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1.
J Med Virol ; 96(7): e29748, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38975633

RESUMO

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.


Assuntos
Terapia Viral Oncolítica , Vírus Oncolíticos , Neoplasias da Próstata , Vincristina , Humanos , Masculino , Neoplasias da Próstata/terapia , Neoplasias da Próstata/tratamento farmacológico , Vincristina/farmacologia , Vincristina/administração & dosagem , Terapia Viral Oncolítica/métodos , Linhagem Celular Tumoral , Vírus do Sarampo/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Células PC-3
3.
Sci Rep ; 14(1): 11431, 2024 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-38763930

RESUMO

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.


Assuntos
Quitosana , Fluoruracila , Receptores de Hialuronatos , Nanopartículas , Neoplasias de Mama Triplo Negativas , Fluoruracila/administração & dosagem , Fluoruracila/farmacologia , Fluoruracila/química , Quitosana/química , Humanos , Receptores de Hialuronatos/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Nanopartículas/química , Linhagem Celular Tumoral , Feminino , Portadores de Fármacos/química , Ácido Hialurônico/química , Sistemas de Liberação de Medicamentos , Antimetabólitos Antineoplásicos/farmacologia , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacocinética , Antimetabólitos Antineoplásicos/química , Sobrevivência Celular/efeitos dos fármacos , Tamanho da Partícula
5.
Sci Rep ; 14(1): 912, 2024 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-38195628

RESUMO

This study aimed at encapsulation of commonly administered, highly cytotoxic anticancer drug Docetaxel (DTX) in camel milk fat globule-derived liposomes for delivery in triple negative breast cancer cells. Prior to liposomal encapsulation of drug, in silico analysis of Docetaxel was done to predict off target binding associated toxicities in different organs. For this purpose, the ADMET Predictor (TM) Cloud version 10.4.0.5, 64-bit, was utilized to simulate Docetaxel's pharmacokinetic and physicochemical parameters. Freshly milked camel milk was bought from local market, from two breeds Brella and Marecha, in suburbs of Islamabad. After extraction of MFGM-derived liposomes from camel milk, docetaxel was loaded into liposomes by thin film hydration method. The physiochemical properties of liposomes were analyzed by SEM, FTIR and Zeta analysis. The results from SEM showed that empty liposomes (Lp-CM-ChT80) had spherical morphology while DTX loaded liposomes (Lp-CM-ChT80-DTX) exhibited rectangular shape, FTIR revealed the presence of characteristic functional groups which confirmed the successful encapsulation of DTX. Zeta analysis showed that Lp-CM-ChT80-DTX had size of 836.6 nm with PDI of 0.088 and zeta potential of - 18.7 mV. The encapsulation efficiency of Lp-CM-ChT80 turned out to be 25% while in vitro release assay showed slow release of DTX from liposomes as compared to pure DTX using dialysis membrane. The in vitro anticancer activity was analyzed by cell morphology analysis and MTT cytotoxicity assay using different concentrations 80 µg/ml, 120 µg/ml and 180 µg/ml of Lp-CM-ChT80-DTX on MDA-MB-231 cells. The results showed cytotoxic effects increased in time and dose dependent manner, marked by rounding, shrinkage and aggregation of cells. MTT cytotoxicity assay showed that empty liposomes Lp-CM-ChT80 did not have cytotoxic effect while Lp-CM-ChT80-DTX showed highest cytotoxic potential of 60.2% at 180 µg/ml. Stability analysis showed that liposomes were stable till 24 h in solution form at 4 °C.


Assuntos
Antimitóticos , Neoplasias de Mama Triplo Negativas , Animais , Humanos , Docetaxel , Camelus , Lipossomos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Preparações de Ação Retardada , Diálise Renal
6.
J Trace Elem Med Biol ; 81: 127324, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37944220

RESUMO

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.


Assuntos
Carica , Doença Hepática Induzida por Substâncias e Drogas , Persea , Ratos , Animais , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Cádmio/análise , Carica/metabolismo , Persea/metabolismo , Frutas/química , Frutas/metabolismo , Superóxido Dismutase/metabolismo , Biomarcadores/metabolismo , Estresse Oxidativo , Peroxidação de Lipídeos
7.
Front Immunol ; 14: 1175535, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37283735

RESUMO

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.


Assuntos
Quitosana , Neoplasias do Colo do Útero , Animais , Feminino , Humanos , Vírus da Doença de Newcastle , Quitosana/farmacologia , Neoplasias do Colo do Útero/terapia , Preparações de Ação Retardada , Imunoterapia , Microambiente Tumoral , Receptores de Hialuronatos
8.
Int J Nanomedicine ; 18: 185-205, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36643861

RESUMO

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.


