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1.
Adv Colloid Interface Sci ; 329: 103184, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38781826

ABSTRACT

With the rapid advancement of nanotechnology, stimuli-responsive nanomaterials have emerged as a feasible choice for the designing of controlled drug delivery systems. Zeolitic imidazolates frameworks are a subclass of Metal-organic frameworks (MOFs) that are recognized by their excellent porosity, structural tunability and chemical modifications make them promising materials for loading targeted molecules and therapeutics agents. The biomedical industry uses these porous materials extensively as nano-carriers in drug delivery systems. These MOFs not only possess excellent targeted imaging ability but also cause the death of tumor cells drawing considerable attention in the current framework of anticancer drug delivery systems. In this review, the outline of stability, porosity, mechanism of encapsulation and release of anticancer drug have been reported extensively. In the end, we also discuss a brief outline of current challenges and future perspectives of ZIFs in the biomedical world.

2.
J Med Chem ; 67(6): 4496-4524, 2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38488146

ABSTRACT

Dysregulation of the ubiquitin-proteasome systems is a hallmark of various disease states including neurodegenerative diseases and cancer. Ubiquitin C-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme, is expressed primarily in the central nervous system under normal physiological conditions, however, is considered an oncogene in various cancers, including melanoma, lung, breast, and lymphoma. Thus, UCHL1 inhibitors could serve as a viable treatment strategy against these aggressive cancers. Herein, we describe a covalent fragment screen that identified the chloroacetohydrazide scaffold as a covalent UCHL1 inhibitor. Subsequent optimization provided an improved fragment with single-digit micromolar potency against UCHL1 and selectivity over the closely related UCHL3. The molecule demonstrated efficacy in cellular assays of metastasis. Additionally, we report a ligand-bound crystal structure of the most potent molecule in complex with UCHL1, providing insight into the binding mode and information for future optimization.


Subject(s)
Neoplasms , Ubiquitin Thiolesterase , Humans , Ubiquitin Thiolesterase/chemistry , Ubiquitin Thiolesterase/metabolism , Ubiquitin/metabolism , Breast , Proteasome Endopeptidase Complex
3.
Comput Biol Med ; 170: 107908, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38217973

ABSTRACT

Electrocardiogram (ECG) are the physiological signals and a standard test to measure the heart's electrical activity that depicts the movement of cardiac muscles. A review study has been conducted on ECG signals analysis with the help of artificial intelligence (AI) methods over the last ten years i.e., 2012-22. Primarily, the method of ECG analysis by software systems was divided into classical signal processing (e.g. spectrograms or filters), machine learning (ML) and deep learning (DL), including recursive models, transformers and hybrid. Secondly, the data sources and benchmark datasets were depicted. Authors grouped resources by ECG acquisition methods into hospital-based portable machines and wearable devices. Authors also included new trends like advanced pre-processing, data augmentation, simulations and agent-based modeling. The study found improvement in ECG examination perfection made each year through ML, DL, hybrid models, and transformers. Convolutional neural networks and hybrid models were more targeted and proved efficient. The transformer model extended the accuracy from 90% to 98%. The Physio-Net library helps acquire ECG signals, including the popular benchmark databases such as MIT-BIH, PTB, and challenging datasets. Similarly, wearable devices have been established as a appropriate option for monitoring patient health without the time and place limitations and are also helpful for AI model calibration with so far accuracy of 82%-83% on Samsung smartwatch. In the pre-processing signals, spectrogram generation through Fourier and wavelet transformations are erected leading approaches promoting on average accuracy of 90%-95%. Likewise, data enhancement using geometrical techniques is well-considered; however, extraction and concatenation-based methods need attention. As the what-if analysis in healthcare or cardiac issues can be performed using a complex simulation, the study reviews agent-based modeling and simulation approaches for cardiovascular risk event assessment.


