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1.
J Med Virol ; 96(7): e29748, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38975633

ABSTRACT

Prostate cancer is a prevalent carcinoma among males, and conventional treatment options are often limited. Cytotoxic chemotherapy, despite its drawbacks, remains a mainstay. We propose a targeted co-delivery approach using nanoscale delivery units for Oncolytic measles virus (OMV) and vincristine (VC) to enhance treatment efficacy. The HA-coated OMV + VC-loaded TCs nanoformulation is designed for targeted oncolytic activity in prostate cancer. The CD44 expression analysis in prostate cancer cell lines indicates a significantly high expression in PC3 cells. The optimization of nanoformulations using Design of Expert (DOE) is performed, and the preparation and characterization of HA-coated OMV + VC-loaded TCs nanoformulations are detailed showing average particle size 397.2 ± 0.01 nm and polydispersity index 0.122 with zeta potential 19.7 + 0.01 mV. Results demonstrate successful encapsulation efficiency with 2.4 × 106 TCID50/Ml and sustained release of OMV and VC from the nanoformulation for up to 72 h. In vitro, assays reveal potent anticancer activity at 10 ± 0.71% cell viability in PC3 cells compared to 73 ± 0.66% in HPrEC and significant morphological changes at 90 µg/ml in dose and time-dependent manner. The co-formulation showed positive cell death 49.5 ± 0.02% at 50 µg PI/ml in PBS and 54.3% cell cycle arrest at the G2/M phase, 8.1% G0/G1 and 5.7% at S phase, with significant mitochondrial membrane potential (MMP) at 50 µg/ml, as assessed by flow cytometry (FACS). The surface-integrating ligand approach enhances the targeted delivery of the oncolytic virus and chemotherapeutic drug, presenting a potential alternative for prostate cancer treatment and suggested that co-administering VC and OMV in a nanoformulation could improve therapeutic outcomes while reducing chemotherapeutic drug doses.


Subject(s)
Oncolytic Virotherapy , Oncolytic Viruses , Prostatic Neoplasms , Vincristine , Humans , Male , Prostatic Neoplasms/therapy , Prostatic Neoplasms/drug therapy , Vincristine/pharmacology , Vincristine/administration & dosage , Oncolytic Virotherapy/methods , Cell Line, Tumor , Measles virus/drug effects , Cell Survival/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Drug Delivery Systems , Nanoparticles/chemistry , PC-3 Cells
2.
Sci Rep ; 14(1): 11431, 2024 05 19.
Article in English | MEDLINE | ID: mdl-38763930

ABSTRACT

Our current study reports the successful synthesis of thiolated chitosan-based nanoparticles for targeted drug delivery of 5-Fluorouracil. This process was achieved through the ionic gelation technique, aiming to improve the efficacy of the chemotherapeutic moiety by modifying the surface of the nanoparticles (NPs) with a ligand. We coated these NPs with hyaluronic acid (HA) to actively target the CD44 receptor, which is frequently overexpressed in various solid malignancies, including breast cancer. XRD, FTIR, SEM, and TEM were used for the physicochemical analysis of the NPs. These 5-Fluorouracil (5-FU) loaded NPs were evaluated on MDA-MB-231 (a triple-negative breast cell line) and MCF-10A (normal epithelial breast cells) to determine their in vitro efficacy. The developed 5-FU-loaded NPs exhibited a particle size within a favorable range (< 300 nm). The positive zeta potential of these nanoparticles facilitated their uptake by negatively charged cancer cells. Moreover, they demonstrated robust stability and achieved high encapsulation efficiency. These nanoparticles exhibited significant cytotoxicity compared to the crude drug (p < 0.05) and displayed a promising release pattern consistent with the basic diffusion model. These traits improve the pharmacokinetic profile, efficacy, and ability to precisely target these nanoparticles, offering a potentially successful anticancer treatment for breast cancer. However, additional in vivo assessments of these formulations are obligatory to confirm these findings.


