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1.
PeerJ ; 11: e15743, 2023.
Article En | MEDLINE | ID: mdl-37601248

Background: The green approaches for the synthesis of nanoparticles are gaining significant importance because of their high productivity, purity, low cost, biocompatibility, and environmental friendliness. Methods: The aim of the current study is the green synthesis of zinc oxide nanoparticles (ZnO-NPs) using seed extracts of Silybum marianum, which acts as a reducing and stabilizing agent. central composite design (CCD) of response surface methodology (RSM) optimized synthesis parameters (temperature, pH, reaction time, plant extract, and salt concentration) for controlled size, stability, and maximum yields of ZnO-NPs. Green synthesized ZnO-NPs was characterized using UV-visible spectroscopy and Zetasizer analyses. Results: The Zetasizer confirmed that green synthesized ZnO-NPs were 51.80 nm in size and monodispersed in nature. The UV-visible results revealed a large band gap energy in the visible region at 360.5 nm wavelength. The bioactivities of green synthesized ZnO-NPs, including antifungal, antibacterial, and pesticidal, were also evaluated. Data analysis confirmed that these activities were concentration dependent. Bio-synthesized ZnO-NPs showed higher mortality towards Tribolium castaneum of about 78 ± 0.57% after 72 h observation as compared to Sitophilus oryzae, which only displayed 74 ± 0.57% at the same concentration and time intervals. Plant-mediated ZnO-NPs also showed high potential against pathogenic gram-positive bacteria (Clavibacter michiganensis), gram-negative bacteria (Pseudomonas syringae), and two fungal strains such as Fusarium oxysporum, and Aspergillums niger with inhibition zones of 18 ± 0.4, 25 ± 0.4, 21 ± 0.57, and 19 ± 0.4 mm, respectively. Conclusion: The results of this study showed that Silybum marianum-based ZnO-NPs are cost-effective and efficient against crop pests.


Asteraceae , Nanoparticles , Zinc Oxide , Silybum marianum , Zinc Oxide/pharmacology , Anti-Bacterial Agents
2.
Biomolecules ; 13(1)2023 01 03.
Article En | MEDLINE | ID: mdl-36671484

The global outbreak of COVID-19 possesses serious challenges and adverse impacts for patients with progression of chronic liver disease and has become a major threat to public health. COVID-19 patients have a high risk of lung injury and multiorgan dysfunction that remains a major challenge to hepatology. COVID-19 patients and those with liver injury exhibit clinical manifestations, including elevation in ALT, AST, GGT, bilirubin, TNF-α, and IL-6 and reduction in the levels of CD4 and CD8. Liver injury in COVID-19 patients is induced through multiple factors, including a direct attack of SARS-CoV-2 on liver hepatocytes, hypoxia reperfusion dysfunction, cytokine release syndrome, drug-induced hepatotoxicity caused by lopinavir and ritonavir, immune-mediated inflammation, renin-angiotensin system, and coagulopathy. Cellular and molecular mechanisms underlying liver dysfunction are not fully understood in severe COVID-19 attacks. High mortality and the development of chronic liver diseases such as cirrhosis, alcoholic liver disease, autoimmune hepatitis, nonalcoholic fatty liver disease, and hepatocellular carcinoma are also associated with patients with liver damage. COVID-19 patients with preexisting or developing liver disease should be managed. They often need hospitalization and medication, especially in conjunction with liver transplants. In the present review, we highlight the attack of SARS-CoV-2 on liver hepatocytes by exploring the cellular and molecular events underlying the pathophysiological mechanisms in COVID-19 patients with liver injury. We also discuss the development of chronic liver diseases during the progression of SARS-CoV-2 replication. Lastly, we explore management principles in COVID-19 patients with liver injury and liver transplantation.