Subject(s)
Algorithms , Artificial Intelligence , Humans , Neural Networks, Computer , Software , Signal Processing, Computer-Assisted , Electrocardiography/methods
4.
Eur J Clin Pharmacol ; 80(4): 493-503, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38261005

ABSTRACT

PURPOSE: Propofol has become the sedative of choice for endoscopy and colonoscopy. However, it has shown associations with various adverse effects, specifically in the geriatric population. In contrast, remimazolam is a novel benzodiazepine, demonstrating a superior clinical safety profile. Hence, this systematic review and meta-analysis aims to clarify the efficacy and safety of remimazolam versus propofol in elderly patients (≥ 60 years) undergoing gastrointestinal endoscopic and colonoscopy procedures. METHODS: Electronic databases including PubMed, Cochrane Library, ScienceDirect, and Google Scholar were explored from inception till January 7, 2024. The Cochrane Risk of Bias Tool for Randomized Controlled Trials (RoB-2) was utilized to evaluate the quality of each included study reported in this meta-analysis. RESULTS: Seven randomized control trials were included, resulting in the pooling of 1,466 patients (remimazolam: 731 patients; propofol: 735 patients). Propofol demonstrated a significantly lower time to loss of consciousness (P < 0.00001, 4 studies, 784 patients) and a greater sedation success after first dose (P = 0.05, 5 studies, 1,271 patients). Remimazolam reported a significantly lower risk of bradycardia (P = 0.02, 5 studies, 1,323 patients), hypoxemia (P < 0.00001, 6 studies, 1,389 patients), and pain on injection site (P < 0.00001, 5 studies, 1,184 patients). No statistically significant differences in sedation time, number of supplemental doses, procedural parameters, and other adverse outcomes were reported. CONCLUSION: As per the results of our analyses, propofol demonstrated comparatively superior efficacy, however, remimazolam demonstrated comparatively superior safety. The debatable evidence generated from this meta-analysis may not currently be powerful enough to advocate for the use of remimazolam in elderly patients undergoing gastrointestinal procedures; hence, further comprehensive studies are necessary in order to arrive at a robust conclusion.


Subject(s)
Propofol , Humans , Aged , Propofol/adverse effects , Randomized Controlled Trials as Topic , Benzodiazepines/adverse effects , Hypnotics and Sedatives , Endoscopy, Gastrointestinal/methods , Colonoscopy/methods
5.
Mol Cancer Res ; 22(3): 254-267, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38153436

ABSTRACT

Survival of dormant, disseminated breast cancer cells contributes to tumor relapse and metastasis. Women with a body mass index greater than 35 have an increased risk of developing metastatic recurrence. Herein, we investigated the effect of diet-induced obesity (DIO) on primary tumor growth and metastatic progression using both metastatic and systemically dormant mouse models of breast cancer. This approach led to increased PT growth and pulmonary metastasis. We developed a novel protocol to induce obesity in Balb/c mice by combining dietary and hormonal interventions with a thermoneutral housing strategy. In contrast to standard housing conditions, ovariectomized Balb/c mice fed a high-fat diet under thermoneutral conditions became obese over a period of 10 weeks, resulting in a 250% gain in fat mass. Obese mice injected with the D2.OR model developed macroscopic pulmonary nodules compared with the dormant phenotype of these cells in mice fed a control diet. Analysis of the serum from obese Balb/c mice revealed increased levels of FGF2 as compared with lean mice. We demonstrate that serum from obese animals, exogenous FGF stimulation, or constitutive stimulation through autocrine and paracrine FGF2 is sufficient to break dormancy and drive pulmonary outgrowth. Blockade of FGFR signaling or specific depletion of FGFR1 prevented obesity-associated outgrowth of the D2.OR model. IMPLICATIONS: Overall, this study developed a novel DIO model that allowed for demonstration of FGF2:FGFR1 signaling as a key molecular mechanism connecting obesity to breakage of systemic tumor dormancy and metastatic progression.


Subject(s)
Breast Neoplasms , Humans , Female , Animals , Mice , Breast Neoplasms/genetics , Fibroblast Growth Factor 2 , Neoplasm Recurrence, Local , Obesity/complications , Signal Transduction , Mice, Inbred BALB C , Receptor, Fibroblast Growth Factor, Type 1/genetics
6.
Front Microbiol ; 14: 1343080, 2023.
Article in English | MEDLINE | ID: mdl-38149269

ABSTRACT

[This corrects the article DOI: 10.3389/fmicb.2023.1233433.].