Assuntos
Quitosana , Nanopartículas , Vírus Oncolíticos , Neoplasias da Próstata , Vacinas , Masculino , Humanos , Vírus do Sarampo/genética , Quitosana/química , Ácido Hialurônico , Neoplasias da Próstata/terapia , Neoplasias da Próstata/patologia , Caspases , Imunoterapia , Nanopartículas/química
9.
Healthcare (Basel) ; 10(12)2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36553864

RESUMO

Brain tumors (BTs) are an uncommon but fatal kind of cancer. Therefore, the development of computer-aided diagnosis (CAD) systems for classifying brain tumors in magnetic resonance imaging (MRI) has been the subject of many research papers so far. However, research in this sector is still in its early stage. The ultimate goal of this research is to develop a lightweight effective implementation of the U-Net deep network for use in performing exact real-time segmentation. Moreover, a simplified deep convolutional neural network (DCNN) architecture for the BT classification is presented for automatic feature extraction and classification of the segmented regions of interest (ROIs). Five convolutional layers, rectified linear unit, normalization, and max-pooling layers make up the DCNN's proposed simplified architecture. The introduced method was verified on multimodal brain tumor segmentation (BRATS 2015) datasets. Our experimental results on BRATS 2015 acquired Dice similarity coefficient (DSC) scores, sensitivity, and classification accuracy of 88.8%, 89.4%, and 88.6% for high-grade gliomas. When it comes to segmenting BRATS 2015 BT images, the performance of our proposed CAD framework is on par with existing state-of-the-art methods. However, the accuracy achieved in this study for the classification of BT images has improved upon the accuracy reported in prior studies. Image classification accuracy for BRATS 2015 BT has been improved from 88% to 88.6%.

10.
Int J Mol Sci ; 23(22)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36430305

RESUMO

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.


Assuntos
MicroRNAs , Neoplasias , Humanos , Microambiente Tumoral/genética , MicroRNAs/metabolismo , Imunoterapia , Neoplasias/genética , Neoplasias/terapia , Fatores Imunológicos
11.
Cancers (Basel) ; 14(18)2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36139618

RESUMO

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".

13.
Front Pharmacol ; 13: 1073004, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36712656

RESUMO

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.

14.
Front Pharmacol ; 12: 728054, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899292

RESUMO

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.

15.
Natl J Maxillofac Surg ; 12(3): 380-386, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35153435

RESUMO

BACKGROUND: A well-versed knowledge of the precise location of various anatomical landmarks is necessary to avoid complications during surgery. The study was conducted for the assessment of the anterior and caudal extent of the inferior alveolar nerve canal, location of inferior alveolar canal and mental foramen, and the depth of the submandibular fossa using computed tomography (CT). MATERIALS AND METHODS: One hundred CT scans were randomly selected for this study accounting for 200 hemimandibles. Both axial and coronal images were obtained and evaluated concurrently. Results were subjected to statistical analysis for correct inferences. RESULTS: A total of 200 hemimandibles (n = 200) from 100 patients with a mean age was 23.89 ± 1.75 years ranging from 21 to 33 years were evaluated. The mean length of the anterior loop was 0.95 mm for all of the observation combined and measurement range from 0 to 5.1 mm. The total frequency of type I, type II, and type III of mental nerve was found as 71%, 4.5%, and 24.5%, respectively. At the level of the first molar, the mean distance from the center of the inferior alveolar canal to the external surface of the buccal cortex (Q) was 5.44 ± 1.38 mm ranging from 2.4 to 10.4 mm. Furthermore, there was no statistically significant difference in MF-IMB (mental foramen to the inferior border of mandible) between the right and left sides of the mandible. (P = 0.87). CONCLUSION: Our study demonstrates that analyzing CT scans using the methods described in this study can be a useful tool in avoiding the iatrogenic injuries to inferior alveolar nerve and arteries during various maxillofacial surgical procedures.