COVID-19 , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Humans , COVID-19/complications , SARS-CoV-2
3.
Life Sci ; 316: 121409, 2023 Mar 01.
Article En | MEDLINE | ID: mdl-36681183

Chimeric antigen receptor (CAR) T therapy has shown remarkable success in discovering novel CAR-T cell products for treating malignancies. Despite of successful results from clinical trials, CAR-T cell therapy is ineffective for long-term disease progression. Numerous challenges of CAR-T cell immunotherapy such as cell dysfunction, cytokine-related toxicities, TGF-ß resistance, GvHD risks, antigen escape, restricted trafficking, and tumor cell infiltration still exist that hamper the safety and efficacy of CAR-T cells for malignancies. The accumulated data revealed that these challenges could be overcome with the advanced CRISPR genome editing technology, which is the most promising tool to knockout TRAC and HLA genes, inhibiting the effects of dominant negative receptors (PD-1, TGF-ß, and B2M), lowering the risks of cytokine release syndrome (CRS), and regulating CAR-T cell function in the tumor microenvironment (TME). CRISPR technology employs DSB-free genome editing methods that robustly allow efficient and controllable genetic modification. The present review explored the innovative aspects of CRISPR/Cas9 technology for developing next-generation/universal allogeneic CAR-T cells. The present manuscript addressed the ongoing status of clinical trials of CRISPR/Cas9-engineered CAR-T cells against cancer and pointed out the off-target effects associated with CRISPR/Cas9 genome editing. It is concluded that CAR-T cells modified by CRISPR/Cas9 significantly improved antitumor efficacy in a cost-effective manner that provides opportunities for novel cancer immunotherapies.


Neoplasms , Receptors, Chimeric Antigen , Humans , CRISPR-Cas Systems/genetics , Receptors, Chimeric Antigen/genetics , Receptors, Chimeric Antigen/metabolism , Immunotherapy , Neoplasms/genetics , Neoplasms/therapy , T-Lymphocytes , Tumor Microenvironment
4.
Am J Cancer Res ; 12(7): 2897-2919, 2022.
Article En | MEDLINE | ID: mdl-35968347

Cancer is the second leading cause of death all around the world. The natural compounds derived from the endophytic flora of fungi are possible solutions to cancer treatment because they are safe for health, cost-effective, biocompatible and have fewer toxicity issues. The active ingredients in endophytic fungi that are responsible for anti-cancer activities are alkaloids, terpenoids, glycosides, saponin, peptides, steroids, phenols, quinones, and flavonoids. This review highlights the anti-cancer activities of entophytic fungus against human papillary thyroid carcinoma (IHH4), human pancreatic (PANC-1), ovarian (OVCAR-3), hepatic (HepG2), lung (A-549), human lymphoma (U937), human skin carcinoma (A431), breast (MCF-7), and Kaposi's sarcoma. The emerging evidence suggested that bioactive compounds isolated from endophytic fungi showed their anti-cancer activities by revealing the disturbance of the microtubule network caused by increased levels of Bax and Bcl-2 proteins that triggers cell cycle arrest at the G2-M phase, by inhibiting the DNA replication via binding with topoisomerase II, by regulating the activity of extracellular signal-regulated kinase and NF-kB, by evaluating the levels of p21, p27, and cyclins B/D1/E that led to cell death by apoptosis and cell cycle arrest. This review will assist readers in better comprehending bioactive chemicals and the beneficial interaction between the fungal endophytes and medicinal plants.

5.
Biomolecules ; 12(7)2022 07 11.
Article En | MEDLINE | ID: mdl-35883527

The number of deaths has been increased due to COVID-19 infections and uncertain neurological complications associated with the central nervous system. Post-infections and neurological manifestations in neuronal tissues caused by COVID-19 are still unknown and there is a need to explore how brainstorming promoted congenital impairment, dementia, and Alzheimer's disease. SARS-CoV-2 neuro-invasion studies in vivo are still rare, despite the fact that other beta-coronaviruses have shown similar properties. Neural (olfactory or vagal) and hematogenous (crossing the blood-brain barrier) pathways have been hypothesized in light of new evidence showing the existence of SARS-CoV-2 host cell entry receptors into the specific components of human nerve and vascular tissue. Spike proteins are the primary key and structural component of the COVID-19 that promotes the infection into brain cells. Neurological manifestations and serious neurodegeneration occur through the binding of spike proteins to ACE2 receptor. The emerging evidence reported that, due to the high rate in the immediate wake of viral infection, the olfactory bulb, thalamus, and brain stem are intensely infected through a trans-synaptic transfer of the virus. It also instructs the release of chemokines, cytokines, and inflammatory signals immensely to the blood-brain barrier and infects the astrocytes, which causes neuroinflammation and neuron death; and this induction of excessive inflammation and immune response developed in more neurodegeneration complications. The present review revealed the pathophysiological effects, molecular, and cellular mechanisms of possible entry routes into the brain, pathogenicity of autoantibodies and emerging immunotherapies against COVID-19.