7.
Dalton Trans ; 53(1): 196-205, 2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38019275

ABSTRACT

The process of water photo-electrolysis possesses the capability to generate sustainable and renewable hydrogen fuels, consequently addressing the challenge of the irregularity of solar energy. Thus, developing highly-efficient and low-cost electrocatalysts for the use in contemporary renewable energy devices is critical. Herein, we report the fabrication of a novel BaCeFex-yBixO6 nanocrystalline material through a one-step solvothermal route using a post-annealing process at 500 °C. The synthesized material was investigated for its light-induced electrochemical HER and OER activities in alkaline media and the results revealed that the as-prepared BaCeFex-yBixO6-500 °C exhibited an excellent OER activity with an overpotential of 100 mV to achieve a current density of 10 mA cm-2, thus outperforming the IrO2 electrocatalyst. Besides its excellent water oxidation performance, the catalyst also demonstrated an admirable HER activity comparable to that of the Pt/C catalyst, indicating that the higher temperature treatment plays a significant role in achieving the maximum performance of the developed electrocatalyst. This work provides insights into the enhancement of light-induced OER and HER activities of bismuth oxides for a wide range of catalytic applications.

8.
Front Microbiol ; 14: 1233433, 2023.
Article in English | MEDLINE | ID: mdl-37901807

ABSTRACT

Hantaviruses are a significant and emerging global public health threat, impacting more than 200,000 individuals worldwide each year. The single-stranded RNA viruses belong to the Hantaviridae family and are responsible for causing two acute febrile diseases in humans: Hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS). Currently, there are no licensed treatments or vaccines available globally for HTNV infection. Various candidate drugs have shown efficacy in increasing survival rates during the early stages of HTNV infection. Some of these drugs include lactoferrin, ribavirin, ETAR, favipiravir and vandetanib. Immunotherapy utilizing neutralizing antibodies (NAbs) generated from Hantavirus convalescent patients show efficacy against HTNV. Monoclonal antibodies such as MIB22 and JL16 have demonstrated effectiveness in protecting against HTNV infection. The development of vaccines and antivirals, used independently and/or in combination, is critical for elucidating hantaviral infections and the impact on public health. RNA interference (RNAi) arised as an emerging antiviral therapy, is a highly specific degrades RNA, with post-transcriptional mechanism using eukaryotic cells platform. That has demonstrated efficacy against a wide range of viruses, both in vitro and in vivo. Recent antiviral methods involve using small interfering RNA (siRNA) and other, immune-based therapies to target specific gene segments (S, M, or L) of the Hantavirus. This therapeutic approach enhances viral RNA clearance through the RNA interference process in Vero E6 cells or human lung microvascular endothelial cells. However, the use of siRNAs faces challenges due to their low biological stability and limited in vivo targeting ability. Despite their successful inhibition of Hantavirus replication in host cells, their antiviral efficacy may be hindered. In the current review, we focus on advances in therapeutic strategies, as antiviral medications, immune-based therapies and vaccine candidates aimed at enhancing the body's ability to control the progression of Hantavirus infections, with the potential to reduce the risk of severe disease.

9.
J Biomol Struct Dyn ; : 1-12, 2023 Oct 14.
Article in English | MEDLINE | ID: mdl-37837423

ABSTRACT

The PPAR family of transcription factors are ligand-activated and regulate diverse functions including metabolic, neurological, and inflammatory diseases, neurodegenerative disorders, fertility or reproduction in the body. Specifically, PPARα is known to play a role in reducing the levels of circulating triglycerides and regulating energy homeostasis in livestock animals. This study aimed to identify phytochemicals that could serve as ligands for modulation of the bovine nuclear peroxisome proliferator-activated receptor alpha (PPARα) using molecular docking studies. Therefore, we investigated 1000 flavonoids belonging to different groups for their ability to bind to PPARα using molecular docking. Out of 1000, 6 top lead compounds with maximum binding affinity, evaluated through molecular docking, were further analysed for physicochemical properties and drug-likeness attributes. The results revealed that two flavonoids, Quercetin-3-o-rhamnoside and (-)- epicatechingallate, which are known fatty acid synthase inhibitors, demonstrated high docking scores with PPARα (-8.66 kcal/mol and -8.49 kcal/mol, respectively) and low RMSD values with PPARα (1.61 kcal/mol and 1.28 kcal/mol, respectively) as compared to PPARα agonist (synthetic), fenofibrate (-6.24 kcal/mol and 2.19 kcal/mol) and thus analyzed further for prediction of stability of docked complexes through MD simulations. MD simulation studies predicted the stability of complexes and the complex of Quercetin-3-o-rhamnoside and (-)- epicatechingallate were found to be stable at 100 ns based on RSMD value and RMSF residue index. Through computational analysis, the screened compounds showed good pharmacokinetic parameters, including non-toxicity, non-carcinogenic, high gastrointestinal absorption and thus can serve as potential drug candidates. Finally, the findings suggest that these phytochemicals have the potential to act as potent PPARα pharmacological agonists to prevent disease mechanisms and their related complications, providing insights into the role of phytochemicals as feed additives in animals for modulating PPARα functions.Communicated by Ramaswamy H. Sarma.