Subject(s)
Chitosan , Fluorouracil , Hyaluronan Receptors , Nanoparticles , Triple Negative Breast Neoplasms , Fluorouracil/administration & dosage , Fluorouracil/pharmacology , Fluorouracil/chemistry , Chitosan/chemistry , Humans , Hyaluronan Receptors/metabolism , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Nanoparticles/chemistry , Cell Line, Tumor , Female , Drug Carriers/chemistry , Hyaluronic Acid/chemistry , Drug Delivery Systems , Antimetabolites, Antineoplastic/pharmacology , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/pharmacokinetics , Antimetabolites, Antineoplastic/chemistry , Cell Survival/drug effects , Particle Size
4.
Saudi J Biol Sci ; 31(3): 103945, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38327663

ABSTRACT

The current research endeavor seeks to unlock the potential of orally administered insulin formulations by utilizing liposomes derived from the fat globule membrane (MFGM) of camel milk as carriers for insulin. This pursuit emerges as a result of the recognized limitations of subcutaneous insulin therapy. The liposomes were meticulously created using the thin film hydration method, followed by comprehensive chemical and morphological analyses. Additionally, comprehensive safety assessments were carried out in vitro and in vivo, revealing significant findings. The Fourier-transform infrared (FTIR) spectrum confirmed the presence of insulin within the liposomes, demonstrating changes in their size and charge. The in vitro cytotoxicity analysis, performed on HEK-293 cell lines through the MTT assay, yielded results indicating a cell viability of over 90%. In the in vivo investigation, diabetic rats induced by STZ were utilized to evaluate the effects of the liposomes, revealing substantial reductions in blood glucose levels, bilirubin, alkaline phosphatase (ALP), albumin, and alanine aminotransferase (ALT) levels. Hepatic histopathological assessments showed signs of recovery across all treatment groups, with no observable microscopic changes in renal tissue. This investigation highlights the significant hypoglycemic effects observed in insulin-loaded liposomes derived from MFGM obtained from camel milk when administered orally.

5.
J Trace Elem Med Biol ; 81: 127324, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37944220

ABSTRACT

BACKGROUND: Cadmium is widely reported to interfere with the proper functioning of cells by disrupting cellular redox balance, causing apoptosis, and leading to hepatocellular damage, neurotoxicity, pulmonary edema, cancer, and cardiac and neurodegenerative diseases. Treatment of Cd toxicity with drugs brings undesirable side effects, making it necessary to remove Cd from the body safely without harmful effects. OBJECTIVE: This study aimed to determine how Cd causing malfunctioning of cells could be treated with antioxidant-rich avocado and papaya fruit juices. This work fixated on elucidating and comparing the effects of avocado and papaya fruit juice on Cd-dependent impairment in memory and spatial learning. In addition, various markers of tissue damage, such as the concentration of biomarkers in liver and kidney tissue, the expression of antioxidant enzymes and Cd-induced lipid peroxidation, were analyzed. METHODOLOGY: in silico studies of the phytochemical constituents of avocado and papaya (ligands) were docked against antioxidant enzymes Catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD) as macromolecules showed strong hydrogen binding with significant binding capacities. To develop the Cd in vivo model, rats were administered CdCl2 (200 ppm) in drinking water for 7 weeks. After induction of Cd toxicity, rats were post-treated with avocado and papaya (10% w/v each) in a standard diet. After post-treatment, memory and learning were assessed using the Morris water maze behavioural test. Biochemical tests for liver and kidney biomarkers were monitored. To determine the level of ROS, lipid peroxidation was determined by Malondialdehyde (MDA) assay. Gene expression of SOD, CAT and GPx were determined via qRT-PCR. RESULTS: This study demonstrated that Cd accumulation in the liver, kidney and hippocampal tissues was reduced after treatment with avocado and papaya. SOD, CAT and GPX gene expression were upregulated after avocado and papaya juice treatment. Moreover, a comparative analysis between avocado and papaya fruit juices clarified that papaya has more active potential for improving memory and learning, upregulating the expression of antioxidant enzymes, and reducing lipid peroxidation in the liver, kidney, and hippocampus. CONCLUSION: This study suggests that a diet containing papaya and avocado can help treat the lethal effects caused by Cd. Because their active constituents can improve health at the cellular and molecular levels.