COVID-19 , SARS-CoV-2 , Blood-Brain Barrier/metabolism , Brain/metabolism , Humans , Spike Glycoprotein, Coronavirus/chemistry
6.
Molecules ; 27(11)2022 May 25.
Article En | MEDLINE | ID: mdl-35684353

Breast cancer (BC) is the second leading cause of death among women, and it has become a global health issue due to the increasing number of cases. Different treatment options, including radiotherapy, surgery, chemotherapy and anti-estrogen therapy, aromatase inhibitors, anti-angiogenesis drugs, and anthracyclines, are available for BC treatment. However, due to its high occurrence and disease progression, effective therapeutic options for metastatic BC are still lacking. Considering this scenario, there is an urgent need for an effective therapeutic strategy to meet the current challenges of BC. Natural products have been screened as anticancer agents as they are cost-effective, possess low toxicity and fewer side effects, and are considered alternative therapeutic options for BC therapy. Natural products showed anticancer activities against BC through the inhibition of angiogenesis, cell migrations, proliferations, and tumor growth; cell cycle arrest by inducing apoptosis and cell death, the downstream regulation of signaling pathways (such as Notch, NF-κB, PI3K/Akt/mTOR, MAPK/ERK, and NFAT-MDM2), and the regulation of EMT processes. Natural products also acted synergistically to overcome the drug resistance issue, thus improving their efficacy as an emerging therapeutic option for BC therapy. This review focused on the emerging roles of novel natural products and derived bioactive compounds as therapeutic agents against BC. The present review also discussed the mechanism of action through signaling pathways and the synergistic approach of natural compounds to improve their efficacy. We discussed the recent in vivo and in vitro studies for exploring the overexpression of oncogenes in the case of BC and the current status of newly discovered natural products in clinical investigations.


Antineoplastic Agents , Biological Products , Breast Neoplasms , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Biological Products/pharmacology , Biological Products/therapeutic use , Breast Neoplasms/metabolism , Female , Humans , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction
7.
Clin. transl. oncol. (Print) ; 24(3): 432-445, marzo 2022.
Article En | IBECS | ID: ibc-203539

Natural products, especially polyphenols (phenolic acids, lignans, and stilbenes) are suggested to be more potent anticancer drugs because of their no or less adverse effects, excess availability, high accuracy, and secure mode of action. In the present review, potential anticancer mechanisms of action of some polyphenols including phenolic acids, lignans, and stilbenes are discussed based on clinical, epidemiological, in vivo, and in vitro studies. The emerging evidence revealed that phenolic acids, lignans, and stilbenes induced apoptosis in the treatment of breast (MCF-7), colon (Caco-2), lung (SKLU-1), prostate (DU-145 and LNCaP), hepatocellular (hepG-2), and cervical (A-431) cancer cells, cell cycle arrest (S/G2/M/G1-phases) in gastric (MKN-45 and MKN-74), colorectal (HCT-116), bladder (T-24 and 5637), oral (H-400), leukemic (HL-60 and MOLT-4) and colon (Caco-2) cancer cells, and inhibit cell proliferation against the prostate (PC-3), liver (LI-90), breast (T47D and MDA-MB-231), colon (HT-29 and Caco-2), cervical (HTB-35), and MIC-1 cancer cells through caspase-3, MAPK, AMPK, Akt, NF-κB, Wnt, CD95, and SIRT1 pathways. Based on accumulated data, we suggested that polyphenols could be considered as a viable therapeutic option in the treatment of cancer cells in the near future.


Hydroxybenzoates/pharmacology , Hydroxybenzoates/therapeutic use , Lignans/pharmacology , Lignans/therapeutic use , Stilbenes/pharmacology , Stilbenes/therapeutic use , Neoplasms/prevention & control , Polyphenols/pharmacology , Polyphenols/therapeutic use , Signal Transduction
8.
J Fungi (Basel) ; 8(2)2022 Jan 24.
Article En | MEDLINE | ID: mdl-35205863