10.
Appl Opt ; 62(26): 6961-6973, 2023 Sep 10.
Article in English | MEDLINE | ID: mdl-37707035

ABSTRACT

In applications of computer color formulation where color stimuli are optically thick (e.g., textiles, coatings, etc.), a simple single-constant or two-constant theory (e.g., Kubelka-Munk model) would suffice. To accurately predict reflectance and transmittance of materials with optical thickness ranging from optically thin to optically thick (e.g., plastics), mathematically complex radiative transfer theories (e.g., many-flux models) have been recommended. A many-flux model can even predict color formulation involving special-effect pigments (e.g., metallic, pearlescent, etc.), but implementation of such models is manyfold complicated. In the current study, applicability of a relatively simple Maheu-Letoulouzan-Gouesbet (MLG) four-flux radiative transfer model to optically varying pigmented polyolefins is thoroughly investigated. First, the MLG model was implemented to determine absorption and scattering coefficients of over 120 pigments where a new mean relative absolute spectral error (MRASE) between measured and calculated spectral reflectance and transmittance of the calibration samples was minimized as an objective function. Second, currently determined absorption and scattering coefficients were further validated by color recipe prediction of 350 historical product colors. Measured and predicted reflectance curves were compared in units of MRASE, CIEDE2000 color difference, metamerism index, root mean square error, and goodness-of-fit coefficient. Moreover, transmission matching was evaluated in units of percent difference between the required and predicted average transmittance. Results showed that with the current implementation of the MLG four-flux model, color recipes of at least 95% of the target colors can be predicted within the acceptability thresholds in units of different error metrics used in the study.

11.
J Acoust Soc Am ; 154(2): 1138-1151, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37606359

ABSTRACT

Noise control strategies are extremely important in industry. Acoustic liners and elastic membranes, which absorb or attenuate sound waves, are key components in ducting systems for active and passive noise reduction. In this article, we design and examine a reactive liner panel cavity with flexible interfaces. The lined panel cavity system is comprised of elastic membranes at the interfaces. The aim is to couple the incoming duct modes with the flexible components and then with the localized modes in the lined region. The governing equations for the lined panel cavity system are solved using a mode-matching technique that assures continuity of the normal velocities at the interfaces and can handle a range of strong coupling and higher-order edge conditions in contrast to the coupled mode theory. The aim is to investigate the effects of reactive liners and elastic membrane interfaces on wave scattering through the proposed acoustic enclosure design. The scattering performance of the proposed lined panel cavity is evaluated in terms of the reflected and transmitted energy flux as well as transmission loss. Analysis shows that the resonances at the membrane interfaces coupled to the linear cavities have a direct impact on power variations and the maximum transmission loss.

12.
Int J Surg Case Rep ; 108: 108448, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37406536

ABSTRACT

INTRODUCTION AND IMPORTANCE: This case report describes the successful surgical management of a 30-year-old male with a non-functional carotid body tumor and a mediastinal paraganglioma occupying the aortopulmonary space. The report highlights the rarity of mediastinal paragangliomas and the challenges in their surgical management. CASE PRESENTATION: The patient underwent pre-op angioembolisation of the carotid body tumor, followed by excision and left cervical lymph node dissection. A large mediastinal mass was identified and resected during surgery without needing a cardiopulmonary bypass. The patient recovered well from surgery. Histopathology confirmed the diagnosis of clinically recurrent paraganglioma. CLINICAL DISCUSSION: Mediastinal paragangliomas are rare and challenging to manage due to their proximity to major vascular structures. Surgical intervention is the preferred treatment, but the risk of complications is high. In this case, the surgical approach involved resection of the mediastinal mass without cardiopulmonary bypass. This approach reduced the risk of complications associated with bypass procedures. The procedure's success underscores the importance of early diagnosis and prompt surgical intervention. CONCLUSION: This case report highlights the successful surgical management of a rare and clinically challenging mediastinal paraganglioma without cardiopulmonary bypass. The report underscores the importance of prompt diagnosis and surgical intervention in mediastinal paragangliomas.