Subject(s)
Carica , Chemical and Drug Induced Liver Injury , Persea , Rats , Animals , Antioxidants/pharmacology , Antioxidants/metabolism , Cadmium/analysis , Carica/metabolism , Persea/metabolism , Fruit/chemistry , Fruit/metabolism , Superoxide Dismutase/metabolism , Biomarkers/metabolism , Oxidative Stress , Lipid Peroxidation
6.
Int J Neurosci ; : 1-5, 2023 Nov 23.
Article in English | MEDLINE | ID: mdl-37996399

ABSTRACT

PURPOSE/AIM OF THE STUDY: This study aims to present a case of Moyamoya disease (MMD) in an adolescent who experienced a subarachnoid hemorrhage (SAH). The purpose is to underscore the importance of considering MMD as a potential cause of SAH in adolescents, particularly in the absence of common causes such as trauma or aneurysmal rupture. The case further highlights the significance of early identification and appropriate management to prevent further complications and improve patient outcomes. MATERIALS AND METHODS: The diagnosis was initially based on findings from a CT angiography and later confirmed through magnetic resonance angiography (MRA) and magnetic resonance imaging (MRI). RESULTS: The case study demonstrates the effectiveness of utilizing MRA and MRI in diagnosing MMD in adolescents. It emphasizes the challenges in areas with limited resources where advanced imaging techniques like digital subtraction angiography (DSA) may not be readily accessible or affordable. The gold standard for MMD diagnosis, DSA, is acknowledged, but the study underscores the importance of alternative imaging methods in resource-constrained settings. CONCLUSION: In conclusion, this case underscores the importance of considering Moyamoya disease as a potential etiology for subarachnoid hemorrhage in adolescents, particularly when common causes are absent. The study highlights the crucial role of MRA and MRI in the diagnosis of MMD, emphasizing their significance in areas with limited resources. Early identification and appropriate management are essential for preventing complications and improving patient outcomes, acknowledging the challenges associated with the accessibility of gold standard diagnostic techniques in certain settings.

7.
J Pak Med Assoc ; 73(10): 2065-2068, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37876072

ABSTRACT

To assess whether prophylactic use of Levofloxacin would reduce the number of febrile neutropenia episodes during the induction phase, a single-centre, case-control study was carried out. Data was collected prospectively of patients who received Levofloxacin prophylaxis during the induction chemotherapy from September 2019 till October 2020. The cases were compared with historical controls who did not receive antibiotics prophylaxis. A total of 121 patients were enrolled, among which 61 patients were cases, whereas 60 patients were controls. The patients who received Levofloxacin prophylaxis had lower rate of febrile neutropenia episodes than patients who did not receive any prophylaxis (p≤0.01) (odds ratio [OR]:0.23, CI 95%). No significant difference in induction mortality was seen between the two groups (p≤0.14). Levofloxacin prophylaxis reduced the rate of febrile neutropenia episodes among patients, but it did not affect the infection related mortality.


Subject(s)
Febrile Neutropenia , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Child , Levofloxacin/therapeutic use , Anti-Bacterial Agents/therapeutic use , Case-Control Studies , Pakistan/epidemiology , Antibiotic Prophylaxis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Febrile Neutropenia/prevention & control , Febrile Neutropenia/drug therapy
8.
Front Immunol ; 14: 1175535, 2023.
Article in English | MEDLINE | ID: mdl-37283735