With the increasing world population, demand for industrialization has also increased to fulfill humans' living standards. Fungi are considered a source of essential constituents to produce the biocatalytic enzymes, including amylases, proteases, lipases, and cellulases that contain broad-spectrum industrial and emerging applications. The present review discussed the origin, nature, mechanism of action, emerging aspects of genetic engineering for designing novel proteases, genome editing of fungal strains through CRISPR technology, present challenges and future recommendations of fungal proteases. The emerging evidence revealed that fungal proteases show a protective role to many environmental exposures and discovered that an imbalance of protease inhibitors and proteases in the epithelial barriers leads to the protection of chronic eosinophilic airway inflammation. Moreover, mitoproteases recently were found to execute intense proteolytic processes that are crucial for mitochondrial integrity and homeostasis function, including mitochondrial biogenesis, protein synthesis, and apoptosis. The emerging evidence revealed that CRISPR/Cas9 technology had been successfully developed in various filamentous fungi and higher fungi for editing of specific genes. In addition to medical importance, fungal proteases are extensively used in different industries such as foods to prepare butter, fruits, juices, and cheese, and to increase their shelf life. It is concluded that hydrolysis of proteins in industries is one of the most significant applications of fungal enzymes that led to massive usage of proteomics.

9.
Chemosphere ; 292: 133411, 2022 Apr.
Article En | MEDLINE | ID: mdl-34958785

The rapidly emerging field of nanotechnology is considered an important achievement in the agriculture sector to increase the pest mortality rate and improve the crop production. The present study evaluates the novel pesticidal and anti-microbial activities of Chrysanthemum coronarium and Azadirachta indica in the nano-suspensions form. The anti-solvent precipitation method was used to formulate nano-suspensions proposed by Response Surface Methodology (RSM). Physicochemical nature of plant extracts and nano-suspensions was characterized through analysis of Zeta-sizer, FT-IR, and HPLC. Characterization results revealed a minimum particle size of 121.1 and 170.1 nm for Chrysanthemum coronarium and Azadirachta indica, respectively. The pesticidal activity of nano-suspension was performed against red flour beetle (RFB) and lesser grain borer (LGB) pests, which showed the maximum mortality rate of 100% with 100% concentration of plant extracts and nano-suspensions of Chrysanthemum coronarium and Azadirachta indica against both insects. In comparison, the combination of these both plant extracts revealed the maximum 100% mortality with a 50% concentration of nano-suspensions (mixing ratio 1:1) after 72 h. The antibacterial activity showed the maximum zone inhibition of 9.96 ± 0.17 and 14.17 ± 0.50 mm against S.aureus and E. coli with nano-suspension of Chrysanthemum coronarium, and 12.09 ± 0.11 and 14.10 ± 0.49 mm with nano-suspension of Azadirachta indica, respectively. It is concluded that individual nano-suspensions showed better pesticidal as well as antimicrobial activities than combinations. However, the constructed nanosuspension can be applied to control the plant pests and diseases simultaneously.


Azadirachta , Chrysanthemum , Escherichia coli , Pest Control , Plant Extracts , Spectroscopy, Fourier Transform Infrared
10.
Environ Sci Pollut Res Int ; 29(41): 61896-61904, 2022 Sep.
Article En | MEDLINE | ID: mdl-34559388

During the past few decades, the treatment of hazardous waste and toxic phenolic compounds has become a major issue in the pharmaceutical, gas/oil, dying, and chemical industries. Considering polymerization and oxidation of phenolic compounds, supercritical water oxidation (SCWO) has gained special attention. The present study objective was to synthesize a novel in situ Fe2O3nano-catalyst in a counter-current mixing reactor by supercritical water oxidation (SCWO) method to evaluate the phenol oxidation and COD reduction at different operation conditions like oxidant ratios and concentrations. Synthesized nano-catalyst was characterized by powder X-ray diffraction (XRD) and transmission electron microscope (TEM). TEM results revealed the maximum average particle size of 26.18 and 16.20 nm for preheated and non-preheated oxidant configuration, respectively. XRD showed the clear peaks of hematite at a 2θ value of 24, 33, 35.5, 49.5, 54, 62, and 64 for both catalysts treated preheated and non-preheated oxidant configurations. The maximum COD reduction and phenol oxidation of about 93.5% and 99.9% were observed at an oxidant ratio of 1.5, 0.75 s, 25 MPa, and 380 °C with a non-preheated H2O2 oxidant, while in situ formed Fe2O3nano-catalyst showed the maximum phenol oxidation of 99.9% at 0.75 s, 1.5 oxidant ratio, 25 MPa, and 380 °C. Similarly, in situ formed Fe2O3 catalyst presented the highest COD reduction of 97.8% at 40 mM phenol concentration, 1.0 oxidant ratio, 0.75 s residence time, 380 °C, and 25 MPa. It is concluded and recommended that SCWO is a feasible and cost-effective alternative method for the destruction of contaminants in water which showed the complete conversion of phenol within less than 1 s and 1.5 oxidant ratio.