13.
BMJ Glob Health ; 8(7)2023 07.
Article in English | MEDLINE | ID: mdl-37479500

ABSTRACT

The Lancet Commission on Diagnostics highlighted a huge gap in access to diagnostic testing even for basic tests, particularly at the primary care level, and emphasised the need for countries to include diagnostics as part of their universal health coverage benefits packages. Despite the poor state of diagnostic-related services in low-income and middle-income countries (LMICs), little is known about the extent to which diagnostics are included in the health benefit packages. We conducted an analysis of seven Asian LMICs-Cambodia, India, Indonesia, Nepal, Pakistan, Philippines, Viet Nam-to understand this issue. We conducted a targeted review of relevant literature and applied a health financing framework to analyse the benefit packages available in each government-sponsored scheme. We found considerable heterogeneity in country approaches to diagnostics. Of the seven countries, only India has developed a national essential diagnostics list. No country presented a clear policy rationale on the inclusion of diagnostics in their scheme and the level of detail on the specific diagnostics which are covered under the schemes was also generally lacking. Government-sponsored insurance expansion in the eligible populations has reduced the out-of-pocket health payment burden in many of the countries but overall, there is a lack of access, availability and affordability for diagnostic-related services.


Subject(s)
National Health Programs , Humans , Indonesia , Nepal , Pakistan , Philippines , Vietnam , Cambodia , India
14.
J Relig Health ; 2023 May 11.
Article in English | MEDLINE | ID: mdl-37166691

ABSTRACT

Life-threatening events including terminal illness intensify the search for meaning and incite individuals to get closer to religion. Terminal patients can often find religious practices as helpful as medical therapy for bettering both physical and mental health. The present research aims to explain the interaction between religion, spirituality, and social support in coping with terminal illness among Muslim hepatitis C patients in Pakistan. A semi-structured open-ended interview guide was utilized to collect the data. Participants expressed that the deployment of religious and spiritual beliefs along with socio-emotional support during illness fostered medical therapy. Participants also revealed that belief in God provided them the strength to be steadfast during the terminal stage of the disease. Religious beliefs enabled terminal participants to accept death as an eventual reality and a normal part of their lives. Furthermore, participants put forward their longing for those kinds of religious practices that terminal diseases usually restrained them from receiving. The emotional support stemming from social relationships also improved resilience to cope with the terminal stage of illness. The study concludes that the interplay of religion, spirituality, and social support normalizes the fear of death, lessens pain, and improves resilience among Muslim hepatitis C patients in Pakistan.

15.
Molecules ; 28(7)2023 Apr 02.
Article in English | MEDLINE | ID: mdl-37049930

ABSTRACT

The synthesis and design of low-cost visible-light-active catalysts for the photodegradation of organic dyes have been regarded as an efficient way to use solar energy in addressing environmental issues. We report the fabrication of MoS2/CdS nanoparticles functionalized with Bi2S3 nanoflakes. The ternary composites of "MoS2/CdS/Bi2S3" were synthesized in situ by a hydrothermal method at different temperatures. The changes in structural, optical, and morphological properties of the synthesized CdS/MoS2/Bi2S3 were explored. The effects of Bi2S3 on CdS/MoS2 were thoroughly studied by performing an X-ray diffractometer (XRD), a scanning electron microscope (SEM), an ultra-violet-visible spectrometer (Uv-vis), and Fourier transform infrared spectroscopic (FT-IR) studies of the nanoparticles. XRD confirms the cubical crystal structure of the nanoparticles. SEM studies possess the modulation in the surface morphology with the tenability in volume ratios of "MoS2/CdS/Bi2S3" composites. It was observed that the bandgaps calculated using absorption measurements could be manipulated from 2.40 eV to 0.97 eV with varying Bi2S3 in the MoS2/CdS nanostructures. FT-IR confirmed the synthesis of "MoS2/CdS/Bi2S3" nanoparticles. On allowing the visible light to fall for 120 min, it was observed that "MoS2/CdS/Bi2S3" degrades the methylene blue up to 90%. The calculated results of "MoS2/CdS/Bi2S3" suggest that the synthesized material could be a strong candidate for photodegradation applications. This research work explains the synthesis of MoS2/CdS/Bi2S3-based nanocomposites for the degradation of dye using a photocatalytic process. The final results show that this catalyst effectively degrades the dye.