ABSTRACT

Introduction: Cervical cancer accounts for one of most common cancers among women of reproductive age. Oncolytic virotherapy has emerged as a promising immunotherapy modality but it comes with several drawbacks that include rapid clearance of virus from body due to immune-neutralization of virus in host. To overcome this, we encapsulated oncolytic Newcastle disease virus (NDV) in polymeric thiolated chitosan nanoparticles. For active targeting of virus loaded nanoformulation against CD44 (cluster of differentiation 44) receptors which are overly expressed on cancer cells, these nanoparticles were surface functionalized with hyaluronic acid (HA). Methods: Using half dose of NDV (TCID50 (50% tissue culture infective dose) single dose 3 × 105), virus loaded nanoparticles were prepared by green synthesis approach through ionotropic gelation method. Zeta analysis was performed to analyse size and charge on nanoparticles. Nanoparticles (NPs) shape and size were analysed by SEM (scanning electron microscope) and TEM (transmission electron microscope) while functional group identification was done by FTIR (fourier transform infrared) and XRD (X-ray diffraction). Viral quantification was done by TCID50 and Multiplicity of infection (MOI) determination while oncolytic potential of NPs encapsulated virus was analysed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay and cell morphology analysis. Results: Zeta analysis showed that average size of NDV loaded thiolated chitosan nanoparticles surface functionalized with HA (HA-ThCs-NDV) was 290.4nm with zeta potential of 22.3 mV and 0.265 PDI (polydispersity index). SEM and TEM analysis showed smooth surface and spherical features of nanoparticles. FTIR and XRD confirmed the presence of characteristic functional groups and successful encapsulation of the virus. In vitro release showed continuous but sustained release of NDV for up to 48 hours. TCID50 for HA-ThCs-NDV nanoparticles was 2.63x 106/mL titter and the nanoformulation exhibited high oncolytic potential in cell morphology analysis and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay as compared to naked virus, in dose dependent manner. Discussion: These findings suggest that virus encapsulation in thiolated chitosan nanoparticles and surface functionalization with HA is not only helpful in achieving active targeting while masking virus from immune system but, it also gives sustained release of virus in tumor microenvironment for longer period of time that increases bioavailability of virus.


Subject(s)
Chitosan , Uterine Cervical Neoplasms , Animals , Female , Humans , Newcastle disease virus , Chitosan/pharmacology , Uterine Cervical Neoplasms/therapy , Delayed-Action Preparations , Immunotherapy , Tumor Microenvironment , Hyaluronan Receptors
9.
Int J Nanomedicine ; 18: 185-205, 2023.
Article in English | MEDLINE | ID: mdl-36643861

ABSTRACT

Background: Oncolytic viruses are reported as dynamite against cancer treatment nowadays. Methodology: In the present work, a live attenuated oral measles vaccine (OMV) strain was used to formulate a polymeric surface-functionalized ligand-based nanoformulation (NF). OMV (half dose: not less than 500 TCID units; 0.25 mL) was encapsulated in thiolated chitosan and outermost coating with hyaluronic acid by ionic gelation method characterizing parameters was performed. Results and Discussion: CD44 high expression was confirmed in prostatic adenocarcinoma (PRAD) by GEPIA which extracted data of normal and cancer tissue from GTEx and TCGA. Bioinformatics tools confirmed the viral hemagglutinin capsid protein interaction with human Caspase-I, NLRP3, and TNF-α and viral fusion protein interaction with COX-II and Caspase-I after successful delivery of MV encapsulated in NFs due to high affinity of hyaluronic acid with CD44 on the surface of prostate cancer cells. Particle size = 275.6 mm, PDI = 0.372, and ±11.5 zeta potential were shown by zeta analysis, while the thiolated group in NFs was confirmed by FTIR and Raman analysis. SEM and XRD showed a spherical smooth surface and crystalline nature, respectively, while TEM confirmed virus encapsulation within nanoparticles, which makes it very useful in targeted virus delivery systems. The virus was released from NFs in a sustained but continuous release pattern till 48 h. The encapsulated virus titer was calculated as 2.34×107 TCID50/mL units, which showed syncytia formation on post-day infection 7. Multiplicities of infection 0.1, 0.5, 1, 3, 5, 10, 15, and 20 of HA-coated OMV-loaded NFs as compared to MV vaccine on PC3 was inoculated with IC50 of 5.1 and 3.52, respectively, and growth inhibition was seen after 72 h via MTT assay which showed apoptotic cancer cell death. Conclusion: Active targeted, efficacious, and sustained delivery of formulated oncolytic MV is a potent moiety in cancer treatment at lower doses with safe potential for normal prostate cells.