Water Pollutants, Chemical , Water Purification , Catalysis , Hydrogen Peroxide/chemistry , Oxidants , Oxidation-Reduction , Phenol/chemistry , Phenols , Water/chemistry , Water Pollutants, Chemical/chemistry , Water Purification/methods
11.
Bioengineered ; 12(2): 12702-12721, 2021 12.
Article En | MEDLINE | ID: mdl-34949157

The overuse of cisplatin (>50 mg/m2) is limited to nephrotoxicity, ototoxicity, gastrotoxicity, myelosuppression, and allergic reactions. The objective of this study was to investigate the nephroprotective effects of Daucus carota and Eclipta prostrata extracts on cisplatin-induced nephrotoxicity in Wistar albino rats. The study involved male Wistar albino rats of 8 weeks weighing 220-270 g. A single injection of 5 mg/kg was injected into the rats for nephrotoxicity. Rats were divided into four groups based on dose conentrations. Blood and urine samples of rats were collected on the 0, 7th, 14th, and 21st days for nephrological analysis. The results showed that Cis + DC/Cis + EP (600 mg/kg) significantly (p < 0.001) increased the body weight and reduced the kidney weight of cisplatin-induced nephrotoxicity in rats (p < 0.001) as compared to Cis group. The results showed that 600 mg/kg administration of Cis + DC/Cis +EP successfully (p < 0.005) improved the urine and plasmin creatinine, Na, and K level compared to the Cis group. Histopathological results confirmed that Cis + EP/Cis + DC effectively improved the renal abnormalities. It is concluded that the co-administration of Cis + EP extract showed exceptional nephroprotective effects at a dose rate of 600 mg/kg.


Cisplatin/adverse effects , Daucus carota/chemistry , Eclipta/chemistry , Kidney Diseases/chemically induced , Kidney Diseases/drug therapy , Protective Agents/therapeutic use , Animals , Body Weight/drug effects , Creatinine/blood , Kidney/drug effects , Kidney/pathology , Kidney Diseases/blood , Kidney Diseases/urine , Male , Organ Size/drug effects , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Potassium/urine , Protective Agents/pharmacology , Rats, Wistar , Sodium/urine , Urination/drug effects
12.
Plants (Basel) ; 10(10)2021 Sep 30.
Article En | MEDLINE | ID: mdl-34685887

Globally, the availability of phosphorus (P) to crops remains limited in two-thirds of the soils, which makes it less accessible to plants and ultimately associated with low crop yields. The present study investigated the effect of phosphorus-solubilizing bacteria (PSB; Pseudomonas spp.) for the improvement of phosphorus in mung bean (Vigna radiata) varieties and growth of net grain and biological yields. Results showed that inoculation of mung bean varieties with PSB at the rate of 100 g/kg seed significantly improved the root and shoot dry weight of about 1.13 and 12.66 g, root and shoot length of 14.49 and 50.63 cm, root and shoot phosphorus content of 2629.39 and 4138.91 mg/kg, a biological yield of 9844.41 kg/ha, number of pods of 17 per plant, number of grains of 9 per pod, grain yield of 882.23 kg/ha, and 1000-grain weight of 46.18 g after 60 days of observation. It was also observed that PSB-treated varieties of mung bean showed the maximum photosynthetic yield, photosynthetic active radiation, electron transport rate, and momentary fluorescent rate of 0.75, 364.32, 96.12, and 365.33 µmol/m2 s, respectively. The highest harvest index of 13.28% was recorded by P-treated mung beans. Results disclosed that inoculation of seeds of mung bean with PSB exhibited different effects in measured parameters. It is concluded that PSB possessed remarkable results in measured parameters compared to the control and highlighted that PSB could be an effective natural sustainable fertilizer for mung bean cultivation in sandy soil.

