the progression of oral diseases by regulating cellular activities and interfering with the immune response. Hydrogen sulfide (H2S) is a gaseous neurotransmitter primarily produced endogenously and is involved in the regulation of cellular activities. The gas is also among the VSCs produced by oral bacteria. In numerous diseases, H2S have been reported to have dual effects depending on the cell, concentration, and donor used. In oral diseases, high production and subsequent utilization of this gas have been reported. Also, this high production is associated with the progression of oral diseases. In this review, we will discuss the production of H2S in oral cavity, its interaction with cellular activities, and most importantly its role in oral diseases.
- Published
- 2022
32. Hydrogen sulfide donors and inhibitors in cancer research: A state-of-the-art review
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Nazeer Hussain Khan, Ebenezeri Erasto Ngowi, Yan Li, Saadullah Khattak, Yingshuai Zhao, null Muhammad Shahid, Ujala Zafar, Irum Waheed, Fatima Khan, Razia Virk, Istaqlal Hussain, Jiebin Cao, Hongxia Liu, Zhihui Liu, Dong-Dong Wu, and Xin-Ying Ji
- Abstract
Hydrogen sulfide (H2S), a gaseous biomolecule, is considered a key player in the regulation of various essential cellular events. Normal physiology is determined by the level of endogenous H2S. Any alterations (upregulation and downregulation) to the level of endogenous H2S may lead to illness, including the onset of tumorigenesis. Over the past two decades, extensive research on the role of H2S in cancer development has affirmed the potential pharmacological means to suppress cancer progression by either inhibiting H2S synthesis in cells or exposing exogenously supplied H2S donors to treat different cancers. Some H2S donors and inhibitors release H2S or affect its synthesis. As a result, they have progressed through the development process into widespread clinical use and become increasingly important. The present study draws a detailed discussion on the types of H2S donors and inhibitors and their role in cancer research. We believe that this state-of-the-art review will empower the synthesis of H2S -based chemopreventive drugs and promote the need for further in-depth exploration of the associations between H2S and cancer treatments in clinical settings.
- Published
- 2022
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33. Prognostic biomarkers, pathogenic studies and treatment of Merkel Cell Carcinoma
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Xinying Ji, Longxiang Xie, Wan Zhu, Zhongyi Yan, Xiangqian Guo, Muhammad Usman Akbar, Saadullah Khattak, Umair Ali Khan Saddozai, Fengling Wang, Muhammad Badar, and Zhang Lu
- Subjects
Merkel cell carcinoma ,business.industry ,Cancer research ,medicine ,medicine.disease ,business - Published
- 2019
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34. Genome-Wide Analysis of Codon Usage Patterns of SARS-CoV-2 Virus Reveals Global Heterogeneity of COVID-19
- Author
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Ebenezeri Erasto Ngowi, Hamza Ali Khan, Saadullah Khattak, Pir Muhammad, Qamar Zaman, Dongdong Wu, Yasir Ali, Xin-Ying Ji, Tao Li, Shabeen Fatima, Mohd Ahmar Rauf, and Azhar Abbas Khan
- Subjects
0301 basic medicine ,viruses ,030106 microbiology ,Genome, Viral ,Biology ,medicine.disease_cause ,Biochemistry ,Genome ,Microbiology ,Article ,Evolution, Molecular ,03 medical and health sciences ,mutational bias ,Phylogenetics ,medicine ,Humans ,heterogeneity of COVID-19 ,skin and connective tissue diseases ,Codon Usage ,Molecular Biology ,Phylogeny ,Genomic organization ,Coronavirus ,Genetics ,Mutation ,Natural selection ,SARS-CoV-2 ,fungi ,virus diseases ,COVID-19 ,natural selection ,QR1-502 ,body regions ,030104 developmental biology ,Codon usage bias ,Host adaptation - Abstract
The ongoing outbreak of coronavirus disease COVID-19 is significantly implicated by global heterogeneity in the genome organization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The causative agents of global heterogeneity in the whole genome of SARS-CoV-2 are not well characterized due to the lack of comparative study of a large enough sample size from around the globe to reduce the standard deviation to the acceptable margin of error. To better understand the SARS-CoV-2 genome architecture, we have performed a comprehensive analysis of codon usage bias of sixty (60) strains to get a snapshot of its global heterogeneity. Our study shows a relatively low codon usage bias in the SARS-CoV-2 viral genome globally, with nearly all the over-preferred codons’ A.U. ended. We concluded that the SARS-CoV-2 genome is primarily shaped by mutation pressure, however, marginal selection pressure cannot be overlooked. Within the A/U rich virus genomes of SARS-CoV-2, the standard deviation in G.C. (42.91% ± 5.84%) and the GC3 value (30.14% ± 6.93%) points towards global heterogeneity of the virus. Several SARS-CoV-2 viral strains were originated from different viral lineages at the exact geographic location also supports this fact. Taking all together, these findings suggest that the general root ancestry of the global genomes are different with different genome’s level adaptation to host. This research may provide new insights into the codon patterns, host adaptation, and global heterogeneity of SARS-CoV-2.