16.
Metabolites ; 13(4)2023 Mar 30.
Article in English | MEDLINE | ID: mdl-37110160

ABSTRACT

As the Urtica dioica L. whole plant's essential oil has presented significant multiple activities, it was therefore evaluated using the GC-MS technique. This essential oil was investigated for its antioxidant, phytotoxic, and antibacterial activities in vitro. The GC-MS analysis data assisted in the identification of various constituents. The study of the essential oil of U. dioica showed potential antioxidant effects and antibacterial activity against the selected pathogens Escherichia coli -ATCC 9837 (E. coli), Bacillus subtilis-ATCC 6633 (B. subtilis), Staphylococcus aureus-ATCC6538 (S. aureus), Pseudomonas aeruginosa-ATCC 9027 (P. aeruginosa), and Salmonella typhi-ATCC 6539 (S. typhi). The library of 23 phytochemicals was docked by using MOE software, and three top virtual hits with peroxiredoxin protein [PDB ID: 1HD2] and potential target protein [PDB ID: 4TZK] were used; hence, the protein-ligand docking results estimated the best binding conformations and a significant correlation with the experimental analysis, in terms of the docking score and binding interactions with the key residues of the native active binding site. The essential oil in the silico pharmacokinetic profile explained the structure and activity relationships of the selected best hits, and their additional parameters provided insight for further clinical investigations. Therefore, it is concluded that the U. dioica essential oil could be a potent antioxidant and antibacterial agent for aromatherapy through its topical application, if further tested in a laboratory and validated.

17.
J Relig Health ; 62(4): 2916-2932, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36877419

ABSTRACT

Religion and spirituality have been key coping mechanisms of Pakistani Muslims amidst natural calamities such as the COVID-19 pandemic. This study aimed to identify and explore the role of religion and spirituality in the recovery of COVID-19 patients in lower socioeconomics. The data for this qualitative research study were collected from 13 people in Pakistan who survived COVID-19 infection during the wave of the Omicron variant. The participants of this study referenced four key themes about their story of getting infected by COVID-19 and recovering from it and referenced religion and spirituality as an overarching aspect of that story. The patients who recovered believed that COVID-19 was a punishment from God for sinful humanity, which was unavoidable. Amidst such a belief, the studied patients tried to avoid hospitalization but prayed to God for mercy, forgiveness, and help in their recovery. A few who took medical treatment also established and/or strengthened their spiritual connections seeking quick recovery from the infection. The participants of this study believed that their religion or spirituality played a medicinal role in their recovery from COVID-19 infection.


Subject(s)
COVID-19 , Spirituality , Humans , Pakistan , Pandemics , SARS-CoV-2 , Religion , Islam , Qualitative Research , Adaptation, Psychological , Social Class
18.
J Taibah Univ Med Sci ; 18(5): 1030-1047, 2023 Oct.
Article in English | MEDLINE | ID: mdl-36926053

ABSTRACT

The SARS-CoV-2 virus targets the antigen converting enzyme 2 (ACE2) receptor, thus resulting in elevated morbidity and an increased risk of severe and fatal COVID-19 infection in individuals with hypertension and diabetes mellitus. Objectives: This study aimed to identify the association between increased susceptibility and severity in order to evaluate their impact in hypertensive COVID-19 patients using in vitro and in silico models. Methods: We identified 80 miRNA binding sites on ACE2 (for different miRNAs) as well as various 30 SNPs in the miRNA binding sites of the 3' untranslated region (3' UTR) in the ACE2 gene using different online software and tools. From August 2020 to August 2021, a total of 200 nasopharyngeal/mouth swabs samples were collected from Multan, Pakistan. In order to quantify the cDNA of ACE2 and miR-3658 genes, we used Rotor Gene qRT-PCR on hypertensive patients with COVID-19 as well as healthy controls. Results: Interestingly, the binding site of miR-3658 corresponding to the 3' UTR of ACE2 featured three SNPs (rs1457913029, C>T; rs960535757, A>C, G; rs1423809569, C>T), and its genomic sequence featured a single SNP (rs1024225815, C>T) with the same nucleotide variation (rs1457913029, C>T) which potentially increases the severity of COVID-19. Similarly, three other SNPs (rs1557852115, C>G; rs770335293, A>G; rs1024225815, C>T) were also found on the first binding site positions of miR-3658. Our in vitro study found that ACE2 gene expression had an effect on miR-3658 in COVID-19 patients who also had hypertension. In both cases, our analysis demonstrated that the in silico model captured the same biological mechanisms as the in vitro system. Conclusion: The identified SNPs could represent potential informative signatures owing to their position in the splicing site of the ACE2 gene.