13.
Leuk Res ; 104: 106554, 2021 05.
Article En | MEDLINE | ID: mdl-33684680

Lymphoma is a heterogeneous group of malignancies, which comprises 4.2 % of all new cancer cases and 3.3 % of all cancer deaths in 2019, globally. The dysregulation of immune system, certain bacterial or viral infections, autoimmune diseases, and immune suppression are associated with a high risk of lymphoma. Although several conventional strategies have improved during the past few decades, but their detrimental impacts remain an obstacle to be resolved. However, natural compounds are considered a good option in the treatment of lymphomas because of their easy accessibility, specific mode of action, high biodegradability, and cost-effectiveness. Vegetables, fruits, and beverages are the primary sources of natural active compounds. The present review investigated the activities of different natural medicinal compounds including curcumin, MK615, resveratrol, bromelain, EGCG, and Annonaceous acetogenins to treat lymphomas. Moreover, in vitro and in vivo studies, classification, risk factors, and diagnosis of lymphoma are also discussed in the present review. The accumulated data proposed that natural compounds regulate the signaling pathways at the level of cell proliferation, apoptosis, and cell cycle to exhibit anti-lymphoma activities both in-vivo and in-vitro studies and suggested that these active compounds could be a good therapeutic option in the treatment of different types of lymphomas.


Antineoplastic Agents, Phytogenic/therapeutic use , Apoptosis/drug effects , Cell Cycle/drug effects , Lymphoma , Signal Transduction/drug effects , Humans , Lymphoma/drug therapy , Lymphoma/metabolism , Lymphoma/pathology
14.
Life Sci ; 264: 118679, 2021 Jan 01.
Article En | MEDLINE | ID: mdl-33130077

Humanin (HN) is a small mitochondrial-derived cytoprotective polypeptide encoded by mtDNA. HN exhibits protective effects in several cell types, including leukocytes, germ cells, neurons, tissues against cellular stress conditions and apoptosis through regulating various signaling mechanisms, such as JAK/STAT pathway and interaction of BCL-2 family of protein. HN is an essential cytoprotective peptide in the human body that regulates mitochondrial functions under stress conditions. The present review aims to evaluate HN peptide's antiapoptotic activities as a potential therapeutic target in the treatment of cancer, diabetes mellitus, male infertility, bone-related diseases, cardiac diseases, and brain diseases. Based on in vitro and in vivo studies, HN significantly suppressed the apoptosis during the treatment of bone osteoporosis, cardiovascular diseases, diabetes mellitus, and neurodegenerative diseases. According to accumulated data, it is concluded that HN exerts the proapoptotic activity of TNF-α in cancer, which makes HN as a novel therapeutic agent in the treatment of cancer and suggested that along with HN, the development of another mitochondrial-derived peptide could be a viable therapeutic option against different oxidative stress and apoptosis-related diseases.


Apoptosis/physiology , Cytoprotection/physiology , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/therapeutic use , Mitochondria/metabolism , Amino Acid Sequence , Animals , Apoptosis/drug effects , Apoptosis Regulatory Proteins/genetics , Apoptosis Regulatory Proteins/metabolism , Apoptosis Regulatory Proteins/therapeutic use , Diabetes Mellitus/drug therapy , Diabetes Mellitus/genetics , Diabetes Mellitus/metabolism , Humans , Intracellular Signaling Peptides and Proteins/genetics , Mitochondria/genetics , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/metabolism , Neurodegenerative Diseases/drug therapy , Neurodegenerative Diseases/genetics , Neurodegenerative Diseases/metabolism
15.
Life Sci ; 263: 118525, 2020 Dec 15.
Article En | MEDLINE | ID: mdl-33031826

Cancer is one of the most leading causes of death and a major public health problem, universally. According to accumulated data, annually, approximately 8.5 million people died because of the lethality of cancer. Recently, a novel RNA domain-containing endonuclease-based genome engineering technology, namely the clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein-9 (Cas9) have been proved as a powerful technique in the treatment of cancer cells due to its multifunctional properties including high specificity, accuracy, time reducing and cost-effective strategies with minimum off-target effects. The present review investigates the overview of recent studies on the newly developed genome-editing strategy, CRISPR/Cas9, as an excellent pre-clinical therapeutic option in the reduction and identification of new tumor target genes in the solid tumors. Based on accumulated data, we revealed that CRISPR/Cas9 significantly inhibited the robust tumor cell growth (breast, lung, liver, colorectal, and prostate) by targeting the oncogenes, tumor-suppressive genes, genes associated to therapies by inhibitors, genes associated to chemotherapies drug resistance, and suggested that CRISPR/Cas9 could be a potential therapeutic target in inhibiting the tumor cell growth by suppressing the cell-proliferation, metastasis, invasion and inducing the apoptosis during the treatment of malignancies in the near future. The present review also discussed the current challenges and barriers, and proposed future recommendations for a better understanding.