- Published
- 2021
35. The Role of Hydrogen Sulfide in Respiratory Diseases
- Author
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Yi-Zhen Wang, Hui-Wen Qi, Saqib Rauf, Di Wang, Ebenezeri Erasto Ngowi, Xin-Ying Ji, Muhammad Sarfraz, Attia Afzal, Dongdong Wu, Saadullah Khattak, Pir Muhammad, Qianqian Zhang, and Nazeer Hussain Khan
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Respiratory Tract Diseases ,hydrogen sulfide ,Review ,Lung injury ,Sulfides ,Biochemistry ,Microbiology ,03 medical and health sciences ,0302 clinical medicine ,Pulmonary fibrosis ,medicine ,Animals ,Humans ,Respiratory system ,Intensive care medicine ,Molecular Biology ,Asthma ,Clinical Trials as Topic ,Lung ,Bronchiectasis ,business.industry ,respiratory diseases ,Mortality rate ,Respiratory disease ,medicine.disease ,equipment and supplies ,QR1-502 ,signaling pathways ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,030220 oncology & carcinogenesis ,metabolism processes ,business ,Signal Transduction - Abstract
Respiratory diseases are leading causes of death and disability around the globe, with a diverse range of health problems. Treatment of respiratory diseases and infections has been verified to be thought-provoking because of the increasing incidence and mortality rate. Hydrogen sulfide (H2S) is one of the recognized gaseous transmitters involved in an extensive range of cellular functions, and physiological and pathological processes in a variety of diseases, including respiratory diseases. Recently, the therapeutic potential of H2S for respiratory diseases has been widely investigated. H2S plays a vital therapeutic role in obstructive respiratory disease, pulmonary fibrosis, emphysema, pancreatic inflammatory/respiratory lung injury, pulmonary inflammation, bronchial asthma and bronchiectasis. Although the therapeutic role of H2S has been extensively studied in various respiratory diseases, a concrete literature review will have an extraordinary impact on future therapeutics. This review provides a comprehensive overview of the effective role of H2S in respiratory diseases. Besides, we also summarized H2S production in the lung and its metabolism processes in respiratory diseases.
- Published
- 2021
36. In vitro efficacy of polymer coated miltefosine drug against leishmania tropica
- Author
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Saadullah Khattak, Momin Khan, Inam Ullah Khan, Muhammad Adnan Shereen, Aamir Sohail, Rahat Ullah Khan, Imdad Ullah Khan, and Mehvish Khokhar
- Subjects
musculoskeletal diseases ,Miltefosine ,Leishmania tropica ,Chromatography ,biology ,Chemistry ,biology.organism_classification ,medicine.disease ,Hemolysis ,Cutaneous leishmaniasis ,Drug delivery ,medicine ,Parasitology ,MTT assay ,Original Article ,Axenic ,IC50 ,medicine.drug - Abstract
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.
- Published
- 2021
37. The Potential of Hydrogen Sulfide Donors in Treating Cardiovascular Diseases
- Author
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Qi-Ying Jiang, Yi-Zhen Wang, Chun-Bo Cai, Hui-Wen Qi, Mi-Rong Jing, Ebenezeri Erasto Ngowi, Dongdong Wu, Xin-Ying Ji, Qing-Lin He, Nazeer Hussain Khan, Saadullah Khattak, Yan-Xia Zhang, and Di Wang
- Subjects
0301 basic medicine ,Cell type ,cardiac protection ,Hydrogen sulfide ,hydrogen sulfide ,Cardiovascular homeostasis ,Neovascularization, Physiologic ,Endogeny ,Review ,030204 cardiovascular system & hematology ,Bioinformatics ,Catalysis ,Inorganic Chemistry ,lcsh:Chemistry ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,gas signaling molecule ,heart function ,Cell Movement ,Administration, Inhalation ,Medicine ,Animals ,Humans ,Physical and Theoretical Chemistry ,Molecular Biology ,lcsh:QH301-705.5 ,Spectroscopy ,business.industry ,Organic Chemistry ,cardiovascular homeostasis ,Cardiovascular Agents ,General Medicine ,Toxic gas ,medicine.disease ,equipment and supplies ,Computer Science Applications ,Oxidative Stress ,030104 developmental biology ,chemistry ,lcsh:Biology (General) ,lcsh:QD1-999 ,Cardiovascular Diseases ,Heart failure ,business - Abstract
Hydrogen sulfide (H2S) has long been considered as a toxic gas, but as research progressed, the idea has been updated and it has now been shown to have potent protective effects at reasonable concentrations. H2S is an endogenous gas signaling molecule in mammals and is produced by specific enzymes in different cell types. An increasing number of studies indicate that H2S plays an important role in cardiovascular homeostasis, and in most cases, H2S has been reported to be downregulated in cardiovascular diseases (CVDs). Similarly, in preclinical studies, H2S has been shown to prevent CVDs and improve heart function after heart failure. Recently, many H2S donors have been synthesized and tested in cellular and animal models. Moreover, numerous molecular mechanisms have been proposed to demonstrate the effects of these donors. In this review, we will provide an update on the role of H2S in cardiovascular activities and its involvement in pathological states, with a special focus on the roles of exogenous H2S in cardiac protection.