Subject(s)
Chitosan , Nanoparticles , Oncolytic Viruses , Prostatic Neoplasms , Vaccines , Male , Humans , Measles virus/genetics , Chitosan/chemistry , Hyaluronic Acid , Prostatic Neoplasms/therapy , Prostatic Neoplasms/pathology , Caspases , Immunotherapy , Nanoparticles/chemistry
10.
Int J Mol Sci ; 23(22)2022 Nov 10.
Article in English | MEDLINE | ID: mdl-36430305

ABSTRACT

miRNAs are 20-22 long nucleotide non-coding ribonucleic acid molecules critical to the modulation of molecular pathways. Immune evasion and the establishment of a suitable tumor microenvironment are two major contributors that support tumor invasion and metastasis. Tumorigenic miRNAs support these two hallmarks by desensitizing important tumor-sensitive regulatory cells such as dendritic cells, M1 macrophages, and T helper cells towards tumors while supporting infiltration and proliferation of immune cells like Treg cells, tumor-associated M2 macrophages that promote self-tolerance and chronic inflammation. miRNAs have a significant role in enhancing the efficacies of immunotherapy treatments like checkpoint blockade therapy, adoptive T cell therapy, and oncolytic virotherapy in cancer. A clear understanding of the role of miRNA can help scientists to formulate better-targeted treatment modalities. miRNA therapeutics have emerged as diverse class of nucleic acid-based molecules that can suppress oncogenic miRNAs and promote the expression of tumor suppressor miRNAs.


Subject(s)
MicroRNAs , Neoplasms , Humans , Tumor Microenvironment/genetics , MicroRNAs/metabolism , Immunotherapy , Neoplasms/genetics , Neoplasms/therapy , Immunologic Factors
11.
Cancers (Basel) ; 14(18)2022 Sep 14.
Article in English | MEDLINE | ID: mdl-36139618

ABSTRACT

Carcinoma of the cervix is one of the most common cancers that claims women's lives every year. Despite preventive HPV vaccines and conventional cancer treatments, approximately 273,000 women succumb to cervical carcinoma every year. Immune system perturbations help malignant cells in immune evasion, tumor establishment, invasion, and metastasis. An insight into immune system players that promote or suppress cervical cancer is important for the development of more targeted therapies with the fewest side effects. Immunotherapy has emerged as the most compliant approach to target cancer because it utilizes a natural course of action to stimulate the immune system against cancer cells. The major immunotherapy approaches for cervical carcinoma include monoclonal antibodies, immune checkpoint blockade therapy, adoptive cell transfer therapies, and oncolytic viruses. In October 2021 the FDA approved pembrolizumab in combination with chemotherapy or bevacizumab as a first-line treatment for cervical cancer. A recent breakthrough has been made in the cancer immunotherapy regimen in which a monoclonal antibody dostarlimab was able to completely cure all colorectal cancer patients, with disease-free progression after 6 months and counting. This creates hope that immunotherapy may prove to be the final nail in the coffin of this centuries-long prevalent disease of "cancer".

12.
Cell Mol Biol (Noisy-le-grand) ; 67(5): 1-5, 2022 Feb 04.
Article in English | MEDLINE | ID: mdl-35818278

ABSTRACT

Toll-like receptors (TLRs) are one of the major sensors to regulate innate immunity. It is present in inactive form within immune cells. However, after recognizing the conserved region of the foreign body, it gets activated by the foreign body, such as bacteria, viruses, fungus, etc. Recently, it is reported that apart from participating in innate immunity, these TLRs also play an important role in apoptosis and cancer. Moreover, very few reported that it is cross-talk with p53 protein within the cell. P53 protein is a transcription factor for many cellular proteins involved in cellular transduction. It directly as well as indirectly regulates a wide variety of cellular processes such as apoptosis, senescence, cell cycle arrest, differentiation, and DNA repair and replication and cancer dynamics. Various studies reported genetic level interaction between p53 and TLRs. However, molecular interaction studies are still few reported. In the present work, we computationally characterized molecular interaction between p53 and toll-like receptors. We used open web resources for docking and analyzing the data. Our molecular docking and molecular dynamics simulation results suggest that there is a significant interaction between p53 and toll-like receptors. The study could important for the possible therapeutic intervention.