16.
Mol Biol Rep ; 47(12): 9939-9949, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33185828

RESUMO

The outbreak of a novel coronavirus namely SARS-CoV-2, which first emerged from Wuhan, China, has wreaked havoc not only in China but the whole world that now has been engulfed in its wrath. In a short lapse of time, this virus was successful in spreading at a blistering pace throughout the globe, hence raising the flag of pandemic status. The mounting number of deaths with each elapsing day has summoned researchers from all around the world to play their part in driving this SARS-CoV-2 pandemic to an end. As of now, multiple research teams are immersed in either scrutinizing various antiviral drugs for their efficacy or developing different types of vaccines that will be capable of providing long-term immunity against this deadly virus. The mini-review sheds light on the possible approaches that can be undertaken to curb the COVID-19 spread. Possible strategies comprise viral vector-based, nucleic acid-based, protein-based, inactivated and weakened virus vaccines; COVID-19 vaccine being developed by deploying Hyleukin-7 technology; plant-based chimeric protein and subunit vaccines; humanized nano-bodies and human antibodies; intravenous immunoglobulin (IVIG) infusion therapy; inhibitors for ACE-2, Angiotensin 1 receptor (AT1R), complement system, viral proteins, host cell protease and endocytosis; shield immunity; IL-6R, NKG2A and hACE2-SARS-CoV-2-RBD interaction blocking monoclonal antibodies; SARS-CoV RdRp-based drugs, traditional Chinese medicine, repositioned and anti-viral drugs. These vaccines and drugs are currently being screened in the clinical trials as several of them have manifested positive results, hence increasing the probability of becoming one of the potential treatments for this disease.


Assuntos
Antivirais/farmacologia , Tratamento Farmacológico da COVID-19 , Vacinas contra COVID-19/farmacologia , COVID-19/prevenção & controle , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Enzima de Conversão de Angiotensina 2/antagonistas & inibidores , Anticorpos Monoclonais/farmacologia , Ensaios Clínicos como Assunto , Reposicionamento de Medicamentos , Humanos , Vírus da Bronquite Infecciosa/imunologia , Transplante de Células-Tronco Mesenquimais/métodos , RNA Mensageiro/imunologia , Proteínas Recombinantes/genética , Anticorpos de Domínio Único/farmacologia , Vacinas Atenuadas/farmacologia , Vacinas de Subunidades Antigênicas/farmacologia , Vacinas Sintéticas/farmacologia
18.
Gastroenterol Res Pract ; 2017: 2098293, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29225617

RESUMO

OBJECTIVES: Mucosal healing has become the new goal of treatment in ulcerative colitis. Fecal calprotectin has been demonstrated to differentiate between mucosal inflammation and mucosal healing. With this project, we investigated whether a reduction in f-calprotectin to <250 µg/g after medical treatment for active ulcerative colitis could predict mucosal healing. MATERIAL AND METHODS: After a baseline colonoscopy, 20 patients with active ulcerative colitis were followed with consecutive fecal calprotectin monthly until two measurements of fecal calprotectin < 250 µg/g or a maximum follow-up of 12 months. A flexible sigmoidoscopy was then performed and Mayo endoscopic subscore was used to evaluate degree of inflammation. Simple Clinical Colitis Activity Index was used for evaluation of clinical disease activity. RESULTS: A total of 16 patients achieved fecal calprotectin < 250 µg/g during follow-up, and all 16 patients had endoscopic mucosal healing (Mayo endoscopic subscore of ≤1) on the second endoscopy. The remaining four patients had persistently high f-calprotectin levels before the second endoscopy with Mayo endoscopic subscore corresponding to endoscopic mucosal healing in three out of four patients. CONCLUSIONS: Fecal calprotectin <250 µg/g after medical treatment for active ulcerative colitis is a reliable marker of endoscopic mucosal healing.

19.
Ann Agric Environ Med ; 23(4): 576-580, 2016 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-28030926

RESUMO

Viral gastroenteritis and other water-borne diseases are the most neglected areas of research in Pakistan. To determine the quality of water, 4 enteric viruses were studied from different localities of Peshawar, Pakistan. The study validates the viral detection method for Rotavirus (RV), Human adenovirus (HAdV), Enterovirus (EV) and Hepatitis A virus (HAV), directly from water sources of rural areas of Peshawar, KPK, Pakistan. Overall, 95 five water samples were tested; among them, 9.47% were positive for RV, 38.94% for HAdV, 48.42% for EV and 12.63% for HAV. The presence of these viruses in water was directly correlated with meteorological data. High prevalence of EV and HAdV was detected frequently in the wet season from May - September, which can be the potential cause of spreading of gastroenteritis in the population. Environmental surveillance is an additional tool to evaluate the epidemiology of enteric viruses circulating in a given community.


Assuntos
Infecções por Adenovirus Humanos/epidemiologia , Água Potável/virologia , Infecções por Enterovirus/epidemiologia , Vírus de RNA/isolamento & purificação , Infecções por Rotavirus/epidemiologia , Infecções por Adenovirus Humanos/virologia , Adenovírus Humanos/isolamento & purificação , Enterovirus/isolamento & purificação , Infecções por Enterovirus/virologia , Hepatite A/epidemiologia , Hepatite A/virologia , Vírus da Hepatite A/isolamento & purificação , Paquistão/epidemiologia , Prevalência , Rotavirus/isolamento & purificação , Infecções por Rotavirus/virologia
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