CRISPR-Cas Systems , Gene Editing , Genetic Therapy , Genome, Human , Neoplasms/therapy , Humans , Neoplasms/genetics , Neoplasms/pathology
16.
Life Sci ; 260: 118421, 2020 Nov 01.
Article En | MEDLINE | ID: mdl-32926920

In December 2019, a novel virus, namely COVID-19 caused by SARS-CoV-2, developed from Wuhan, (Hubei territory of China) used its viral spike glycoprotein receptor-binding domain (RBD) for the entrance into a host cell by binding with ACE-2 receptor and cause acute respiratory distress syndrome (ARDS). Data revealed that the newly emerged SARS-CoV-2 affected more than 24,854,140 people with 838,924 deaths worldwide. Until now, no licensed immunization or drugs are present for the medication of SARS-CoV-2. The present review aims to investigate the latest developments and discuss the candidate antibodies in different vaccine categories to develop a reliable and efficient vaccine against SARS-CoV-2 in a short time duration. Besides, the review focus on the present challenges and future directions, structure, and mechanism of SARS-CoV-2 for a better understanding. Based on data, we revealed that most of the vaccines are focus on targeting the spike protein (S) of COVID-19 to neutralized viral infection and develop long-lasting immunity. Up to phase-1 clinical trials, some vaccines showed the specific antigen-receptor T-cell response, elicit the humoral and immune response, displayed tight binding with human-leukocytes-antigen (HLA), and recognized specific antibodies to provoke long-lasting immunity against SARS-CoV-2.


Antibodies, Viral/immunology , Antigens, Viral/immunology , Betacoronavirus/immunology , Epitopes/immunology , Viral Envelope Proteins/immunology , Viral Vaccines/administration & dosage , Viral Vaccines/immunology , COVID-19 , COVID-19 Vaccines , Coronavirus Infections/immunology , Coronavirus Infections/prevention & control , Coronavirus Infections/virology , Humans , Pandemics/prevention & control , Pneumonia, Viral/immunology , Pneumonia, Viral/prevention & control , Pneumonia, Viral/virology , SARS-CoV-2
17.
Int J Biol Macromol ; 161: 1272-1285, 2020 Oct 15.
Article En | MEDLINE | ID: mdl-32502609

Clay-based composites were prepared, characterized, and applied for the elimination of Blue FBN (BFBN) and Rose FRN (RFRN) dyes. The Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), Thermogravimetric (TGA) and X-ray diffraction analyses were performed to check the interaction of dye molecule with adsorbents. The analysis showed a successful interaction between adsorbent and dyes ions. The experimental data was best fitted with Freundlich isotherm for both dyes (BFBN and RFRN). The findings revealed that at 80 min the adsorption grasped equilibrium in the case of both dyes and succeeded the pseudo-second-order kinetics model. Furthermore, the enthalpy (ΔH°), Gibbs free energy (ΔG°) and entropy (ΔS°) changes suggested that adsorption was exothermic, physical and spontaneous in nature. The maximum adsorption capacities were determined as 76.39% for BFBN and 59.85% for RFRN dye at pH 2.0 and 30 °C. Composites found to be stable at higher temperature and regenerated using MgSO4 eluting agent. The textile effluent colour was removed up to 50.35 and 54.95% using raw and modified clay, respectively. The modified clay showed promising efficiency for adsorption of synthetic BFBN and RFRN dyes from aqueous solution, which could be a viable option for the treatment of industrial wastewater and textile effluents.