Subject(s)
Neoplasms , Toll-Like Receptors , Tumor Suppressor Protein p53 , Humans , Immunity, Innate/genetics , Molecular Docking Simulation , Signal Transduction , Toll-Like Receptors/genetics , Toll-Like Receptors/metabolism , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
14.
Front Pharmacol ; 13: 1073004, 2022.
Article in English | MEDLINE | ID: mdl-36712656

ABSTRACT

Cervical carcinoma is one of the most prevalent gynecological cancers throughout the world. Cisplatin is used as first line chemotherapy for treatment of cervical cancer, but it comes with plethora of side effects. The aim of this study was to develop hyaluronic acid coated, thiolated chitosan nanocarriers using green synthesis approach, for CD44 targeted delivery and sustained release of Cisplatin in cervical cancer cells. After synthesis through ionic gelation method, Zeta analysis showed that the nanoparticle size was 265.9 nm with a zeta potential of +22.3 mV and .226 PDI. SEM and TEM analysis confirmed the spherical shape and smooth surface of nanoparticles. FTIR and XRD showed the presence of characteristic functional groups, successful encapsulation of drug, and crystalline nature of nanoparticles respectively. Drug loading and entrapment efficiency were calculated to be 70.1% ± 1.2% and 45% ± .28% respectively. Analysis of in vitro drug release kinetics showed that drug release followed the Higuchi model at pH 6.8 and 7.4 and Cisplatin release for up to 72 h confirmed sustained release. In vitro analysis on cervical cancer cells HeLa and normal cervical epithelial cells HCK1T was done through cell morphology analysis, trypan blue assay (concentration range of 10-80 µg/ml), and MTT cytotoxic assay (concentration range of 10-90 µg/ml). The results showed a higher cytotoxic potential of HA coated, thiolated chitosan encapsulated Cisplatin (HA-ThCs-Cis NP) nanoformulation as compared to pure Cisplatin in HeLa while in HCK1T, pure Cisplatin showed much higher toxicity as compared to HA-ThCs-Cis nanoformulation. These findings suggest that CD44 targeted delivery system can be a useful approach to minimize offtarget toxicities, give sustained release and better cellular uptake in cancer cells.

15.
Front Pharmacol ; 12: 728054, 2021.
Article in English | MEDLINE | ID: mdl-34899292

ABSTRACT

The initial stage of prostatic adenocarcinoma (PaC) has been treated with surgery and radiation therapy, but the advanced stages need systemic novel treatment. Since 2010, several advanced therapeutic innovations have been introduced in various randomized clinical trials to improve survival and reduce morbidity and mortality. Several of these therapeutics have shown substantial survival assistance globally, even in the advanced stages of metastatic castration-resistant prostatic adenocarcinoma (mCRPC). This article describes advanced PaC therapy regimens including chemotherapeutic options, hormonal therapies (abiraterone, enzalutamide), immunotherapeutic agents, and bone-modifying agents. We discussed various pros and cons of gene therapy approaches including Crispr/Cas9 mediation, oncolytic viruses, suicidal genes, and micro-RNA based antitumor therapy. The mCRPC microenvironment is characterized by elevated prostate-specific antigen (PSA) levels, which ultimately trigger the androgen receptor (AR) and its dependent signaling pathways. The advanced therapeutics target these receptors and inhibit the steroidogenic enzymes that play an important role in increasing testosterone (T) and dihydrotestosterone (DHT) levels in the body. These advanced therapeutic novelties also target AR-independent oncogenic signaling pathways by focusing on DNA damage repair (DDR) pathways and their mechanisms. Some of these options appear to be very attractive strategies for acute and chronic stages of PaC and mCRPC treatment by overcoming the mechanisms of resistance.