19.
Int J Biol Macromol ; 232: 123476, 2023 Mar 31.
Article in English | MEDLINE | ID: mdl-36731696

ABSTRACT

With the advancement in 3D bioprinting technology, cell culture methods can design 3D environments which are both, complex and physiologically relevant. The main component in 3D bioprinting, bioink, can be split into various categories depending on the criterion of categorization. Although the choice of bioink and bioprinting process will vary greatly depending on the application, general features such as material properties, biological interaction, gelation, and viscosity are always important to consider. The foundation of 3D bioprinting is the exact layer-by-layer implantation of biological elements, biochemicals, and living cells with the spatial control of the implantation of functional elements onto the biofabricated 3D structure. Three basic strategies underlie the 3D bioprinting process: autonomous self-assembly, micro tissue building blocks, and biomimicry or biomimetics. Tissue engineering can benefit from 3D bioprinting in many ways, but there are still numerous obstacles to overcome before functional tissues can be produced and used in clinical settings. A better comprehension of the physiological characteristics of bioink materials and a higher level of ability to reproduce the intricate biologically mimicked and physiologically relevant 3D structures would be a significant improvement for 3D bioprinting to overcome the limitations.


Subject(s)
Bioprinting , Tissue Scaffolds , Tissue Scaffolds/chemistry , Printing, Three-Dimensional , Tissue Engineering , Technology
20.
World J Microbiol Biotechnol ; 39(3): 80, 2023 Jan 17.
Article in English | MEDLINE | ID: mdl-36646906

ABSTRACT

Plant mediated synthesis of metallic nanomaterials has emerged as a non-toxic and economical approach to their applications in diverse fields especially in biomedical sciences. Herein, this study first time reporting the use of Bombax ceiba flower extract for synthesis of selenium nanoparticles (SeNPs). Initially, SeNPs were confirmed by turning the color of reaction mixtures from light yellow to brick-red. Scanning electron microscope (SEM) and Transmission electron microscopy (TEM) images showed spherical shaped nanoparticles with smooth surface, size ranges between 30 and 150 nm. Dynamic light scattering (DLS) showed 100-150 nm for the distribution of particle size. X-ray diffraction (XRD) analysis revealed SeNPs crystallinity and confirmed by matching with selenium JCPD card No. 06-362. Energy-dispersive X-ray (EDX) spectra showed presence of pure Se peaks that corroborate the conversion of selenium ions into its elemental form by bio-reduction. Fourier-transform infrared spectroscopy (FTIR) spectra demonstrated that involvement of -OH, C-H, C=C, and C=O functional groups for SeNPs formation. Raman Spectra peaks at 250 cm-1 represent asymmetric trigonal selenium (t-Se). Ultraviolet-visible spectrophotometer (UV-Vis) peaks at 296 and 306 nm which is an indication of surface plasmon resonance (SPR). Moreover, maximum antibacterial activity of SeNPs were observed against Staphylococcus aureus- a gram positive bacteria that possess zone of inhibition (ZOI) 20 mm and Klebsiella pneumonia and Pseudomonas aeruginosa-gram negative bacteria with ZOI 28 mm, respectively, at concentration 100 µg/ml. In addition, the surface functionalities induced through extract components adhere over Se binds with urea and give its detection up to 1mM in milk sample. Conclusively, synthesized SeNPs may function as a potential antibacterial pharmaceutical candidate.


Subject(s)
Bombax , Metal Nanoparticles , Nanoparticles , Selenium , Selenium/chemistry , Urea , Nanoparticles/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Spectroscopy, Fourier Transform Infrared , Metal Nanoparticles/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry
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