Alginates/chemistry , Biocompatible Materials/chemistry , Clay/chemistry , Wastewater/chemistry , Water Purification , Adsorption , Coloring Agents/chemistry , Hydrogen-Ion Concentration , Kinetics , Models, Chemical , Physical Phenomena , Spectroscopy, Fourier Transform Infrared , Temperature , Thermodynamics , Thermogravimetry , Water Pollutants, Chemical/chemistry , Water Purification/methods , X-Ray Diffraction
18.
Drug Metab Rev ; 52(3): 408-424, 2020 08.
Article En | MEDLINE | ID: mdl-32546018

Despite to outbreaks of highly pathogenic beta and alpha coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and human coronavirus, the newly emerged 2019 coronavirus (COVID-19) is considered as a lethal zoonotic virus due to its deadly respiratory syndrome and high mortality rate among the human. Globally, more than 3,517,345 cases have been confirmed with 243,401 deaths due to Acute Respiratory Distress Syndrome (ARDS) caused by COVID-19. The antiviral drug discovery activity is required to control the persistence of COVID-19 circulation and the potential of the future emergence of coronavirus. However, the present review aims to highlight the important antiviral approaches, including interferons, ribavirin, mycophenolic acids, ritonavir, lopinavir, inhibitors, and monoclonal antibodies (mAbs) to provoke the nonstructural proteins and deactivate the structural and essential host elements of the virus to control and treat the infection of COVID-19 by inhibiting the viral entry, viral RNA replication and suppressing the viral protein expression. Moreover, the present review investigates the epidemiology, diagnosis, structure, and replication of COVID-19 for better understanding. It is recommended that these proteases, inhibitors, and antibodies could be a good therapeutic option in drug discovery to control the newly emerged coronavirus.HighlightsCOVID-19 has more than 79.5% identical sequence to SARS-CoV and a 96% identical sequence of the whole genome of bat coronaviruses.Acute respiratory distress syndrome (ARDS), renal failure, and septic shock are the possible clinical symptoms associated with COVID-19.Different antivirals, including interferons, ribavirin, lopinavir, and monoclonal antibodies (mAbs) could be the potent therapeutic agents against COVID-19.The initial clinical trials on hydroquinone in combination with azithromycin showed an admirable result in the reduction of COVID-19.The overexpression of inflammation response, cytokine dysregulation, and induction of apoptosis could be an well-organized factors to reduce the pathogenicity of COVID-19.


Antiviral Agents/therapeutic use , Betacoronavirus , Coronavirus Infections/drug therapy , Drug Discovery , Pneumonia, Viral/drug therapy , Antibodies, Monoclonal/therapeutic use , Betacoronavirus/chemistry , Betacoronavirus/genetics , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Humans , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , SARS-CoV-2 , Serine Endopeptidases/physiology , Serine Proteinase Inhibitors/therapeutic use , Virus Replication , COVID-19 Drug Treatment
19.
Nutr Cancer ; 72(3): 386-397, 2020.
Article En | MEDLINE | ID: mdl-31287738

Cancer remains a second leading cause of deaths and major public health problem. It occurs due to extensive DNA damage caused by ultraviolet radiations, ionizing radiations, environmental agents, therapeutic agents, etc. Among all cancers, the most frequently diagnosed cancers are lung (12.7%), breast (10.9%), colorectal (9.7%), and gastric cancer (7.81%). Natural compounds are most favorable against cancer on the count of their anti-cancerous ability, easy to avail and efficient. Among natural compounds, polyphenols (flavonoids, catechin, hesperetin, flavones, quercetin, phenolic acids, ellagic acid, lignans, stilbenes, etc.) represent a large and diverse group used in the prevention and treatment of cancer. Natural flavonoids are derived from different plant sources and from various medicinal plants including Petroselinum crispum, Apium graveolens, Flemingia vestita, Phyllanthus emblica, etc. Natural flavonoids possess antioxidant, anti-inflammation, as well as anti-cancerous activities through multiple pathways, they induce apoptosis in breast, colorectal, and prostate cancers, lower the nucleoside diphosphate kinase-B activity in lung, bladder and colon cancers, inhibit cell-proliferation and cell cycle arrest by suppressing the NF-kB pathway in various cancers, etc. The current review summarized the anticancer activities of natural polyphenols and their mechanisms of action.


Antineoplastic Agents/pharmacology , Neoplasms/drug therapy , Plants, Edible/chemistry , Plants, Medicinal/chemistry , Polyphenols/pharmacology , Anthocyanins/pharmacology , Anticarcinogenic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Antioxidants/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Flavonoids/pharmacology , Humans , Neoplasms/prevention & control , Polyphenols/therapeutic use , Quercetin/pharmacology , Tea/chemistry
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