16.
Cureus ; 13(11): e19768, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34950547

ABSTRACT

Background and aim For years, interferon-based treatment has been offered to patients with chronic hepatitis C virus (HCV) infection; however, the complexity of the treatment, efficacy, and adverse effects were the primary concerns. All these concerns were addressed with the introduction of directly acting antivirals (DAAs) to treat chronic HCV. Sofosbuvir and velpatasvir are second-generation DAAs used in combination for the treatment of chronic HCV infection. The aim of our study was to determine and compare the efficacy and safety profile of the sofosbuvir and velpatasvir combination in treating patients with chronic hepatitis C with or without cirrhosis. Materials and methods This descriptive study was conducted at the Department of Medicine, Khyber Teaching Hospital, Peshawar, from March 15th to September 15th, 2021 after approval from the Institution Research and Ethical Review Board (IREB). Diagnosis of HCV was based on the detection of hepatitis C ribonucleic acid (RNA) fragments by reverse transcription-polymerase chain reaction (RT-PCR). Liver status was assessed with liver function tests and imaging. Sofosbuvir (400 mg) and velpatasvir (100 mg) were administered once daily for 12 weeks, followed by polymerase chain reaction (PCR) for HCV RNA after 12 weeks of completion of treatment for determination of sustained virologic response at 12 weeks (SVR12). Patients with cirrhosis also received weight-based ribavirin. Adverse events experienced by the study participants during the course of treatment were recorded. Data were collected regarding patients' demographics, laboratory parameters, SVR12, and adverse events, and were then analyzed using SPSS, version 22 (IBM SPSS Statistics, Armonk, NY). Results A total of 58 patients with cirrhosis and 58 patients without cirrhosis with chronic HCV were enrolled. The rate of SVR12 in patients with cirrhosis was 89.7% (52 patients achieved SVR12), compared to 98.3% in patients without cirrhosis (57 patients achieved SVR12). Subgroup analysis of patients with cirrhosis revealed that patients who have failed to achieve SVR12 were mostly males, had prolonged disease duration, and low hemoglobin at baseline; however, the association of these factors with SVR12 was not significant. The incidence of adverse events among all study participants was 46.5%. Among the cirrhotic cohort, 37 (63.8%) patients experienced adverse events, while only 17 (29.3%) patients among the non-cirrhotic cohort had adverse events. A total of 24 patients with cirrhosis (41.37%) reported mild complaints. The most commonly reported adverse event was gastrointestinal (GI) upsets (46.2%), followed by fatigue (33.9%), while 19.9% developed miscellaneous adverse events such as headaches, rash, and insomnia. Conclusion The combination of sofosbuvir and velpatasvir is highly effective and safe in patients with HCV with or without cirrhosis. However, this combination's efficacy was slightly higher in non-cirrhotic patients (98.3%) than in cirrhotic patients (89.7%).

17.
Int J Biol Macromol ; 185: 419-433, 2021 Aug 31.
Article in English | MEDLINE | ID: mdl-34166695

ABSTRACT

Hydrogels were prepared by mixing protein and carbohydrate-based biopolymers to increase the mechanical properties and efficient cell adhesion and proliferation for wound healing applications. Microcrystalline cellulose (MCC) and its 6-deoxy-aminocellulose derivatives (6-deoxy-6-hydrazide Cellulose (Cell-Hyd), 6-deoxy-6-diethylamide Cellulose (Cell-DEA), and 6-deoxy-6-diethyltriamide Cellulose (Cell-DETA)) were embedded in methacrylated gelatin (GelMA). GelMA and 6-deoxy-aminocellulose derivatives were synthesized and characterized by spectroscopic techniques. MCC and cellulose derivatives embedded GelMA gels were characterized by FTIR, SEM and Tensile mechanical testing. SEM images revealed that, porosity of the amine MCC incorporated GelMA was decreased compared to GelMA and MCC incorporated GelMA. Tensile strain of GelMA 61.30% at break was increased to 64.3% in case of GelMA/Cell-HYD. In vitro cytocompatibility and cell proliferation using NIH-3T3 cell lines showed cell density trend on scaffold as GelMA/Cell-DETA>GelMA/Cell-Hyd > GelMA. Scratch assay for wound healing revealed that GelMA/Cell-DETA showed complete wound closure, while GelMA/Cell-Hyd and GelMA exhibited 85.7%, and 66.1% wound healing, respectively in 8 h. In vivo tests on rats revealed that GelMA/Cell-DETA exhibited 98% wound closure on day 9, whereas GelMA/Cell-Hyd exhibited 97.7% and GelMA 66.1% wound healing on day 14. Our findings revealed that GelMA embedded amine MCC derivatives hydrogels can be applied for achieving accelerated wound healing.