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- 2021
38. Knowledge, Attitude, and Perception of Cancer Patients towards COVID-19 in Pakistan: A Cross-Sectional Study
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Saadullah Khattak, Muhammad Faheem, Bilawal Nawaz, Maqbool Khan, Nazeer Hussain Khan, Nadeem Ullah, Taj Ali Khan, Rahat Ullah Khan, Kashif Syed Haleem, Zhi-Guang Ren, Dong-Dong Wu, and Xin-Ying Ji
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Health Knowledge, Attitudes, Practice ,Adolescent ,SARS-CoV-2 ,Health, Toxicology and Mutagenesis ,COVID-19 ,cancer ,knowledge ,attitude ,perception ,Pakistan ,Public Health, Environmental and Occupational Health ,Cross-Sectional Studies ,Neoplasms ,Surveys and Questionnaires ,Humans ,Perception ,Pandemics - Abstract
Background: Cancer patients, being immunocompromised, are at higher risk of coronavirus disease (COVID-19). The current study determines cancer patients’ knowledge, attitude, perception, and impact of the COVID-19 pandemic. Method: A cross-sectional online survey was conducted in Pakistan from 1 April 2020 to 1 May 2020. The study respondents were cancer patients with ages equal to or greater than 18 years. Following a request for participation, the URL for the survey was distributed on numerous channels. Other social media platforms, including WeChat, WhatsApp, Facebook, Twitter, Instagram, Messenger, and LinkedIn, were used to increase cancer patient interaction. The questionnaire comprised five different sections such as: (1) sociodemographic information, (2) knowledge, (3) attitude, (4) perception, and (5) impact of COVID-19 on cancer patients. Descriptive medical statistics such as frequency, percentage, mean, and standard deviation were used to illustrate the demographic characteristics of the study participants. To compare mean knowledge scores with selected demographic variables, independent sample t-tests and one-way analysis of variance (ANOVA) were used, which are also practical methods in epidemiological, public health and medical research. The cut-off point for statistical significance was set at a p-value of 0.05. Results: More than 300 cancer patients were invited, of which 208 agreed to take part. The response rate was 69.33% (208/300). Gender, marital status, and employment status had a significant association with knowledge scores. Of the total recruited participants, 96% (n = 200) (p < 0.01) knew about COVID-19, and 90% were aware of general symptoms of COVID-19 disease, such as route of transmission and preventive measurements. In total, 94.5% (n = 197) (p < 0.01) were willing to accept isolation if they were infected with COVID-19, and 98% (n = 204) (p < 0.01) had reduced their use of public transportation. More than 90% (n = 188) (p < 0.01) of cancer patients were found to be practicing preventative measures such as using a face mask, keeping social distance, and avoiding handshaking and hugging. Around 94.4% (n = 196) (p < 0.01) of cancer patients had been impacted by, stopped or had changed cancer treatment during this pandemic, resulting in COVID-related anxiety and depression. Conclusion: The included cancer patients exhibited a good level of COVID-19 knowledge, awareness, positive attitude, and perception. Large-scale studies and efforts are needed to raise COVID-19 awareness among less educated and high-risk populations. The present survey indicates that mass-level effective health education initiatives are required for developing countries to improve and reduce the gap between KAP and COVID-19.
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- 2022
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39. Potential Biomarkers of miR-371–373 Gene Cluster in Tumorigenesis
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Saadullah Khattak, Mohd Ahmar Rauf, Junaid Ali Shah, Yong Cai, and Jingji Jin
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Untranslated region ,microRNA ,miR-371–373 gene cluster ,Oncogene ,tumor suppressor ,Science ,Paleontology ,Cancer ,RNA ,Review ,Biology ,medicine.disease ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,oncogene ,Space and Planetary Science ,Gene cluster ,medicine ,Cancer research ,Carcinogenesis ,Gene ,Ecology, Evolution, Behavior and Systematics - Abstract
microRNAs (miRNAs) are small non-coding RNA transcripts (20–24 nucleotides) that bind to their complementary sequences in the 3′-untranslated regions (3′-UTR) of targeted genes to negatively or positively regulate their expression. miRNAs affect the expression of genes in cells, thereby contributing to several important biological processes, including tumorigenesis. Identifying the miRNA cluster as a human embryonic stem cell (hESC)-specific miRNAs initially led to the identification of miR-371, miR-372, miR-373, and miR-373*, which can ultimately be translated into mature miRNAs. Recent evidence suggests that miR-371–373 genes are abnormally expressed in various cancers and act either as oncogenes or tumor suppressors, indicating they may be suitable as molecular biomarkers for cancer diagnosis and prevention. In this article, we summarize recent studies linking miR-371–373 functions to tumorigenesis and speculate on the potential applications of miR-371–373 as biomarkers for cancer diagnosis and treatment.
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- 2021
- Full Text
- View/download PDF
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