Subject(s)
Cellulose/pharmacology , Gelatin/chemistry , Methacrylates/chemistry , Wound Healing/drug effects , Animals , Cell Proliferation , Cellulose/chemistry , Disease Models, Animal , Female , Hydrogels/chemistry , Mice , NIH 3T3 Cells , Rats , Spectroscopy, Fourier Transform Infrared , Tensile Strength , Tissue Scaffolds
18.
Math Biosci Eng ; 18(3): 2882-2908, 2021 03 28.
Article in English | MEDLINE | ID: mdl-33892576

ABSTRACT

Among the other cancer types, the brain tumor is one the leading cause of cancer across globe. If the tumor is properly identified at an earlier stage, then the chances of the survival can be increased. To categorize the brain tumor there are several factors including texture, type and location of brain tumor. We proposed a novel reconstruction independent component analysis (RICA) feature extraction method to detect multi-class brain tumor types (pituitary, meningioma, and glioma). We then employed the robust machine learning techniques as support vector machine (SVM) with quadratic and linear kernels and linear discriminant analysis (LDA). For training and testing of the data validation, a 10-fold cross validation was employed. For the multi-class classification, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy and AUC were, respectively, 97.78%, 100%, 100%, 99.07, 99.34% and 0.9892 to detect pituitary using SVM Cubic followed by meningioma with accuracy (96.96%0, AUC (0.9348) and glioma with accuracy (95.88%), AUC (0.9635). The findings indicates that RICA feature based proposed methodology has more potential to detect the multiclass brain tumor types for improving diagnostic efficiency and can further improve the prediction accuracy to achieve the clinical outcomes.


Subject(s)
Brain Neoplasms , Glioma , Brain , Brain Neoplasms/diagnosis , Glioma/diagnosis , Humans , Machine Learning , Support Vector Machine
19.
Cureus ; 13(2): e13121, 2021 Feb 04.
Article in English | MEDLINE | ID: mdl-33692915

ABSTRACT

Non-gestational choriocarcinoma of the ovary is a very rare neoplasm. It carries a worse prognosis as compared to gestational choriocarcinoma (GCC). Here, we report a case of non-gestational ovarian choriocarcinoma. The patient initially presented in a medical emergency with abdominal pain, a feeling of heaviness in the lower abdomen, cough, and dyspnea. The patient had four healthy children, and the last childbirth was five years ago. There was no history of any abortion or stillbirth in the past four years. A highly vascular left adnexal mass was observed on ultrasound abdomen and pelvis. Compute CT chest, abdomen, and pelvis were performed, which revealed metastatic left ovarian choriocarcinoma features. It also showed vascular metastases of the carcinoma in the kidneys, liver, and lungs. We report this case specifically emphasizing ultrasound, multidetector computed tomography (MDCT), and CT angiography findings.

20.
Cureus ; 13(2): e13208, 2021 Feb 07.
Article in English | MEDLINE | ID: mdl-33717747

ABSTRACT

Background and objective In low- and low-to-middle-income countries (LMICs), the incidence of treatment-related mortality (TRM) in patients with acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) is up to 52%. This study aimed to determine the mortality rate at the end of the induction phase of the treatment among patients with ALL and lymphoma at a tertiary care cancer center. Methods This retrospective study analyzed outcomes after induction chemotherapy in pediatric patients with acute leukemia and lymphoma at a tertiary care cancer center from January 2015 to December 2016. Information regarding demographics, clinical characteristics, and laboratory investigations were extracted and reviewed. Results Of the total 160 patients, 110 were males, and the mean age of the sample was 4.6 +2.8 years. B-cell leukemia (pre-B-ALL) was diagnosed in 84% (n=134), while 10% (n=6) had acute T-cell leukemia (pre-T-ALL) and 6% (n=10) had lymphoma. Sixteen patients (10%) died within the defined induction period, with 14 deaths occurring due to infections and two deaths resulting from chemotherapy-related toxicity. Conclusion Based on our findings, there is a significant prospect of mortality from infections during induction chemotherapy in patients with pediatric hematological malignancies.

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